A MANUAL OF HYPODERMATIC MEDICATION. 
THE 
TREATMENT OF DISEASES 
THE 
HYPODERMATIC METHOD. 
BY 
EGBERTS BARTHOLOW, M.A., M.D., LL.D., 
Professor of Materia Medica and General Therapeutics in the Jefferson Medical 
College of Philadelphia; Fellow of the College of Physicians of Phila- 
delphia; Member of the American Philosophical Society; Honorary 
Member of the Medical and Chirurgical Faculty of Maryland, 
of the New York and Ohio State Medical Societies; 
Cartwright Lecturer for the year 1880, etc., etc. 
FOURTH EDITION, REVISED AND ENLARGED. 
PHILADELPHIA : 
J. B. LIPPINCOTT & CO. 
London : 16 Southampton Street, Strand. 
1882. Copyright, 1882, by J. B. Lippincott & Co. TO 
COL. JOHN M. CUYLER, 
Surgeon TJ. S. Army, 
I DEDICATE THIS EDITION OF MY MANUAL, 
GRATEFUL REMEMBRANCE OF PERSONAL KINDNESS 
TESTIFY MY ADMIRATION OF HIS MORAL AND 
AND TO 
INTELLECTUAL GIFTS, 
HIS FIDELITY TO PRINCIPLE, 
AND 
HIS GREAT PROFESSIONAL AND ADMINISTRATIVE 
CAPACITY AS A MEDICAL OFFICER 
OF THE ARMY. Je pense meme, a raison de ces circonstances, que I’absorption sous-cutanee, 
qui n’a etc employee jusqu’ici sur rhomme que par exception, devra devenir 
methode generale pour I’administration de tousles medicaments energiques, 
et it I’etat de purete. 
Bernard. 
Who that has suffered from a painful local affection can think of the allevi- 
ation of his sufferings which follows from the subcutaneous injections of an 
anodyne without gratitude? 
Sir W. Jennee. 
Die neueste Zeit, mehr und mehr einer nicht skeptischen aber rationell 
critischen Auffassung in therapeutischen Dingen zuneigend, hat diesen ge- 
waltigen Apparat pharmaceutischer und dynamischer Mittel grossentheils 
tiber Bord geworfen, und beschrankt sich auf wenige, aber in eminenter Weise 
bewahrte, locale Methoden. Dieser gliickliche Uemschwung kniipft sich zum 
Theil an die Hinfiilining der hypodermatischen Injectionen, welche die symp- 
tomatische Behandlung der Nouralgien ausserordentlich vereinfacht und 
vervollkommnet, die meisten alteren Yerfahren ersetzt und iiberflussig ge- 
macht haben. Eulenherg. PREFACE 
TO THE FOURTH EDITION. 
The rapid progress made in therapeutical science ren- 
ders necessary frequent revision of any work devoted to its 
exposition. This is especially true of hypodermatic thera- 
peutics, which deals with the active principles,—the new- 
est products of chemical research, which may be made 
available for this method of administration. Hence, since 
the publication of the third edition of this manual, so much 
has been contributed to this subject, that many changes, 
and considerable addition of new material, has been found 
necessary. I have rewritten much of the work, and have 
added new matter to the extent of one hundred and four- 
teen pages of text. As heretofore, I have incorporated 
those new contributions to therapeutics which seem so 
well grounded as to be permanent additions to knowledge. 
In the substitution of the term hypodermatic for the 
familiar word hypodermic, my action may or may not be 
generally approved, but the change is urgently demanded 
in the interests of a correct nomenclature. To make the 
attempt at substitution successful it will be necessary to 
have the co-operation of medical authors. The unanimity 6 
PREFACE TO THE FOURTH EDITION. 
of scholars in regard to the incorrectness of hypodermic is 
surely sufficient justification for combined effort. 
When referring to the subject of “ iridium points” for 
needles, I did not know the precise origin of the application 
of this remarkable metal for this purpose. I have learned 
since the printing of that part of the work that we owe 
this important improvement to Dr. William Judkins, of 
Cincinnati. 
R. B. 
1509 Walnut Street, 
Philadelphia, Pa. PREFACE 
TO THE THIRD EDITION. 
Several years having elapsed since the publication of 
the second edition of this manual, important alterations 
have been rendered necessary by the advance in knowl- 
edge. But few changes seem desirable in the first part, 
devoted to “ History, Technology, and General Thera- 
peutics,” but many changes and numerous additions have 
been made in the second part, or “ Special Therapeutics.” 
Chapters have been added on the following topics: The 
Morphia Habit and its Treatment, Duboisia, Pilocarpine, 
Chloroform, Chloral Hydrate, Apomorphia, Aquapuncture ; 
and all of the other chapters have had important addi- 
tions made to them, and some of them have been entirely 
rewritten. The size of the volume has been considerably 
increased, and its usefulness enhanced, it is believed, by 
these alterations and additions. 
As this is now the only work on the subject in the Eng- 
lish language before the profession, and as this embodies the 
results of the most recent investigations, the author ventures 
to express the belief that it must continue to be useful to 
those for whom it was originally intended. The exhaustion 
of two editions and the demand for a third indicate that 
7 8 
PREFACE TO THE THIRD EDITION. 
the manual supplies an existing want. The author has, 
therefore, felt encouraged to increase the size and enlarge 
the scope of the manual, so as to make it still more worthy 
of the approval of the medical profession. 
The hypodermatic method has been greatly extended in 
range since it was first employed for the relief of pain. The 
applications of various agents by this mode to the treat- 
ment of different morbid states are even more important 
than the use of anodynes, and it is probable, as other active 
principles are discovered, the method will receive still greater 
extension. As, however, no good can exist in this world 
without a corresponding evil, the usefulness of the subcu- 
taneous medication is embarrassed by a most serious abuse 
in the employment of the hypodermatic syringe for the pur- 
pose of narcotic stimulation. It is no exaggeration to say 
that this abuse is becoming a gigantic evil, to the extent 
and dangers of which the medical profession should be fully 
alive. The author has set forth this subject, as amply as 
the limits of such a manual will permit, in a chapter on the 
morphia habit, and he begs now to add another warning in 
regard to the danger of the lengthened use of morphia sub- 
cutaneously ; for no matter how much the original prescrip- 
tion may have been justified in the condition of the patient, 
and how conscientious the physician in his efforts to prevent 
abuse, if the habit be formed, the mental and moral degrada- 
tion which ensues will always be referred to as the blunder 
or the crime of Dr. So-and-so. 
1509 Walnut Street, 
R. B. 
Philadelphia. PREFACE 
TO THE SECOND EDITION. 
This edition is not a mere reprint of the first. Numer- 
ous and important additions have been made in various 
parts of the work. I have sought to incorporate every 
real improvement in hypodermatic medication which has 
been announced since the appearance of the first edition. 
Much has been proposed that does not appear to me to be 
of permanent value, and hence I have omitted it, in con- 
formity with my original design of keeping on the strictly 
practical side of my subject. Whilst I have omitted much 
that seemed wanting in the essential quality of utility, I 
have not felt at liberty to reject from consideration any 
remedy a knowledge of whose uses might aid the physi- 
cian in an emergency. 
Now that the first enthusiasm which attended the intro- 
duction of this method has died away, we are in a posi- 
tion to estimate accurately its true merits. It is gratifying 
to me to observe that the judgments pronounced in the 
first edition, in regard to the various agents employed in 
this way, have been confirmed by a larger personal experi- 
ence and by the general voice of the medical profession. 
The hypodermatic method is, certainly, a very important 
9 10 
PREFACE TO THE SECOND EDITION. 
addition to our resources, and no physician can be con- 
sidered as doing justice to his clientele who does not give 
them the advantage, in suitable cases, of its great curative 
value. 
In conclusion, I have to express my obligations to the 
reviewers for their very favorable notices of the first edi- 
tion, and to the medical profession for the estimate which 
they have placed on my labors. 
27 West Bth Street, 
R. B. 
Cincinnati. PREFACE 
TO THE FIRST EDITION. 
As a teacher of Therapeutics, and as a practitioner, it 
has frequently been brought to my notice that the informa- 
tion existing in our language on the subject of hypodermatic 
medication is exceedingly meagre. I have been urged by 
students and practitioners to prepare a convenient manual, 
to embody in small compass what is really known of value 
on this subject. This little work is the result. 
Those who do me the honor to read my book will find 
that I have drawn largely upon my personal experience in 
the use of the hypodermatic method. This fact, together 
with the necessity I was under not to enlarge my work 
beyond the boundaries of a “ manual,” will, I trust, excuse 
the apparent dogmatism of my statements. As, however, 
the experience and observation of one individual, how 
great soever may have been his opportunities, must neces- 
sarily, in so extensive and important a subject, be incom- 
plete, I have not neglected the contributions of English, 
French, and German physicians to this department of 
practical medicine. 
I am indebted to the present resident physicians of the 
Grood Samaritan Hospital for important aid. Drs. De 
11 12 
PREFACE TO THE FIRST EDITION. 
Courcey and Rutter, with a scientific zeal which does 
them honor, submitted themselves to experiments in order 
to elucidate some important points in the physiological 
action of morphia and atropia. Dr. Galbraith made and 
recorded the observations. 
Dr. J. S. Unzicker, of this city, a very capable physi- 
cian and pharmaceutist, has placed me under obligations 
for numerous careful experiments, to determine what agent, 
if any, is best suited to prevent change in solutions pre- 
pared for hypodermatic use. 
Cincinnati, Ohio. 
R. B. TABLE OF OO^TEISTTS. 
History or Subcutaneous Medication 17 
PAGE 
The Method . 30 
Definition 30 
The Solution 31 
Extemporaneous 82 
The Syringe 36 
Permanent 34 
Mode of Injecting 43 
Remedies administered by the Hypodermatic 
Method 47 
Local and. Systemic Eeeects oe Subcutaneous 
Injections 49 
The Actions and Uses of the Remedial Agents 
EMPLOYED HyPODBRMATICALLY 55 
Alkaloids of Opium 55 
Morphia and its Salts 55 
The Preparation 55 
The Dose 59 
Physiological Actions 61 
Accidents 71 
Therapy 77 
Codeia and its Salts 118 
Physiological Effects 118 
Therapy 119 
Narceine 119 
Liquor Opii Compositus 119 
The Opium or Morphia Habit 120 
Treatment of the Opium Habit 132 
13 14 
TABLE OF CONTENTS. 
PAGE 
Atropia 140 
The Solution 140 
The Dose 141 
Physiological Effects 142 
Antagonism of Atropia and Physostigma 161 
Therapy 150 
Atropia and Pilocarpine 173 
Atropia and Muscaria 183 
Atropia and Quinia 187 
Atropia and Bromal Hydrate 188 
Atropia and Aconite 189 
Homotropine 190 
Morphia and Atropia .. 192 
History of Antagonism.......... 193 
Physiological Effects 199 
Therapy 223 
Duhoisia 229 
Physiological Effects 229 
Hyoscyamia 232 
Therapy 230 
Solution 233 
Physiological Effects 234 
Therapy 234 
Hyoscine 236 
Strychnia 237 
History 237 
Solution 237 
Physiological Effects 239 
Therapy 243 
The Antagonisms of Strychnia 251 
Strychnia and Chloral 251 
Strychnia and Bromide of Potassium. 257 
Oonia 261 
Strychnia and Nitrite of Amyl 259 
The Solution 261 
Physiological Effects 262 
Therapy '. 263 TABLE OF CONTENTS. 
15 
Curara (Woorara) 265 
page 
The Solution 265 
Physiological Actions 265 
Therapy 267 
Nicotia 270 
The Solution. 270 
Physiological Effects 270 
Therapy 271 
Hydrocyanic Acid 272 
Physiological Effects 272 
Therapy . 272 
Physostigma—Eserine 275 
‘ The Solution 275 
Physiological Effects 276 
Therapy 277 
Pilocarpine 281 
The Solution 281 
Physiological Effects 281 
Therapy.... 284 
Amyl Nitrite 286 
Actions and Uses 286 
Chloroform 288 
Physiological Effects.. 289 
Therapy 292 
Ether and Alcohol 294 
Actions and Uses 294 
Chloral Hydrate 298 
The Solution 298 
The Dose 298 
Physiological Effects 298 
Therapy 300 
Chloral and Morphia 301 
Caffein 303 
The Solution 303 
The Dose 303 
Physiological Effects ' 303 
Therapy 303 16 
TABLE OF CONTENTS. 
PAGE 
Apomorphia 305 
The Solution 805 
Physiological Effects 305 
Therapy 306 
Ergotin 308 
The Solution 308 
Physiological Effects 310 
Quinia 323 
Therapy 316 
The Solution . . 323 
Actions and Uses 325 
Carbolic Acid 331 
The Solution 331 
Physiological Effects 331 
Mercury 334 
Therapy 332 
The Solution 334 
Physiological Effects 336 
Arsenic . 842 
Therapy 337 
Actions and Uses i 342 
Aquapunctitre 346 
Irritant Injections 349 
Injection of Ammonia into the Veins 353 THE TREATMENT OF DISEASES 
THE 
HYPODERMATIC, OR SUBCUTANEOUS, 
METHOD. 
HISTORY OF SUBCUTANEOUS MEDICATION. 
With the opening of the present century began 
attempts to utilize the skin as a medium for the 
introduction of medicaments into the blood. 
Chrestien, of Montpellier, who is also celebrated 
for his researches on the medicinal value of the 
salts of gold, published in 1804 a treatise on the 
iatraleptic method. This work was translated 
into .German by Bischoff the following year. 
Various papers of minor importance appeared in 
French and German literature during the first 
quarter of the century. Lembert, in 1828, and 
Richter, in 1835, discussed, in more or less elab- 
orate essays, the endermic method, and Madden, 
of Edinburgh, in 1838, published an experimental 
inquiry into the physics of cutaneous absorption. 
It is in a high degree probable that Madden’s 
research had its inspiration in the recent devel-  HISTORY OF SUBCUTANEOUS MEDICATION. 
18 
opments in regard to the curative effects obtained 
by the inoculation and implantation of medicines. 
About 1836, Lafargue had published the results 
accomplished by his method; that is, the inser- 
tion of morphia into the skin along the trajectory 
of the nerve affected with neuralgia. Lafargue 
invented a needle-trocar, with which he could 
effectively deposit morphia in the form of a paste 
in the skin. Ascribing the curative results of 
this practice to the pustules that formed at the 
site of the inoculations, he studied with care 
their development and structure. Although it 
was early discovered that the benefit derived 
from the inoculation of morphia was in no way 
related to the pustules produced, the good re- 
sults of the method were most conspicuous, and 
attracted wide-spread attention at that time. Val- 
leix, Cazenave, Malgaigne, Hayem, and others in 
France, Langenbeck, Bertrand, and Yon Bruns 
in Germany, Rynd in Dublin, and Drs. Washing- 
ton and Taylor in New York, repeated the prac- 
tice of Lafargue, in some instances modifying 
the method. These observers, and probably the 
most of- those who practised the inoculations, 
were not concerned, as was the originator of the 
method, as to the mode of development and the 
special forms assumed by the pustules, but re- 
ferred the curative effect to the action of morphia 
on the sensory nerves of the part. It is not sur- 
prising, then, that modifications in the mechan- 
ical details wrere soon introduced. In 1839, Drs. HISTORY OF SUBCUTANEOUS MEDIC A TION. 
19 
Taylor and Washington, of Yew York, on be- 
coming acquainted with Lafargue’s method and 
the important curative effects obtained from the 
inoculations, also inserted morphia along the 
course of the affected nerve in cases of neuralgia. 
Instead of inserting morphia in paste by the in- 
oculation plan, they injected a solution of morphia 
beneath the skin with an Anel’s syringe, an 
opening having been made previously for this 
purpose. Anel’s syringe, the real progenitor of 
the modern hypodermatic instrument, is a small 
syringe having an elongated tapering nozzle, fine 
enough for entrance into the lachrymal duct. To 
convert this into an instrument for subcutaneous 
injection it is only necessary to put a cutting 
point on the small extremity of the canula. 
About the same time, and no doubt influenced 
by Lafargue’s successful practice, Dr, Holland, as 
Dr. Wilson* informs us, “cured a case of neural- 
gia by inserting -A grain of morphia in four 
punctures over the deltoid.” It was also, there 
is reason to believe, the publication of Lafargue’s 
results which induced Mr. Rynd, of Dublin, to 
set about the invention of a complicated instru- 
ment for introducing under the skin a solution 
of morphia by its own gravity. Besides the in- 
oculation method, the endermic use of morphia 
began to be discussed and to be much employed 
about the twentieth year of the present century. 
* St. George’s Hospital Reports, vol. iv. p. 19 (Foot-note). 20 
HISTORY OF SUBCUTANEOUS MEDICATION. 
Brown-Siiquard has always advocated the ender- 
mic method, which he holds is in some respects 
superior to the subdermic. Sieveking * has found 
the endermic plan work well in cases of persistent 
neuralgia, and this experience extends hack be- 
yond the period when was brought forward the 
hypodermatic method, with which he compares 
the endermic. There was, therefore, an abundant 
experience in the local use of morphia just before 
the introduction of the hypodermatic method. It 
was not, however, until the experiments of Dr. 
Alexander Wood, of Edinburgh, were published, 
that the method of subcutaneous insertion of 
morphia began to he properly appreciated. 
Doubtless also in imitation of Lafargue, Wood 
began in 1843 the use of a crude syringe (similar 
to the Anel), with which he injected a solution 
of morphia through an opening previously made 
in the skin. In 1855, or twelve years after the 
first attempts to execute his conception, Wood 
published! an account of his method. It is cer- 
tain, however, that the physicians of Edinburgh 
had become familiar with subcutaneous medica- 
tion by personal communication with Dr. Wood 
before any account of it had appeared in the 
journals of the day. During this time Mr. Ilynd, 
of, Dublin, was carrying on his investigations, 
and he atfirms that “the subcutaneous injection 
* The Lancet, 1861, vol. i.: “ Clinical Remarks on Neural- 
gia.” 
f The Edinburgh Medical and Surgical Journal, 1855. HISTORY OF SUBCUTANEOUS MEDICATION. 
21 
of medicinal substances to combat neuralgia was 
first used by myself in Meath Hospital in 1844.” 
It is obvious that the practice as thus far de- 
veloped had for its chief, if not only, object, to 
obtain the local effects of morphia. Even so late 
as 1861, Hr. Sieveking was concerned chiefly 
about the local action in the endermic and sub- 
dermic application of morphia. We find that 
Hr. Wood began with the same notion, for he 
strongly insisted on the importance of injecting 
the medicament into spots painful on pressure. 
“ The local effect depends,” he says, “ much upon 
the affinity between the particular medicine ad- 
ministered and the tissue to which it is applied.” 
Hot, like Lafargue, seeing a relation between the 
forms of pustules and the curative action on the 
nerves affected, but an “ affinity” between the 
morphia and the morbid state of the nerves, Wood 
attributed the cures effected by the new method 
to the local action. He did not fail to observe, 
as, indeed, he graphically described, the systemic 
or general effects which so speedily follow the 
subcutaneous injection of morphia. 
The question of priority of discovery has been 
warmly disputed. As is usual when great im- 
provements are made in the arts and the sciences, 
the way to discovery is prepared by the work of 
many investigators. The inventor finally co- 
ordinates the results of his predecessors, and 
adds the experiment or the needed acquisition 
which completes the discovery. Wood estab- 22 
HISTORY OF SUBCUTANEOUS MEDICATION. 
lished his right to he regarded as the discoverer 
of the hypodermatic method, by using the syringe 
for injecting a solution of morphia, and by the 
publication of his experiments and their results. 
Mr. Rynd, who claims to have been the first to 
employ the new method, must be ranked with 
those who were working in the same direction,— 
like Drs. Taylor and Washington of this coun- 
try,—but who failed to make public their im- 
provements or discoveries in time to substantiate 
a claim to priority. Dr. Sieveking asserts that 
“ Dr. Kurzak, of Vienna, was the first, he be- 
lieves, to employ the subcutaneous or hypodermic 
method, which was then largely used by Dr. 
Wood, of Edinburgh.”* There is no reference 
to the authority for this statement, hence we are 
compelled to resort to contemporaneous German 
works for evidence. The treatise of Prof. Dr. 
Eulenberg,f the most thorough and elaborate 
which has thus far been published on this subject, 
and which is peculiarly rich in its bibliographical 
lists, contains no reference to Dr. Kurzak’s claims 
to priority, or to any work done by him on this 
subject. Dr. Eulenberg also in a more recent 
publication! on the same topic, Dr. Erlenmeyer,§ 
* The Lancet, 1861, vol. i. p. 105. Supra. 
f Die hypodermatischen Injectionen der Arzneimittel, etc. 
Berlin, 1867, p. 10. 
t Percutane, intracutane, und suhcutane Arzneiapplication, 
Allgemeine Therapie, i. 328. 
§ Die subcutanen Injectionen der Arzneimittel, p. 1. HISTORY OF SUBCUTANEOUS MEDICATION. 
23 
and Dr. Lorent* are equally unmindful of Kur- 
zak’s claim to be recognized as the discoverer of 
hypodermatic medication. 
How far, if at all, the progress of physiolog- 
ical research influenced the endermic and sub- 
dermic application of remedies cannot now be 
stated with precision; nevertheless there are some 
important facts which have a distinct relation to 
the subject under consideration. The first re- 
search into the action of a medicament made by 
the physiological method was conducted by Ma- 
gendie, about 1819, upon the upas and mix vomica, 
and on strychnia. In the course of this research 
Magendie first demonstrated that poisons acted 
by absorption into the blood. To ascertain the 
general effects of the remedy being examined, he 
introduced some of it under the skin of the thigh, 
and then observed the actions as they occurred. 
This experiment was performed in 1819.f In 
the course of this research, also, he tested the 
rate of absorption from different parts, including 
the veins. Subsequently, Bernard, pursuing his 
investigations into the action of curara, and also 
in his studies of the poisons, introduced the med- 
icament, the subject of experiment, under the 
skin.J It was, therefore, perfectly well known 
* Die hypoderm. Inject, nach clinischen Erfahrungen. 
Leipzig, 1865, p. 1. 
t Ann. de China, et de Physiol., vol. xvi., 1819. 
f Leqons sur les Effets des Substances toxiques et medica- 
menteuses. Paris, 1857, p. 272. 24 
HISTORY OF SUBCUTANEOUS MEDICATION. 
to physiologists that medicines introduced under 
the skin were rapidly absorbed, producing their 
characteristic effects, at the time when Lafargue 
was studying the forms of pustules caused by the 
endermic application of morphia, and Mr. Eynd, 
of Dublin, was inventing an instrument for the 
more efficient introduction of morphia into the 
skin. 
It is the more surprising that the progenitors 
of the hypodermatic method should have referred 
the curative action of morphia to the local im- 
pression, since they observed that it produced 
the most decided systemic effect. Although 
Wood directed that “ the instrument is not to be 
put into the place where the patient complains of 
pain, but into the spot where you find you can 
awaken pain on pressure,” he accurately describes 
the rapidity and extent of the narcotic impres- 
sion. The injunction to insert morphia into the 
spot painful on pressure had its origin in the 
practice of Yalleix, who, in his work on neural- 
gia, then in the first flush of its popularity, had 
recommended the method of Lafargue. That 
Wood fully appreciated the extent of the sys- 
temic effect of morphia when administered hypo- 
derraatically is evident in the following pas- 
sage : 
“ It is truly astonishing how rapidly it affects 
the system. If you throw in a large quantity 
of morphia, you will see the eyes immediately 
injected and the patient narcotized, and in a few HISTORY OF SUBCUTANEOUS MEDICATION. 
25 
minutes afterwards you will see him in a profound 
sleep.” 
Making such observations, it is impossible that 
he should be unaware of the effect of the remedy 
thus administered on the centres of conscious 
impressions; but he yet attributed the curative 
effect in neuralgia to the local action. 
It was reserved for Mr. Charles Hunter to dem- 
onstrate the important fact that the application 
of the injection to the painful points, as con- 
tended for by Wood, was really unnecessary, and 
that equally good effects followed the introduc- 
tion of the injection into a distant part. Mr. 
Hunter’s first paper appeared in 1859, and was 
entitled “ Experiments relative to the Hypoder- 
mic Treatment of Disease.” These experiments, 
made on animals, demonstrated that hypoder- 
matic injections “ acted by absorption; that they 
acted quicker than by the endermic method, or 
than stomachic doses; that they acted more effec- 
tually ; and that a small injected dose was equiva- 
lent to a much larger one by the stomach.” Mr. 
Hunter was permitted to use the method of Wood 
on two patients afflicted with neuralgia, in care 
of Dr. Pittman in St. George’s Hospital. As 
“ both had abscess in the neuralgic site, from the 
continuance of the localization,” the point of 
introduction of the injection was varied, and it 
was found,—“ first, that in neuralgia equal bene- 
fit followed distant injection of the cellular tissue 
as followed the injection of the neuralgic site ; 26 
HISTORY OF SUBCUTANEOUS MEDICATION. 
secondly, that localization was not necessary to 
benefit a given part; and, thirdly, that for certain 
reasons it was better not to localize,—the chief 
being: 1, the infliction of unnecessary pain; 
2, the almost certain risk of irritating, thicken- 
ing, or inducing matter in the part from repeti- 
tion ; and, 8, it became evident that a large class 
of neuralgia would be excluded from this treat- 
ment if it was necessary to inject the neuralgic 
site.” 
Great praise must he awarded Mr. Hunter for 
his success in demonstrating these important 
conclusions, and tor popularizing his method. 
His industry in collecting facts and presenting 
them to the profession was indefatigable- His 
views were perseveringly advanced, with an in- 
telligent appreciation of the nature and impor- 
tance of his facts. He read papers before soci- 
eties ; he published articles in the “ Medical 
Mirror,” “ Lancet,” “ Medical Times and Ga- 
zette,” and “ British and Foreign Medico-Chirur- 
gical Review;” he issued a pamphlet* containing 
all of his previous papers and some additional 
facts, and he enlisted, by personal effort, many 
of the physicians and surgeons of London in a 
trial of the new therapeutical expedient. 
It was thus, chiefly through the efforts of Mr. 
Hunter, that the method of Wood, previously 
* On the Speedy Relief of Pain and other Nervous Affec- 
tions by means of the Hypodermic Method. Churchill, Lon- 
don, 1865. HISTORY OF SUBCUTANEOUS MEDICATION. 
27 
confined to Edinburgh and to Dublin, became 
naturalized in England. Mr. Hunter’s papers 
in the “ Medical Times and Gazette” attracted 
the attention of Courty, of Montpellier, and Be- 
hier, of Paris, who popularized the new method 
in France. It was soon after tried and reported 
upon favorably by Scanzoni, of Wurtzburg; Op- 
polzer, of Vienna; Graefe, of Berlin, and nu- 
merous other eminent authorities on the Conti- 
nent. In 1865 a small treatise, by Dr. Lorent, of 
Bremen, appeared at Leipsic. A monograph, by 
Dr. Erlenraeyer, passed to the third edition in 
1866. In 1867 the second edition of the elab- 
orate work of Dr. Albert Eulenberg was pub- 
lished in Berlin. Dr. Eulenberg gives a list of 
two hundred and twenty articles and essays in 
various languages, but chiefly in German, which 
appeared on this subject from 1855 to the date of 
publication of the second edition of his work. 
From these facts may be seen the extraordinary 
extension which has been given to this method 
of treatment on the Continent. 
The method of Wood, as illustrated by Hun- 
ter, met with a more favorable reception on the 
Continent than in the country of its origin. 
cording to Dr. Anstie,* “ it is still very much 
unappreciated” in England. It is true that the 
principal English physicians and surgeons think 
highly of the method, and now employ it largely, 
* The Practitioner, July, 1868.  HISTORY OF SUBCUTANEOUS MEDICATION. 
but, as Dr. Anstie informs us, there are “ prac- 
titioners who will not admit that there can he any 
particular advantage in it which the old way of 
giving medicines does not offer.” 
The hypodermatic method, soon after its publi- 
cation by Wood, was introduced into the United 
States. Dr. Fordyce Barker, of New York, 
whilst in Edinburgh in 1856, was presented by 
Prof. Simpson with a hypodermatic syringe. 
Soon after his return home, in May, 1856, he used 
this instrument, and was, consequently, the first 
in this country to practise the method of Wood. 
Prof. Barker’s syringe was the model from which 
Tiemann’s instruments were made. In August, 
1857, the late Prof. George T. Elliot published 
some observations on the hypodermatic method. 
It thus appears that the new mode of using medi- 
cines was known and employed in New York 
when Dr. Buppaner’s articles appeared in 1860 
in the “Boston Medical and Surgical Journal,” 
the first on this subject published in this country. 
Not only was the hypodermatic method as 
taught by Wood early naturalized in the United 
States, but, as we have already shown, it was prac- 
tised in New York before Wood made public his 
discovery, or before the earliest date assigned by 
Mr. Rynd, of Dublin, for his use in this way of re- 
medial agents. Dr. Isaac E. Taylor, in a commu- 
nication to the “New York Medical Gazette,”* 
* April 23, 1870. HISTORY OF SUBCUTANEOUS MEDICATION. 
29 
shows that Dr. Washington and he used practi- 
cally the same method in the New York City 
Dispensary so long ago as 1839. The idea was 
suggested to them hy the results of Lafargue’s 
method of inoculation. Instead, however, of 
inserting the solid medicament by means of a 
grooved needle, as was Lafargue’s practice, these 
gentlemen punctured the skin with a lancet, and 
by means of an An el’s syringe threw a solution 
of the medicine under the skin. This mode of 
operating was the same practically as that sug- 
gested and used by Wood in 1855. 
When the first edition of this work was pub- 
lished (1869), I was not aware of the above 
facts in regard to the introduction of the hypo- 
dermatic method in this country. It affords me 
sincere pleasure to attribute to my own country- 
men the credit to which they are justly entitled. THE METHOD. 
Definition.—Mr. Hunter, in 1859, proposed the 
word hypodermic as the name for the new method, 
in imitation of terms already in use, as epidermic, 
etc. The word hypodermic is compounded of 
two Greek words, utw, under, and dsppa, the skin. 
This word is condemned by all scholars, who are 
unanimous that the term should he—in accord- 
ance with the rules of construction—hypoder- 
matic. That eminent philologist and Oriental 
scholar, Mr. Fitzedward Hall, H.C.L., assures me 
that under no circumstances is hypodermic allow- 
able. It is, however, so firmly established, and 
in such universal use, that the substitution of 
the more correct term can be accomplished only 
by combined effort. In former editions of this 
work I have followed almost universal custom in 
using hypodermic, but in the present edition, and 
in the fourth edition of my “ Practical Treatise 
on Materia Medica and Therapeutics,” I have 
departed from custom to do my part towards 
the introduction of the more correct phrase, hypo- 
dermatic. The word subcutaneous expresses the 
same idea, and is in all respects appropriate. 
By this method the medicament is introduced 
beneath the skin, usually into the subcutaneous 
30 THE METHOD. 
31 
areolar tissue, but also into tbe muscles. Further, 
the instrument may be employed to inject medi- 
cines into the serous cavities, into the veins, into 
the parenchyma of organs, and into the tissues 
of morbid growths. Although these topics are 
in some respects foreign to subcutaneous medica- 
tion, it is my purpose to include them in the 
present edition, since the same process is fol- 
lowed practically in all eases when the hypoder- 
matic syringe is the instrument emplo}Ted. The 
method consists in— 
1. A suitable solution of the medicament; 
2. An instrument for injecting the solution 
beneath the skin, into the subcutaneous areolar 
tissue, or into the tissues of muscles, organs, or 
new formations. 
The Solution,—A medicine employed for 
hypodermatic use should be capable of perfect 
solution in the vehicle, which is usually distilled 
water. Particles of medicine undissolved are not 
only not in a condition to be readily absorbed, 
but also act as irritants to the tissue, producing 
inflammation and abscess. 
The solution should be free from dirt or foreign 
matter of any description, and should be neutral, 
or, at least, without decided acid or alkaline 
property. Any substance which will coagulate 
the blood, or produce violent irritation, is unfit 
lor hypodermatic use. 
A solution, even of a neutral substance, should 
not be too concentrated. Pure distilled water is 32 
SUBCUTANEOUS MEDICATION. 
entirely harmless, and the quantity of fluid in- 
jected is, within certain limits, a matter of indif- 
ference, provided suitable care he used in select- 
ing the site and in injecting. Concentrated 
solutions, easterns paribus, are more apt to produce 
local irritation than dilute solutions. Moreover, 
if the solution of a powerful alkaloid he very con- 
centrated, a drop too much injected may produce 
dangerous symptoms. In ordinary syringes, a 
few drops remain at the bottom of the cylinder 
and in the needle; hence it is difficult, in using 
a very concentrated solution, to inject the precise 
amount desired, or, indeed, to approximate to it 
very closely. 
Solutions may he extemporaneous or permanent. 
For reasons to be detailed presently, extempora- 
neous solutions are generally to he preferred. 
The agent to he injected should he dissolved, at 
the moment when required, in clean water. Dis- 
tilled water is not essential, is not even better 
than ordinary river-, spring-, or well-water free 
from visible impurities. Distilled water quickly 
becomes cloudy on exposure to air, because of 
the growth in it of a minute but visible vegetable 
organism. I find, after ample experience, that 
river-water that does not contain recognizable im- 
purities is perfectly suitable for the solution of 
alkaloids and other agents used subcutaneously. 
If distilled water be employed for making the 
solution, it should be freshly distilled. 
For the purpose of preparing extemporane- THE METHOD. 
33 
ous solutions, powders of a given weight are 
made in advance. It is, unfortunately, quite 
impracticable to properly subdivide and make 
into powders those alkaloids that are given 
in hundredths of a grain. Morphia, morphia 
and atropia, pilocarpine, apomorphia, and some 
others may be put up in powders for solution as 
required, but the same arrangement is not prac- 
ticable for many other remedies. Gelatine tab- 
lets, containing a definite measure of the medi- 
cament incorporated with gelatine when fluid, 
have been in use for several years, especially in 
England. The gelatine disks or tablets are slow 
to dissolve, and the absorption of the gelatine is 
imperfect, so that local irritation is apt to result 
from them. 
The most important improvement lately made 
in this respect is the “ hypodermic tablets” pre- 
pared by Messrs. Wyeth, of Philadelphia, at the 
suggestion of Dr. S. Augustus Wilson, of the 
same city. They are compressed pellets, con- 
taining definite measures of the agents usually em- 
ployed mixed with sulphate of soda. The com- 
pression is effected by a machine, and the tablet, 
when complete, is a circular disk, about one-fifth 
of an inch in diameter and a line in thickness. 
The quantity of sulphate of soda in. each tablet 
is one-fourth of a grain, which is intended to 
furnish a proper basis and to aid in the solution 
of the alkaloid. All agents now employed hy- 
podermatically are put up in this form and fur- 34 
S ÜBCUTANEO US MEDIC A TION. 
wished to “ the trade” in quantity. When it is 
proposed to use a tablet subcutaneously, it is 
dissolved in sufficient water, preferably in warm 
water, and is then drawn up into the syringe in 
the usual way. Tablets that have become old 
dissolve slowly, and careful and patient tritura- 
tion is necessary to effect perfect solution. 
Permanent solutions are prepared from formulae 
and kept on hand for use as required. The most 
carefully prepared solution rapidly deteriorates 
by keeping. In a few days a faint cloud appears, 
and soon after the solution becomes turbid. The 
cloudiness and turbidity of an alkaloid solution, 
made with pure distilled water and free from 
visible impurities, are due to the development of 
a minute organism,—the penicilium. This plant 
grows partly at the expense of the alkaloid, and 
hence whilst the solution increases in turbidity 
it declines in power. Filtration removes the 
visible impurities, but a solution which has once 
been turbid is ever afterwards unfit for subcuta- 
neous injection. A solution long kept, although 
it may not be turbid, or if turbid has been fil- 
tered, will, when injected, often cause an indu- 
rated and painful swelling, which remains for 
months, and is slowly absorbed or suppurates. 
In some cases a cyst forms at the site of such an 
injection, slowly enlarges, and when finally emp- 
tied is found to contain gelatinous, purulent mat- 
ter, with a small slough of connective tissue. 
If permanent solutions are to be used, it is THE METHOD. 
35 
extremely desirable to prepare them with men- 
strua that will not undergo change, or to make 
such additions to ordinary solutions as will pre- 
vent the growth of the penicilium. The distilled 
waters of cherry-laurel and of eucalyptus have 
been used successfully, and solutions made with 
them do not exhibit any change for several 
weeks at least. They are not irritating, and do 
not affect the system in the quantity required 
for subcutaneous administration. The imitation 
cherry-laurel and eucalyptus waters, prepared by 
triturating the oil of bitter almonds, and eucalyp- 
tol, with magnesia and water, are far inferior for 
this purpose to the waters made by distillation; 
nevertheless, in the absence of the genuine, the 
artificial water may be used for a short period. 
The addition of certain antiseptics to the 
aqueous solution of alkaloids is an efficient 
method of preventing change. Two to four 
minims of carbolic acid to the ounce of solution 
of morphia will act efficiently for several weeks 
in preventing the growth of penicilium. A 
minim of carbolic acid to the drachm of solution 
is not enough to act injuriously, and will con- 
tinue an antiseptic action for several months. 
This agent increases a very little the pain and 
smarting which attend the injection at the first 
moment, but then a state of lessened sensibility 
follows. Two to four grains of salicylic acid to 
the ounce of solution will also prove effective in 
preventing change, but it increases the irritation 36 
SUBCUTANEOUS MEDICATION. 
—the smarting which attends the injection. 
Resorcin may he substituted for salicylic acid, as 
it is almost free from irritating qualities and is 
equally as effective as an antiseptic. Boracic and 
benzoic acids, like carbolic acid, have the power 
to stop the growth of the penicilium, hut are 
more irritant than the latter and than resorcin. 
The mineral acids are effective both to prevent 
change and to increase the solubility of many of 
the alkaloids, hut they are much too irritating to 
he employed for the preparation of solutions for 
subcutaneous injection. Indeed, the acids are 
responsible for most of the abscesses, the slough- 
ing, and the tetanus which have followed the in- 
fection of medicaments. My conclusion is that 
it is far better to make extemporaneous solutions 
than to rely on any formula, how well adapted 
soever it may appear to be to the purpose in 
view. 
The Syringe.—The instrument used by Wood 
in his first experiments was a Fergussoji’s syringe, 
intended for the injection of liquor ferri chloridi 
into nsevi. This instrument, like the Anel’s 
and the Pravaz syringe (French), required a pre- 
liminary opening to be made in the skin, through 
which the canula could be passed. Mr. Hunter 
made a most necessary and important improve- 
ment when he had a cutting point put on the 
canula for transfixing the skin.* The details of 
* On the Speedy Relief of Pain and other Nervous Affec- 
tions, etc. Pamphlet. London, 1865. THE METHOD. 
37 
the manufacture have been further elaborated, 
and now very perfect instruments can be ob- 
tained. The material of which the barrel is 
constructed is glass, bard rubber, celluloid, Ger- 
¥ig. 1. 
Glass Syringes, 
man silver, pure silver, or gold. Glass is fragile, 
and the bore of glass tubing is so unequal that it 
is difficult to obtain a piece uniform in calibre 
throughout. The fragility is corrected by enclos- 
ing the tube in metal, leaving a slit through which 38 
SUB GUTA NEO US MED IGA TION. 
the contents can be inspected and the graduation 
read. In the original glass syringes, and in the 
inferior ones now made, the mountings of the 
cylinder are fastened on hy sealing-wax or other 
cement, and hence loosen easily, and leak, or 
give way altogether. The new material known 
as “ celluloid” is well adapted to the making of 
cylinders. As it is moulded in a soft state, per- 
fect uniformity in the calibre can he secured, and 
as it can be made transparent, the contents are 
visible. Although possessed of a transparency 
almost equal to glass, it is not fragile, and will 
not break by falling on a tiled or stone floor. On 
the other hand, it is soluble in chloroform, and 
when the syringes made of it require repairs 
they can be made only at the shops of the cellu- 
loid company. Hard rubber is a suitable mate- 
rial for syringes, but they are usually made very 
poorly. An exception to this statement is the 
syringe of Leiter, of Vienna, made so that the 
parts fit accurately without screws, and hence 
very readily cleaned and very durable. Of course 
the contents of a hard rubber syringe are not 
visible, but the graduation of the piston may be 
accurate. 
Silver, according to my experience, is the best 
material for making hypodermatic syringes. It 
is practically indestructible, and is not acted on 
by any fluid introduced into the tissues. The 
barrel can be constructed with a uniform bore, 
and an accurately-fitting piston assured. The THE METHOD. 
39 
objection to it is that its contents are invisible; 
but the piston-rod can be graduated with the 
utmost nicety. German silver may be substi- 
Silver Syringe and Needles. 
German Silver Syringe. 
tuted for pure silver, as no solutions are injected 
that would corrode this material. Gold has also 
been utilized for the construction of syringes. 
They are beautiful in appearance, durable and 40 
SUBCUT A NEC US MEDIC A TION. 
satisfactory in usage, but tliey are expensive, 
entirely out of proportion to their utility. 
The needle is a very important part of the in- 
strument. The needles furnished with most in- 
struments are too large, and have an abrupt 
shoulder at the cutting extremity, which makes 
Fig. 4. 
The Author’s Silver Syringe, with Gold Needles, Iridium Pointed, 
as made by Wm. Autenreith, Cincinnati, Ohio. 
the perforation of the skin difficult. The needle 
should be as small as possible, and the cutting 
part should have a lancet-shape, hut without the 
groove or depression which some makers put in. 
The best needle is made of gold, with a hardened 
or an iridium point, as now made by Mr. Auten- THE METHOD. 
41 
reith, of Cincinnati. Steel is the visual material, 
but it is more apt to cause after-troubles, such as 
nodules, abscesses, etc., because it undergoes oxi- 
dation, especially when put away damp. The 
needle should have a wire passed through it when 
not in use, for the double purpose of excluding 
any solid particles and preventing the closure of 
the calibre. Every instrument should he provided 
with several “ rimmers,”—long, tapering, and 
Fig. 5. 
Riramers. 
very fine steel rods used by watchmakers,—which 
are very useful for cleaning out obstructed nee- 
dles. As in the intervals of the use of syringes 
the piston dries and will not work properly, the 
barrel should be closed by a cap, which is put on 
or screwed on when the needle is removed. A 
few drops of water may be drawn in, and then 
the cap adjusted. In this way the piston is kept 
moist and in working order as effectively as if it 
were in frequent use. Dr. Whittaker, of Cincin- 
nati, first proposed to use them. Weiss, of Lon- 
don, has invented a new piston, which promises 
to be very useful. It is made of hard rubber, 
thin enough to be flexible and adapt itself to the 
barrel of the syringe, so that no leather packing is 
required. The superiority of this piston in neat- 
ness, cleanliness, and effectiveness is obvious. 42 
SUB CUT A NEO US MEDIC A TION. 
Undoubtedly the utmost circumspection is 
necessary in the use of the needles,—for dis- 
eased blood, or specific virus, may be transmitted 
from one person to another. Besides the cleanli- 
ness enjoined, the practitioner must see to it that 
needles used in infected persons must not be 
again employed in those free from infection. 
Fig. 6. 
Box containing Syringe, Needles, and Hypodermic Tablets, proposed 
by Dr. J. W. White, and made by Gemrig. 
There are several methods by which the hypo- 
dermatic syringe may be charged with the re- 
quired dose of the solution. The fluid may he 
drawn up into the barrel by aspiration, or the cap 
of the barrel may be unscrewed, the piston re- 
moved, and the solution poured into the barrel. 
The former is more convenient. If air enter when 
the fluid is being drawn up, it may be readily 
expelled by inverting the barrel and moving up THE METHOD. 
the piston until a drop of the fluid presents itself 
at the orifice of the needle. In using a glass 
instrument which is graduated, more of the solu- 
tion should he drawn into the barrel than it is 
contemplated to administer, and, fixing the eye 
upon those divisions of the scale representing 
the amount to he injected, the piston is made to 
traverse slowly the proper space. In filling my 
silver instrument I pursue the following method: 
I pour into a minim-glass the proper quantity of 
the solution. The needle being screwed into its 
place, I insert the point into the solution and 
draw the whole amount into the barrel of the 
syringe by slowly elevating the piston, inclining 
to one side the minim-glass, in order to take up 
the last drop. If air have entered, I invert the 
syringe and push up the piston slowly until it is 
all expelled. An allowance of one minim should 
he made for loss when more than ten minims 
are used. 
Mode of Injecting.—Take up between the 
thumb and forefinger of the left hand a loose 
fold of skin in some convenient situation. Push 
m the needle with a quick and decided motion, 
at a right angle to the direction of the fold. The 
resistance ceasing, it will be known that the 
needle has perforated the skin, and the point of 
the needle may also now be freely moved about 
hi the subcutaneous areolar tissue. It is better 
to pass the needle for an inch or more under the 
skin, to have sufficient space for the fluid. The 44 
SUBCUTANEOUS MEDICATION. 
injection must be made slowly, drop by drop, so 
that tbe fluid may diffuse itself without ruptur- 
ing any small vessels or the fibres of the connec- 
tive tissue. When all has been injected, with- 
draw the needle slowly, pressing at the same 
time upon the puncture to prevent escape of the 
fluid. A few minutes’ pressure will suffice to 
retain the fluid, and to arrest the little bleeding 
which sometimes takes place. A hit of isinglass 
plaster may also be applied to the puncture, but 
this is generally unnecessary. By some persons 
the fluid is always injected into a muscle; and 
this is the method of using strychnia in paralysis, 
hut it is not frequently adopted for other agents 
employed hypodermatically. To inject into a 
muscle, for example the hrachialis anticus, make 
it tense by flexing the forearm, and then by a 
quick motion thrust the needle directly into the 
muscle. It is claimed for this method that it is 
less painful andTess liable to be followed by ab- 
scess than by the injection under the skin, hut it 
is obviously improper if any considerable amount 
of fluid is to be injected. 
In practising the hypodermatic injection, it is 
important to avoid puncturing a vein. Serious 
depression of the powers of life, fainting, and 
sudden and profound narcotism have been pro- 
duced by injecting a solution of morphia directly 
into a vein. Fatal collapse might he induced by 
injecting air into a large vein along with the 
solution. THE METHOD. 
45 
Bony prominences should also be avoided, for 
in these situations the skin is not sufficiently 
loose to permit the ready entrance of the fluid, 
and inflammation and abscess will follow a too 
forcible injection. 
The puncture should not he made, as a rule, 
into inflamed parts. I have known a bad phleg- 
mon produced by injection into the tissues of an 
inflamed wrist. 
It is not necessary to follow the original method 
of Wood, and inject into those points in which 
pain can he awakened by pressure. Some excep- 
tions to this rule undoubtedly exist, as will here- 
after be shown, but they are not numerous. The 
arm, the outer face of the thighs, the calves, the 
abdomen, and the back are suitable places for 
the injection. The arm, about the insertion of 
the deltoid, is generally selected. Eulenberg 
makes the assertion that the effect is slower 
when the injection is made in the back than in 
any other situation.* I have not been able to 
observe any difference in the rapidity of effect 
as influenced by the site of the puncture. If, as 
sometimes happens, the patient prefer injection 
into the painful part, it will be well to yield to 
his prejudices, provided no contra-indication exist 
thereto. 
If the patient be timid and intolerant of pain, 
the sensibility of the skin may be lowered by 
* Die hypodermatische Injection, etc., op. cit., p. 62. 46 
SUBCUTANEOUS MEDICATION. 
ether or rhigolene spray. A piece of cotton 
cloth moistened with chloroform and held on the 
skin a few minutes is nearly as effective as the 
douche, and much more convenient. Sometimes 
redness and swelling take place at the site of the 
injection. This is best relieved by a cold wet 
compress. REMEDIES ADMINISTERED BY THE HYPODER- 
MATIC METHOD. 
Source. 
Preparation for Subcutaneous 
f Morphia and its salts. 
Codeia and its salts. 
Narceine. 
Apomorphia. 
J Atropia and its salts. 
I Homotropine. 
Use. 
Opium. 
Belladonna. 
Duboisia. 
Hyoscyamus, 
Duboisine and its salts. 
Hyoscyamia and its salts. 
Alcohol. 
J Whiskey, Brandy. 
\ Diluted Alcohol. 
Chloral Hydrate. 
Chloroform. 
Chloral. 
Chloroform. 
Ether. 
Ether. 
Nux Yomica. 
Strychnia and its salts. 
{Aqueous Extract (Ergotin). 
Sclerotinic Acid. 
Ergotinine. Fluid Extract. 
Fluid Extract. 
Ergot. 
TJstilago Maidis. 
Digitalis. 
f Digitaline and its salts. 
I Tincture of Digitalis, 
f Conia and its salts. 
I Conia and Morphia. 
Conium. 
Tabacum. 
Aconite. 
Nicotine and its salts, 
f Aconitia and its salts. 
I Napelline. 
f Extract. 
I Eserine and its salts. 
Physostigma. 
47 48 
SUBCUTANEOUS MEDICATION. 
CURARA. 
Curara. 
Curarine. 
Hydrocyanic Acid. 
Hydrocyanic Acid. 
Colchicia and its salts. 
Pilocarpine and its salts. 
Muscarine and its salts. 
Caffeine and its salts. 
Quinia and its salts. 
Colchicum. 
Pilocarpus. 
Muscaria. 
Caffea. 
Cinchona. 
Carbolic Acid. 
Resorcin. 
Arsenic. 
Carbolic Acid. 
Resorcin. 
Liquor Potassii Arsenitis. 
Corrosive Chloride of Mer- 
cury. 
Peptonate of Mercury. 
Nitrate of Silver, 
Mercury, 
Silver. 
lodine. 
Lugol’s Solution. 
Tincture of lodine. 
Iron. 
Ferrum Dialysatum. 
Liquor Ferri Sulphatis 
Aquapuncture. 
Water. 
Pepsin. 
Ammonia. 
Salines. 
Glycerite of Pepsin. 
Aqua Ammonise. 
Salts of Sodium and Potas 
sium. LOCAL AND SYSTEMIC EFFECTS OF SUBCUTANEOUS 
INJECTIONS. 
All agents injected under the skin, even water, 
produce some irritation at the point of puncture. 
Smarting, burning, followed by redness, and a 
more or less extensive swelling or wheal, are the 
usual phenomena. Very acute pain is caused 
when a nerve is punctured. When a few drops 
only are injected, there may be some trivial red- 
ness to indicate the point where the needle en- 
tered, and no after-swelling or irritation. The 
resulting wheal, when considerable fluid is in- 
jected, resembles the swelling of urticaria or of 
erythema nodosum. An indurated nodule may 
form, to suppurate slowly, and discharge after 
some weeks or even months. In such a case more 
or less sloughing usually occurs, including the are- 
olar tissue and a portion of the skin, a depressed 
cicatrix resulting. Sometimes a frank abscess, 
sometimes an induration, and, rarely, a cyst are 
produced by the injection. There can he no doubt 
that, if the proper precautions are taken, and the 
tissues of the individual injected are sound, no 
induration or inflammation will result from the 
injections. If the rules already laid down for the 
preparation of solutions are not complied with; if 
49 50 
SUBCUTANEOUS MEDICATION. 
the syringe or needle is dirty or rusty; if injury 
is done by rough handling; or if the patient is in 
a cachectic state, the local accidents above de- 
scribed may happen. Inflammation has resulted 
from partial puncture of the skin and forcing in 
the fluid violently. In some of the reported 
cases, all accessible parts of the body have been 
covered with cicatrices, partly-healed sores and 
ulcers, and recent abscesses. Making due allow- 
ance for the sensational spirit in which these cases 
have been narrated, there are still facts enough 
to show conclusively that through carelessness 
in the preparation of solutions, in the treatment 
of the syringe and needles, and in the method of 
injecting, inflammation and abscesses will result. 
The puncture of a vein may cause some loss of 
blood, or the formation of a purpuric spot, and 
the fluid may be thrown directly into the blood, 
or be drawn into the vein through the opening 
made by the needle. In the former case there 
will be an almost instantaneous action of the 
medicine; in the latter, slower yet rather quick 
and powerful effects. These will be described 
wdien the remedy concerned is under discussion. 
In a few instances, the injury of nerves at the 
site of former punctures has induced tetanus, 
but the nervous system was prepared by the dis- 
ease for which the injections were originally 
used, or by the cachexia induced by the chronic 
morphinism. 
The systemic effects produced by the hypoder- SYSTEMIC EFFECTS. 
51 
malic injection of remedies must now be com- 
pared with the stomachal administration. A 
remedy entering the blood through the stomach 
is affected in its physiological and therapeutical 
action by the condition of that organ. Disease— 
for example, gastric catarrh—may hinder if not 
entirely prevent diffusion through the mucous 
membrane. The rate and extent of absorption 
are influenced by the presence of other ingesta, 
by the state of repletion of the veins, and by the 
condition of the liver. The digestive fluid un- 
doubtedly exerts a chemical action on many 
remedial agents, forming combinations some- 
times more, sometimes less powerful. Again, as 
the state of the nerves has an important influ- 
ence on absorption, it is obvious that those reme- 
dies which depress the activity of nerves must 
constantly lessen by repetition the power of the 
stomach to convey them into the circulation. 
On the other hand, when a medicine suitable for 
the purpose is thrown under the skin, its physio- 
logical and therapeutical effects are produced in 
the fullest degree and in the most characteristic 
form. It follows that the therapeutical properties 
of a drug must differ not only in degree, but also 
in kind, according as it enters the blood through 
the stomach or by the subcutaneous areolar tis- 
sue. Experience and observation abundantly 
demonstrate the truth of this statement. The 
subcutaneous use of certain drugs has developed 
very valuable therapeutical properties, which 52 
SUBCUTANEOUS MEDICATION. 
the stomachal administration had not even sug- 
gested. Bernard * affirms that this mode of ad- 
ministering remedies, which has hitherto been 
the exception, must become the general method 
for the use of active principles. The advantages 
of this method over other methods, considered 
from the point of view of practical therapeutics, 
are manifold. 
The effect is produced more speedily, and the 
whole effect of the quantity introduced. 
The results are more permanent and curative. 
Gastric disturbance rarely occurs, and irritation 
of the stomach is avoided. 
The administration may be made to persons 
unwilling or unable to swallow. 
It follows, then, that remedies suitable for this 
purpose may be used hypodermatically, to pro- 
duce— 
Ist. All of the physiological and therapeutical 
effects which can be accomplished by them when 
given by the stomach; and, 
2d. The physiological and therapeutical effects 
peculiar to this method. 
The hypodermatic method may he employed 
for— 
1 st. A local action only. 
2d. The general or systemic effects. 
* Archives Generales, 1864. LOCAL EFFECTS. 
53 
To cure naevi, aneurisms, varicose veins, etc., by coagulat- 
ing the blood (liq. ferri subsulphatis; liq.ferri perchloridi, etc.). 
To destroy morbid growths, goitre; or irritant injections into 
substance of tumors (tinct. iodinii iod. ; acetic acid in cancer, 
etc.). 
LOCAL EFFECTS 
REMOTE OR 
SYSTEMIC EFFECTS. 
In Insomnia. 
Melancholia. 
Mania. 
Puerperal mania. 
Delirium tremens, etc 
In Epilepsy. 
As a cerebral sedative. 
Chorea. 
As a moderator of reflex ae 
tion 
Eclampsia 
Hysteria. 
Hydrophobia, etc 
In Paralysis, etc. 
Tetanus. 
As a motor excitant. 
As an anodyne 
In the various forms of Neu 
ralgia, etc. 
Spasmodic cough. 
Wh oopi ng-cough. 
In affections of thoracic vis 
cera 
Asthma. 
Angina pectoris 
Bronchitis. 
Pleuritis. 
Pericarditis, etc 
Dyspepsia. 
Vomiting of pregnancy 
Sea-sickness. 
Cholera morbus. 
In affections of digestive sys 
tem 
Colic. 
Intussusception. 
Enteritis. 
Peritonitis. 
Hepatic colic. 
Scirrhus, etc. 54 
SUBCUTANEOUS 
MEDICATION. 
Dysmenorrhoea. 
Uterine colic. 
Nephritic colic. 
In affections of the genito- 
urinary apparatus 
Spasmodic stricture. 
Spasm of sphincter vesicae. 
Spermatorrhoea. 
In fevers. 
Chordee, etc. 
Periodical fevers, etc. 
Kheumatism. 
Syphilis, etc. 
In blood diseases. 
Opium. 
Belladonna. 
Strychnia. 
Physostigrna, etc 
As an antidote. THE ACTIONS AND USES OF THE REMEDIAL AGENTS 
EMPLOYED HYPODERMATICALLY. 
THE ALKALOIDS OF OPIUM. 
MORPHIA AND ITS SALTS. 
History.—Morphia was the first remedy used 
subcutaneously. After the inoculation experi- 
ments of Lafargue, first published about 1836, 
Dr. Alexander Wood, of Edinburgh, began in 
1844 to insert a solution of morphia under the 
skin. Although this is the origin of the subcu- 
taneous method as now practised, it is perfectly 
demonstrable that Magendie, in the course of 
his physiological experiments, was in the habit 
of inserting poisons under the skin, to procure 
their characteristic effects, long before the earli- 
est date assigned for the origin of the hypoder- 
matic method. 
The Preparation.—A solution, a “ hypoder- 
mic tablet,” or a powder of given weight may 
be used. There is no general agreement as to 
the salt of morphia which is best; but as the 
sulphate is most soluble, and, when neutral, not 
move irritating than any other salt, it should be 
55 MORPHIA AND ITS SALTS. 
preferred. The muriate is much used in Ger- 
many, and Eulenberg’s formula is as follows: 
R Morphise muriatis, gr. iv ; 
Acidi muriatici, gtt. iv ; 
Aquse destil., sji. M. 
In this formula the acid serves to increase the 
solubility of the morphia and to prevent the de- 
velopment and growth of the penicilium. It has 
already been set forth that acid solutions are 
highly irritating, and have produced much mis- 
chief by exciting a local inflammation, followed 
by suppuration and sloughing. The committee 
appointed by the Medico-Chirurgical Society to 
examine the subject of subcutaneous medication 
reported in favor of a solution made with acetate 
of morphia, dissolved by the aid of sufficient 
acetic acid and afterwards carefully neutralized 
with liquor potassa. The committee wisely re- 
mark : “ In using drugs which require an acid 
to render them soluble in water, it was found 
that very acid solutions are apt to irritate, and 
the solutions were, therefore, carefully neutral- 
ized. Very alkaline solutions should be avoided 
for the same reason.” * Dr. Anstie, in his much- 
quoted paper on “ the Hypodermic Injection of 
Remedies,” says that “ morphia' should be used 
in the form of acetate, dissolved with a mini- 
mum of acetic acid in hot distilled water, five 
* The Medico-Chirurgical Transactions, vol. I p. 565, THE PREPARATION. 
57 
grains to the drachm.” * Dr. Lawson recom- 
mends a solution of the muriate, in the propor- 
tion of ten grains to two drachms, so that six 
minims contain a half-grain of morphia, f “ This 
solution,” says Dr. Lawson, “is always solid at 
ordinary winter temperature and generally so in 
summer, and it must be heated before each in- 
jection.” A more recent English writer, Dr. 
Wilson, after making an elaborate review of the 
subject, concludes “ that the solvent for morphia 
should be distilled water without any admixture 
of acid.”J This expression of Dr. Wilson now 
represents the common sentiment of practical 
physicians, and the use of acid as a means of 
increasing the solubility of morphia or of pre- 
venting change in the solution has been aban- 
doned. Much difference of opinion yet obtains 
as to the degree of concentration of the solution. 
The formulae above given, so concentrated as to re- 
quire heat to effect a solution, are not to be com- 
mended. The precipitation which takes place 
on cooling, and the danger of giving an overdose, 
are insuperable objections. The physicians re- 
plying to Dr, Kane’s queries § have, with few ex- 
ceptions, resorted to rather dilute solutions, some- 
times after unfortunate experiences with more 
concentrated. My personal observation is in 
* The Practitioner, July, 1868. 
f On Sciatica, Lumbago, etc., p. 93. 
+ St. George’s Hospital Reports, vol. iv., 1869. 
| The Hypodermic Injection of Morphia, New; York, 1880. 58 
MORPHIA AND ITS SALTS. 
favor of a rather dilute solution. The acetate 
and muriate of morphia, advised by some au- 
thors and practical physicians, are really less 
desirable, as they are less soluble than the sul- 
phate. On the whole, we cannot improve on the 
formula of Magendie, and this, which I have 
recommended in former editions of this manual, 
continues to maintain the first place in my judg- 
ment : 
55: Morphine sulphatis, £r. xvi; 
Sig. —Fifteen minims contain one-half a grain. 
Aquas, M. 
The advantages of this formula are the com- 
plete solubility and sufficient concentration for 
the fullest effect of the morphia. 
As in all solutions of morphia, and indeed of 
the alkaloids in general, a change takes place 
too subtile for recognition by our jjresent means 
of investigation, by reason of which solutions of 
some days’ duration become unfit for use, the 
addition of an antiseptic is necessary when the 
preparation is intended to he kept. Besides this 
change of unknown character, the penicilium 
develops in solutions of alkaloids at the ex- 
pense of the principal, not only weakening the 
strength, but also rendering the solution highly 
irritating. From two to four minims of carbolic 
acid may he added to the above formula, or for 
simple water may he substituted cherry-laurel 
or eucalyptus water, as has been elsewhere sug- 
gested. THE DOSE. 
59 
For reasons explained when solutions in gen- 
eral were under discussion, it is preferable to 
have at hand the materials for extemporaneous 
solutions. A “ hypodermic tablet” or a morphia 
powder of the required strength is conveniently 
carried, and as regards liability to accident, is 
much superior to any permanent solution. Since 
I have adopted the method of extemporaneous 
solutions I have not had occur the hard nodules 
and the points of suppuration and sloughing, 
which were not infrequent when permanent so- 
lutions were employed. A number of those re- 
sponding to the inquiries of Dr. Kane * report a 
like experience, that the abscesses formerly 
quite common when a permanent solution was 
used ceased to he produced when the solution 
was made at the time of injecting. 
The Dose,—The dose of morphia for hypo- 
dermatic use varies from to |of a grain. In 
commencing, it should not exceed one-third of that 
ordinarily administered internally. It is prudent in 
all cases to test the physiological capabilities of 
the patient by a small dose before resorting to the 
maximum amount. Patients vary in their sus- 
ceptibility. Women are, as a rule, more easily 
atfected than men. One-twelfth of a grain is a 
sufficient dose for many of the conditions requir- 
ing an injection. Persons habituated to the use 
of the drug, or those suffering pain, will hear a 
* Supra, p. 47. 60 
MORPHIA AND ITS SALTS. 
larger quantity. The maximum doses may be 
administered with safety if combined with atro- 
pia (see post). As Brown-Sequard has indicated, 
large doses of morphia, when combined with 
atropia, exert a more decided curative effect in 
obstinate neuralgias. It may be necessary in 
such cases to give J, or even 1 grain of morphia, 
with Jg- of a grain of atropia. 
In order to maintain a constant physiological 
effect, but slight increase of the dose is neces- 
sary. This is one of the greatest advantages of 
the hypodermatic method, especially in cases re- 
quiring the protracted use of morphia. 
Hypodermatic injections of morphia are rarely 
advisable in the case of children, yet as their 
utility is unquestionable in certain convulsive 
disorders of early life, it may be necessary to 
employ them. From to of a grain, accord- 
ing to age, may be regarded as a safe quantity, 
but the administration of so powerful a remedy 
should not be undertaken without careful consid- 
eration of the dangers involved. 
So many accidents have happened from the 
incautious or improper use of morphia hypoder- 
raatically that I must repeat the injunction to 
proceed cautiously. Before deciding on the dose, 
ascertain if the malady requiring it he one in 
which a special susceptibility to the action of 
morphia exists. Is it a case of tumor or abscess 
of the brain? of chronic alcoholismus? of idio- 
syncrasy in respect to the cerebral effects? of PHYSIOLOGIC A L A CLIO AS. 
61 
weak heart? of obstructive pulmonary lesions? 
of deficient excretion ? etc. If any of these con- 
ditions be present, the dose must be small. On 
the other hand, if the habit of opium-taking 
have been.formed, if there be excessive pain, or 
if the case be one of uraemic convulsions, the 
dose may be large. 
Physiological Actions.—The effects of mor- 
phia injected beneath the skin are local and sys- 
temic. At the moment the injection is practised, 
pain is produced by the penetration of the skin, 
and a sensation of smarting and burning follows 
as the fluid diffuses through the subcutaneous 
tissue. ' The latter sensation is the greater the 
larger the amount of fluid, the more concentrated 
the solution, and the more irritating the salt of 
morphia used. Under the usual circumstances 
it is not severe or persistent. Besides a little 
redness at the site of injection and some tender- 
ness, no other local symptom appears when a 
few drops are inserted, and these results cease in 
a few hours. When, however, ten minims or 
more are administered, considerable swelling is 
produced, a large wheal forms, and the part is 
tender for several hours. Repeated injection at 
one point will produce much irritation, tender- 
ness, and even inflammation. The accidents re- 
sulting at the point of injection under some cir- 
cumstances will be described hereafter. 
The effect of morphia on the tactile and pain 
sense of the part into which it has been injected 62 
MORPHIA AND ITS SALTS. 
has been much disputed. In coming to a con- 
clusion the various results which may he pro- 
duced hy the injection must have due considera- 
tion. Frequent injections or a single irritant 
injection may induce such a local congestion as to 
exalt the functional irritability of the peripheral 
nerves, when, of course, the tactile and pain sense 
will be exalted. An unirritating morphia injec- 
tion lessens the tactile and pain sense for some 
distance about the point of insertion, as has been 
affirmed hy Eulenberg,* Chouppe,f and others. 
On the other hand, when local irritation and con- 
gestion have resulted, the opposite condition ob- 
tains, as has been stated by De Renzi,| Mitchell, 
Morehouse and Keen,§ and others. In this way 
may he explained the contradictory observations 
made on this important point. Further sup- 
port to the view of the local action of morphia is 
given by the effects which follow the application 
of a solution to a nerve-trunk, for when a nerve 
is so treated its power to transmit impressions is 
lessened. 
The local effects of morphia are quite subordi- 
nate to the systemic. The rate of diffusion of 
morphia is very near!}7 the same for the connec- 
tive tissue of any region. Any differences that 
may exist are due to the number of vessels in 
* Die hypoder. Injectionen, etc., supra. 
f British Med. Journal, April 10, 1875. (Abstract.) 
J New York Med. Journal, vol. xviii. p. 214. (Abstract.) 
\ The Amer. Jour, of the Med. Sciences, July, 1865. PHYSIOLOGICAL EFFECTS. 
63 
the part and to an accidental intra-venous injec- 
tion. As the round of the circulation is made 
within a minute, the effects become manifest 
within that time, into what part soever the solu- 
tion may be thrown. When, unhappily, the 
solution enters a vein, the effect is not instanta- 
neous, although very prompt. Under ordinary 
circumstances, within a minute after the injec- 
tion is practised, the cerebral effects, which vary 
with the dose, the idiosyncrasies of the individ- 
ual, and usage, are experienced. A feeling of 
giddiness, faintness, depression, and nausea, ac- 
companied by pallor of the face and contracting 
pupils, is the effect experienced at the first onset 
of the morphia impression by those not habitu- 
ated to it. A deadly faintness, anxiety and 
alarm, extreme pallor, cold surface, and weak 
circulation are not infrequently produced in sus- 
ceptible subjects on being injected for the first 
time by even so small a dose as the twelfth of a 
grain. Usually the preliminary depression and 
pallor are succeeded by a flushed face, a feeling 
of heat and fulness of the head, increased action 
of the heart, tingling and redness of the extrem- 
ities, and a general sense of discomfort. Very 
often some pain is felt in the abdomen, due to 
the movements of gas, and loud borborygmi 
occur. The mouth grows dry and pasty; the 
taste loses its acuteness, and the mastication 
and swallowing of food become awkward and 
difficult. The pupil contracts, and vision is 64 
MORPHIA AND ITS SALTS. 
rather hazy. The sense of hearing is obscured 
somewhat by the tinnitus. A minute dose will 
not impair the equilibrium, although more or 
less dizziness occur, but a full dose will render 
walking uncertain, even prevent the necessary 
co-ordination of the muscles. There will be 
present, indeed, the usual symptoms and appear- 
ance of intoxication. Various odd sensations 
are experienced. One has an overpowering 
sense of muscular fatigue; another has a feeling 
of weight on the nape of the neck and the 
shoulders; a third has a splitting headache, with 
resounding tinnitus and incessant and severe ver- 
tigo ; a fourth feels a sudden glow, then a sink- 
ing at the epigastrium, sudden nausea and vom- 
iting occur, after which he is languid, exhausted, 
hut has a sense of comfort; and a fifth is merely 
depressed and gloomy. There are but few wdio 
experience the traditional exhilarating effects, in 
which the mind is filled with delightful visions 
and the body is pervaded with an exquisite sense 
of well-being. By him to whom there are denied 
the higher joys of morphia intoxication, a grate- 
ful sense of freedom from all bodily discomforts, 
and the added feeling of delightful existence 
quite independent of surrounding circumstances, 
seem to he experienced. It is in this sense of 
all-pervading present comfort that the fascina- 
tion of opium apparently consists, rather than in 
active exhilaration of the mind. When to the 
sufferer not only relief hut a pleasing existence PHYSIOLOGICAL EFFECTS. 
65 
is given, when from the weary fatigue is made to 
vanish and work becomes a pleasurable exertion, 
and when for the disappointments and troubles 
of life a peaceful calm and content are substi- 
tuted, it is not surprising that those in whom 
these transformations have been wrought should 
ardently desire their continuance. 
The first stimulating effect of morphia on the 
cerebrum is of very variable duration. In some 
persons a condition of somnolence follows in a 
few minutes, and then more or less profound 
sleep persists for many hours. The sleep is 
often accompanied by vivid—usually horrifying— 
dreams; there is much talking and agitation, and 
in some persons a somnambulistic state is induced. 
Other subjects, again, fall into a deep sleep, with 
snoring, even stertorous, respiration. A large 
proportion of those taking morphia have but 
snatches of light sleep, with long intervals of 
wakefulness, and many are kept wide awake in 
a very active mental state, but experience a pro- 
found sense of comfort and peace. Those made 
actively wakeful usually are very drowsy and 
sleep heavily after the immediate effects of the 
morphia have declined. When the action has 
begun, the circulation, respiration, and tempera- 
ture are characteristically affected. 
Mr. Hunter * first pointed out the effect of mor- 
phia administered subcutaneously on the pulse 
* On the Speedy Relief of Pain, etc., p. 83. 66 
MORPHIA AND ITS SALTS. 
and respiration. “In mania,” he says, “ I have 
reduced the pulse from 120 to 80 in four min- 
utes,’’ and he also observed “ the diminished 
rate of respiration.” I have been most fortunate 
in securing the co-operation of some internes of 
the Good Samaritan Hospital, who submitted 
themselves to experiment in preparation for the 
graphical representation of the results of the 
morphia action. 
In the accompanying diagram are represented 
the effects on the pulse, respiration, and temper- 
ature of Hr. Rutter, who had received, whilst in 
a perfectly normal state, one-fourth of a grain of 
morphia subcutaneously. In the febrile condition 
of the system the temperature-curve would not 
contain the elevation which marks the above tra- 
cing, hut a depression corresponding to those of 
the respiration and pulse. A considerable rise in 
the blood-pressure also is produced. A sphygmo- 
graphic tracing may or may not have scientific 
value. So much depends on the adjustment of the 
instrument, on the amount of spring-pressure, and 
on the nervousness of the patient, that perfectly 
accurate sphygmograms are somewhat difficult 
to accomplish. Those subjoined were obtained 
from Hr. Hrake before and after the administra- 
tion of one-fourth grain of morphia-hypodermat- 
ically. The first or normal tracing was taken 
with a spring-pressure of 200 grammes, the 
sphygmograph being fitted with the modifica- 
tions of Hr, Burdon-Sanderson, which permit a PHYSIOLOGICAL EFFECTS. 
67 68 
MORPHIA AND ITS SALTS. 
more accurate adjustment of the spring than is 
possible in Marey’s instrument. 
Tracing of normal pulse.—Spring-pressure of 200 grammes. 
Soon after taking the normal tracing, the medi- 
cament was given and the apparatus remained 
in situ. When the usual effects were produced 
at their maximum, the second tracing was taken 
at the same spring-pressure. There being no 
Tracing of pulse after the subcutaneous injection of morphia.—Spring- 
pressure, 200 grammes. 
change in the conditions of the experiment, 
except the administration of morphia, the result 
must represent the true effects of this agent. 
The second tracing, as compared with the first, 
exhibits the following deviations from the nor- 
mal : 
The altitude of the wave is less, the ascent 
more oblique, the summit more rounded, and 
the dicrotic rebound less distinct,—peculiarities 
indicating a considerable rise in the tension of 
the arterial system. 
Ophthalmoscopic examination of the fundus PHYSIOLOGICAL EFFECTS. 
69 
oculi made when the effects of morphia are at 
their maximum, discloses an increased vascularity 
of the retina and a somewhat cloudy or blurred 
state of the papilla. The drum membrane also 
exhibits a more considerable injection than is 
normal. The increased tension of the vascular 
system begins to decline soon after it attains 
the maximum; the pulse then becomes quicker 
but softer, and secretions previously suspended 
flow freely. Itching of the nose is very usual, 
and some subjects experience a general itching 
of the surface during the whole period of the 
action. Moisture appears on the skin about the 
time the pulse relaxes, and considerable sweat- 
ing persists up to the end of the morphia influ- 
ence. The tongue moistens as the skin perspires, 
and doubtless, also, the gastro-intestinal mucous 
membrane then resumes secretion and excretion. 
Probably, also, during the period of its maxi- 
mum action, morphia suspends or enfeebles the 
activity of the pancreas and liver. Digestion is 
stopped for a time if a full dose of morphia be 
given after a meal, and, as a rule, constipation 
results; but this is by no means invariable, for 
in some instances the bowels continue to act 
regularly, and occasionally constipation has been 
removed by morphia injections. The diminished 
excretion of bile is shown by the yellowness of 
the conjunctiva, the muddy tint of the skin, 
and the lighter color of the faeces. The urine 
also has a higher tint than normal, due to the 70 
MORPHIA AND ITS SALTS. 
presence of bile-pigment and to the greater 
density. The rather scanty urine is referable 
to two factors,—to the diminished functional 
activity of the kidneys, and to the increased 
diaphoresis. 
With the decline in the morphia narcosis, some 
patients experience headache, confusion of mind, 
anorexia, and nausea; but these results are not so 
constant as after the internal use of this agent. 
If the injection be administered at night, the 
nausea and vomiting are experienced on rising 
in the morning. Perfect quiet, a cup of hot cof- 
fee taken before rising, an ice-bag to the cervical 
spine, and a full dose of bromide of potassium, 
may be administered for the relief of these 
symptoms when they are severe. 
The extent and persistence of the foregoing 
physiological effects will depend upon the quan- 
tity of morphia injected. Very large doses excite 
not only immediate disturbance in the functions 
of the brain, but secondary disturbances in the 
process of elimination of the narcotic from the 
blood. The occurrence of these unpleasant and 
depressing effects of the morphia narcosis is an 
additional reason for cautious tentative experi- 
ments in any case in which the physiological 
tolerance of this agent is unknown. 
Phenomena somewhat different in character, 
as well as in degree, from those which I have 
described under this head, follow the subcuta- 
neous injection of large doses. The following ACCIDENTS. 
71 
symptoms were observed by me after the injection 
of one grain of sulphate of morphia: 
In ten minutes the patient had fallen asleep so 
soundly, sitting upright in bed, that he could not 
be aroused. At the end of an hour I found him 
in a state of profound narcotism, his pulse 50 
and feeble; respiration 10 and labored, with 
stertor; skin cold and sweating; face pale and 
ghastly. The conjunctives were deeply injected; 
pupils minutely contracted, and insensible to the 
strongest gas-light. No reflex movements could 
be excited by touching the eyes, or by irritation 
of the fauces. These formidable symptoms were 
relieved by the subcutaneous use of atropia, the 
physiological antagonist of morphia. 
Accidents.—Although morphia, when rightly 
administered subcutaneously, may be freely used, 
accidents do occur, and a clear conception of 
their causes and character becomes necessary. 
These accidents may be local or systemic: local, 
due to the site, manner of injecting, and con- 
dition of the subject; systemic, the impression 
of the remedy on the cerebral, respiratory, and 
circulatory organs. 
The local irritation produced by subcutaneous 
injections has been briefly referred to in connec- 
tion with the solutions. Improperly prepared 
solutions of morphia, long-kept solutions, a rusty 
and dirty needle, the forcible introduction of a 
large quantity of fluid, are fruitful causes of local 
inflammation and induration or abscess. Re- 72 
MORPHIA AND ITS SALTS. 
peated injection at tlie same site sets up a hyper- 
plasia of the subcutaneous connective tissue, re- 
sulting in the formation of indurations, which 
may slowly suppurate, or induce such a highly 
vascular state of the parts that finally injections 
here become very dangerous. 
When a vein in the skin is perforated by the 
needle, a very sudden and powerful impression is 
produced, if, as usually happens, the morphia solu- 
tion be sucked into the vessel. If the needle enter 
a vein and the solution be thrown directly into the 
blood-current, the effect produced is still more 
sudden and powerful. The interval between the 
act of injecting and the effect of the morphia is 
greater in the former case; in the latter, the 
effect may seem to be instantaneous, almost. 
The difference being quantitative rather than 
qualitative, there need be no separate considera- 
tion of the effects resulting from the two modes 
of the accident. There are three kinds of re- 
sults : slow and feeble action of the heart, con- 
traction of the arterioles, and therefore anaemia 
of the brain, causing syncope; the same condi- 
tions, associated with weakened contractile power 
of the cardiac muscle, resulting in failure of the 
heart; and profound narcotism, terminating in 
paralysis of the respiratory centre. 
When the injection is making, the vein per- 
forated, no difference in the operation is ob- 
served, except the escape of blood; when the 
injection is delivered into a vein, the fluid passes ACCIDENTS. 
73 
in with an unusual readiness. Dizziness, oppres- 
sion of breathing, singing in the ears, a fearful 
apprehension, intense throbbing in the head, 
dimness of vision, are immediately experienced; 
the face becomes deadly pale, the eyesight dim, 
the pupils contract, the pulse is small and slow, 
the respiration shallow and sighing, and thus, on 
the instant, the patient falls unconscious in a 
syncopal state. After a time consciousness is 
slowly regained, vomiting occurs, intense head- 
ache and vertigo are felt, and on every attempt 
to sit up the faintness comes on again. There 
are great differences in the duration of these 
symptoms, according to individual peculiarities; 
they may continue from an hour or two to twelve 
hours or longer, and, after the subsidence of the 
effects directly due to the morphia, more or less 
indigestion, constipation, hebetude of mind, and 
stupor persist for several days. 
If the heart muscle have undergone the changes 
produced by myocarditis, fatty degeneration, or 
fatty infiltration, or the right heart be dilated and 
weak in consequence of obstructive pulmonary 
lesions or other causes, the syncopal state induced 
by the injection of morphia may speedily result 
in death. In such cases, immediately on receiv- 
ing the injection, the patient turns pale, reels, 
falls into unconsciousness, and, with a deep sigh, 
expires. Such a sudden termination is, however, 
not common. More frequently the fatal result 
is due to excessive action of the remedy,—to 74 
MORPHIA AND ITS SALTS. 
coma and suspension of the functions of the re- 
spiratory centre. Such cases pursue the course 
of opium narcosis. The patient after receiving 
the injection passes into a condition of stupor, 
presently becomes profoundly insensible, the re- 
flexes are abolished, the pupil minutely con- 
tracted, the respirations slow and shallow, the 
face pale, and the skin relaxed and cold. The 
rapidity of the effect depends on the amount ad- 
ministered, the point of insertion, and the sus- 
ceptibility of the individual receiving the injec- 
tion. 
Idiosyncrasy is an important factor in deter- 
mining ill results. There are persons, women 
especially, so susceptible to the action of opium 
and its alkaloids, that the minutest quantity will 
produce unpleasant effects. In such subjects a 
small medicinal dose will cause faintness, ex- 
treme vertigo, nausea, and profound depression 
of the vital powers, lasting from a few hours to 
several days. In such cases, even on the follow- 
ing day, great depression, faintness, and nausea 
occur on attempting to assume the upright posi- 
tion, and a dazed, confused, and “ groggy” con- 
dition of the head continues for some days 
longer. In the subjects of this peculiar suscepti- 
bility, a full medicinal dose may cause a fatal 
result by syncope. 
Chronic alcoholism develops a state in which 
ordinary medicinal doses may cause a dangerous 
narcotism or sudden failure of the heart. The A CCIDENTS. 
75 
structural changes which occur in the brain, es- 
pecially in the medulla oblongata, in the walls of 
the heart, and in the kidneys, explain the nature 
of these results. 
Habit diminishes the danger of accidents. 
When, in the case of a morphia-taker, a strong 
solution is sucked or thrown directly into a vein, 
the following effects are observed: an intense 
tingling occurs over the body generally, but es- 
pecially over the extremities; often extensive 
Avheals appear; the skin is swollen and deeply 
red; the action of the heart becomes rapid and 
tumultuous, and all the arteries of the body beat 
vehemently; an intense headache, with strong 
throbbing, occasions extreme distress, and is in- 
creased by every movement. Such symptoms 
will persist for a half-hour or longer, and not 
infrequently are followed by nausea. Notwith- 
standing enormous doses may be taken with 
impunity, they may be dangerous when, after a 
period of reduced quantity, considerably larger 
doses are suddenly administered. Several deaths 
have been caused in this way. Hence those re- 
ducing their daily allowance must be warned of 
the danger incurred by taking a dose considera- 
bly larger, although within the limits of former 
indulgence. 
The treatment of the various accidents caused 
by the subcutaneous injection of morphia in- 
cludes prophylactic as well as therapeutical expe- 
dients. No physician should administer a mor- 76 
MORPHIA AND ITS SALTS. 
phia injection without first assuring himself of 
the quantity. Deaths have been caused by the 
administration of approximate quantities. The 
rules with regard to dose, already given, should 
be carefully adhered to. The condition of the 
patient, idiosyncrasies, and existing diseases 
should he ascertained. Morphia should always 
he given with atropia, unless some contra-indica- 
tion of the latter exist. It has been proposed to 
put a ligature about the limb, in readiness to be 
tightened should it he found that a vessel has 
been entered. It need hardly he observed that 
such preparations are too suggestive to be made 
with nervous subjects, and are rather unbecom- 
ing. As the symptoms occur only when the 
remedy reaches the brain, a ligature may fail to 
he useful. The person injected should lie recum- 
bent, and if faintness comes on, the head should 
be lowered below the body. The measures of 
chief importance for the cases of syncope are 
inhalation of ammonia (cautiously), artificial res- 
piration, and stimulation of the chest muscles 
by the faradic current, enemata of turpentine 
or alcohol, the intravenous injection of ammo- 
nia, and inhalations of amyl nitrite or its sub- 
cutaneous injection. The condition of narcosis 
requires the subcutaneous use of atropia to coun- 
teract the respiratory and cardiac depression, 
faradization of the chest muscles, the subcu- 
taneous use also of caffein, stimulant enemata, 
etc. THERAPY. 
77 
Therapy.—The subcutaneous injection of mor- 
phia may be used to relieve pain, to relax spasm, 
to subdue inflammation, to cure specific diseases, 
and to antagonize toxic agents. An anatomical 
arrangement seems best adapted to embrace all 
of the therapeutical facts under these several 
heads. Accordingly, I shall consider the uses of 
morphia in— 
Diseases of the brain and nervous svstem, of 
the respiratory and circulatory system, of the 
digestive apparatus, of the genito-urinary organs, 
and of constitutional or specific origin; in cer- 
tain surgical diseases and operations, and as a 
physiological antidote. 
Diseases of the Brain and Nervous System. 
Psychical Disorders.—Mr. Hunter was the first 
to indicate the utility of, and to employ, the hypo- 
dermatic injection of morphia in the treatment 
of psychical disorders. He enunciated an impor- 
tant truth in the following observations: “For 
derangements of the cerebral nervous system we 
have in the hypodermic method a means of treat- 
ment far superseding in its immediate efficacy 
any other mode of medication.” In another 
place he further remarks, “ In this class of cases 
[mania] a single dose, administered beneath the 
skin, will at once break the neck of the disease. 
It will often at once stop the delirium, correct 
the mental aberration, and remove the exhaus- 78 
MORPHIA AND ITS SALTS. 
tion.” * Notwithstanding the striking advantages 
thus shown to result from the hypodermatic treat- 
ment of mania, some years elapsed before it 
came to be employed. Indeed, so late as May, 
1869, we find a distinguished asylum superin- 
tendent f repeating the expression of Dr. Anstie, 
“that despite the satisfactory working of the 
hypodermic method, and the greatly increased 
power of handling remedies which it gives us, it 
is still very much unappreciated.” Dr. Robert- 
son believes that “ this remark applies to the 
employment of the hypodermic injection of mor- 
phia in the treatment of mental disease.” Ac- 
cording to the same authority, Dr. Mackintosh 
published a paper in 1861 on “ The Subcutaneous 
Injection of Morphia in Insanity,” and the re- 
ports of the Somerset Asylum contain allusions 
to the advantages of this method. Lorent,J Er- 
lenmeyer,§ and Eulenberg)) support the observa- 
tions of Hunter by their individual experiences. 
Maudsley,f who places opium at the head of all 
the remedies employed in the treatment of in- 
sanity, considers the subcutaneous injection of 
morphia “ a valuable expedient.” Reissner,** 
* On the Speedy Relief of Pain, etc., pp. 18, 19. 
+ C. Lockhart Robertson, in Practitioner, May, 1869, p. 272. 
% Die hypodermatischen Injectionen, etc., op. cit., p. 16. 
\ Die subcutanen Injectionen, etc., op. cit., p. 28. 
|| Die hypodermatische Injection, etc., op. cit., p. 154. 
f Reynolds’s System of Medicine, vol. ii. p. 60. 
** Bulletin General de Therapeutique, Jan. 30, 1870, p. 89. THERAPY. 
79 
who has experimented largely with the hypoder- 
matic method in the various forms of mania, 
comes to conclusions less favorable than those 
above expressed. In acute mania he had no 
permanent good results. Dr. Yix has, how- 
ever, adduced a remarkable case in which a 
single injection of morphia cured a recent ease 
of acute mania. In melancholia, Reissner’s re- 
sults were not more favorable than in acute 
mania. In chronic mania the etfects were 
variable: some patients were calmed for weeks 
and months; in others large doses were without 
benefit. Reissner considers general paralysis 
unsuited for the action of morphia, and that it 
is contra-indicated in cases of mental disorder 
complicated with heart or stomach disease, 
rigidity of the arteries, tuberculosis, and in 
certain epileptics. 
More recently, Dr. O. J. B. Wolff has at- 
tempted a more accurate determination of the 
indications for the use of morphia subcutane- 
ously in mental diseases. The state of the arte- 
rial tension is Wolff’s guide to the use of mor- 
phia. If the sphygmograph shows a low state of 
the arterial tension with a slow pulse, small doses 
are indicated. On the other hand, as large doses 
of morphia, by over-excitation, cause paresis of 
the sympathetic, these are indicated when the 
pulse is quick and tension high. He advises 
caution in the use of large doses in the obese 
and the aged. He thinks the subcutaneous in- MORPHIA AND ITS SALTS. 
80 
jection of morphia very useful in both curable 
and incurable cases.* 
Krafft-Ebing reports excellent results from the 
use of morphia subcutaneously in cases of lype- 
mania, especially when there exist at the same 
time neuralgic troubles. He has been equally 
fortunate by this method in the treatment of 
“ moral hypochondriasis complicated with hyper- 
sesthesia of the spinal cord,” and “in forms of 
mental alienation determined sympathetically in 
the predisposed by neuralgias and neuropathies.” 
The existence of a neuralgic element constitutes 
an indication for the use of morphia subcutane- 
ously in simple mania and in hysterical mania. 
Krafft-Ebing considers the same mode of treat- 
ment the most efficacious for the relief of the 
insomnia so common in the insane.f My own 
experience, which has been limited, however, 
is very favorable to the subcutaneous injection 
of morphia. In a case of acute melancholia, 
characterized by insomnia and intense restless- 
ness, I found this method of treatment exceed- 
ingly useful. A grain of morphia reduced the 
pulse from 140 to 96, quieted the agitation, and 
procured sound and refreshing sleep. 
Robertson in the paper referred to gives three 
typical cases of different forms of insanity—re- 
cent mania, chronic mania, and melancholia—in 
* Archiv fur Psychiatric nnd Nervenkranhheiten, Band ii. 
f Bulletin General de Therapeutique, Jan. 30, 1870, p. 474. THERAPY. 
81 
which the hypodermatic injection was successful. 
The indications for the employment of this 
method are the following: 
Prolonged wakefulness. 
Maniacal excitement. 
Obstinate and persistent refusal of food, or 
drink, or medicine. 
Destructive and suicidal tendencies. 
Maudsley adds a caution here, which I tran- 
scribe for the benefit of my readers: “It will be 
well to have in mind that neither opium by the 
mouth, nor morphia hypodermically injected, will 
always quench the fury of acute mania, and that 
successive injections of morphia, followed by brief 
snatches of fitful sleep, have been followed, also, 
by fatal collapse.” 
The evidences of the beneficial effect of the 
injection are the following : 
Prolonged and healthy sleep. 
Less excitement on awakening. 
Illusions or delusions less strong. 
Willingness to take food. 
Absence of any tendency to collapse, although 
pulse, temperature, and respiration are reduced. 
To produce the best results, larger doses than 
those I have indicated as proper in general are 
necessary in the treatment of mania. Hunter 
administered | and 1 grain; Robertson speaks 
of i grain of the acetate of morphia injected 
every four hours, and in one case of 1 grain in- 
jected night and morning. In cases which have 82 
MORPHIA AND ITS SALTS. 
occurred under my observation, extraordinary 
tolerance of the morphia was exhibited; and in. 
that case to which I have made special reference, 
1 grain was found necessary to procure suffi- 
ciently prolonged sleep. 
It is in the beginning of mania that the hypo- 
dermatic injection of morphia is most conspicu- 
ous for good. The timely use of the syringe may 
avert this disorder in that critical period when 
the occurrence of unusual excitability and sleep- 
lessness indicates that an outbreak is imminent. 
This observation is especially true of puerperal 
mania. The introduction of chloral hydrate has 
modified somewhat the treatment of maniacal 
affections by the subcutaneous use of morphia; 
but, as Wolff has shown, each has its own sphere 
of applications. 
Delirium Tremens.—We owe to Mr. Hunter the 
first suggestion of the hypodermatic treatment of 
delirium tremens. It was afterwards employed by 
Ogle, Semeleder, Lorent,* Eulenberg,f Ruppa- 
ner,| and others. Dr. Anstie, in an able paper on 
“Alcoholism,”! thus formulates his views as to 
the utility of this method : 
“ Opium should never be administered by the 
stomach, but always in the form of morphia 
* Op. cit. 
f Op. cit. 
t Hypodermic Injections, 2d ed., p. 132. 
\ Reynolds’s System of Medicine, vol. ii. p. 90. THERAPY. 
83 
injected, in the dose of y to \ 
or J grain.” 
The treatment of delirium tremens has under- 
gone a radical change within the past few years. 
This is well expressed in the following observa- 
tions by Dr. Anstie; 
“ In former times—indeed, a very few years 
since—the notion universally prevailed that the 
delirious symptoms were owing to the exhaustion 
which was chiefly kept up by want of sleep; and, 
consequently, that the production of continuous 
sleep for several hours was the sole and all- 
important means of cure. It was therefore the 
custom to ply the patients with larger and larger 
successive doses of opium, with the view of 
drowning the delirium in narcotic stupor. Great 
mischief arose from this wide-spread belief and 
practice. In the first place, it has often happened 
that the patient, without ever sleeping at all, has 
passed first into a condition of coma-vigil, next 
of stertorous breathing, and at last sunk, fairly 
poisoned with opium.” * 
I have quoted these strong but just expressions 
to warn my readers against the abuse of the hypo- 
dermatic injection of morphia in the treatment of 
delirium tremens. 
The following are the indications for the use 
of this method in this disease : 
* Reynolds’s System of Medicine, vol. ii. pp. 88, 89. 84 
MORPHIA AND ITS SALTS. 
The condition of “ horrors,” or wakefulness, 
preceding delirium. 
Excessive and uncontrollable vomiting of food, 
drink, and medicine. 
Mild cases, in which there is little tendency to 
depression of the vital forces, in which the assim- 
ilation of food proceeds satisfactorily. 
It is contra-indicated in severe and protracted 
cases, with great depression of the vital forces 
and non-assimilation of food; 
In cases in which serious organic lesions of 
liver or kidneys have occurred; 
In cases in which the delirium tremens is 
consecutive to traumatic or other serious lesion 
of brain. 
In cerebro-spinal meningitis opium is the best 
remedy, especially in the onset of that disorder, 
and according to Radcliffe* the hypodermatic in- 
jection of morphia is the best method of admin- 
istration. Erlenmeyer,t who appears not to have 
had any personal experience with the hypoder- 
matic use of morphia in this disease, refers to the 
experience of Bois. According to Eulenberg,| 
Niemeyer used this method as a palliative in an 
epidemic at Rastadt and Carlsruhe. It relieved 
the pain and cramps, and quieted the extreme 
restlessness (gross TJnruhe), which are marked 
* Reynolds’s System of Medicine, vol. ii. p. 702. 
f Die subcutanen Injectionen, op. cit., p. 31. 
J Die hypodermatische Injection, op. cit., p. 156. THERAPY. 
phenomena in these cases. Dr. B. Arnold, of 
Donzdorf, reports favorably of its use in these 
cases.* According to Stilk, f the opium treat- 
ment was very serviceable in the disease as he 
observed it in Philadelphia. The author’s expe- 
rience is fully confirmatory of the published ob- 
servations. He has witnessed remarkable cures 
effected by the timely, and even heroic, use of 
morphia subcutaneously. It is especially ser- 
viceable in the early stage—stage of irritation— 
and ceases to be useful when depression of func- 
tion—paresis—occurs. 
In the psychical disorders insomnia is a promi- 
nent symptom, for the relief of which the mor- 
phia injection is especially indicated. When in- 
somnia is the substantive disorder, a combination 
of morphia and atropia is better than morphia 
alone,—a fact which I shall develop in a future 
chapter. 
In the treatment of coup-de-soleil, sunstroke, 
very unexpected and gratifying results have been 
obtained by Dr. Hutchinson at the Pennsylvania 
Hospital.| He injected one-fourth of a grain of 
the sulphate of morphia, which produced almost 
instant relief, and was followed by rapid recovery. 
Hysteria.—ln England Hunter,§ in Germany 
* Schmidt’s Jahrbucher, vol. cxxvii. s. 163. 
f Epidemic Meningitis. Philadelphia, 1868. 
J Pennsylvania Hospital Reports, vol, ii. p. 291. 
$ On the Speedy Relief of Pain, etc., 1, c. MORPHIA AND ITS SALTS. 
Lander and Fronmiiller,* were the first to em- 
ploy the hypodermatic method with morphia in 
the treatment of hysterical convulsions. Lorent f 
recommends it in hysterical melancholy. In my 
own experience, no remedy has acted so promptly 
and satisfactorily in terminating a hysterical par- 
oxysm as this. One-twelfth to one-eighth of a 
grain of sulphate of morphia is sufficient for 
this purpose; but in this disease, owing to the 
craving for narcotic stimulation, it is not proper 
to administer a remedy efficacious indeed, hut so 
apt to induce appetite for its repetition. 
Epilepsy.—Brown-Sequard was the first to in- 
dicate the utility of hypodermatic injections of 
morphia in epilepsy. He combined with it atro- 
pia. Results as important as they were unex- 
pected have followed this method. It has been 
found that not only are the paroxysms in violent 
cases quickly relieved, but permanent benefit also 
has been obtained by diminishing the number, 
frequency, and severity of succeeding attacks. 
This remedy disputes with bromide of potassium 
the first place in the amelioration and cure of 
epilepsy. One may succeed when the other fails; 
both, of course, fail frequently. It is impor- 
tant, then, to have clear notions as to the kind 
of cases in which one or the other should he pre- 
ferred. 
As has been pointed out by S. W. Duckworth 
* Eulenberg, 1. c. 
f Op. cit., p. 17. THERAPY. 
87 
Williams,* Russell Reynolds,f and myself,| bro- 
mide of potassium is more effective in cases of 
grand mat in which the paroxysms occur fre- 
quently, with great violence, and during the day- 
time, and less effective in those which occur 
chiefly at night. The bromide is more effective 
in epileptoid convulsions symptomatic of “ coarse 
organic lesion of the brain.” It is less effective 
in the petit mol and in convulsive tic. 
The hypodermatic injection of morphia is pref- 
erable in epilepsy the paroxysms of which occur 
at night, in the petit mat, and in convulsive tic. 
It is not proper, as a general rule, in cases of 
epileptoid character dependent upon cerebral 
lesion. 
When the paroxysms succeed one another rap- 
idly, and are violent, the injection may be made 
during an attack, and without loss of time. Or- 
dinarily two or three times a week will suffice, 
and, whenever practicable, the- onset of an ex- 
pected attack should be anticipated. A very 
marked amelioration in obstinate cases may be 
thus induced. With the decline in number and 
violence of the seizures there will be witnessed 
under this treatment most gratifying improve- 
ment in the mental condition. For the treatment 
of epilepsy, seven or eight minims of my solu- 
* On the Bromide of Potassium in Epilepsy and Certain 
Psychical Affections. Pamphlet. 
f The Practitioner, vol. i. p. 5. 
J Fiske Fund Prize Essay, 1871, p. 38. 88 
MORPHIA AND ITS SALTS. 
tion, or one-fourth of a grain, will he a sufficient 
quantity for each injection. Notwithstanding the 
good effects of this practice, the certainty of in- 
ducing a morphia habit by frequent repetition of 
the narcotic impression is a serious objection to 
the method, and it is, consequently, rarely em- 
ployed at the present time. 
Scanzoni was the first to use the hypodermatic 
injection of morphia in eclampsia. This practice 
was followed by Lander, Hermann, and Leh- 
mann, with good results.* The injection is much 
safer than the inhalation of chloroform, almost 
as prompt in its effects, and quite as efficient 
in suspending the morbid reflex excitability. In 
the convulsions of infancy, whether dependent 
upon reflex irritation of teething, worms, indi- 
gestible food, etc., the hypodermatic injection of 
a small quantity (one-thirtieth to one-sixteenth 
of a grain) of sulphate of morphia will promptly 
terminate the paroxysms. This treatment must 
he conducted with caution in very young sub- 
jects. It will he prudent in any case to attempt 
relief by the ordinary measures, especially by 
the removal of the cause of irritation, before 
resorting to so powerful an agent. The dose 
for this purpose should not exceed one-sixteenth 
of m grain, and may he sufficiently powerful in 
one-half this quantity (one-thirty-second of a 
grain). 
* Erlenmeyer, op. cit., p. 35. THERAPY. 
89 
One of the most important recent contribu- 
tions to our therapeutical resources is the demon- 
stration, made by Prof. Loomis, of New York, 
of the remarkable curative power possessed by 
the hypodermatic injection of morphia in the con- 
vulsions of albuminuria. Heretofore the presence 
of albumen in the urine has been held to contra- 
indicate the use of the preparations of opium; 
hut the observations of Loomis have established 
the fact of an antagonism between the action of 
morphia on the one hand and of that condition 
of the intra-cranial circulation which occurs in 
albuminuria on the other. In albuminuria the 
arterial tension is low, the perivascular lymph- 
spaces are distended with serum, and the brain- 
substance is anaemic. In this state of things 
Traube found a sufficient explanation of the 
convulsions which by others were supposed to be 
caused by uraemia. 
In the treatment of uraemic convulsions, con- 
siderable doses of morphia are not only well 
borne, but are demanded by the conditions pres- 
ent. For an adult half a grain may be adminis- 
tered at once, and this must be repeated promptly 
if the convulsions continue, or if they recur after 
having ceased for a time. As much as two grains 
may be injected within a few hours in severe 
cases. The author must, however, repeat the 
caution that such heroic medication must not 
be undertaken without due consideration and an 
accurate diagnosis. 90 
MORPHIA AND ITS SALTS. 
Chorea.—Hunter* and Levick,f of Philadel- 
phia, employed the hypodermatic injection of 
morphia in this disease with success. When the 
jactitations are incessant and violent, prevent- 
ing sleep and causing injury to the soft parts, 
the patient wearing out at length, the use of 
morphia subcutaneously has undoubted value. 
It is useful in those cases in which Trousseau£ 
was in the habit of prescribing enormous doses 
of morphia internally. But over ordinary cases 
of chorea, as Dr. Bristowe§ has shown, “ specific 
forms of treatment have little or no real influ- 
ence,” and suitable hygienic means will as cer- 
tainly conduct the case to a favorable termina- 
tion. Nevertheless, in the very violent cases to 
which I have referred there is no means of treat- 
ment equal to the hypodermatic injection of mor- 
phia. Generally speaking, such cases require 
the maximum doses, as Trousseau’s use of ten, 
twelve, and even fourteen grains of morphia 
daily with success sufficiently indicates. Com- 
mence with one-fourth of a grain, and increase 
according to the effect produced: it will rarely 
be necessary to exceed one grain at a single 
injection. 
Tetanus and Hydrophobia.—Hunter used the 
hypodermatic method in cases of traumatic teta- 
* Loc. cit., p. 27. f American Journal of Med. Sciences. 
+ Clinique Medicaie de I’Hotel-Dieu, tome ii. pp. 195, 196. 
\ The Practitioner, No, X., April, 1869, p. 195. THERAPY. 
91 
nus, “ giving sleep and diminishing the spasms,” 
but without permanent relief, death ensuing in 
each. Ruppaner* injected two cases with the 
liq. opii comp., which very much assuaged the 
sufferings of the patients, but did not retard 
the fatal termination. He urgently recommends 
further trials with this agent. More favorable 
results were obtained by others. Thus, Eulen- 
bergf used it with success in a case of traumatic 
tetanus. In idiopathic tetanus, and in trismus 
neonatorum, more favorable results have been 
obtained, but these forms of trismus are much 
more amenable to treatment than the traumatic. 
HemarquayJ obtained good results in the treat- 
ment of cases of tetanus during the second siege 
of Paris, by a new mode of using subcutaneous 
injections. He carried the needle deeply into the 
contracted muscles, and, if possible, to the point 
of entrance of the nerves. He thus injected the 
masseters, the muscles of the neck, the sterno- 
cleido-mastoid, the sacro-lumbar muscles, etc. 
He used in this way one to two grains of the mu- 
riate of morphia daily, with the effect to relax the 
spasms and permit the nourishment of the patient. 
Of three cases treated in this way, two recovered 
and one died; but the fatal result in this case was 
due not to the tetanus, which was relieved by 
the injections, but to pyaemia. The subcu- 
* Hypodermic Injections, p. 136. f Op. cit., p. 136. 
t Bull. Gen. de Therapeutique, Oct. 15, 1871, p. 299, et seq. 92 
MORPHIA AND ITS SALTS. 
taneous use of the extract of Calabar bean 
(physostigma), or of woorara, is much more 
effective in the treatment of tetanus. . 
The sufferings of the patient affected with hy- 
drophobia may be much diminished by the hypo- 
dermatic injection of morphia, hut I am aware 
of no case in which the fatal termination has 
been averted. 
Local Muscular Cramp and Spasm.—Eulenberg 
has used the subcutaneous injection of morphia 
in the muscle-spasm succeeding amputation of 
the thigh. I have obtained the greatest advan- 
tage from this method of treatment in the pain- 
ful jactitations of the muscles which occur in 
cases of fracture. In a case of fracture of the 
femur on the paralyzed side of a hemiplegic 
patient, the injection procured instant relief to 
the very violent and persistent muscular spasms 
which occurred in a few" hours after the injury. 
As is well known, Dr. Marshall Hall was the 
first to point out the fact that in paralysis of 
cerebral origin the muscular irritability is not 
lost, and may indeed be greater than normal; 
afterward confirmed by Duchenne de Boulogne, 
and now universally admitted. In the patient 
to whom I refer the muscular irritability existed 
in an exaggerated degree. Besides the pain 
which the violent spasm produced, union of 
the fractured femur would have been impossible 
if no means had existed for terminating the 
muscular spasms. THERAPY. 
93 
Neuralgia..—The greatest triumphs of the hy- 
podermatic method have been achieved in the 
treatment of neuralgia. As Dr. Anstie, in the 
able article already referred to, remarks, “ The 
advantages of morphia, hypodermatically admin- 
istered, over opiate medication by the stomach, 
are such as would be a priori incredible, nor can 
they as yet be fully explained. In particular, 
it is impossible to account for the far greater 
permanence of its action in relieving nerve-pain, 
which is so marked that its discovery has in- 
itiated quite a new era in the treatment of severe 
neuralgias.” * 
Following the classification of Valleix, the 
neuralgias are divisible into two classes : 
I. Superficial Neuralgias. 
The first class is subdivisible into the follow- 
ing : 
11. Visceral Neuralgias. 
Trifacial. 
Cervico-occipital. 
Cervico-brachial. 
Intercostal. 
Lumbo-abdominal. 
Crural. 
The second class will be more conveniently 
referred to in connection with internal dis- 
eases. 
Sciatic. 
* Op. cit. MORPHIA AND ITS SALTS. 
94 
It would be unprofitable to devote space to a 
special consideration of nerve-pain according to 
its anatomical seat, for the principles of treat- 
ment are the same. I propose to make observa- 
tions on the most important varieties, to illus- 
trate the hypodermatic treatment in all. 
Neuralgia of the fifth nerve,- or trifacial, is the 
most important of the whole group. It occurs 
more frequently, is more painful, and is more 
difficult to cure. But from the lightest case of 
facial pain, due to irritation of decayed teeth or 
cold, up to the atrocious and incurable epilepti- 
form tic, there are numerous gradations in re- 
spect to severity and curability. 
In toothache the hypodermatic injection of mor- 
phia is often immediately curative. It is, of 
course, less permanently beneficial when caries 
exists, but even in this case it affords great re- 
lief. It may also be used to diminish the pain 
of extraction. The facial neuralgia of preg- 
nancy is promptly cured by it, as I have repeat- 
edly ascertained by trial. This fact was first 
pointed out, I believe, by Dr. H. R. Storer, of 
Boston, the eminent gynaecologist of that city. 
These cases, as is well known, are extremely 
obstinate under the old methods of treatment, 
and those who have suffered from them on 
former occasions are exceedingly grateful for 
the relief so promptly and permanently afforded 
by the hypodermatic method. 
The attacks of neuralgic pain experienced in THERAPY. 
95 
any portion of the distribution of the fifth are 
readily relieved by the same means. This re- 
mark is true of migraine, hemicrania, clavus hyster- 
icus, and other forms of neuralgic headache. I 
need hardly remind the reader that this method 
of treatment is not proper in that form of head- 
ache which often -precedes and is a symptom of 
cerebral hemorrhage. That severe and obstinate 
neuralgia of the fifth known as tic douloureux is 
generally curable by the hypodermatic injection 
of morphia, and if not curable, is always much 
ameliorated by this means. A single or two or 
three injections may not suffice, but the persever- 
ing use of full doses may at length be success- 
ful. In obstinate cases the dose may be raised 
from one-fourth to one grain twice a day. Even 
that intractable form of tic douloureux described 
by Trousseau,* under the name “ epileptiform 
neuralgia,” may be much ameliorated by this 
means, and the existence of the patient elevated 
from a condition of abject misery to compara- 
tive comfort. The extent of the curative influ- 
ence exerted by the hypodermatic injection in 
cases of tic douloureux will depend upon the age 
of the patient and upon the presence or absence 
of structural changes in the nerve or in the 
brain. Certainly the injection, properly used, 
will render unnecessary those severe surgical 
measures sometimes practised (section of the 
* Clinique Medicale, tome ii. p. 100, et seq. 96 
MORPHIA AND ITS SALTS. 
nerve) for temporary relief to the agony which 
the patient endures. I cannot too strongly in- 
sist that for decided relief of these severe cases 
very large doses are necessary—one grain twice 
a day. It is quite common to hear that hypo- 
dermatic injections have been tried in a certain 
case and have failed; but upon inquiry it will be 
found that they have not been properly made, 
or that a sufficient quantity of morphia has not 
been used. In a case of severe epileptiform tic 
now in my charge, a hypodermatic injection had 
been used by another practitioner without avail, 
but in my hands a half-grain of morphia does 
not fail to induce sound and refreshing sleep for 
the whole night, and great comfort and freedom 
from pain for some hours on the following day. 
What is equally gratifying in this case, the epi- 
leptiform convulsions have been rendered nota- 
bly milder. 
Cervico-oecipital and cervico-hrachial neuralgia are 
more amenable to treatment than tic douloureux. 
A few injections of morphia will generally suffice 
to cure them. 
I have had most gratifying success in the treat- 
ment of herpes zoster by this means. The hypo- 
dermatic injection at once suspends the severe 
pain and burning (intercostal neuralgia) which 
accompany this disease, and cuts short the dura- 
tion of the eruption. 
!Next to the severer forms of tic, the most 
troublesome neuralgic disorder with which we THERAPY. 
97 
Lave to deal is sciatica. I may affirm with regard 
to this what Dr. Anstie has remarked about epi- 
leptiform tic, that the hypodermatic method has 
inaugurated quite a new era in its remedial 
management. 
In severe and protracted cases, in which 
changes in the nerve and in the nutrition of the 
limb have taken place, permanent relief cannot 
always he guaranteed to the patient; but the 
injections steadily continued in the maximum 
doses will in a great majority of eases effect a 
cure finally. When morphia fails, atropia may 
he tried, and vice versa; or both, as is preferable 
in my experience, may be employed together. 
Dr. Lawson,* who has had an unfortunate per- 
sonal experience with this painful and trouble- 
some malady, and has also had a number of 
cases under treatment, concludes that the hypo- 
dermatic injection of morphia “ is almost the only 
remedy far sciatica.” He advises the injection to 
be made into the thigh, four inches below the 
hip-joint, and over the course of the nerve. Al- 
though I can coincide in judgment with Dr. 
Lawson in respect to the utility of the subcuta- 
neous injection of morphia in the treatment of 
acute or recent cases of sciatica, I must demur 
as to chronic or old cases. In these relief to 
pain and amelioration of the condition may be 
* The Medical Times and Gazette, Nov. 12, 1870, p. 650, 
and also, Sciatica, Lumbago, and Brachialgia, London, 1872. 98 
MORPHIA AND ITS SALTS. 
certainly effected by the morphia injections, but 
curative results less certainly. We have in the 
deep injection of chloroform a more decidedly 
curative agent, and to the article on this .subject 
the reader is now referred. 
Notwithstanding the exceeding utility of hy- 
podermatic injections of morphia in the treat- 
ment of neuralgia, no judicious physician will 
rely on them exclusively in the management of 
severe cases. A suitable dietary and regimen 
must be enforced; constipation and other reflex 
sources of nervous disturbance must be corrected, 
and amemia relieved by iron, cod-liver oil, the 
hypophosphites, etc. The part which cachexias 
—syphilitic, plumbic, mercurial, and paludal— 
may play must not be overlooked in the selection 
of remedies. Even where curative results are 
not attained, where relief to pain only is the re- 
sult, the existence of the patient may be ren- 
dered tolerable. 
Is it necessary to confine the injections to the 
“ painful points,” or to the site where pain is 
felt? I have already indicated my belief that 
the position of Mr. Charles Hunter is in the 
main correct, and that “ localization” of the in- 
jection is not necessary. There is by no means 
a unanimity of opinion on this point. Hr. 
Wood, the discoverer of the method, Behier, 
Erlenmeyer, Lorent, Eulenberg, and Mitchell, 
Morehouse, and Keen, think that better results 
are obtained by injection into the painful spot. THE RAPT. 
99 
Dr. Anstie, although believing that remote injec- 
tion is in general as effective, maintains that ex- 
ceptions are occasionally met with. Eulenberg 
bases his opinion on the fact that tactile and 
pain sensibility are diminished at the site of 
the injection. This point is disputed. Immedi- 
ately after the injection is practised, the neigh- 
borhood of the puncture is more sensitive to 
impressions, hut after a time a decline in sensi- 
bility occurs. Repeated injection, if followed 
by inflammatory action, increases the local sensi- 
tiveness, hut, otherwise, division of the nerves 
in the skin by the needle lessens the sense of 
pain. 
When the neuralgia is seated deeply in the 
trunk, the injection must necessarily he prac- 
tised at some remote point. When the neural- 
gia is superficial, the nerve accessible, it is an 
easy task to inject the fluid into the tissues ad- 
jacent. This practice—the injecting into the 
neighborhood of the nerve—is more efficient 
than remote injection in cases of sciatica, herpes 
zoster, and other superficial neuralgic affections, 
especially in cases of long standing, in which 
we may suppose the sheath of the nerve or the 
nerve itself has become altered. For it has been 
found that under such circumstances, the neural- 
gic pain being local and produced by lesions of 
the nerve, as, for example, in many cases of sci- 
atica, the injection of various irritant substances 
into the vicinity of the diseased nerve will often 100 
MORPHIA AND ITS SALTS. 
be followed by a notable diminution of the pain 
and sometimes by a cure. This important fact 
has been demonstrated by Luton,* Berlin,f and 
Ruppaner.| It is probable that in this way local 
injections sometimes succeed when remote in- 
jections fail. 
Diseases of the Respiratory and Circulatory Systems. 
There are various neuroses of the respiratory 
tract quickly relieved by the subcutaneous use 
of morphia, and certain inflammatory affections 
modified to a remarkable extent. The first named, 
merely functional disorders, will be considered 
first. 
Laryngismus Stridulus.—This reflex spasm of 
the laryngeal muscles is quickly relieved by the 
hypodermatic injection of morphia. As simple 
attacks occurring in children are readily cured 
by less powerful measures, this method should 
be reserved for the more important cases. In 
adults the same condition of the laryngeal mus- 
cles may be due to the pressure of an aneurism 
or other tumor on the recurrent laryngeal nerve, 
and is quickly arrested by the morphia injection. 
Hysterical aphonia, may be immediately removed 
by one injection, but I must urge the injunction 
that morphia must be given with great circum- 
spection to hysterical and nervous subjects gen- 
* Archives Generates, 18G7, p. 506. f Ibid. 
X Hypodermic Injections, op. cit. THERAPY. 
101 
erally, since they quickly fall into the morphia 
habit. 
Cough.—Cough maintained by habit—for ex- 
ample, the cough succeeding to whooping-cough 
—is quickly improved by this treatment; some- 
times a few injections effect a cure, but if not, 
decided amelioration. Whooping-cough in the 
spasmodic stage is greatly benefited by the in- 
jection of minute quantities of morphia and 
atropia in combination : -gY to grain of mor- 
phia and to grain of atropia. The cough 
of bronchitis, of phthisis, of aneurism, etc., is 
often surprisingly relieved by very small doses 
of morphia thus administered. 
Asthma.—For the relief of an asthmatic par- 
oxysm there is no means now known compara- 
ble to the hypodermatic injection of morphia, or 
of morphia and atropia. This fact I have main- 
tained for many years—in the first and subse- 
quent editions of this work. Within a few years 
past there have been frequent allusions in period- 
ical medical literature to the good effect of mor- 
phia subcutaneously in spasmodic difficulty of 
breathing, notably in asthma. Prof. See has 
especially been prominent in urging this method 
of treatment, and Prof. Hirtz declares it produces 
“ marvellous results.” The following are the 
effects to be expected in ordinary cases: 
It promptly relieves the paroxysm and enables 
the sufferer to lie down and sleep quietly; it 
lengthens the interval between the seizures and 102 
MORPHIA AND ITS SALTS. 
renders succeeding paroxysms milder. Usually 
I combine atropia with morphia, to give larger 
doses with safety, for in this as in some other 
neuroses the maximum doses are sometimes re- 
quired to give relief. Although the relief afforded 
is most grateful and surprising, it cannot be al- 
leged, I think, that any cases are cured, but that 
decided amelioration has been obtained in many 
who have been subjected to the treatment for 
some time, is a well-assured fact. 
The dose necessary will vary with the suscep- 
tibility and habit. Those unaccustomed to the 
subcutaneous use of morphia and susceptible 
may be relieved by one-twelfth of a grain. This 
will be a sufficient dose to begin the treatment 
in any subject, but habit will lessen the power 
and diminish the relief, so that increasing doses 
will be necessary. There is always danger of 
the morphia habit forming in these cases. The 
relief afforded is so prompt and grateful that 
patients wish to have the syringe in their own 
hands. The remedy is soon abused and an in- 
curable habit formed. Moderation is the condi- 
tion of benefit, for if the patient is allowed to 
pursue his own inclination and consume an enor- 
mous quantity of morphia, a state of the nervous 
system is soon reached in which the remedy is 
constantly necessary. 
Emphysema.—The hypodermatic injection of 
morphia gives more relief to the paroxysmal dif- 
ficulty of breathing in emphysema than any other THERAPY. 
103 
remedy. Judiciously used, and not permitted to 
become a habit, it is a precious resource. Even 
more apt is the subcutaneous use of morphia to 
become a habit in emphysema than in asthma, 
and with even more disastrous results. Having 
witnessed several unfortunate examples of the 
morphia habit in such subjects, I desire to im- 
press on my readers the necessity for caution in 
the use of this remedy. 
Hiccough.—Usually the hypodermatic injection 
of morphia gives prompt relief in this neurosis. 
It is not effective when hiccough comes on in 
the course of abdominal—chiefly hepatic—dis- 
eases, for the treatment of which morphia has 
been employed. It is effective the more nearly 
the disease approaches the neurotic form, and is 
less effective the more serious the lesions of 
which hiccough is a symptom. 
Acute Inflammatory Affections of the Respiratory 
Organs.—An acute catarrh of the nares, pharynx, 
larynx, and bronchi—a common cold—may be 
aborted by the timely administration of a minute 
quantity to | gr.) of morphia subcutaneously. 
It is probably the most effective treatment which 
we can employ in the treatment of this disease 
throughout its course, if the initial stage has 
passed. It is equally effective in the initial stage 
of bronchitis, and throughout its subsequent 
stages. An attack of 'pneumonia may be pre- 
vented by a full dose of morphia at the forma- 
tive stage. I make this statement with full 104 
MORPHIA AND ITS SALTS. 
knowledge of its importance, and because I have 
seen cases which appeared to me to have so re- 
sulted by this treatment. It is difficult to decide 
on the affirmative of this proposition, for if a 
case supposed to be the beginning of pneumonia 
is stopped as it begins, how shall its true charac- 
ter be determined ? To be successful it is essen- 
tial that a full dose (£ to | gr.) be given just as 
the preliminary congestion is developing. lam 
the more inclined to maintain this ground since 
Prof. A. L. Loomis has recently (1881) strongly 
advocated the treatment of the first stage of 
pneumonia by the hypodermatic injection of 
morphia. When so skilful a diagnostician and 
therapeutist as Dr. Loomis maintains the superi- 
ority of this plan of treatment I am strongly in- 
clined to adopt it, the more especially as my own 
observations have in a measure prepared me 
for it. 
There can be no two opinions in regard to the 
success of the treatment of pleuritis by the sub- 
cutaneous injection of morphia. Here, as in the 
maladies above referred to, it is possible by a 
timely use of the remedy to abort an attack of 
pleurisy. If the disease has passed the initial 
stage, the same treatment is the best up to the 
occurrence of exudations. 
The Cardiac Neuroses.—l have had very satis- 
factory results from this method in the treatment 
of that form of angina pectoris which consists 
essentially in a neuralgic affection of the cardiac THERAPY. 
105 
nerves. It is also recommended by Bamberger 
in the same disease, and by Erlenmeyer, Lorent, 
Eulenberg,* and other authorities. In the so- 
called “ restraint neuroses” of the heart, a few 
cases of which have fallen under my observation, 
the very formidable symptoms were quickly re- 
moved by the morphia injection. Whether the 
symptoms are dependent on irritation of the 
pneumogastric or reflex irritation through the 
sympathetic, the good effects of the injection are 
equally evident. As Handheld Jonesf asserts,— 
an opinion in which my own experience coin- 
cides,—the inhibitory action is frequently ex- 
erted through the gastric nerves. Rheumatic, 
malarial, and saturnine affections of the nervous 
apparatus unquestionably exert an influence in 
the production of cardiac neuroses.;}; These 
agree in producing pain, anxiety, breathless- 
ness, and great depression of the heart’s action, 
and are quickly relieved by the hypodermatic 
injection of morphia. Of course permanent 
relief will be obtained from suitable treatment 
for the cachexia on which these neuroses are 
dependent. 
Violent and irregular action of the heart, when 
a functional trouble merely, is quickly relieved 
by this treatment. Usually a minute dose suffices. 
* Die hypbdermatischen Injection, op. cit. 
f Functional Nervous Disorders, p. 215, Am. ed. 
I Ibid., p. 218. 106 
MORPHIA AND ITS SALTS. 
When palpitation and irregularity are due to 
narrowing and obstruction at the aortic orifice, 
the hypodermatic injection of morphia seems to 
me very questionable, if not positively unsafe, 
practice. There is, however, a condition of the 
heart in which this treatment does most conspic- 
uous good: in the case of dilated right cavities, 
with cough, difficult breathing, low state of the 
vascular tension, ischaemia of the arteries, gen- 
eral oedema, dry skin, and scanty urine. Fre- 
quently, under these circumstances, the appetite 
is lost, the stomach intolerant, and the medicines 
used for relief, notably digitalis, increase the 
existing distress and are rejected by vomiting. 
The good effected by the injection of gr. to 
gr. of morphia is most striking: the cough lessens, 
the breathing becomes easy, the arterial pulse 
grows stronger and fuller, the skin perspires 
freely, the kidneys act more energetically, and 
the stomach becomes quiet, so that food is taken 
with some relish. Beside these good effects in 
the changed state of the functions, others are 
experienced from remedies, especially digitalis, 
which can now be taken. 
Diseases of the Digestive Apparatus. 
The late Dr. Anstie formulated the following 
point of practice : Whenever opium or morphia 
is indicated in any case of disease, and anorexia 
or vomiting or obvious gastric disturbance exists, 
the remedy should be administered by subcuta- THERAPY. 
107 
neous injection. Although morphia, when ex- 
hibited in suitable doses by hypodermatic injec- 
tion, is less apt to produce nausea and vomiting 
than when administered by the stomach, this rule 
is by no means of constant application. 
Dyspepsia.—Dr. Clifford Allbutt, of Leeds, 
England, advocates the hypodermatic use of 
morphia in nervous dyspepsia with intolerance 
of food.* There can be no doubt of its utility. 
Not only is the stomach rendered more tolerant 
of food, hut an appetite is created, and hence the 
effects are peculiarly grateful. Here, again, I 
must interpose a caution: nervous subjects are 
so lifted up out of the Slough of Despond by 
morphia that a craving is quickly established. 
The symptom gastralgia is usually quickly relieved 
by this remedy, as also the pain of gastric ulcer ; 
but it does more. By allaying pain and arrest- 
ing vomiting waste is stopped and the strength 
nurtured. In the treatment of acute gastritis the 
subcutaneous use of morphia is invaluable, for it 
relieves the pain and vomiting, checks the in- 
flammation, and obviates the necessity for dis- 
turbing the organ by drugs. 
One-fourth of a grain is a sufficient quantity 
to be injected daily in cases of dyspepsia, gas- 
tralgia, and ulcer. In acute gastritis, this quan- 
tity may be necessary every four or six hours. 
The site of the injection is of little consequence, 
* The Practitioner, vol. ii., 1869, p, 341. 108 
MORPHIA AND ITS SALTS. 
but patients generally prefer the epigastric re- 
gion. 
Scirrhus.—ln cases of scirrhus of any portion 
of the digestive tract, especially of the stomach, 
no palliative is comparable to the hypodermatic 
injection of morphia. The existence of a patient 
afflicted with scirrhus of stomach is not only pro- 
longed, but is rendered comparatively peaceful 
and calm, by this treatment, for it diminishes or 
arrests the vomiting, enables the food to be assim- 
ilated, gives freedom from pain, promotes sleep, 
and thus saves the strength.. 
Cholera.—The most instantaneous and striking 
relief is afforded by the hypodermatic injection 
of morphia in sporadic cholera. It is indicated in 
this disorder after the irritant cause, whatever it 
may be, is evacuated from the intestinal canal. 
From one-sixth to one-half a grain, according to 
the severity and violence of the attack, may be 
injected into the epigastrium. The subcutane- 
ous injection is strongly indicated in epidemic or 
Asiatic cholera. In this disease, the gastrointes- 
tinal raucous membrane is not in a condition to 
appropriate remedies; hence the subcutaneous 
method is eminently rational. 
Dr. Patterson,* of the British Seamen’s Hos- 
pital, Constantinople, has employed the hypoder- 
matic injection of morphia in a recent cholera epi- 
demic. Of 10 cases “ treated in the usual manner,” 
* Medical Times and Gazette, Jan. 27, 1872. THERAPY. 
109 
9 died and 1 recovered. Of 42 cases treated by 
morphia subcutaneously, 22 recovered and 20 
died. Of these 42 cases, 8 were in articulo mortis 
when admitted, 1 bad a severe disease of the 
liver, 1 was far advanced in consumption, 1 was 
sixty years of age, 1 was near her confinement, 
and 3 were intemperate. Dr. Asche* treated 
two cases of cholera by this method successfully. 
According to the author’s experience, for the first 
symptoms in cholera, the morphia injection is 
the most serviceable remedy, but when cramps 
occur and collapse is imminent, morphia must 
be supplemented by chloral. A combination of 
these agents possesses peculiar curative power in 
true cholera, as the author has ascertained by 
actual trial. 
The Vomiting of Pregnancy has been relieved by 
the hypodermatic injection when all other means 
had failed. For the milder cases this treatment 
is unnecessary and improper; but in those severe 
eases in which life is reduced to the lowest ebb 
by the continual vomiting, and in which forced 
abortion has hitherto seemed the appropriate 
remedy, it is eminently successful. In all severe 
cases in which the ordinary remedies fail to give 
relief, recourse should be had to the hypoder- 
matic method. A daily morning injection (tr to 
\ grain) administered during the period of great- 
* Schmidt’s Jahrbucher der Gesammten Medicin, Band 125, 
s. 331-7. 110 
MORPHIA AND ITS SALTS. 
est difficulty, will enable gestation to proceed 
without danger to the mother, and without the 
necessity of adopting that serious alternative— 
abortion. 
Colic.—lt is the present practice to employ 
this method for relieving the pain and spasm of 
colic. In most of these cases, of course, further 
treatment is necessary: constipation must be re- 
lieved ; obstructions be overcome; the saturnine 
cachexia be removed; but the injection, by re- 
lieving spasm of the muscular layer of the bowel, 
permits these objects to be accomplished much 
more easily and speedily than would otherwise 
be possible. Cases of hepatic colic, within the 
range of my observation, have been quickly re- 
lieved by the hypodermatic injection of morphia, 
where opium internally failed to produce the 
least mitigation of the pain, and where the in- 
halation of chloroform procured only the most 
temporary respite. When pain is very excessive, 
the reader should remember small doses may 
not suffice, but one-fourth and even one-half a 
.grain may be necessary, repeated according to 
circumstances. 
The same observations are applicable to ne- 
phritic and uterine colic. 
Peritonitis,—Opium being the remedy par ex- 
cellence for inflammation of serous membranes, 
the hypodermatic injection of morphia should be 
employed in all cases in which promptness and 
completeness of effect may be desired. This is THERAPY. 
especially the case in peritonitis, whether pri- 
mary or secondary. Moreover, as in many cases 
of this disease the alimentation is of prime im- 
portance, and as nausea and vomiting are fre- 
quently present, the stomach administration 
should be deprecated, and the hypodermatic be 
preferred. 
Neuralgia.—ln the various forms of neuralgic 
pain which affect the abdominal organs, whether 
gastralgia, enteralgia, hepatalgia, nephralgia, etc., no 
remedy procures so prompt and, in many cases, 
complete relief as the hypodermatic injection of 
morphia. 
Constipation.—ln many cases of colic due sim- 
ply to constipation, the injection not only relieves 
the pain hut overcomes the constipation. It is 
true that in many cases the first injection tempo- 
rarily suspends the peristaltic movements, hut 
■when habitually used this effect disappears, and 
the normal movements are not diminished, but 
promoted. Cases in which constipation existed 
have thus been corrected during a course of 
hypodermatic injections. A physiological fact 
which I have already noted throws light upon 
this: in a few seconds after the injection bor- 
borygrai and distinct intestinal movements are 
observed. If, then, constipation exist in cases in 
which it may be desirable to use the hypoder- 
matic injection of morphia, this circumstance 
need not be considered a contra-indication. 112 
MORPHIA AND ITS SALTS. 
Diseases of the Genito-urinary Organs, 
I have already indicated the utility of the 
hypodermatic injection of morphia in nephralgia 
and nephritic colic. Lorent* refers to its use in 
parenchymatous nephritis to relieve the head- 
ache of ursemic intoxication. To this experi- 
ence must he added the remarkable observations 
of Loomis in respect to the exceptional utility 
of morphia injections in uraemic convulsions. 
When, however, the action of the kidneys is defi- 
cient, excretion lessened, or elimination checked, 
morphia is contra-indicated. 
Affections of the Bladder and Urethra.—ln cases 
of chronic cystitis I have given great relief by 
the hypodermatic injection. It suspends those 
violent expulsive efforts which occasion the prin- 
cipal suffering. In acute cystitis the injection, by 
procuring quiet to the organ and by diminishing 
the irritability of the mucous membrane, will 
directly contribute to the cure. The sufferings 
of the patient afflicted with calculus may be thus 
prevented until operative measures can relieve 
him permanently. Spasm of the bladder is quickly 
relieved by the same means; as also that painful 
but obscure affection, “ the bar,” which some- 
times succeeds too violent and prolonged sexual 
intercourse. The hypodermatic injection may 
* Die hypodermatischen Injectionen, op. cit. THERAPY. 
113 
also be used to relieve spasmodic stricture, but for 
this purpose it is by no means equal in my expe- 
rience to chloroform. It is convenient to blunt 
the sensibility preliminary to the operation of 
catheterism, and is a capital means for relieving 
chordee and prolonged and teasing erections. But 
to prevent unpleasant erections and nocturnal 
losses, the use of morphia and atropia together is 
preferable to morphia alone. For information 
on this subject I refer the reader to the chapter 
on “ Morphia and Atropia.” 
The hypodermatic injection of morphia is ca- 
pable of a variety of important uses in obstetric 
practice. It promptly arrests those false and, irreg- 
ular pains at the beginning of labor, which annoy 
the woman without advancing the case. In pri- 
miparse it has been used to diminish the suffer- 
ings of labor. It is much better than morphia 
by the stomach to procure rest and sleep during 
a prolonged first stage. No remedy is equal to 
the hypodermatic injection of morphia for the 
relief of after-pains. In all of these circum- 
stances no fear need be entertained that the 
judicious use of the injection will interfere with 
regular uterine contractions. The quantity to 
be administered will vary from one-sixth to one- 
fourth of a grain; the latter amount need rarely 
be exceeded. 
The pain of dysmenorrhoea can be promptly re- 
lieved by subcutaneous injection of morphia; 
but for all pelvic pain, as Dr. Anstie has re- 114 
MORPHIA AND ITS SALTS. 
marked, atropia is the best remedy. As a palli- 
ative in scirrhus of the uterus and of the mammae 
the hypodermatic injection of morphia is much 
superior, in respect of economy and effective- 
ness, to the stomach administration of the same 
drug. Lastly, on this topic, in all cases of se- 
vere pain involving any of these organs the 
hypodermatic injection of morphia is indicated. 
William Henry Fuller writes enthusiastically of 
the groat value of the hypodermatic injection of 
morphia for relieving the pain of acute rheuma- 
tism. I shall have some remarks to make in a 
succeeding chapter upon the use of morphia and 
atropia in that disease, and will not now antici- 
pate. I have used with great advantage the 
hypodermatic injection of morphia to relieve the 
nocturnal pains of tertiary syphilis. Besides the 
complete and permanent relief to the pain which 
I have procured by persistence in the injections, 
I have observed also remarkable improvement 
in the lesions of bones and muscles. Hot only 
in syphilitic but other forms of disease in which 
pain precedes, and in which an altered condi- 
tion of the nerves produces structural changes, I 
have observed that relief to the pain is followed 
by cessation of the morbid process in the part. 
This fact is well shown in zoster, an affection of 
the skin dependent upon some functional dis- 
turbance of its sensory nerves, which disappears 
very promptly after relief of the hypersesthesia. 
Diseases of Constitutional or Specific Origin.—Dr. THERAPY. 
115 
Of course, in neuralgia, the hypoder- 
matic injection should not be used to the exclu- 
sion of the iodide of potassium. In the cases 
in which I have employed it the pain persisted 
notwithstanding repeated use of large doses of 
the iodide,—a condition of things not unfre- 
quently encountered, for long use of this rem- 
edy and to the point of saturation—to borrow a 
term from the chemists—induces a tolerance 
fatal to therapeutical efficiency. 
In Certain Surgical Diseases and Operations.—To 
prevent shock, and to relieve pain after opera- 
tions and injuries, the hypodermatic injection of 
morphia is not as much used as it should he. 
Ho means affords such relief as this in the first 
few hours after fracture or dislocation. The re- 
duction of dislocations may be facilitated and 
the pain prevented by the "injection, in cases 
where it is undesirable or impracticable to use 
chloroform. It has recently been shown * that 
the reduction of strangulated hernia is much facili- 
tated by the same means. In all operations re- 
quiring the knife, to prevent the after-pain, to 
sustain the vital powers, and to maintain the 
necessary quietude of wounded parts, the hypo- 
dermatic injection of morphia should be used. 
To aid Chloroform Narcosis.—Bernard f made 
* The Practitioner, August, 1869. 
f Bulletin General de Therapeutique, vol. Ixxvii. p. 241, et 
seq. 116 
MORPHIA AND ITS SALTS. 
the important discovery that the use of morphia 
subcutaneously, previously to the inhalation of 
chloroform, aided materially in the production of 
anaesthesia, and with a much smaller quantity of 
chloroform, and prolonged the stage of narcosis 
so that continued inhalation was not required. 
Nussbaum, the distinguished surgeon of Mu- 
nich, soon after made a similar observation inde- 
pendently. Bernard advised the subcutaneous 
use of morphia before commencing the inhala- 
tion; Hussbaum, after the condition of analge- 
sia had been induced. Prof. William Warren 
Greene, M.D., then of Pittsfield, Mass., some 
time afterward announced the same fact, without 
being aware, apparently, of the recommendation 
of Bernard and the practical application of the 
discovery to surgical practice by Nussbaum. 
The practice of the injection before beginning 
the inhalation diminishes the irritation of the 
air-passages, prevents the coughing and strug- 
gling, and, doubtless, also removes the danger of 
cardiac paralysis, which in some rather rare cases 
takes place with the first action of the anaesthetic 
on the cardiac ganglia. In many subjects pro- 
tracted vomiting and great depression of the 
vital powers occur on recovery from the anaes- 
thetic state : a morphia injection will prevent 
these results. It appears in a high degree prob- 
able that the subcutaneous injection of morphia 
will obviate the tendency to death by cardiac 
or respiratory failure in the anaesthetic state. THERAPY. 
117 
As it does prolong the anaesthetic stage with a 
lessened quantity of chloroform, it seems incred- 
ible that surgeons will neglect so important an 
addition to their resources. 
As a Physiological Antagonist.—The antagonism 
existing between morphia and atropia has been 
abundantly proved by clinical facts. The nature 
of this antagonism and the practice based on it 
will he considered in the section devoted to this 
subject. Morphia has been used successfully as 
an antagonist in poisoning by gelsemium, and by 
veratrum viride. In a case of poisoning by gel- 
semium, narrated by Dr. Courtwright,* the symp- 
toms were promptly relieved by the subcutaneous 
injection of morphia. Two grains of morphia 
sulphate were required to antagonize a table- 
spoonful of the saturated tincture, about equal 
in strength to the official fluid extract. Several 
cases of successful treatment of opium-poisoning 
by veratrum viride have been reported, and in 
many cases an alarming degree of depression 
caused by veratrum viride has been removed by 
the administration of tincture of opium. The 
clinical experience has been confirmed by trials 
on animals.f 
* Cincinnati Lancet and Observer, vol. xxxvii., 1876, p. 961. 
f Cartwright Lectures for 1880, “ On the Antagonism be- 
tween Medicines and between Remedies and Diseases/’ New 
York, 1881, p. 77. CODEIA AKD ITS SALTS. 
The Preparation.—The only salt of codeia 
readily procurable is the sulphate. As the 
strength of this alkaloid is barely one-half that 
of morphia, the dose for hypodermatic injection 
is from one-eighth to one-half—even to one 
grain. As, however, commercial codeia is apt to 
contain morphia, large doses ought not to be 
given until the strength of the specimen used is 
ascertained. Extemporaneous solutions should 
be prepared from powders of the strength re- 
quired. 
Physiological Effects.—The actions of codeia 
are similar to those of morphia. It is less nau- 
seant and more hypnotic. It probably, also, has 
less effect in restraining the intestinal movements, 
and in lessening the irritability of the bladder. 
The various secretions and excretions are less 
affected by codeia than by morphia. Codeia has 
also less pain-relieving power. Whilst thus, in 
the whole range of the action, codeia is less pow- 
erful than morphia, it has more distinctly a hyp- 
notic action and less nauseating and constipating 
effects. When the usual medicinal dose—one- 
fourth to one-half a grain—is administered sub- 
cutaneously, the same local effects are produced 
by codeia as by morphia. The systemic action is 
118 THERAPY. 
119 
as prompt, but is less decided; the stage of stim- 
ulation is less pronounced and shorter in dura- 
tion, and the action of the heart and the arterial 
tension are less elevated than is the case with 
morphia. From these actions it may be inferred 
that codeia is possessed of valuable qualities 
which might be utilized in preference to morphia 
in various morbid states. 
Therapy.—Codeia may be used in the various 
maladies in which morphia is now administered 
hypodermatically, but it presents no advantages 
except in those cases in which a special hypnotic 
action is desired,—in mania, hypochondria, and de- 
lirium tremens, with the limitations already en- 
joined in the case of morphia. In diabetes it has 
been employed with distinct advantage by the 
stomach, and will probably be found more effect- 
ive by the subcutaneous areolar tissue. In the 
neuroses of the respiratory organs codeia will prob- 
ably prove more advantageous than morphia. 
Narceine has been used subcutaneously, but 
without any advantage,* and morphia and nar- 
ceine combined have been employed hypodermat- 
ically by Lubinski.f 
Extractum Opii and Liquor Opii Composites 
(Squibb’s) have also been administered by the 
hypodermatic method, but they are greatly infe- 
rior to morphia. 
* Eulenberg, Allg. Therapie—Percutane, Intracutane und 
Subcutane Arznei-Application, p. 82. 
f Ibid. THE OPIUM OR MORPHIA HABIT AND ITS 
TREATMENT. 
The introduction of the hypodermatic syringe 
has placed in the hands of man a means of in- 
toxication more seductive than any which has 
heretofore contributed to his craving for narcotic 
stimulation. So common now are the instances 
of its habitual use, and so enslaving is the habit 
when indulged in by this mode, that a lover of 
his kind must regard the future of society with 
no little apprehension. It may well be ques- 
tioned whether the world has been the gainer or 
the loser by the discovery of subcutaneous medi- 
cation, For every remote village has its slave, 
and not unfrequeutly several, to the hypodermatic 
syringe, and in the larger cities men in business 
and in the professions, women condemned to a 
life of constant invalidism, and ladies immersed 
in the gayeties of social life, are alike bound to 
a habit which they loathe, but whose bonds they 
are powerless to break. Lamentable examples 
are daily encountered of men and women, re- 
gardful only of the morphia intoxication and 
indifferent to all the duties and obligations of 
life, reduced to a state of mental and moral 
weakness most pitiable to behold. 
120 EFFECTS. 
121 
Usually the habit is formed in consequence of 
the legitimate use of the hypodermatic syringe in 
the treatment of disease. Employed in chronic 
painful maladies for a long period, it is discov- 
ered, when an attempt is made to discontinue 
the injections, that the patient cannot or will not 
bear the disagreeable, even painful, sensations 
which now occur. More frequently, when the 
injections are to he used for a long time, the 
patient is unwisely intrusted with the instru- 
ment, and taught all the mysteries of the solu- 
tions and the mode of administration. Under 
these circumstances, there being no restrictions 
on the sale of the drug, the patient rapidly in- 
creases the dose, and presently comes to use a 
quantity of morphia which may seem almost 
incredible. Twenty, forty, sixty grains of mor- 
phia daily the author has known to be consumed 
by persons who have come under his observa- 
tion, and Levinstein* records cases in which, iu 
a short time, 1 gramme (15 grs.) was the daily 
allowance. To maintain a constant etfect on the 
organism there must be a material increase in 
the amount administered every few days, and 
ultimately in most subjects a condition of the 
nervous system is brought about in which the 
new dose simply relieves the horrors and bodily 
depression left by the preceding quantity. Slaves 
to a vice beyond their control, they no longer 
* Die Morphiumsucht. Berlin, 1877. 122 
the opium or morphia habit. 
experience the feeling of well-being, the exhil- 
aration, the intoxication, which were produced 
at first. There are very obvious differences in 
the physical and mental effects of moderate doses 
used for a comparatively short period and large 
doses administered for years. It will conduce 
to a clearer conception of the subject to treat of 
these two classes of morphiamaniacs in separate 
paragraphs. 
1. Small Doses for a Short Period.—lf the in- 
jection have been administered in a moderate 
quantity—half to a grain several times a day for 
six months—and at a fixed hour, the patient be- 
gins to experience characteristic nervous sensa- 
tions as the time for the injection approaches; 
he becomes uneasy, restless, “fidgety;” he is 
wakeful, his senses are abnormally acute, and 
he has more or less headache and vertigo; his 
feelings are easily touched; a globus rises in 
the throat; nausea and troublesome borborygmi, 
with some intestinal pain, occur; general malaise, 
a sensation of fatigue, accompanied with mus- 
cular pains and decided inability for physical 
exertion, with depression and a cold sweat, are 
felt. These are the sensations, in less or greater 
degree, according to the time which has inter- 
vened, that inform the individual of the need of 
a new dose. Marvellous, indeed, is the change 
when the injection is practised. All the dis- 
agreeable, even painful, sensations and the dread- 
ful unrest, which had but a moment before EFFECTS. 
123 
caused an indescribable discomfort, have now 
vanished, and in their stead are present a feeling 
of perfect comfort, and an active state of body 
and mind equal to any etfort. How grateful is 
the patient for the feeling of relief, and how im- 
possible to forego the use of a drug which so 
transforms his feelings and imparts a glow to the 
world about him! 
If the injections are suspended suddenly and 
entirely, very severe nervous disturbances are 
induced. An obstinate headache, vertigo, tin- 
nitus; wakefulness, coming on after a short 
period of somnolence, interspersed with snatches 
of sleep disturbed by horrible dreams; during 
the waking moments an inexpressible anxiety and 
gloom and depression; unappeasable restlessness, 
with an overpowering sense of fatigue and a 
deep-seated aching in the members; nausea, 
vomiting, repugnance to 'food, intestinal pain, 
diarrhoea, sometimes of a colliquative character; 
very great depression of the powers of life, a 
weak, small pulse, becoming rapid and thready 
on exertion; coldness of the surface, a cold, 
clammy sweat, are the formidable symptoms 
developed by the sudden withdrawal of mor- 
phia, when used for some months in moderate 
quantity. 
2. Large Doses for a Long Period.—The symp- 
toms already detailed are present in these cases, 
but are more pronounced. The physiognomy of 
the morphiamaniac is peculiar: his face is pallid, 124 
THE OPIUM OR MORPHIA HABIT. 
eyes dull and glazed, pupil small and sluggish, 
countenance strange and weird, expression un- 
earthly. His skin has an earthy, sallow tint, the 
nutrition impaired either in the direction of an 
increased accumulation of fat, the tissues being 
soft and watery, the muscles small and wanting 
in contractile energy, or in the way of general 
emaciation. Whether gaining or losing in weight, 
feebleness is a characteristic of the bodily state. 
The least exertion causes a rapid pulse and accel- 
erates the breathing. The appetite is poor and 
digestion is feeble. Great repugnance is felt to 
animal food, and, indeed, towards all the more 
substantial articles of diet, and fluids and fruits 
are almost wholly used. This abnormal taste is 
in part due to the dry mouth and cracked tongue, 
—physical conditions unfavorable to the sense of 
taste,—and in part to the poor digestion. The 
secretions of the intestinal canal and of its an- 
nexed organs, notably the liver, are so dimin- 
ished in amount as to affect digestion seriously, 
hence the stools are dry, hard, scyhala-like, yel- 
low or grayish in color, and coated with tough 
mucus. So insensible does the raucous mem- 
brane become that the- faeces are retained for 
lengthened periods, hemorrhoids form, and an 
obstinate eczematous eruption appears at the 
margin of the anus. After a time, the retained 
faeces set up a high degree of irritation, an acute 
gastro-intestinal catarrh is produced, and an 
attack of cholera morbus occurs, with sometimes EFFECTS. 
125 
very serious depression of the powers of life. 
In some individuals, it is true, the hypodermatic 
use of morphia does not impair the appetite and 
the digestive power, and does not interfere with 
the normal and regular action of the intestines; 
but these cases are exceptional. Gastro-intestinal 
attacks, such as I have described, occur in some 
morphiamaniacs every few weeks; in others 
every few months,—several times, certainly, dur- 
ing the course of the year. The effect of the 
capricious and bizarre appetite, of the lessened di- 
gestive power, and of the diminished absorption, 
is to impair the quality of the blood,—to induce 
a serious kind of anaemia. Hone of the organs 
of the body can perform their functions properly 
under these circumstances; hence the mental and 
physical feebleness of the morphiamaniac. There 
is a function, however, which suffers especially,— 
the reproductive. The first effect of the use of 
morphia to a moderate extent is to increase the 
sexual feelings, but a considerable dose admin- 
istered for the first time will depress or suspend 
the power of erection. Victims of the subcuta- 
neous use of morphia soon lose all sexual feeling, 
and are deprived of the power of erection and 
the production of semen. During the continu- 
ance of the habit no semen whatever is secreted, 
and no nocturnal losses occur; when the habit 
ceases, the secretion of semen is resumed and 
involuntary evacuations again take place. Mor- 
phia suspends the function without otherwise 126 
THE OPIUM OR MORPHIA HABIT. 
impairing it, for we find that these subjects pos- 
sess the same virility after the cessation of the 
morphia habit that they possessed before. The 
same result occurs in women. When the mor- 
phia habit is established, the menstrual function 
ceases and tbe sexual life is entirely suspended, 
and tbe woman is as absolutely without all of 
those feelings and instincts pertaining to her sex- 
ual relations as if they had never existed. As 
in man, this suspension of the sexual life is co- 
existent with the morphia habit, for the natural 
order is restored when the vice ceases. 
Levinstein emphasizes the occurrence of albu- 
minuria and diabetes in cases of morphia habit. 
I have made many urinary examinations in these 
cases, and have as yet met with no instances of 
these maladies. It is true, in a few examples of 
considerable hepatic disturbance, I have noted 
the presence of sugar in the urine, but it was 
not permanent, and they could not, therefore, be 
regarded as cases of diabetes. Without pre- 
suming to call in question Levinstein’s accuracy, 
it may be affirmed of cases met with in this 
country, that they are not due to the subcutaneous 
use of morphia. 
The frequent use of the syringe, often the 
hasty introduction of the needle, and the use of 
a rusty and dirty needle, the injection of badly- 
prepared solutions, the repeated injection into 
certain localities, have a disastrous effect. Large, 
hard nodules form, which slowly suppurate, ex- EFFECTS. 
127 
tensive sloughing may take place, and septicae- 
mia and pyaemia sometimes occur with a fatal 
result. In a large proportion of these morphia- 
maniacs, suppuration, abscesses of considerable 
size, and ulcers are produced. I have seen the 
arms, the abdomen, the thighs and legs, a mass 
of ulcers, of abscesses in various stages of forma- 
tion, and of cicatrices. 
Bujardin-Beaumetz* narrates a case in which 
the injuries thus produced resulted in death. M. 
Calvel f has collected many cases of abscesses, 
traumatic fever, and other accidents produced 
by the injections, but he rightly enough refers 
them to the causes above mentioned,—the state 
of the needle, improperly-prepared solutions, and 
the cachexia induced by the morphia habit. 
Braithwaite | reports a most instructive case of 
morphia habit of six years’ duration, in which 
there occurred numerous abortions. In a new 
pregnancy at six months, a vast abscess formed 
in the thigh, from which erysipelas developed, 
and a high degree of constitutional disturbance 
arose. Nevertheless, delivery occurred at terra, 
and an attempt was then made to stop the mor- 
phia suddenly, but most serious troubles resulted, 
the erysipelas reappeared, and the attempt had 
to he abandoned. On the other hand, some 
* Bulletin General de Therapeutique, Jan. 1879, p. 87. 
f These de Paris. 
X Lancet, 1878, p. 874. 128 
the opium or morphia habit. 
escape these accidents entirely. One of the most 
inveterate subjects I have ever encountered was 
a man living in the wilds of Texas, who used a 
glass hypodermatic syringe that had been broken 
many times and mended with successive deposits 
of sealing-wax, until only the rusty old needle 
remained in view, and yet escaped all accidents. 
Several instances have been reported—one al- 
ready quoted—in which death was produced by 
the suppuration and the systemic condition there- 
by induced. That there is a special state of the 
tissues induced by morphia, to which the forma- 
tion of abscesses is due, is hardly admissible. 
The causes mentioned above are quite sufficient 
to account for them. 
After a time the repetition of the injection 
does not induce any pleasurable sensations. For 
a few minutes after the insertion of the morphia 
the patient experiences mental sensations of a 
most depressing kind, hut gradually a condition 
of well-being follows, consisting chiefly in relief 
from the horrible mental and physical agony 
which comes on as the morphia influence declines. 
The morphiamaniac never has sound and re- 
freshing sleep. Although, after a period of 
wakefulness due to the stimulant action of the 
narcotic, he lapses into a condition of somno- 
lence more or less profound, it is disturbed by 
dreams and visions of the most horrifying as- 
pect, entirely without the range of human expe- 
riences. If the individual awake in the midst EFFECTS. 
129 
of these weird dreams, some time elapses before 
he can realize his situation, and then comes over 
him, like a flood, a dreadful sense of the posi- 
tion in which the morphia has placed him. 
Doubtless the visions of the English Opium- 
Eater, which are not realized in the experiences 
of those who take opium as a test experiment, 
were actually present during sleep or the half- 
waking state. It results from this condition of 
the brain during sleep that the organ is not ade- 
quately rested, hence the sense of fatigue of 
mind which is felt on awaking, and which is 
removed only by the narcotic. In many sub- 
jects, ultimately, sound sleep is never produced, 
and a certain proportion pass into that condition 
of obstinate wakefulness known as coma vigil. 
The action of morphia must then be supple- 
mented by the bromides, chloral, etc., for this 
condition is one of imminent danger to the 
mind. In spite of all the means which can be 
used, some of these cases pass into a busy, active, 
and trembling delirium,—delirium tremens,—or 
into acute mania or acute melancholia, with 
strong suicidal impulses.* 
In the more severe cases of morphia habit, 
attacks of fever similar to ordinary intermittents 
take place irregularly. In my experience these 
attacks are usually associated with an acute 
gastro-intestinal catarrh, and are preceded by 
* Leidesdorf, London Medical Record, Nov. 15, 1876. 130 
THE opium or morphia habit. 
constipation and a much overloaded colon. They 
occur more usually in the summer and fall, 
rarely in the winter, and they may appear in 
regular order for several days as quotidian inter- 
mittent, or assume the remittent type, termi- 
nating in two or three days in a profuse sweat. 
"When the paroxysms are quotidian, they are 
identical with quotidian ague,—there is a chill, 
followed by fever and a sweat. Although they 
may be regular, they are usually irregular, and 
are not amenable to quinia, but do readily yield 
to an increased quantity of morphia. Very great 
depression of the powers of life may occur in 
some of these cases when a chill is coincident 
with a severe attack of cholera morbus. I have 
known instances in which the objective phenom- 
ena of a seizure were similar to those of a “ per- 
nicious intermittent.” 
Besides the immediate results of the morphia 
habit by hypodermatic use, the unfortunate mor- 
phiamaniac is assailed by dangers accidental and 
contingent, but nevertheless of high importance. 
A sudden illness, the performance of a surgical 
operation, may be seriously complicated if the 
physician or surgeon in attendance is not aware 
of the existence of the habit and the extent to 
which it is indulged. Still more serious are 
cases of sudden insensibility or impairment of 
the language faculty, for then the patient cannot 
communicate the fact of the habit. 
Sufficient data do not exist as yet to permit an EFFECTS. 
131 
exact statement of the anatomical changes occur- 
ring in the morphiamaniac, except the anaemia 
or cachexia; but experiments on animals indi- 
cate that slow changes occur, similar to those in 
chronic alcoholismus. 
When, in the old and confirmed cases of mor- 
phia habit, an attempt is made to withdraw the 
morphia suddenly, the most serious symptoms 
are produced. As soon as the effect of the last 
dose taken has passed off, they describe various 
uneasy sensations,—of creeping and crawling in 
the skin; tingling in the hairy scalp, in the hands 
and feet, and other places; a more or less profuse, 
often very profuse, perspiration breaks out over 
the body; the nose runs freely with a watery 
mucus, and sneezing comes on in paroxysms; 
nausea is experienced, and after a time vomiting 
occurs; the bowels become relaxed, and soon an 
exhausting watery diarrhoea comes on; the pulse 
grows quick and the action of the heart excit- 
able and more feeble as the waste goes on by 
vomiting and purging; the urine may he albu- 
minous or contain sugar, as affirmed by Levin- 
stein, and the nervous system falls into a very 
unstable condition. As these symptoms pro- 
gress, the mind is disturbed by horrible de- 
pression during the waking moments, and by 
strange, fantastic, weird dreams during the brief 
snatches of sleep. Great depression of the vital 
powers comes on as the case progresses, and 
in old morphiamaniacs a condition of collapse 132 
THE opium or morphia habit. 
ensues. Having had one experience of this kind, 
I shall not be again induced to repeat it, if for 
no other, for strictly humanitarian reasons, since 
the mental and physical sufferings are truly 
horrible. Levinstein advocates this method and 
succeeds, but one may accomplish results in an 
asylum not attainable in ordinary practice, where 
the patient possesses entire liberty of action. 
But Levinstein’s experience is not agreeable to 
any humanitarian. Although the details are 
brief, it is obvious that his patients suffer se- 
verely and are in danger of death. He describes 
two degrees of collapse,—the mild and the severe, 
—in which the patients pass into the condition of 
the algid stage of cholera, and may require, to 
save them from death, a hypodermatic injection 
of morphia. The only permanent cures are, in 
the experience of the author, those in whom the 
reduction was gradual. I do not deny that by 
the immediate withdrawal a cure may be effected 
in a few days or weeks, but such cures are not 
permanent. The time in which they are effected 
does not relieve the system of the terrible un- 
rest, the wakefulness, and the longing, which 
persist for months after the withdrawal of mor- 
phia. On the other hand, by the slow, almost 
insensible diminution of the daily amount, the 
nervous system has the opportunity to adapt 
itself to the change, and hence the unrest and 
the longing die out. 
Treatment oe the Morphia Habit* The TREA TMENT. 
133 
amount of difficulty in the treatment of any case 
will depend on sex, constitutional peculiarities, 
the length of time the habit has continued, and 
the per diem quantity which has been adminis- 
tered. When the physician or an attendant has 
administered the injections and the patient has 
not acquired the method, the task is compara- 
tively easy. I have usually succeeded by follow- 
ing these rules: 
Diminish the dose very gradually, without the 
knowledge of the patient. 
Never stop the injections suddenly. 
Never use morphia alone for a lengthened 
period, but with atropia. 
As the morphia is diminished, increase the 
proportional quantity of atropia until the effects 
of the latter preponderate. 
When the effects of the atropia are fully expe- 
rienced, the patient will generally begin to com- 
plain that the injection has lost its peculiar influ- 
ence, has become unpleasant, and will desire 
that it be discontinued. 
But the difficulty of breaking up the morphia 
habit is vastly greater in the case of confirmed 
subjects who have used the syringe themselves 
for years. What method must be pursued in 
these cases ? I am firmly of the opinion that 
the morphia should be very gradually diminished, 
—so gradually as to make but little demand on 
the moral strength and the self-control. If the 
patient is required to suffer the horrible sensa- 134 
THE OPIUM OR MORPHIA HABIT. 
tions produced by the want of morphia, the treat- 
ment will fail, for he will prefer indulgence 
though it lead to death. The patient’s co-opera- 
tion must be secured, and he must decide for him- 
self that the attempt shall be made. Strangely 
enough, the morphiamaniac’s impatience must 
he held in check. When under the influence of 
the morphia they have great confidence in their 
self-control, and they demand that a large reduc- 
tion shall be at once made. It is never safe to 
yield to these importunities, for when the flood 
of desire comes rolling in they are powerless to 
resist, and when cheating begins the attempt is 
a failure. It is a fundamental rule,—reduce the 
morphia by insensible degrees. 
The patient must give up the custody and use 
of the syringe to some one else, and must have 
the quantity necessary to make him comfortable 
at certain regular intervals, and without failure. 
If the daily quantity used is not large,—say four 
grains,—the syringe should be given up at once, 
and the morphia be administered by the stomach 
in proportional quantity,—i.e., about three times 
as much. Thus, if four grains was the daily 
allowance subcutaneously, at least twelve grains 
will be needed by the stomach. The rule may 
be formulated as follows: Give by the stomach a 
sufficient quantity to make and keep the patient comfort- 
able. It is a most important advantage gained 
to exchange the subcutaneous mode of admin- 
istration for the stomachal,—for, although the TREATMENT. 
135 
effect is slower in the latter, it is better main- 
tained, and the patient experiences less sudden 
and severe changes in his feelings. What is 
even more important, the chain of morbid asso- 
ciations connected with the hypodermatic syringe 
is broken up, and the patient feels hopeful, and 
anticipates release from his bondage because 
already freed from the necessity of puncturing 
his skin. 
When the per diem, allowance of morphia hy- 
podermatically is from one scruple to a drachm, 
considerable reduction must take place before 
the syringe can he abandoned, hut it should be 
dropped at the earliest moment. 
The rate of reduction should not he more rapid 
than one-sixteenth of a grain hypodermatically, 
and one-fifth of a grain by the stomach , each three 
to eight days. The necessary time must he given 
to it, though a year or more may he required. 
Haste on the part of the physician and impa- 
tience on the part of the subject will defeat the 
purpose in view, and when the bounds are once 
broken the work must he begun again. Fesiina 
lente is the proper rule to follow, and a wise and 
firm patience is the highest attribute of the 
physician. 
Are there any aids to treatment ? Is there not 
some drug which may destroy the appetite for 
the narcotic ? These questions are constantly 
asked, and they may he answered in the affirma- 
tive, hut not in accordance with popular notions. 136 
THE opium or morphia habit. 
The success of the plan proposed may he facili- 
tated by several expedients. It is of the first 
importance to correct the abnormal condition of 
the digestive functions. One or two compound 
cathartic pills at night will change the character 
of the evacuations, and induce a more healthy 
state of the intestines. As a stomachic and nerve 
tonic, a solution of strychnia in a mineral acid is 
highly useful: 
R Strychniae, gr. i; 
Acid, muriatic, dil., ipj. M. 
Sig.—Ten minims in a tablespoonful of water three times 
a day, before meals. 
If the stomach is irritable and the hepatic 
function torpid, the following prescription is 
serviceable: 
R Acid, carbolic., 
Sig.—One drop in water three times a day, before meals. 
Tinct. iodinii, aa gss. M 
If there is merely an atonic condition of the 
digestive functions, the tincture of nux vomica, 
in doses of ten to fifteen drops three times a day, 
may be very useful. Under the same circum- 
stances, quinine is indicated, especially in solu- 
tion with a mineral acid; or the quinine may be 
given in combination with iron, as in the elixir 
of phosphate of iron, quinia, and strychnia; or 
the tinctures of cinchona, with the other bitters, 
may be prescribed in combination. The fluid 
extract of cuca or coca (Erythroxylon Coca) has TREATMENT. 
137 
been used with distinct advantage in many cases 
as a tonic and restorative. According to some 
experienced observers, it has an effect on the 
nervous system which entitles it to be regarded 
as supplying a need or a craving. 
The most important point in the management 
of these cases is the alimentation. If the mor- 
phiamaniac can take food and digest it, the diffi- 
culty in the treatment is reduced one-half. It is, 
in fact, a useless effort to give tonics if the food- 
supply is wanting, or inappropriate, or undi- 
gested. Milk, egg-nog, animal broths, should 
be given freely, and as soon as possible steak, 
chops, and other substantial food. Their diges- 
tion may be aided by the simultaneous adminis- 
tration of pepsin, pancreatine, and mineral acids. 
If the stomach refuses everything else, it will 
probably take milk, or milk and lime-water. If 
but little food enters the stomach, it may be sup- 
plemented by rectal alimentation,—notably by 
injections of defibrinated blood, on the plan of 
Dr. Smith, of Hew York. If food can be taken 
in a small quantity only, it should be taken fre- 
quently,—every three hours. The supreme point 
is to renovate the blood, so that all the organs 
shall functionate properly. With an improved 
state of the cerebral nutrition there will come a 
more manly feeling, a firmer will, and a higher 
moral sense. 
The use of alcohol is a highly important ques- 
tion. When the nervous system is losing the 138 
THE opium or morphia habit. 
loved morphia impression, it will take kindly to 
alcohol. There is a loss rather than a gain in the 
substitution of alcohol for morphia, and, unfor- 
tunately, this is an exchange which has not unfre- 
quently been made. Levinstein refers to cases, 
and I have known the trade to be made in both 
ways. Although alcohol in any of its forms 
must be used with caution, it is undeniably ser- 
viceable. A whiskey toddy at bed-hour may in- 
duce quiet and refreshing sleep; wine at dinner 
in moderation will promote digestion. But I 
especially warn the practitioner against a pro- 
cedure which the patient will he inclined to 
adopt, that is, to take sufficient alcohol to cause 
a distinct impression on the nervous system, in 
place of the morphia impression. This must 
result disastrously, for when the alcohol influ- 
ence expires there will occur such a condition of 
depression that more alcohol or more morphia 
will be necessary. 
To procure quiet and refreshing sleep is essen- 
tial in these cases. When the morphia is very 
gradually diminished, the function of sleep may 
not be disturbed, and if proper care is used will 
not be. When, however, the morphia is de- 
creased rapidly, or is suddenly stopped, the most 
agonizing feeling of unrest is felt all over the 
body, but especially in the members, conjoined 
with the most absolute wakefulness. Under these 
circumstances chloral is extremely useful, indis- 
pensable, indeed, for by procuring sound and TREATMENT. 
139 
refreshing sleep life even may be saved. During 
the course of treatment chloral will he necessary 
now and then, but the utmost circumspection is 
required to prevent the substitution of a chloral 
for a morphia habit. The patient is always 
clamorous for some agent as a substitute. 
Occupation is an important adjunct to the 
treatment, for every disagreeable sensation in- 
creases with the attention given to it. The oc- 
cupation should give employment to both mind 
and body, and should he engrossing but not 
harassing. Depressing news, the ordinary an- 
noyances of life, and especially anxiety of every 
kind and degree, should he removed from these 
patients, that there may be no excuse for the 
smallest departure from the prescribed course. 
Travel may he serviceable, hut there are so many 
contingencies as to involve risk of failure in the 
treatment. Furthermore, there are the fewest 
number in a pecuniary condition to justify the 
attendance and the largely increased expenditure. 
But change of scene, in so far that the individual 
is removed from the associations connected with 
his habit, is always desirable. ATROPIA. 
The Solution.—The sulphate is the salt chiefly 
employed for hypodermatic use. This supplies 
all the conditions : it is readily .soluble in water; 
the solution is free from irritating qualities. The 
formula which I employ is the following: 
R Atropiae sulphat., gr. ij ; 
Aquae destil., M. 
Five minims of this solution represent one- 
forty-eighth of a grain. A much stronger solu- 
tion may be used, as the following: 
R Atropise sulphat., gr. i; 
Aquae destil., sji. M. 
A minim of this represents one-sixtieth of a 
grain. Or the following may he preferred: 
R Atropia? sulphat., gr. i; 
Aquae destil., pj. M. 
A minim of this contains one-one-hundred- 
and-twentieth of a grain. I prefer the first 
solution for these reasons: 
It is sometimes desirable to inject very minute 
quantities in susceptible subjects, and this cannot 
he done when the solution is very concentrated. 
140 The dose may be much more varied in a weak 
solution. 
DOSE. 
141 
I have elsewhere stated the general objections 
to strong solutions, which apply to atropia. 
A penicilium develops very rapidly in an atro- 
pia solution, and at the expense of the atropia; 
the more concentrated the solution the greater 
the loss. 
On account of the rapid growth of the penicil- 
ium, the solution of atropia should not be kept 
too long, but should be prepared in small quan- 
tity frequently during warm weather. Filtration 
will, of course, free the solution from visible 
impurities, but considerable loss of strength will 
be noticeable each time. 
Dose.—Extraordinary discrepancies are to be 
found in the statements of various authorities as 
to the quantity of atropia which may be used 
subcutaneously. Dr. Anstie * notes with surprise 
the large quantity advised by Trousseau, to 
of a grain,—a quantity sufficient to produce most 
serious toxic symptoms. Dr. Ruppanerf gives 
the dose at -g- to of a grain, Lorenll at of 
a grain, and Courty employed as much as of a 
grain at a single operation. Five minims of the 
solution which I recommend to the reader, or 
of a grain, is the largest amount desirable to use 
* The Practitioner, op. cit. 
f Hypodermic Injections, op. cit. 
J Die hypoder. Inject., 1. c. 142 
ATROPIA. 
in most cases. Very great differences in the 
susceptibility to the atropia influence are found 
to exist. Children bear a much larger propor- 
tional amount than adults. Women are much 
more susceptible than men. Persons having a 
light complexion are much more easily influenced 
by it than those having a dark complexion. A 
delicate female, having light-blue eyes and flaxen 
hair, possesses, according to my observation, the 
maximum susceptibility. For such subjects two 
minims of my solution, or yiy of a grain, is a 
sufficient dose to commence with, and even this 
amount may occasion serious symptoms. To 
produce a curative effect in many severe cases of 
neuralgia, e.g., sciatica, much larger doses than I 
have recommended may be necessary. It will 
rarely be required, however, to inject more than 
Jy of a grain at one time. 
Physiological Effects.—The local symptoms 
at the point of puncture are the same as those I 
have described for morphia. 
A peculiar dryness and pallor of the lower lip 
is the first systemic effect to be observed. The 
dryness quickly invades the mucous membrane 
of the mouth, fauces, and larynx, rendering deg- 
lutition somewhat difficult, and the voice husky. 
At the same time the pupil begins to dilate, 
reaching its maximum dilatation in about thirty 
minutes. With the dilatation of the pupil there 
occur also deranged accommodation—the vision 
being presbyopic—and dimness of vision, the PHYSIOLOGICAL EFFECTS. 
143 144 
ATROPIA. 
outlines of objects being blurred and indistinct. 
Flushing of the face, more or less deep accord- 
ing to the temperament of the patient, fulness of 
the head with supraorbital pain and sense of 
distention, and giddiness, are now experienced. 
With the development of these effects we observe 
increased action of the heart and rise in the bod- 
ily temperature. The pulse rises in a few minutes 
to nearly twice the normal number of beats, and 
the thermometer exhibits elevation of tempera- 
ture ; but the correspondence between pulse-rate 
and temperature characteristic of fever does not 
exist. In the diagram, page 143, the influence of 
atropia upon the pulse and respiration move- 
ments, and upon the temperature, is exhibited. 
I subjoin also a sphygmographic tracing show- 
ing the influence of atropia on the arterial ten- 
sion. This must be compared with the first 
tracing on page 68, which is the normal tracing 
of Dr. Drake, upon whom the observation was 
made. 
At this period the subjective sensations of the 
patient, as well as the objective phenomena, are 
those of fever; the skin is hot and burning, and 
dry; the pulse full and bounding; the face 
flushed; the eyes injected; the head aches; the PHYSIOLOGICAL EFFECTS. 
145 
ears ring; the mouth is dry and hot; the volun- 
tary movements are disordered in consequence 
of the vertigo and of the impairment of the 
muscular sensibility; objects appear confused, 
and distances cannot he correctly appreciated; 
hallucinations and illusions occur; when sleep 
takes place it is disturbed by vivid dreams, some- 
times frightful, sometimes pleasing, the patient 
awaking and holding conversation with imagi- 
nary persons. Sometimes a somnambulistic state 
is produced, in which the patient walks about as 
if engaged in his usual avocations, talks with the 
objects of his visions, and quarrels and struggles 
with those who would oppose and restrain him. 
Sometimes the face and forehead are of a vivid 
red hue, resembling in color the eruption of scar- 
latina; the fauces are also red and injected, and, 
to complete the resemblance to this eruptive fever, 
a whitish fur covers the tongue, through which 
the red and enlarged papillae project. 
The dryness of the mouth, after some hours, is 
replaced by a moist condition, in which a viscid, 
sticky, and somewhat odorous secretion makes 
its appearance. Corresponding to this change in 
the mucous membrane of the mouth some in- 
crease in the peristaltic movements of the intes- 
tines is to be observed, the evacuations being 
somewhat loose. 
Frequent desire to evacuate the bladder is now 
experienced, with diminished power, the emis- 
sion of urine taking place slowly and with diffi- 146 
ATROPIA. 
culty, and sometimes, indeed, only after repeated 
efforts does the flow occur. 
The mental effects, generally such as I have de- 
scribed, are sometimes of a character to awaken 
grave anxiety. Great depression of mind, a 
melancholic state, with a suicidal tendency, at 
night horrible dreams and visions, leading to 
acts of violence, have been noted by me in some 
exceptional cases. I mention this so that the 
reader will ascertain what peculiar mental effects, 
if any, have followed the atropia injection, and 
avoid repeating it if the sensations' above de- 
scribed have been experienced by the patient. 
Such, in general, are the effects produced by 
the hypodermatic injection of a full medicinal 
dose. These effects continue about twenty hours; 
the dilatation of the pupil, the disorders of vis- 
ion, and the slowness and difficulty of micturi- 
tion being the last symptoms to disappear. 
Atropia cannot be considered very actively 
toxic. The symptoms which it produces afford 
ample warning of danger before the life of the 
individual is really placed in jeopardy. The 
sensations which accompany the full manifesta- 
tion of its physiological effects are so unpleasant 
that the patient early seeks relief, and the symp- 
toms are so characteristic that a mistaken diag- 
nosis is hardly possible. 
When a fatal dose is received, all the effects 
which I have described exist in an exaggerated 
degree. The pulse finally becomes small and PHYSIOLOGICAL EFFECTS. 
147 
thready, the action of the heart weak, and cold- 
ness of the surface succeeds to the unnatural 
warmth. This change in the symptoms indi- 
cates that the “ irritability” of the organic mus- 
cular fibre is exhausted. 
In order to a thorough comprehension of its 
therapeutical action, we must form some exact 
notions of the mode in which these physiological 
effects are produced.* 
The facts to be investigated are these: 
The dilatation of the pupil. 
The dryness of the mouth (arrest of secretion). 
The increased action of the heart and lungs. 
The rise of body heat. 
The influence on sensibility and motility. 
Several opinions have prevailed as to the mech- 
anism by which the dilatation of the pupil is ac- 
complished. 
This effect, as well as the presbyopia, is now 
known to be produced through the influence of 
atropia on the organic muscular fibre. By con- 
traction of the radiating fibres of the iris, which 
are innervated by the sympathetic, the pupil 
dilates; by a similar action on the muscle of 
accommodation, the lens is elongated, its diame- 
ter diminished, and the subject becomes presby- 
* I have examined this whole question in my Prize Essay 
of the American Medical Association for 1869, on Atropia 
its Physiological Effects and Therapeutical Uses, to which 
the reader is referred for full information. 148 
ATROPIA. 
opic. It is probable, also, tbat this effect is facil- 
itated by the paralyzing action of atropia on the 
oculo-motor nerve. 
A number of experiments have been made to 
determine the character of the influence exerted 
by atropia upon the heart and lungs. The part 
tbat paralysis of the pneumogastric plays; the 
part tbat direct stimulation of the cardiac portion 
of the sympathetic takes in the production of the 
phenomena, have been earnestly discussed. The 
inhibiting influence of the pneumogastric on the 
action of the heart is well understood: if the 
terminal filaments of this nerve are paralyzed, 
the action of the heart increases. It has been 
found, however, by Lemattre,* that the action of 
the heart is increased by atropia, notwithstand- 
ing division of the pneumogastric; this agent 
must, therefore, exert an immediate stimulant 
action on the cardiac ganglia of the sympathetic. 
This same effect is witnessed on the organic mus- 
cular fibre of the arterioles, as demonstrated by 
Lemattre in the vessels of the frog’s foot and 
confirmed by myself. I have demonstrated an- 
other fact: the contraction of the vessels after a 
time ceases, and relaxation takes place. This 
change is coincident with a weakened action of 
the heart; in other words, the atropia finally ex- 
hausts the irritability of the organic muscular 
fibre. This is a capital fact, which must not be 
* Archives Generates, 1.864. PHYSIOLOGICAL EFFECTS. 
149 
forgotten in our therapeutical employment of 
atropia. - 
The rise in body-heat is a product of increased 
oxidation due to the greater activity of the cir- 
culation. The redness of the skin and mucous 
membrane is due to the larger amount of blood 
pumped into the capillaries and the increased 
arterial tension. The increased oxidation finds 
expression in a much greater excretion of urea 
and the urates. 
There are several physiological facts which 
explain the action of atropia in arresting secre- 
tion of the pulmonary and intestinal mucous 
membrane. Prevost * has demonstrated that 
ablation of the spheno-palatine ganglion is fol- 
lowed by greatly increased secretion from the 
Schneiderian mucous membrane. The action 
which atropia exerts on the ganglia of the sym- 
pathetic must he the opposite of this. 
Patients brought fully under the influence of 
atropia generally experience considerable disor- 
der of voluntary movement. This effect is com- 
pounded of vertigo, diminished sensibility of the 
sensory nerves, loss of co-ordinating power, and 
paresis of the muscular system of animal life. 
A very curious phenomenon was observed by 
Frazer f in frogs paralyzed by atropia many 
* Archives de Physiologic Normale et Pathologique, vol. i. 
f Previously Undescribed Tetanic Symptoms produced by 
Atropia in Cold-blooded Animals. From Transactions of the 
Eoyal Society of Edinburgh. Edinburgh, 1869. 150 
ATROPIA. 
hours. When they lay limp and motionless, 
completely paralyzed and apparently dead, it was 
found that cutaneous irritation immediately ex- 
cited tetanic spasms. I had noted previously 
(Prize Essay) that during the combined action of 
atropia and physostigma these convulsant and 
tetanic spasms could be excited at once. This 
remarkable fact serves to show the close rela- 
tionship in action of those agents which belong 
to the two groups respectively of paralyzers and 
tetanizers. 
Therapy.—lt will be convenient to arrange 
the subjects under this head in the same way as 
in the section on the therapeutical applications 
of morphia. 
Diseases of the Brain and Nervous System. 
Cerebral Diseases.—The subcutaneous injection 
of atropia is contra-indicated in inflammatory 
affections of the brain and meninges, for a con- 
stant result of the toxic effect of this remedy is 
hypenemia of these organs. I have seemed to 
produce some good results, and certainly have 
relieved the referred pains of the extremities in 
cases of general paralysis. The “ late rigidity” 
which comes on in many cases of hemiplegia, 
and which is often accompanied by severe pain 
in the affected limbs, has been much benefited by 
the hypodermatic injection of atropia. The pains 
of progressive locomotor ataxia, and that annoying THERAPY. 
151 
disturbance of the sensory nerves, “ the fidgets ” 
which so constantly attends upon this disorder, 
may he relieved by this means. It has seemed 
to me that the subcutaneous injection of atropia 
exercised some influence also in retarding the 
progress of this disorder. Lorent has used the 
injection of atropia with advantage for relieving 
the pains which accompany chronic meningitis and 
myelitis. According to the views of Brown- 
Sequard, who holds that belladonna, by pro- 
ducing contraction of the arterioles, diminishes 
the supply of blood to the cord, the hypoder- 
matic injection of atropia ought to be very ser- 
viceable in myelitis. But it is now known that 
the increased action of the heart, and the greater 
arterial tension produced by atropia, favor hyper- 
semia of these parts. 
The hypodermatic injection of atropia is ser- 
viceable in certain cases of delirium tremens. The 
indications for its use are these: 
Obstinate insomnia with great restlessness. 
Weakened action of the heart; coldness of the 
surface; clammy sweat. 
Failure of nutrients, bromide of potassium, 
chloral, and hypodermatic injections of morphia, 
to quiet the delirium and induce sleep. 
In similar conditions in the psychical disorders 
the subcutaneous injection of atropia is service- 
able. This method of treating these disorders 
has the sanction of the eminent authority of 
Graefe. My own observation entitles me to in- 152 
ATROPIA. 
sist on this caution : the use of atropia is un- 
suited to cases in which there is hyperaemia of 
the nervous centres, or in cases of excitement 
with power. Moreover, it is not suited to cases 
of melancholia, for the reason already stated, 
that in many persons it produces great despond- 
ency of mind. 
Certain cases of mania, characterized by rest- 
lessness, motor activity, and mental as well, with 
hallucinations and incoherent rambling, the phys- 
ical state being that of weakness and relaxation, 
are sometimes remarkably benefited by atropia. 
Ringer* describes such a case, and shows that 
atropia is nearly if not quite as useful as hyoscy- 
amia has been in analogous cases. 
In 'puerperal mania, the general system being 
in the condition of weakness and depression, 
atropia is often successful in securing sleep and 
improving the mental state. 
Atropia cannot be considered a hypnotic in the 
true sense of that terra. It is sometimes said to 
produce this effect indirectly; by allaying pain, 
it is believed to render sleep possible. This, in 
the opinion of the author, is not a correct state- 
ment of the ground of its utility in certain cases. 
It is sometimes very useful as a hypnotic in cases 
of wakefulness and coma-vigil, dependent upon 
cerebral anaemia. 
Neuralgia. The subcutaneous injection of 
* The Practitioner, vol. xviii. p. 166. THERAPY. 
153 
atropia is not as effective in the treatment of the 
neuralgias in general as morphia by the same 
method. The systemic effects of atropia are 
also more unpleasant. For these reasons mor- 
phia is generally preferred. Nevertheless, when 
morphia fails to produce the desired result, or 
disagrees with the patient, as is sometimes the 
case, atropia may be used. In certain neuralgias, 
it must he admitted also, atropia is to be pre- 
ferred to morphia, e.g., in pelvic pain, in which 
Dr. Anstie considers it superior to morphia, in 
sciatica, and in certain cases of tic douloureux. In 
the pain of the various forms of dgsmenorrhoea, 
in ovarian neuralgia, and in the pelvic pain expe- 
rienced a few days after delivery, and due to the 
pressure of the womb on certain nerves, atropia 
by subcutaneous injection is most serviceable. 
The principal triumphs of atropia over neural- 
gia have been in cases of sciatica. It is now ad- 
mitted that atropia is one of the best remedies 
for this disease. First proposed and used by 
Mr. Hunter, it was afterward employed by Be- 
hier, Courty, Oppolzer, Lorent, and others. It 
has been found, however, that distant injection, 
and even injection into the subcutaneous tissue 
of the affected thigh, do not produce such good 
results as throwing the fluid deeply into the 
neighborhood of the affected nerve. More fre- 
quently, indeed, than in any other form of neu- 
ralgia, except the most obstinate and protracted 
cases of tic douloureux, the nerve itself, or its 154 
ATROPIA. 
sheath, has undergone structural alteration; the 
limb is often diminished in size, its temperature 
and sensibility lowered, and the power of its 
muscles impaired. Under these circumstances 
more advantage is to be derived from local than 
from distant injection, just as Luton, Bertin, and 
Ruppaner have cured such cases by the injection 
of irritants into the affected parts. 
In severe cases of sciatica and tic douloureux 
one-fortieth of a grain of sulphate of atropia may 
be injected; hut it should not be forgotten that 
this quantity will excite very severe symptoms in 
susceptible subjects. Generally, five minims of 
my solution, or one-forty-eighth of a grain, will 
produce decided atropinism. Cessation of the 
pain is not immediate upon the systemic effects, 
as Mr. Hunter originally pointed out; indeed, 
the pain is often at first increased, but improve- 
ment takes place after a variable interval, and 
is often more permanent than after the morphia 
injection. 
Tetanus and Hydrophobia.—ln tetanus, atropia 
has been used in numerous eases, but without 
success. Recovery has undoubtedly occurred in 
certain chronic cases, and in idiopathic tetanus; 
but it does not appear that the result was fairly 
attributable to the subcutaneous injection of atro- 
pia. Within the sphere of my observation, it has 
been freely used in cases of tetanus and hydro- 
but without permanent benefit. 
Epilepsy.—Brown-Sequard proposed the subcu- THERAPY. 
155 
taneons use of atropia in epilepsy, but be com- 
bined it with morphia. Erlenmeyer used it, but 
with a negative result. My own experience with 
atropia in this disease is as combined with mor- 
phia. The subcutaneous injection of atropia 
may be employed, instead of the internal use 
of belladonna, on the method of Trousseau.* 
Recent experience at Leidesdorfs clinic has 
demonstrated that atropia has remarkable cura- 
tive power in epilepsy. Its administration was 
based on the property possessed by it of reducing 
the reflex function in small doses. Large doses, 
as is well known, have the opposite effect on the 
reflex faculty. A number of cases have been re- 
ported cured. The daily use of yi¥ grain sub- 
cutaneously is probably a suitable amount. 
Diseases of the Respiratory and Circulatory Organs. 
The subcutaneous injection of atropia is appli- 
cable to the treatment of certain neuroses of the 
thoracic viscera. 
Asthma.—Courty was the first to employ atro- 
pia subcutaneously for the relief of asthma. He 
injected the solution over the pneumogastric 
nerve. Belladonna, in large doses, is now held 
to be the best remedy by Hyde Salter, Prof. See, 
and others, f Prof. See recommends belladonna 
because it is a “ vascular and cardiac” agent, and 
* Clinique Medicale, tome ii. 
f The Practitioner, July, 1869. 156 
ATROPIA. 
“ because the means of modifying respiration is 
to be found in the power to alter the pulmonary 
circulation.” The hypodermatic injection of atro- 
pia is preferable to the internal use of belladonna 
for the following reasons : 
The relief which it affords is greater and more 
lasting. 
The eifect is more speedy and certain. 
In my experience cases of emphysema and 
spasmodic breathing, due to dilatation, of the 
right cavities of the heart, are not so much ben- 
efited by atropia as asthma. I think it prudent 
to add a caution here: as atropia exhausts the 
irritability of the sympathetic ganglia, it is not 
proper to push the use of this agent in cases in 
which the muscular tissue of the heart is weak- 
ened by dilatation or fatty degeneration. 
In order to procure the greatest relief to the 
asthmatic paroxysm, the injection should be 
made promptly at the beginning of the attack. 
The dose will vary from gL to Gf a grain. It 
may be inserted at any convenient situation. 
Succeeding attacks should be anticipated if pos- 
sible, the injection being made when the first 
warnings are felt by the patient. As the effect 
of the atropine injection reaches its maximum in 
about a half-hour, it will at this time be per- 
ceived whether a sufficient quantity has been 
administered. 
This method of administering belladonna is 
much to be preferred to the stomach administra- THERAPY. 
157 
tion, or to the methods of fumigation, pulveriza- 
tion, or inhalation, notwithstanding fumigation 
is strongly urged by Prof. See * in some lectures 
on the subject of asthma. 
The administration of atropia may occasion 
much distress in the case of those asthmatics 
who suffer from dryness of the bronchial mucous 
membrane, and who experience relief when the 
secretion of mucus becomes abundant. I have 
known most alarming dyspnoea produced by the 
use of atropia in such subjects, and I therefore 
record a warning for the benefit of the inexperi- 
enced. 
Harley f—influenced by the fact that great in- 
crease of the heart’s action follows the adminis- 
tration of atropia, a fact, indeed, previously 
much insisted on by Y. Bezold—recommends 
this agent as a cardiac stimulant in conditions 
of great depression of this organ. It is certainly 
exceedingly useful in those restraint neuroses 
in which the inhibitive action is exerted through 
the pneumogastric, for by paralyzing the termi- 
nal filaments of this nerve and stimulating the 
cardiac ganglia of the sympathetic, the action of 
the heart is quickly improved and the depression 
overcome. It is in this action, according to 
Prof. See, that we have an explanation of the 
utility of atropia in asthma. 
* Bulletin General de Therapeutique, 15 Aout, 1869. 
f Gulstonian Lectures, also Vegetable Neurotics. 158 
ATROPIA. 
Diseases of the Digestive Apparatus. 
Atropia, it will be remembered, first arrests 
secretions of the intestinal mucous membrane, 
but in the reaction which ensues from this state 
increased secretion takes place. It promotes 
peristaltic movements by its action on the circu- 
lar fibres of the intestinal tube. 
Vomiting.—Sea-sickness and the vomiting of 
pregnancy are both relieved by subcutaneous 
injection of a small quantity—2lb- to of a 
grain—of atropia. But the good effects are not 
constant, and, when successful, diminished by 
repetition. 
Colic.—The various forms of colic may be re- 
lieved by this agent, but it is not so effective in 
most of them as morphia. It is adapted to cases 
of colic dependent upon constipation or upon 
lead-poisoning, but the most desirable resultsare 
obtained by the conjoined administration of mor- 
phia and atropia. 
Cholera.—ln the algid stage of cholera, during 
the last epidemic in the Southwest, the subcu- 
taneous use of atropia appeared to bring on 
reaction in some very unfavorable cases. It is 
desirable to give the agent further trial in any 
succeeding epidemic. 
Diseases of the Urinary and Genital Organs. 
For all varieties of pelvic pain, as Dr. Anstie 
has informed us, the subcutaneous injection of THERAPY. 
159 
atropia is the best agent. I need not repeat here 
what has already been said on this topic. 
Bladder Diseases.—ln dysuria and enuresis it is 
often most effectual. Belladonna has long had a 
deserved pre-eminence in the treatment of noc- 
turnal incontinence of urine. Atropia by subcu- 
taneous injection is the most effective way of 
administering it. 
Irritation of the bladder, when arising from a 
nervous erythisrn, may be relieved in the same 
way. That troublesome disorder, spermatorrhoea, 
is most successfully treated by the hypodermatic 
injection of atropia. Two indications are to be 
supplied in many of these cases: the erotic sen- 
sations which originate during the sleeping state 
are to be suppressed ; the reflex act of emission 
to be prevented. No agent accomplishes this 
more successfully than the subcutaneous injec- 
tion of atropia at bedtime and at such intervals 
as observation has shown to be necessary. 
Constitutional Diseases. 
Remarkable relief to the pain and soreness of 
acute rheumatism has been obtained by Lorent 
from the subcutaneous injection of atropia. This 
treatment has been suggested by Harley as if it 
were an original idea with himself. He recom- 
mends that the atropia be injected in the neigh- 
borhood of the inflamed joint. I have followed 
this practice with great relief to the patient. 
One injection of of a grain daily will gener- 160 
A TROPIA. 
ally be sufficient to quiet the pain ; but morphia 
may be combined with it advantageously, if the 
patient be wakeful. It has seemed to me to ex- 
ercise no little influence over the severity and 
duration of the disorder. 
As a Physiological Antagonist.—The subject of 
the antagonism of morphia and atropia will be 
discussed in the next chapter. 
The subcutaneous injection of atropia may be 
used against the toxic symptoms of certain vas- 
cular agents, as aconite, veratrura viride, tartar 
emetic, digitalis, which produce great depression 
of the heart’s action. It has been proposed, also 
on insufficient grounds, for relief of poisoning 
by hydrocyanic acid. In my prize essay on atro- 
pia I have shown that hydrocyanic acid in toxic 
doses acts too speedily for atropia to influence 
the result, and that animals fully under the 
effects of atropia are quickly poisoned by an 
ordinary toxic dose of the acid. 
Atropia is the antagonist to pilocarpine, mus- 
carine, and (eserine), and may be 
used to overcome and remove the lethal symp- 
toms caused by either of these agents. The 
following observations, taken from my Cart- 
wright Lectures, are appropriately reproduced 
here. ATROPIA AND PHYSOSTIGMA. 
161 
ANTAGONISM OF ATROPIA AND PHYSOSTIGMA. 
History.—For the first time, in 1864, Klein- 
wachter treated a case of poisoning by atropia 
by the internal administration of physostigma, 
the symptoms being relieved to a great extent. 
In 1867, Bourneville, in a thesis on the treatment 
of tetanus by physostigma, related a single ex- 
periment in which the effects produced by a 
quantity of the powdered kernel, introduced into 
the stomach of a cabiai, were overcome by the 
subcutaneous injection of atropia. In 1868 I 
made a number of experiments proving the ex- 
istence of the antagonism. The most important 
research was that of Professor Thomas R. Fraser, 
of Edinburgh, in 1869, who performed a great 
variety of experiments, and introduced new prin- 
ciples for the guidance of future researches of the 
same kind.* This investigation was followed by 
the report of the Committee of the British Med- 
ical Association, Dr. J. Hughes Bennett, Chair- 
man.f 
Antagonism.—Before proceeding to the anal- 
ysis of the published facts and experiments, we 
must have a definite conception of the actions of 
the two agents. In what respect do atropia and 
* “On the Antagonism between the Actions of Physo- 
stigma and Atropia.” Prom the Trans, of the Koy. Soc. of 
Edinburgh, vol. xxvi. 
f Brit. Med. Jour, for 1874. 162 
ATROFIA. 
physostigma differ ? I have already described tbe 
deliriant effect of atropia, its power to dilate the 
pupil, to stimulate the heart and the respiration, 
to arrest secretion, to flush and at the same time 
dry the skin. Physostigma does not affect the 
cerebral functions; it contracts the pupil, para- 
lyzes the voluntary muscles, but does not impair 
sensibility, increases secretion, energizes the heart- 
beats and raises the arterial tension, and causes 
death by paralysis of the respiratory muscles. 
Placed in opposition, we find that the points of 
difference are: on the brain, atropia causing de- 
lirious excitement, with hallucinations and illu- 
sions,—physostigma not affecting this organ at 
all; on the pupil, atropia causing dilatation by 
stimulating the radiating ffbres innervated by 
the sympathetic,—physostigma causing contrac- 
tion by paralyzing the radiating ffbres, thus leav- 
ing the third nerve unopposed; on the respira- 
tion, atropia stimulating the respiratory centre,— 
physostigma paralyzing the muscles of respira- 
tion ; on the heart, atropia increasing the rate of 
movement without adding to the power,—physo- 
stigma increasing the power without hastening 
the movements of the heart; on secretion, atropia 
drying the mouth and the secretions of the intes- 
tinal tube,—physostigma increasing the salivary 
flow and the secretions of the whole intestinal 
canal; on the voluntary muscular system,atropia 
causing paralysis of the motor nerves,—physo- 
stigma producing spinal paralysis. As regards ATROPIA AND PHYSOSTIGMA. 
163 
the lethal effects, the tendency to death by paral- 
ysis of the respiratory muscles, produced by phy- 
sostigma, is overcome by atropia. Or, as it is 
expressed by Professor Fraser, “ atropia prevents 
the fatal effect of a lethal dose of physostigma 
by so influencing the functions of certain struc- 
tures as to prevent such modifications from being 
produced in them by physostigma as would result 
in death. The one substance counteracts the 
action of the other, and the result is a physio- 
logical antagonism so remarkable and decided 
that the fatal effects, even of three and a half 
times the minimum lethal dose of physostigma, 
may he prevented by atropia.” 
The first reported example of atropia-poison- 
ing treated by physostigma proved a success. 
The first experiment made with the definite pur- 
pose of ascertaining whether an antagonism ex- 
isted, also, apparently proved the point. But the 
first sustained and sufficiently extended experi- 
ments made to test the antagonism were those 
undertaken by myself in 1868, before the pub- 
lished observation of Bourneville. While ac- 
knowledging the superiority in every way of the 
research undertaken by Fraser, I respectfully 
submit that my investigations, as published in 
my prize essay * of the American Medical Asso- 
ciation, clearly preceded his by a year. Claims 
of priority are, however, ungracious, and I do 
* Trans, of the Am. Med. Assoc, for 1869. 164 
ATROPIA. 
not therefore urge mine. In his historical re- 
view, Professor Fraser has not sufficiently, 1 
think, put my claim on its proper basis. Quoting 
from my essay, he takes a sentence or two from 
the general conclusions, which do not adequately 
convey the whole meaning of my researches. 
Thus, he says, “ Dr, Bartholow deduces a num- 
ber of general conclusions regarding the mutual 
counteraction of the two substances on several of 
the structures and functions modified by them. 
The following quotation contains an epitome of 
his views : ‘ Atropia is not a physiological antag- 
onist to physostigma, except in regard to their 
action on the organic nervous system. It would 
be improper, then, to use atropia against poison- 
ing by Calabar bean.’ ” As I shall presently 
show, my conclusions have been confirmed by 
subsequent investigations,—the antagonism ex- 
isting in the actions on the nervous system of 
organic life, as I had demonstrated. After the 
detail of some typical cases, out of a large num- 
ber of similar experiments, I came to the follow- 
ing conclusions: 
“ Atropia and physostigma are antagonistic as 
to their influence over the respiratory movements, 
—atropia increasing and physostigma retarding 
them. 
“ They are antagonistic in their action on the 
heart,—atropia producing excitation of the car- 
diac ganglia, and physostigma paralyzing them. 
“ They arc opposed in respect to their action ATROFIA AND PHYSOSTIGMA. 
165 
on the sympathetic,—atropia causing increased 
action, and physostigma paralyzing this system. 
“ They have opposite effects on the pupil in 
virtue of opposite effects on the sympathetic,— 
atropia dilating the pupil by its action on the 
radiating fibres of the iris, and physostigma con- 
tracting the pupil by paralyzing the radiating 
fibres.” 
My conclusions of 1868 have not been invali- 
dated by the subsequent investigations, and hence 
the experimental data must have been accurate. 
I therefore venture to submit that Professor Fra- 
ser’s quotation from my essay does not adequately 
represent my opinions. Apparently without in- 
vestigating on his own account, and accepting a 
very restricted excerpt from my paper, Dr. H. C. 
Wood* says, “ In 1869, Professor Roberts Bartho- 
low, of Cincinnati, on the strength of a few really 
indecisive experiments, arrived at a conclusion 
opposite to that of Bourneville.” Dr. Wood has 
absolutely no warrant for this positive assertion. 
So far from coming to a conclusion opposed to 
that of Bourneville, it was to the same purport, 
and based on a number of really decisive experi- 
ments. I have dwelt on my own views longer 
probably than they deserve, but historical accu- 
racy is of some moment, and no man wishes his 
proper opinions mangled and distorted by others. 
* Therapeutics, Materia Medica, and Toxicology, 3d ed., 
p.’ 320. 166 
ATROPIA. 
The quotation I have made from Fraser’s paper 
indicates his belief in the existence of an antag- 
onism in the lethal effects of atropia and physo- 
stigma of wide range, and his experiments, which 
were very numerous and carefully made, certainly 
support his opinion. The Committee of the Brit- 
ish Medical Association hold this antagonism in 
less favor; although they admit its existence, they 
find it is more limited in range than Dr. Fraser 
had supposed. Their general conclusion is: “ sul- 
phate of atropia antagonizes to a certain extent 
the fatal action of Calabar bean,” yet they main- 
tain that, “ for all practical purposes, atropia as 
an antidote to Calabar bean is useless, and not to 
be compared with the effects of chloral hydrate.” 
In the first part of this strong statement, the Com- 
mittee confirm the conclusion to which I had 
come, several years before, in respect to the use 
of atropia as an antagonist to the toxic effects of 
physostigma. 
The special points of antagonism have been 
elaborately studied by various observers. As re- 
spects the heart, atropia first causes a rise of the 
blood-pressure, but this is followed by the oppo- 
site condition, or diminution of blood-pressure, 
while the action of the heart continues accelerated. 
Physostigma slows the movement by lengthening 
the diastolic pause, and increases the vigor of the 
contraction, and also raises the arterial tension. 
By Arnstein and Sustschinsky,* the excitability 
* Centralbl. f. d. med. Wiss., No. 40, 1807. ATROPIA AND PHYSOSTIGMA. 
167 
of the cardiac branches of the vagi was found to 
be increased by physostigrna, and lessened by 
atropia. The experiments of Rossbach and Froh- 
lich, in all respects remarkable and novel,* seem 
not to confirm these observations. Kohler f and 
Harnack and Wilkowski J found that physostigrna 
lessened the pulse-rate, after the peripheral fila- 
ments of the vagi were completely paralyzed by 
atropia. Harnack,§ in a polemical paper strongly 
characterized by the fortiter in re, controverts the 
views put forth by Rossbach and Frolich, and by 
Rossbach alone, in respect to the action of atro- 
pia on the heart and on the pupil. Kohler holds 
that physostigrna slows the heart by paralyzing 
the accelerator nerve. It had already been shown 
that atropia stimulated the accelerator nerve (Be- 
zold and Bloebaum). Tachaujj and 
maintain that the retardation of the heart is due 
to a paralyzing action of physostigrna on the car- 
diac ganglia, but Laschkewich** shows that this 
retardation is due to stimulation of the inhibitory 
apparatus. The rise of arterial tension produced 
by physostigrna is probably due to contraction of 
the constrictor fibres of the arterioles, since strong 
* Pharmacol. Untersuchungen, Wurzburg, 1873, p. 77. 
f Archiv f. exper. Pathol, u. Pharmacol., i. p. 277. 
% Ibid., v. p. 204. I Ibid., iv., 1875, p. 146. 
|| Archiv d. Heilkunde, vi. 69. 
f Hermann’s Lehrhuch der experiment. Toxicologic, p. 339. 
** “ Beobachtungen iiber die physiol. Wirkungen der Cala- 
barhohne,” Yirchow’s Archiv, xxxv. p. 291. 168 
ATROPIA. 
local contractions of tlic intestine are produced 
by this agent when it is thrown into an artery 
supplying a small part of the bowel (Bauer).* 
How much soever the explanations differ, the 
fact remains that atropia and physostigraa act in 
an opposed manner on the heart. As respects 
the respiration, there are fewer differences of 
opinion. That physostigma causes death by pa- 
ralysis of respiration, the heart continuing in 
action after respiration has ceased, seems abun- 
dantly established, f On the other hand, it is 
generally conceded that atropia stimulates the 
respiratory function. Physostigma suspends, ul- 
timately, reflex excitability, and is a spinal para- 
lyzer; hence the function of respiration is only 
affected (Laschkewich, Tachau). On the other 
hand, the respiratory centre is stimulated by atro- 
pia, an acceleration of breathing takes place when 
the vagi have been divided (Bezold andßloebaum). 
It is, therefore, clear that these agents are opposed 
in their actions on the function of respiration. 
The point of opposition most conspicuous, and 
that which first suggested the existence of the 
antagonism, is the effect on the pupil—eserine 
causing contraction, and atropia dilatation of the 
pupil. Marked differences of opinion exist as 
to the mechanism of the antagonism. By some 
the contraction of the pupil caused by eserine is 
referred to a paralyzing action on the dilator 
* Hermann, op. cit. 
f Hermann, op. cit., p. 341. ATROPIA AND PHYSOSTIGMA. 
169 
fibres (Fraser, Hirscbmann *), and by others to a 
spasm of the sphincter fibres (Griinhagen and 
liogow,f Bezold and Goetz). That the latter 
view is correct seems supported by the fact that 
the effect of pbysostigma on the muscular layer 
of the intestine is to induce tetanic contraction 
or spasm. Further, when the pupil is contracted 
by eserine the contraction is readily overcome 
by atropia, but the atropinized pupil resists the 
action of eserine. 
The delirium, hallucinations, and illusions 
caused by atropia are in no respect affected by 
pbysostigma. In all of the instances of poison- 
ing by Calabar bean reported, the mind re- 
mained unaffected until near the end, when, car- 
bonic-acid poisoning coming on, stupor and 
drowsiness supervened. All respiratory poisons, 
pure and simple, are accompanied at the close of 
life by the carbonic narcosis due merely to the 
suspension of hsematosis. Carbonic-acid narco- 
sis is an important element in the morbid corn- 
plexus of atropia-poisoning. These agents do 
not, therefore, have an antagonistic action on the 
cerebrum. 
In the spinal effects of atropia and physo- 
stigma there are obvious differences. They are 
both paralyzers, but atropia causes, in cold- 
blooded animals, a subsequent tetanic condition. 
* Archiv f. Anat. u. Physiol., 18G3, p. 309. 
f Ccntrulbl. f. d. med. Wissensch., 18G3 p 577 170 
ATROPIA. 
When atropia and physostigma are administered 
simultaneously, this tetanic condition occurs at 
once,—a fact which I was the first to demon- 
strate; and so exalted is the reflex function of 
the spinal cord, that a slight tap on the surface 
of the body causes a tetanic spasm, the condition 
in the intervals being that of relaxation. In 
several of the cases of atropia-poisoning, tris- 
mus was a marked symptom. Atropia affects 
the spinal cord, Ringer and Murrell have shown ;* 
and the paralysis induced by it, they maintain, 
is largely spinal, although it does impair the irri- 
tability of the motor-nerve trunks. According 
to the experiments of Dr. Mary Putnam Jacobi, 
the sensibility of the sensory nerves is impaired 
by atropia. Physostigma, on the other hand, 
increases the irritability of the sensory nerves 
and is a spinal paralyzer, leaving the motor 
nerves and the muscles intact. These agents, 
therefore, agree on more points than they differ 
in their action on the spinal cord. 
As respects the function of secretion, there is 
an obvious difference in action between physo- 
stigma and atropia. An increased flow of saliva, 
of the intestinal juices, of the tears, and of the 
sweat, is a constant result of the action of physo- 
stigma, and is due, according to Heidenhain,f 
to a central excitation of the secretory nerves. 
* Jour, of Anat. and Physiol., xi., Part xi. 
f Arch. f. d. ges. Physiol., v. p. 40: quoted by Hermann. ATROPIA AND PHYSOSTIGMA. 
171 
This conclusion seems established by the fact 
that the increased secretion of saliva failed to 
occur when the chorda tympani was divided near 
the submaxillary gland. The action of atropia 
is the opposite of this—it suspends secretion, 
most probably by paralyzing the end organs of 
the nerves in the gland, for, as Schiff has shown, 
arrest of the secretion of the submaxillary gland 
follows division of the chorda tympani. In- 
creased outpouring of saliva takes place when 
the divided extremity of the nerve is galvanized; 
whence it may be concluded that physostigma 
stimulates the secretory centres. 
On the motor functions, and on the muscles, 
atropia and physostigma act differently. I have 
already emphasized the tetanizing action of atro- 
pia on cold-blooded animals, and the trismus 
which occurs in so many cases of poisoning. 
Botkin * was the first to show that atropia par- 
alyzed the motor-nerve trunks, and Laschke- 
wichf and Fraser proved that, in poisoning by 
Calabar bean, the irritability of the motor nerves 
and the contractility of the muscles were unaf- 
fected. The action on the motor functions is 
therefore different and not opposed. 
In summing up the results of the various re- 
searches, it may be regarded as established: 1. 
That physostigma, or eserine, and atropia are 
antagonistic in their effects on the pupil. 2. That 
* Yirchow’s Arcliiv, xxiv. p. 85. f Ibid., loc. cit. 172 
ATROPIA. 
they act differently, hut probably not antagonist- 
ically, on the heart, unless we accept the views 
of Kohler and Bezold and Bloebaura,—the for- 
mer maintaining that physostigma paralyzes the 
accelerator nerves of the heart, and the latter 
that atropia stimulates these nerves. 3. That 
they are opposed in their action on respiration, 
physostigma paralyzing, and atropia stimulating 
the respiratory function. 4. That they are not 
opposed in their action on the cerebrum, atropia 
producing delirium, and physostigma having no 
effect on the cerebral functions, while both cause 
more or less carbonic-acid narcosis. 5. That 
they act differently and not in an opposed man- 
ner on the spinal cord and nerves, both produc- 
ing paralysis, but atropia does, and physostigma 
does not impair the irritability of motor nerves. 
As regards the sensory nerves, physostigma aug- 
ments their irritability, while atropia seems 
rather to lessen it, if any effect is produced. 
6. That they act oppositely on secretion, phy- 
sostigma stimulating and atropia arresting the 
secretions in general. 
It follows from these considerations that the 
lethal effects of physostigma, due to paralysis of 
respiration, are overcome by atropia by sustain- 
ing the respiratory function. The Committee of 
the British Medical Association assert that “ the 
antagonism exists within very narrow limits,” 
hut this happens to he sufficient to avert death 
when doses little more than lethal have been ad- ATROFIA AND PILOCARPINE. 
ministered; still, the use of physostigma against 
the lethal effects of atropia is of doubtful pro- 
priety. The paralyzing effect of physostigma 
on respiration may, doubtless, he successfully 
overcome by the suitable application of atropia. 
ATROPIA AND PILOCARPINE. 
The antagonism of action between belladonna 
and pilocarpus, or atropia and pilocarpine, is one 
of the most interesting, as it is one of the most 
exact, in the whole series of antagonisms of 
medicinal agents. The functional disturbance 
produced by atropia has been sufficiently elabo- 
rated in the preceding sections. Our task is now 
chiefly concerned with the peculiar powers and 
attributes of pilocarpine. The history of jabo- 
randi affords us a capital illustration of the 
benefit of physiological research as applied to 
the study of remedies. When it was first intro- 
duced, a great many observers in all parts of the 
world set about the study of its actions. In an 
almost incredibly short time we were put in 
possession of its actions, and the range of its 
uses was at once indicated. All has been abun- 
dantly confirmed by trials on man, and the first 
conclusions arrived at have only been supported 
by subsequent investigations. The literature of 
pilocarpus is already vast. I will call your atten- 
tion only to the subject of its antagonistic action. 
We must first form a definite conception of what 
pilocarpine does. 174 
ATROPIA. 
In a few minutes after the alkaloid pilocarpine 
has been injected subcutaneously, or taken into 
the stomach, the action of the heart increases, 
the face flushes, and a subjective sense ok heat is 
felt throughout the body, but especially about 
the face. The increased action of the heart does 
not take place when very large doses are ad- 
ministered, and the increase from small doses is 
not maintained after the characteristic sweating. 
The pupil contracts, spasm of the accommoda- 
tion occurs, and recession of the near point takes 
place. More or less headache is experienced, 
and there are present a feeling of frontal tension 
and transient vertigo. Soon after the flushing 
of the face and the subjective sense of heat are 
experienced, perspiration begins, first on the 
forehead usually, and then over the whole body, 
and presently the sweating is enormous, the 
skin literally pouring out water. Simultaneously 
with, or often before, the sweating, the salivary 
glands become active, and presently mouthful 
after mouthful of saliva is discharged, so that the 
quantity may be measured by ounces, even pints. 
In some instances the one secretion seems to be 
substituted for the other. Thus, when the salivary 
flow is great, the sweat is less, and vice versa, but 
the usual experience is that both secretions are 
enormously increased. With the full develop- 
ment of the salivary and sudoral discharge, the 
pulse declines in force, in volume, and in the 
number of beats, the face becomes pale, the ATROPIA AND PILOCARPINE. 
175 
strength diminishes, and a feeling of exhaustion 
is experienced. The temperature, which was 
slightly or not at all increased during the stage 
of excitement, descends somewhat below normal 
after the sweating. The secretion of urine is 
rather less than normal, but the bladder is irrita- 
ble and the desire to micturate is frequent. The 
surface of the body is cool, and a sense of chilli- 
ness is experienced. Drowsiness comes on, as a 
result of the exhaustion, and is not a direct 
effect of the remedy on the brain. When the 
preparations of pilocarpus are taken into the 
stomach, and, to a much less extent, when the 
active principle is thrown in under the skin, 
more or less nausea, even vomiting, is produced, 
and not unfrequently a watery diarrhoea. 
The opposition of actions, between an agent 
causing such functional disturbances as I have 
just described and atropia, is apparent at a glance. 
Let me briefly indicate the main points as a pre- 
liminary to the study of the mechanism of the 
antagonism. The first increase in the cardiac 
movements caused by pilocarpine is of very short 
duration, and is followed by feebleness of the 
heart and diminished arterial tension; atropia 
induces and maintains a quickened heart-beat 
and a high arterial tension during at least the 
whole duration of the action of pilocarpine. A 
subjective sensation of heat and flushing of the 
face is caused by both, but is very transient in 
the case of pilocarpine. Contraction of the pupil 176 
ATROPIA. 
is produced by pilocarpine, dilatation by atropine. 
Dryness of the mouth and of the skin results 
from atropia, profuse secretion from pilocarpine. 
Both of these agents tend to cause nausea and 
vomiting, and a watery diarrhoea. Both render 
the bladder more or less irritable, and atropia 
increases the urinary secretion a little, while pil- 
ocarpine diminishes it. As regards the nervous 
system of animal life, no antagonism exists. 
Pilocarpine does not atfect the cerebral func- 
tions directly, while atropia causes delirium. 
Pilocarpine induces weakness of the muscular 
system, but atropia brings on a tetanic condition 
by stimulation of the cord, and paralysis by an 
action both on the cord and on the peripheral 
motor nerves. In all those actions involving the 
functions of the organic nervous system there is 
very complete antagonism, but in respect to the 
nervous system of animal life no antagonism' is 
possible. 
The only examples of application of the an- 
tagonism to the treatment of poisoning, which 
I have been able to find, are two eases of poison- 
ing by belladonna liniment, received into Uni- 
versity College Hospital in charge of Dr. Sydney 
Ringer.* Pilocarpine was injected subcutane- 
ously in both, without any obvious influence 
over either. The experience in the more im- 
portant of the two cases demonstrated that one 
* Lancet, March 4, 1876. ATROPIA AND PILOCARPINE. 
177 
grain and a third of pilocarpine failed to excite 
perspiration, when one-third of a grain of the 
same sample caused in healthy persons most 
profuse sweating. It is obvious that belladonna 
is relatively more intense, as it is more pro- 
longed, in its effects. 
The first experiments to determine the antag- 
onism of atropia and pilocarpine were those of 
Yulpian,* and were confined to the salivary and 
sweat secretions. When the saliva and sweat 
are pouring out in a stream from the action of 
pilocarpine, the flow of secretion is almost in- 
stantly arrested by the administration of atropia. 
The mechanism of this antagonism has been 
thoroughly investigated by Yulpian,f Langley,| 
Marme,§ Petrina,)) and numerous other investi- 
gators. Pilocarpine stimulates the nerve ends in 
the glands, and, as Heidenhain long ago proved, 
atropia paralyzes the end organs of these nerves. 
The chorda tympani and the sympathetic fila- 
ments distributed to the submaxillary gland 
being divided, pilocarpine still has power to cause 
increased secretion, as Langley has shown, thus 
proving that this agent also stimulates the gland 
cells. In this respect, also, it is probable that 
atropia has an antagonistic action. The experi- 
* Gaz. Hebdom., 1875-76, p. 81. 
f Loc. cit. 
% Jour, of Anat., and Physiol., xi. Part 1, pp. 173, et seq. 
§ Virchow u. Hirsch, Jahresbericht, 1878, p. 173. 
|| Deutsch. Arch. f. klin. Med., xxi. p. 258. 178 
A TROFIA. 
merits of Langley on this point have been con- 
firmed by ISTawrocki,* Fuchsinger,f and the other 
observers just named. 
The increase of secretion caused by pilocar- 
pine is not limited to the skin and salivary glands, 
hut extends to the mucous membrane of the 
nose, bronchi, and intestinal canal, although to 
a less extent. The arrest of these secretions by 
atropia is not less prompt and decided. The 
increased secretion caused by the subcutaneous 
injection of one-fourth of a grain of pilocarpine 
muriate or sulphate is arrested by T grain of 
atropia. In a personal trial of this quantity of 
pilocarpine, I found that the salivary flow began 
in three minutes, and in five minutes I was 
drenched by perspiration, the flush of the face 
and sense of warmth had ceased, the surface felt 
cold, and a condition of extreme bodily depression 
came on. A marvellous change was wrought by 
the subcutaneous injection of T-J-¥ grain of atro- 
pia. In three minutes the sense of depression 
began to decline, in five minutes the surface 
grew warm again and the flow of sweat and 
saliva ceased, so that by the end of ten minutes 
the disturbances caused by each had disappeared 
and I was in the same condition as if neither 
had been taken. 
The first effect of pilocarpine on the heart is to 
* Centralbl. f. d. med. Wissensch., vi. p. 97. 
| Pfliiger’s Archiv, xv. p. 483. ATROPIA AND PILOCARPINE. 
179 
increase its action. This is coincident with flush- 
ing of the face. Belladonna, after a very brief 
preliminary slowing, greatly increases the action 
of the heart, and also flushes the face. The in- 
creased action due to pilocarpine is brief, and is 
followed by slowing and feebleness of movement. 
The resemblance in action is only apparent. The 
increased movement produced by atropia may be 
explained, as we have seen, in either of two 
modes,—by paralysis of inhibition, or by stimu- 
lation of the accelerator fibres. The increased 
action due to pilocarpine is a result of the dilata- 
tion of the arterioles. It is just here that the 
antagonism exists. The man ©metric observa- 
tions of Kahler and Soyka,* the experiments of 
Langley, Hardenhewer,f and Robin,J alike dem- 
onstrate that pilocarpine lowers the vascular ten- 
sion by a paralyzing action, causing dilatation of 
the arterioles. The sudden withdrawal of the 
blood to the peripheral vessels necessarily causes 
increased action of the heart. Belladonna ex- 
actly antagonizes these effects: it raises the arte- 
rial tension by inducing contraction of the arte- 
rioles. The depression in the heart’s action, and 
irregularity of rhythm, due to the action of pilo- 
carpine on the motor apparatus, and which suc- 
* “ Kymographische Yersuche iiber Jaborandi,” Arch. f. 
exper. Path. u. Pharmacol., vii. p. 435. 
f Berlin, klin. VVoch,, No. 10, 1877. 
t “ Etude Physiologique et Therapeutique sur la Jabo- 
randi,” Jour, de Therap., various numbers for 1875, 180 
ATROPIA. 
ceed to the preliminary increased movement, are 
antagonized by atropia (Service).* 
The temperature variations observed by all who 
have carefully investigated this point are ex- 
plained by the circulatory disturbance. Accord- 
ing to Robin, just before sweating begins, and 
when it is going on actively, the temperature 
rises, but this does not appear to be a constant 
result. When the sweating has reached its max- 
imum the temperature begins to fall, the decline 
reaching from 0.5° to 2° F., and this reduction 
of body heat persists for several hours,—it may 
be for twenty-four hours (Robin, Curschmann,f 
Weber,| Ringer and Gould,§ et al.). The decline 
of temperature caused by pilocarpine is antago- 
nized and prevented by atropia. By raising the 
vascular tonus, and arresting or preventing the 
profuse discharge of saliva and sweat, atropia 
restores the normal equilibrium, and conse- 
quently the fall of temperature is prevented. 
Extending our investigation now to the eye, 
we find that the most exact opposition of actions 
exists in the effects of pilocarpine and atropine 
on this organ. Myosis, spasm of accommoda- 
tion, and recession of the near point are produced 
by pilocarpine; and the exactly opposite effects— 
* Jour, of Anat. and Physiol., April, 1879. 
f Berlin, klin. Woch., June 18, 1877. 
J Centralbl. f. d. med. Wissensch., No. 44,1877. 
§ Lancet, Jan. 80, 1875. ATROPIA AND PILOCARPINE. 
181 
dilatation of the pupil, paralysis of the accom- 
modation, and removal of the distant point—are 
produced by belladonna (Konigshofer, Tweedy,* 
Galezowski,f et al.). 
That pilocarpine directly affects the brain is 
doubtful. It is true, headache, vertigo, tinnitus 
aurium, etc., have been observed from consider- 
able doses; and drowsiness, even sleep, accom- 
panies the state of languor and depression caused 
by the profuse salivary and sudoral discharge and 
the lowered vascular tonus. These secondary 
results of the action of pilocarpine are not antag- 
onistic to the delirium, hallucinations, and illu- 
sions of atropia. In the cases narrated by Dr. 
Dinner the delirious excitement of belladonna- 
poisoning was not modified by the action of pilo- 
carpine,—so that, viewed from either the theoret- 
ical or the practical stand-point, the existence of 
an antagonism on the brain must be denied. 
The nausea and vomiting caused by pilocarpine 
are probably not affected, or are increased, by 
atropia. When the action of the drug ceases, 
the stomachal distress occasioned by it ceases 
also,—hence, in this indirect mode, atropia may 
prevent or arrest it. 
I have already indicated some points of simi- 
larity of action between pilocarpine and atropia,— 
the quickened heart and flushed face,—but these, 
* Lancet, Jan. 30, 1875. 
f Med. Times and Gaz,, 1877, ii. p. 358. 182 
ATROPIA. 
as has been shown, are apparent, and not real. 
They both agree, however, in the insusceptibility 
of children to their action. The observations 
of Ringer and Gould are very precise in regard 
to this insusceptibility of children to the action 
of jaborandi. They found that the quantity 
which sufficed to produce profuse sweating in 
adults affected children very slightly or not at all. 
Children are equally insusceptible to the effects 
of belladonna. 
To sum up the results of the investigation, we 
find that belladonna and pilocarpus are antago- 
nistic in their action : 1. On the secretions, espe- 
cially of sweat and saliva, pilocarpus promoting 
and belladonna arresting them. 2. On the heart 
and arterial system, pilocarpus slowing and en- 
feebling the heart and depressing the vascular 
tonus, belladonna stimulating the cardiac move- 
ments and raising the arterial tension. 3. On the 
eye, pilocarpus contracting the pupil, inducing 
spasm of accommodation, and approximating the 
nearest and most remote points of vision, bella- 
donna dilating the pupil, paralyzing accommoda- 
tion, and making the vision presbyopic. 
On the brain there is no real antagonism. The 
excitement, the delirium with hallucinations and 
illusions, and the subsequent coma, caused by 
atropia, are not affected by any of the actions of 
pilocarpine. The soporose state brought on by the 
latter, as I have pointed out, is a secondary effect, 
the result of exhaustion and cerebral anaemia. ATROPIA AND MUSCARIA. 
183 
Continuing the subject of the antagonistic 
relations of atropia, we have next to consider 
the mutual interactions of 
ATROPIA AND MUSCARIA. 
As muscaria, or muscarine, is comparatively 
little known, it may he useful to make a prelim- 
inary statement of its history and characteristics. 
It is obtained from amanita muscaria, the fly 
fungus. We owe to Schmiedeberg and Koppe 
the discovery of the alkaloid, and to Schmiede- 
herg and his pupils the full and accurate infor- 
mation now in our possession in regard to its 
physiological actions.* Muscarine has strong 
alkaline and basic properties, uniting with acids 
to form salts. It is a colorless substance having 
the consistence of syrup, is readily soluble in 
water, and its salts deliquesce rapidly on expo- 
sure to air. It seems to be actively toxic,— 
grain producing in the human subject very de- 
cided symptoms. The effects, taking a general 
view, are as follows : Considerable gastrointesti- 
nal disturbance, nausea, vomiting, and diarrhoea, 
and violent colic, due to a tetanic contraction of 
the muscular layer of the bowel, are produced 
by it. An active and rather pleasurable delirium, 
rambling, and incoherence, not unlike that of 
* Das Muscarin, das giftige Alkaloid des Fliegenpilzes, etc., 
Leipzig, 18G9; also, Arch. f. exper. Pathol, u. Pharmacol., 
iv. and vi. Hermann, op. cit. 184 
ATROPIA. 
alcohol, are caused by the fungus, so that it is 
used as an intoxicant by some of the inhab- 
itants of Eastern Asia. In toxic doses the ex- 
citement is followed by more or less profound 
stupor, epileptiform attacks, trismus, and aboli- 
tion of all reflex movements. During the stage 
of pleasurable intoxication the pupil is con- 
tracted, vision is dim, objects are seen as through 
a mist, and also probably double. • The action of 
the heart is weakened and finally arrested in the 
diastole, the respiration is labored and stertor- 
ous, the salivary secretion is increased, the sur- 
face of the body becomes cold, and death ensues 
from failure of the heart. 
On the brain, it is probable that muscaria acts 
in two modes, directly and indirectly; it first 
excites the cells of the gray matter, and ultimately 
paralyzes them; the heart being weakened, less 
blood passes to the brain, and hence this organ is 
in a condition of anaemia. On the eye muscarine 
produces peculiar effects. It causes spasm of the 
accommodation and a marked degree of myosis, 
by stimulation of the motor oculi. The vision is 
disturbed, therefore, by the spasm of the accom- 
modative apparatus and by the myosis, which 
limits the amount of light admitted to the retina. 
The secretions generally are increased by mus- 
carine, but it especially stimulates the salivary 
secretion. According to Provost,* the bile and 
* Gaz. Med. de Paris, 1870, iii. p. 213. ATROPIA AND MV SC ARIA. 
185 
the pancreatic and urinary secretions are in- 
creased. It promotes the salivary secretion by 
stimulating the end organs of the nerves, and 
this is independent of a centric influence, for it 
takes place after the trunks of the nerves have 
been divided.* It is probable, if Prevost’s view 
is correct, that the increase of the other secre- 
tions is due to the same mode of action. 
A slight and momentary increase in the car- 
diac movements is first produced by muscarine, 
but this is followed ‘by retardation. Direct ap- 
plication of this agent arrests the heart in the 
diastole, but mechanical, chemical, or electrical 
irritation will induce contraction. Section of 
the vagi does not prevent this effect. It raa\ 
therefore be concluded that muscarine acts on, 
the motor ganglia in the substance of the heart, 
and not on the muscle, nor on the apparatus of 
inhibition. A very considerable decline in the 
blood-pressure is a constant result, after a short 
preliminary rise. The walls of the vessels relax, 
as Bogosslowsky f has shown, and, as the action 
of the heart is at the same time depressed, it is 
obvious that the vascular tension must be reduced. 
During the stage of delirious excitement, the 
respiration is rather hurried, but when the sub- 
sequent depression comes on, the respiration 
*F. A. Falck, Der Antagonismus d. Gifte. Yolkmann’s 
Samml. klin. Vortr., No. 159, 1879. 
f Centralbl. f. d. med. Wissensoh., 97, 1870. 186 
ATROPIA. 
becomes slower and shallower, this result being 
due to a paralyzing action of muscarine on the 
respiratory centres. 
When we come to compare these disturbances 
of function caused by muscaria with those pro- 
duced by atropia, we must admit, with Schmiede- 
berg, that no example of physiological antagonism 
could be more exact. On the brain, the intoxi- 
cation, with cerebral anaemia, of muscarine is 
opposed by the active delirium and cerebral hy- 
persemia of atropia. On the eye, the contracted 
pupil of muscaria, due to stimulation of the cir- 
cular fibres innervated by the third nerve, is 
opposed by the dilated pupil of atropia, produced 
by stimulation of the radiating fibres, innervated 
by the sympathetic. The effect of atropia on the 
eye is relatively more powerful, for, when the 
pupil is contracted by muscarine, it can be dilated 
by atropine, but, when dilated by atropia, it can- 
not then be contracted by muscarine. On the 
function of secretion the antagonism is not less 
striking. Muscarine promotes the salivary secre- 
tion by stimulating the end organs of the nerves 
in the gland, and atropia arrests this secretion 
by paralyzing these nerves.* But atropia is 
relatively more powerful here, also, for, when 
the salivary secretion is arrested by atropia, 
* Luchsinger, “Die Wirkungen von Muscarin u. Atropin 
auf d. Schweissdriisen d. Katze,” etc., Archiv f. d. ges. Phj's., 
18, 1878, p. 501. ATROPIA AND QUINTA. 
187 
muscaria cannot re-establish it, yet the secretion 
caused by the latter is promptly arrested by the 
former. This opposing mechanism probably ex- 
tends to the hepatic and pancreatic secretions as 
well. The intestinal cramp caused by muscarine 
is removed by atropine. On the heart, nothing 
can be more perfect than the opposing actions of 
these agents. This fact is frequently adduced 
by physiologists as a striking exemplification of 
the doctrine of antagonism. If the heart is ar- 
rested in the diastole by muscarine, it is started 
again by atropia. If an animal is first brought 
under the influence of atropia, the heart is not 
stopped by muscarine, notwithstanding it is so 
readily poisoned by this agent. The antagonism 
is equally exerted on the respiratory function,— 
muscarine lessens the respiratory movements and 
finally arrests them, while atropia stimulates this 
function. 
Thus, viewed from all sides, these agents are 
exactly antagonistic. Is a function disturbed by 
one agent in a particular mode, it is also dis- 
turbed by the other agent in an opposite mode. 
In fact, we should search in vain for an illustra- 
tion of the law of antagonisms more perfect than 
that subsisting between atropia and muscaria. 
ATROPIA AND QUINIA. 
The only systematic experimental investigation 
of the antagonism between atropia and quinia 
which I have been able to find is that of Pautel- 188 
ATROPIA. 
ejeff* Clinical experience on this point is abun- 
dant enough, but we are not now concerned with 
this aspect of the question. Pantelejeff has as- 
certained that quinia arrests the heart in diastole, 
and that the subsequent administration of atropia 
causes the heart to resume its contractions. This 
result was observed both in frogs and in rabbits. 
In the latter animals, when the action of the 
heart was resumed after the suspension of its 
movements, the auricles began to contract before 
the ventricles. Examination of the web of the 
frog’s foot disclosed the interesting fact that, after 
the subcutaneous injection of quinia, the calibre 
of the arterioles was lessened by contraction of 
their walls, while the opposite effect, or dilata- 
tion, followed the administration of atropia. 
Quinia causes a rise in the blood-pressure, after 
a brief preliminary fall, and atropia retards it. 
BROMAL HYDRATE AND ATROPIA. 
One of the subjects undertaken by the Com- 
mittee of the British Medical Association, to 
whose important labors I have so often to refer, 
was the investigation of the antagonism of bro- 
mal hydrate and atropia. This research was 
especially in charge of Professor McKendrick, 
and the scope of it was limited to the lethal 
effects. All of the facts are comprehended in 
* Lancet, July 31, 1880, p. 176. ATROPIA AND ACONITE. 
189 
the conclusions to which he was conducted by 
his experiments, as follows : 
“ 1. There is a distinct physiological antago- 
nism between bromal hydrate and atropia. 2. Af- 
ter a fatal dose of bromal hydrate, the introduc- 
tion of atropia arrests excessive secretion from 
the salivary glands and mucous surfaces of the 
lungs, and thus obviates the tendency to death 
from asphyxia caused by the accumulation ot 
fluids in the air-passages. Atropia also causes 
contraction of the blood-vessels, and thus antag- 
onizes the action of bromal hydrate, which causes 
dilatation of these vessels by paralysis of the 
sympathetic nerve. 3. While atropia may save 
life after a fatal dose of bromal hydrate, the 
converse apparently does not hold good, as we 
never have succeeded in saving life after a fatal 
dose of atropia by the subsequent injection of 
bromal hydrate.” 
ATROPIA AND ACONITE. 
The last application of the physiological antag- 
onism of atropia is that with aconite, for which 
we are indebted to Dr, J. Milner Fothergilh* 
These researches are not extensive, but they 
probably represent the actual state of the antag- 
onism. A priori, a very perfect and extended 
opposition of actions would be presumed to ex- 
* The Antagonism of Therapeutic Agents. Philadelphia, 
1878, p. 41. 190 
ATROPIA. 
ist. Aconite, a respiratory and cardiac depres- 
sant, ought to be neutralized by atropia, a respi- 
ratory and cardiac stimulant. The facts in the 
main support this supposition, “ Thus, to a 
rabbit weighing two pounds six ounces, I gave,” 
says Dr. Fothergill, “ three grains of atropia, 
and six minutes afterward grain of aconitine; 
the animal survived. A week afterward the 
same rabbit had the aconitine alone, and died in 
two hours and a half.” Small doses of atropia 
he found had very striking effects on animals to 
which lethal doses of aconitine had previously 
been administered. The animals all recovered 
from doses of aconitine which subsequently 
killed them all when administered without the 
atropia. “It was found, however, that if the 
administration of the atropia wTas delayed be- 
yond sixteen minutes, it was powerless to arrest 
the lethal action of aconitine.” 
HOMOTROPINE. 
A new alkaloid has been obtained from atropia 
by chemical means. The first step consists in 
splitting up atropia into iropine and tropic acid. 
Tropeins are produced by the action of dilute 
hydrochloric acid on the salts of tropine. From 
the amygdalate of tropine is thus produced homo- 
iropine, an alkaloid of much promise. 
The effects of homotropine are similar to, but 
milder and of shorter duration than those of 
atropia. The tetanizing effect of atropia, which HOMOTROPINE. 
191 
in cold-blooded animals follows after twenty-four 
to seventy-two hours, occurs at once from the 
use of bomotropine. The action of the heart is 
increased by hornotropine by a paralyzing action 
on the intra-cardiac inhibitory apparatus. In 
man hornotropine retards and renders irregular 
the heart-beat. It acts very quickly on the iris, 
dilating the pupil widely in fifteen to twenty 
minutes, and affects the accommodative appa- 
ratus equally rapidly. The ocular effects sub- 
side comparatively quickly, and in twenty-four 
hours the accommodation is restored. In these 
respects hornotropine presents marked advan- 
tages over atropia. It deserves trial in the treat- 
ment of various diseases. MORPHIA AHD ATROPIA. 
So numerous and important are the uses of 
these agents when administered together that a 
consideration of the combination in a separate 
chapter seems necessary and desirable. The two 
agents are used together in varying proportions, 
and much depends on an accurate adjustment of 
the quantities to the powers respectively. A 
penicilium develops in the solution, and slowly 
diminishes its activity by growing at the expense 
of the alkaloids. 
A permanent solution may be prepared as fol- 
lows : 
B Morphiae sulphatis, gr. xvi ; 
Atropiae sulphatis, gr. ss ; 
Acidi carbolici, gr. viij ; 
Aquae lauro-cerasi, !|i. M. 
Sig.—Five minims contain grain of morphia and T|-2 
grain of atropia. 
Powders for extemporaneous solutions may he 
prepared as follows: 
R Morphise sulphatis, i}i; 
Atropiae sulphatis, gr. ss. M. 
Fiat pulv. No. cxx. 
Sig.—Each powder contains £ grain of morphia and 
grain of atropia. 
192 HISTORY. 
193 
On the whole, these are to be preferred: they 
are convenient to handle, readily soluble, accu- 
rate, and therefore satisfactory. The relative 
proportions of morphia and atropia in the solu- 
tions, as in the powders of the mixed alkaloids, 
will be governed by the character of the cases 
for which they are administered. 
History,—The following historical review of 
the subject of the physiological antagonism 
existing between morphia and atropia is re- 
produced here from my Cartwright course of 
lectures. 
By the year 1810 considerable experience of an 
empirical kind had accumulated in regard to the 
antagonism of opium and belladonna; for we 
find that in this year Joseph Lipp published an 
inaugural thesis on the toxic effects of belladonna 
berries, and on the curative powers of opium. 
We owe to Graves, the great Dublin clinician, 
the first really scientific suggestion of an antag- 
onism. He supposed that the state of the pupil 
would afford an indication in fevers of the need 
of opium or belladonna—the former to be given 
when the pupil was dilated, the latter when it 
was contracted. Acting on this suggestion, Dr. 
Thomas Anderson,* of Edinburgh, employed 
belladonna against opium-poisoning—a mydriatic 
against a myositic—with success. Two years sub- 
* Braith waite’s Retrospect, 1855, Part xxx. p. 301. 194 
MORPHIA AND ATROPIA. 
sequently, Dr. William H. Mussey,* of Cincin- 
nati, seeing the account of Dr. Anderson’s cases, 
tried the same expedient successfully in a case of 
attempted suicide with laudanum. In July, 1859, 
Mr. Benjamin Bell,f of Edinburgh, published an 
account of two cases, in which symptoms of pois- 
oning produced by the subcutaneous injection of 
atropia were removed by considerable doses of 
morphia. Influenced by these results of Mr, Bell, 
in December of the same year Mr. Seaton,X of 
Leeds, treated eight cases of poisoning by bella- 
donna berries with opium,—seven of the eight 
cases recovering. In January, 1862, Dr. C. C. 
Lee,§ of Philadelphia, reported two cases, one of 
opium-poisoning treated by belladonna, and one 
of belladonna-poisoning treated by opium, the 
result a success in each case. Dr. Lee also en- 
tered into some detail on the literature of the sub- 
ject, referring to the experiences of Anderson, 
Mussey, and Seaton, and to the adverse experi- 
ments of Brown-Sequard. During the same year 
(1862), the most important paper which had hith- 
erto been published made its appearance from the 
pen of Dr, William F, Horris,|| In this paper 
the cases illustrating an antagonism of action 
* Cincinnati Med. Observer, vol. i., 1856, p. 70, There 
were but two volumes issued of this periodical, when it was 
united with the Lancet. 
f Edinburgh Med. Jour., vol. iv., 1859, p. 1. 
J Mod. Times and G-az., Dec. 3, 1859, p. 551. 
§ Am. Jour, of the Med. Sci., vol. xlii. || Ibid., vol. xliv. HISTORY. 
195 
between opium and belladonna, which had been 
previously published, were tabulated ; and a full 
historical account of the subject, from which sub- 
sequent writers have drawn their information, 
and to which I am much indebted, is there given. 
In 1865 an admirable paper, based on clinical and 
experimental observations made at the military 
hospital for wounds and injuries of the nerves, 
and embodying the results of an immense expe- 
rience, wTas published by Drs. Mitchell, More- 
house, and Keen,* In the following year (1866) 
Dr. Constantin Paulf published a monograph, 
supporting the view of the existence of such an- 
tagonism. Since this time the cases, papers, and 
monographs have so greatly multiplied that it 
would be impracticable to name them all in this 
historical review. I have collected all the pub- 
lished cases for statistical study, and will refer to 
the more important papers and monographs here- 
after. The cases thus far collected by me num- 
ber one hundred and sixty of opium and bella- 
donna-poisoning, in which the one drug was used 
to counterbalance the effects of the other. 
The history of this subject wmuld not be com- 
plete without some reference to the opinions of 
*Am. Jour, of the Med. Sci., July, 1865, vol. 1. p. 67. 
“On the Antagonism of Atropia and Morphia. Founded on 
Observations and Experiments made at the United States Hos- 
pital for Injuries and Diseases of the Nervous System.” 
fDe I’Antagonisme en Pathologic et en Therapeutique, 
1866, pp. 92-115. 196 
MORPHIA AND ATROPIA. 
those who doubt the existence of the antagonism, 
or disbelieve in it utterly. The opposition to the 
generally accepted view is based chiefly upon re- 
searches on animals. The most influential of 
these experimentalists is Brown-Sequard.* His 
observations have been made for the most part on 
guinea-pigs and rabbits. Bois f studied the effects 
of these agents on cats. He regards the follow- 
ing experiments as conclusive against the view 
that an antagonism exists. To a cat he gave a 
dose of morphia just less than sufficient to cause 
death; when entirely recovered from the effects 
of this quantity, he gave to the same cat a dose 
of atropia having effects just short of lethal. 
When a sufficient time had elapsed to insure com- 
plete recovery from that dose, he administered 
those quantities together, when the result was 
fatal. Camus J investigated the action of the al- 
kaloids of opium, and the antagonism of atropia 
and morphia, using cats and pigeons, while On- 
sum § conducted his researches on frogs. In what 
mode soever, or on what animals, the investiga- 
tions were conducted, the results were uniformly 
opposed to the existence of an antagonism. I 
may now anticipate so far as to say that the meth- 
ods of investigation pursued were not free from 
* Jour, de la Physiol., etc., tome iii., 1860, p. 726. 
f Gaz. des Hop., 71, 1865. 
% Gaz. Hebdom., 2 ser., xii. 32, 1865. 
| Schmidt’s Jahrbiicher, Band 128, p. 288, abstract. HISTORY. 
197 
sources of fallacy, and that the results obtained 
were largely vitiated. The most elaborate series 
of experiments on this topic, embracing animals 
and men, were those of Harley,* hut his facts ad- 
mit of a different interpretation from that which 
he has given them. His fundamental error con- 
sists in regarding as examples of antagonism only 
those in which the opposition of actions exists 
throughout the whole range of effects, which, as 
I have already stated, is hardly true of any 
known examples. 
In 1870, Hr. Koningf published a dissertation 
on the supposed antagonism of morphia and 
atropia, his research being conducted on animals. 
As had his predecessors in this inquiry, Koning 
decided adversely to the existence of this antag- 
onism, although he noted the antagonizing in- 
fluence of these agents on the pupil, the respi- 
ration, and the action of the heart. In 1878, 
Frohlich,| of Wurzburg, experimented with 
these agents on frogs and cats. His experiments 
rather indicated the existence of points of oppo- 
sition, but not sufficient to prevent death from a 
lethal dose of both agents. In 1874 § appeared the 
report of the committee appointed by the British 
Medical Association, Professor J. Hughes Ben- 
* The Old Vegetable Neurotics, p. 280, and p. 291. 
f Schmidt’s Jarbucher, vol. cxlix. p. 18. 
% Pharmakologische Untersuchungen, 1878, pp. 224 and 
231. 
§ Brit. Med. Jour., 1874, vol. ii., various numbers. 198 
MORPHIA AND ATROPIA. 
nett, M.D., of Edinburgh, Chairman. In making 
the report on this division of the subject—the 
antagonism of morphia and atropia—the reporter 
says: “ Extraordinary pains were taken to deter- 
mine the question whether or not morphia and 
atropia were antagonistic of one another; and 
the researches now to be described will be found 
to add largely to our precise and exact knowledge 
as compared with the unfounded and contradic- 
tory opinions which have hitherto prevailed. 
The conclusions at which they arrived, after ex- 
periments on the rabbit chiefly, are as follows: 
“ 1. Sulphate of atropia is physiologically an- 
tagonistic to the meconate of morphia within a 
limited area. 2. Meconate of morphia does not 
act beneficially after a large dose of sulphate of 
atropia, for in these cases the tendency to death 
is greater than if a large dose of either substance 
had been given alone. 3. Meconate of morphia 
is not specifically antagonistic to the action of 
sulphate of atropia on the vaso-inhibitory nerves 
of the heart; and, 4, the beneficial effect of sul- 
phate of atropia after the administration of large 
doses of meconate of morphia is probably due to 
the action sulphate of atropia exercises on the 
blood-vessels. ... It may also assist up to a 
certain point, not precisely fixed in these experi- 
ments, by stimulating the action of the heart 
through the sympathetic, and obviating the ten- 
dency to death from deficient respiration observed 
after large doses of morphia.” PHYSIOLOGICAL EFFECTS. 
199 
In 1876 the same investigation was undertaken 
by Corona, dogs and cats being the animals em- 
ployed. He arrived at the singular conclusion 
that a partial physiological antagonism existed 
between morphia and atropia, but not a thera- 
peutical antagonism,—for whilst morphia is use- 
ful in atropia-poisoning, in poisoning by morphia 
the effects are not removed by atropia. In this 
opinion Corona stands quite alone. In the fol- 
lowing year (1877), Dr. Hans Heubach reviewed 
the literature of the subject, and undertook a new 
investigation of the supposed antagonism, con- 
fining his experimental research to animals. 
These investigations, carried on at Binz’s labora- 
tory at Bonn, support the view of a limited an- 
tagonism in the cardiac and respiratory organs 
but not in general. 
Physiological Effects.—Although much has 
been said in the preceding pages upon the physi- 
ological effects of morphia and atropia, when 
separately administered, it is necessary now to 
show the influence which they reciprocally exert 
when administered together. Their so-called 
“ physiological antagonism” may be most con- 
spicuously exhibited by a comparison of their 
individual with their combined action on the 
different parts of the body. 
1. On the Nervous System.—Both act upon the 
brain,—atropia producing delirium, hallucina- 
tions, and disturbed sleep; morphia causing, gen- 
erally, somnolence. Both relieve pain, but this 200 
MORPHIA AND ATROPIA. 
effect is much more decidedly the property of 
morphia. Both produce disorders of motility, 
staggering, difficulty of co-ordinating muscular 
movements, vertigo, confusion of mind, and 
headache. When given together, these effects 
are curiously modified. 
Morphia corrects the hallucinations and phan- 
tasms of atropia. 
Atropia in small doses—of a grain—in- 
creases the hypnotic power of morphia; hut if 
the quantity of atropia he sufficient, it over- 
powers the effects of morphia on the cerebrum, 
causing wakefulness or disturbed sleep, phan- 
tasms, and illusions. 
The pain-relieving power of morphia is in- 
creased by atropia. 
The disorders of motility, and the vertigo, are 
not diminished when the two agents are used 
together, hut the after-headache and confusion 
of mind are much less. 
When toxic doses are used, the narcotism of 
morphia is overcome by atropia, and vice versa. 
In a case which occurred to myself, and which I 
have already referred to, serious symptoms pro- 
duced by 1 grain of morphia were relieved by 
of a grain of atropia. As, however, the 
effects of atropia are much more prolonged than 
morphia, it is not easy to exactly counterbalance 
the effects of one by the other. The cases of 
morphia-poisoning, in which atropia was used as 
an antidote, that have fallen under my observa- PHYSIOLOGICAL EFFECTS. 
201 
tion, received too much atropia, the toxic symp- 
toms of the latter remaining long after the 
narcotism of the morphia had disappeared. 
Upon the organic nervous system these agents 
seem exactly to antagonize each other. 
Morphia produces contraction of the pupil, 
and a tetanic condition, according to Graefe, of 
the muscle of accommodation; atropia produces 
dilatation of the pupil, and contraction of the 
ciliary muscle. When used together, these ef- 
fects may he precisely balanced. It takes, how- 
ever, but a minute quantity of atropia to over- 
come the action of morphia on the pupil. When 
these effects on the pupil are balanced, it does 
not follow that the muscle of accommodation is 
in a condition to act in a normal manner, for 
visual defects frequently remain. 
Morphia and atropia antagonize each other’s 
action on organic muscular fibre. Morphia pre- 
vents the contraction of the arterioles produced 
by atropia, and, as a consequence of this action, 
prevents the subsequent relaxation of the mus- 
cular fibre. They antagonize each other, there- 
fore, as respects their action on the arterial ten- 
sion. 
On Circulation and Respiration.—Morphia de- 
presses the action of the heart; atropia is a 
powerful cardiac stimulant. Morphia produces 
pallor of the surface, and reduces the external 
temperature; atropia causes redness and injec- 
tion of the skin and elevation of the body-heat. 202 
MORPHIA AND ATROPIA. 
The extent to which they modify each other’s 
action is well exhibited in the annexed diagram. 
It will be seen that the antagonism between 
them does not extend to the respiratory func- 
tion ; for, whilst morphia administered alone de- 
pressed the respiration from 17 to 12 per min- 
ute, morphia and atropia combined reduced the 
number from 18 to 10. When Dr. De Courcey 
received the morphia alone, he experienced much 
less soporific effect than when both agents were 
injected together; and to this quiescent state of 
the cerebral functions is to be attributed the 
slower respiratory movements. The morphia 
exercises a marked influence over the increase 
of body-heat produced by atropia. Notwith- 
standing this, the flushing of the face and the 
strong subjective sense of heat are experienced 
by the patient almost as fully when morphia is 
administered with atropia as when atropia is 
given alone. 
In the experiment represented on the dia- 
gram, the quantity of atropia was not sufficient to 
produce the full degree of antagonism, otherwise 
the pulse-line would have continued on the same 
plane. In so far as the atropia influence prepon- 
derates* a progressive rise in the pulse-rate is 
noted. 
8. On the Digestive Apparatus.—As regards dry- 
ness of the mucous membrane of the mouth, 
fauces, larynx, etc., there is no antagonism, but 
both agents produce this state and exalt it when PHYSIOLOGICAL EFFECTS. 
203 204 
MORPHIA AND ATROPIA. 
administered together. Morphia tends to pro- 
duce constipation; atropia relaxes the bowels. 
When administered together, they produce al- 
most immediately intestinal movements, fre- 
quently borborygmi, and sometimes sharp pain, 
and the bowels are kept in a soluble state. The 
sickness and nausea, and the not uncommon 
great depression of the vital powers caused by 
morphia are opposed by atropia. These agents 
may therefore be given together in cases in 
which morphia cannot be borne alone. The 
after stomachal effects of morphia—indigestion, 
loss of appetite, a pasty tongue—are much di- 
minished by the atropia, but are not absolutely 
prevented. Atropia itself is capable of produ- 
cing these stomach disorders when used in con- 
siderable doses; hence, to produce the result 
which I have described, the proportion of mor- 
phia and atropia should be as follows : 
Morphia, I of a grain ; 
Atropia, T|-¥ of a grain. 
4. On the Gemto-urinary Organs.—These agents 
are antagonistic as to their effects on the kidneys 
and the urinary excretion. Morphia suspends 
and atropia promotes the functional activity of 
the kidneys. By inducing congestion of the 
Malpighian tufts, and increasing the vis a tergo, 
atropia acts as a diuretic, and with the additional 
water there strains off from the blood the larger 
amount of urates produced in the more rapid 
metamorphosis of tissue. Morphia increases PHYSIOLOGICAL ANTAGONISM. 
205 
the action of the sudoriparous glands, and atro- 
pia diminishes it, thereby in the one case lower- 
ing, in the other case exalting, the functional 
activity of the kidneys. 
Both produce dysuria, but this result comes 
of a different action in each case. Morphia 
impairs the contractile power of the muscular 
coat of the bladder, so that it contracts with 
difficulty, the emission of urine taking place 
slowly; atropia maintains steady tonic contrac- 
tion of the sphincter, so that it dilates slowly 
under the voluntary effort, when the desire to 
micturate is experienced. 
Both morphia and atropia impair the sexual 
appetite; atropia at once, and morphia when 
long used. 
A comparison of the actions on man shows 
that opium and belladonna act oppositely, or in 
an opposite manner, on the brain, on the pupil, on 
the circulation, on the lungs, on the stomach, and on 
the skin. Opium, with the exceptions named, 
causes somnolence and stupor; belladonna, ex- 
citement, hallucinations, and delirium. When 
administered jointly and in the proper propor- 
tions, sopor, closely approximating natural sleep, 
is the result. This was well exhibited in the 
case of Dr. Legg,* whose patient, a boy of five 
years, drank by mistake a mixture of equal parts 
of liniment of opium and liniment of belladonna. 
71 Med. Times and Gaz., Nov. 3, 1866, p. 474. 206 
MORPHIA AND ATROPIA. 
The effects of the belladonna, owing to its more 
rapid action, first dominated the situation, when 
there was delirium with hallucinations, the hoy 
driving sheep and picking up money from the 
bed; hut then drowsiness supervened and heavy 
sleep, when he was not forced awake and kept 
walking. The violence of this ambulatory treat- 
ment was wholly unnecessary, and indeed inju- 
rious, for, if he had been permitted to sleep, the 
antagonism on the respiration and circulation 
would have sufficed to save life. Facts of the 
same kind were observed in a case jointly cared 
for by Dr. Mussey, of Cincinnati, and myself. 
A hoy of eight years, the son of a physician of 
Cincinnati, was given internally by mistake an 
anodyne application for earache, containing two 
grains of morphia and one grain and a half of 
atropia. When the toxic symptoms were well 
advanced the mistake was discovered, and Dr. 
Mussey and myself were summoned. We found 
the pupils fully dilated, the face flushed, and an 
active delirium, in which the boy fought and 
struggled violently against imaginary enemies. 
After an hour or two of this excitement, a sopo- 
rose state came on, and was very profound for a 
number of hours. As, however, the respiration 
was full, strong, and rhythmical, the pulse reg- 
ular and of good volume, we decided to await 
the result of the antagonism. Dr. Mussey had 
published one of the first cases of opium-poison- 
ing illustrating the antagonistic action of bella- PHYSIOLOGICAL ANTAGONISM. 
207 
donna, and I had seen several cases, so that we 
were perfectly agreed as to the proper course, 
and the result justified our decision. Another 
case in which the simultaneous administration of 
opium and belladonna was due to accident was 
reported by Dr. Cotter.* A young lady swal- 
lowed a liniment composed of opium and bella- 
donna, the amount taken being equivalent to 
twenty-five grains of the extract of belladonna 
and twelve grains of opium. At first the symp- 
toms of belladonna-poisoning were largely in 
excess; after some hours she appeared like one 
helplessly drunk, and was so drowsy as to he 
kept awake with great difficulty; then another 
period of excitement came on, and this was fol- 
lowed by a period of profound sleep, from which 
she awoke relieved. Such are the facts as 
taught us by these accidental experiments on 
man. What is the clinical experience available 
for further study of the problem ? 
As a result of large observation and experience 
of the effects of these agents on man, Drs. Mitch- 
ell, Morehouse, and Keen conclude that “ the 
headache and phantasms of atropia are certainly 
thus controlled [ie., by morphia], as well as the 
partial deafness and visual defects which in high 
doses it occasions. On the other hand, when 
morphia has been fully used, the drowsiness and 
stupor which are the best tests of its power 
* Am. Jour, of the Med. Sci., vol. 1. p. 67, et seq. 208 
MORPHIA AND ATROPIA. 
disappear before the influence of atropia. . . . 
Perhaps the most peculiar cerebral symptom of 
atropia is its tendency to cause phantasms and 
illusions. We found under doses of of a 
grain these were common, and in some men 
could always be brought on. Usually they were 
absent so long as the eyes remained open, but 
arose at once on closing them. This condition 
was singularly subdued by morphia. Drowsi- 
ness caused by morphia was as surely lessened 
or destroyed by the counter agency of atropia; 
and, in fact, atropia given alone and in full 
doses is very apt to cause a restless night to fol- 
low, so that it is assuredly in no sense a hyp- 
notic.” 
Harley strongly insists on the modifying influ- 
ence of morphia over the cerebral effects of atro- 
pia, “ The influence of opium in converting the 
insomnia of belladonna into sleep, and the influ- 
ence of belladonna in determining not only sleep, 
but narcotism in individuals under the influence 
of opium, are illustrated in several examples. 
Some of the cases,” he further says, “ serve to 
give greater force to these observations, and teach 
us that we must be careful how we employ opium 
as a means of converting the restlessness and in- 
somnia following excessive doses of belladonna 
into quiet sleep.” Harley, strangely enough, does 
not regard these different cerebral effects as due 
to an antagonistic action, but as synergistic. It 
is, nevertheless, evident enough that his observa- PHYSIOL 0 GICA L AN TAG ON ISM. 
209 
tions are confirmatory of those of Mitchell, More- 
house, and Keen, who state with more precision 
the exact features of the reciprocal influence. In 
fact, at the present time professional opinion is 
no longer divided on this point, and morphia and 
atropia, and opium and belladonna, are constantly 
prescribed together to secure an hypnotic effect, 
not attainable by the exhibition of either remedy 
alone. Clinical experience on man has been con- 
firmed by observations on animals, so far as the 
facts are applicable. Thus, Erlenmayer* shows 
that the exciting effect of atropia on the brain is 
lessened by the narcosis of morphia. Harley’s 
experiments on dogs were similar in results: “ The 
cerebral effects of atropia are,” he says, “ inten- 
sified and prolonged,—the insomnia which results 
from excessive doses is converted into narcotism, 
or a mixture of narcotism and delirium.” Ileu- 
hach,f whose researches were carried on in Binz’s 
laboratory, was led to similar conclusions. Obvi- 
ously, the actions of such agents on the brains of 
animals can be compared only according to the 
extent of development, for, the brain of man be- 
ing more complex in structure and more highly 
specialized, must be affected both with less sever- 
ity and in a greater variety of manifestations. 
In animals the effect of the narcotic is necessarily 
* Berlin, klin. Woch., loc. cit. 
f Arch. f. experiment. Pathol, u. Pharmakol., 1878, Band 
viii. p. 31. “ Antagonismus zwischen Morphin u. Atropin. 210 
MORPHIA AND ATROPIA. 
limited to the cephalic organs possessed by them, 
whereas in man, not only to those, but to the 
higher special organs he is possessed of, is the 
influence distributed. In animals the narcotic 
more affects the motor centres and the centres of 
respiration and circulation, while in man its ef- 
fects are exerted not only upon these centres, but 
upon the higher centres and upon the mental 
sphere. Do Ave not have in this difference in 
development the reason of the much greater toxic 
power in animals of morphia and atropia when 
administered simultaneously ? Bernard* has sig- 
nalized this important point in his introduction 
to the study of experimental medicine. After 
declaring that observations on animals, in respect 
to the functions of the cerebro-spinal nerves, and 
the vase-motors and secretors of the sympathetic, 
and on circulation and digestion, hygiene and 
toxicology, are perfectly and at all points applica- 
ble to man, he indicates conditions under which 
the observations on animals are not thus applica- 
ble. For example: “ From the physiological 
point of view, the experimental study of the or- 
gans of sense and of the cerebral functions must 
be made on man necessarily, because on the one 
hand man is above the animals in respect to those 
faculties of which they are not possessed, and, 
on the other, animals are unable to indicate the 
* Introduction a I’Etude de la Medecine Experimentelle.” 
Paris, 1865, p. 219. PHYSIOLOGICAL ANTAGONISM. 
211 
nature of tliose sensations of which they may 
become conscious.” 
My conclusion, after the examination of the 
experimental and clinical evidence, therefore, is, 
that, as respects the brain, opium and belladonna 
exert opposing actions. The illusions, hallucina- 
tions, and busy delirium caused by belladonna 
are counteracted by opium. The result of their 
conjoined action is sopor, deepening into coma 
when the quantity of both is large. When ad- 
ministered simultaneously, if the etfects of atropia 
preponderate, there will occur periods of excite- 
ment and delirium, interspersed with relatively 
shorter periods of sopor and coma. The more 
decidedly opium preponderates, the less there will 
be of delirium, and the more of sopor. When 
opium is in excess, the tendency is to coma and 
stertorous breathing, after a period of sopor. 
There are some highly important points in re- 
gard to the antagonistic action of morphia and 
atropia on the pupil. Graves, as is well known, 
first proposed to make use of this antagonism as 
a guide to treatment. There can be no doubt 
that this antagonism exists,—that opium contracts 
and belladonna dilates the pupil; opium weak- 
ening and belladonna stimulating the radiating 
fibres of the iris. There are, however, occasional 
exceptions. As the state of the pupil is usually 
regarded as a guide to the use of the antagonist 
in cases of poisoning, it becomes in a high degree 
important to know if this indication can or can 212 
MORPHIA AND ATROPIA. 
not be depended on, and to what extent. In 
Case XIY. of a list of unsuccessful cases, we 
find that a very large quantity of morphia was 
given to counteract the effects of some belladonna 
liniment taken by accident, and that, notwith- 
standing the apparent preponderance in the ac- 
tion of the morphia, the pupil continued dilated. 
In one of the successful cases of joint adminis- 
tration of opium and belladonna, in which the 
symptoms produced by the latter much prepon- 
derated, the pupil was minutely contracted. It 
has been observed occasionally, in cases of opium- 
poisoning, that at a certain stage in the narcosis 
the pupil dilated. On the other hand, in profound 
belladonna narcosis, the largely dilated pupil has 
suddenly contracted in some occasional cases. 
These are exceptional manifestations, it is true, 
but, as there are two examples in 120 eases, the 
value of the indication afforded by the state of 
the pupil is correspondingly weakened. The an- 
tagonism between morphia and atropia may be 
exerted without the contraction caused by the 
former, or the dilatation by the latter, being 
entirely overcome. Xo fewer than twenty cases 
illustrate this proposition. The rate at which 
these agents act on the pupil varies greatly. 
Atropia acts both more promptly and for a much 
longer time. Atropia has, also, a more powerful 
action,—for, of the twenty cases which show 
that the size of the pupil may not be much 
affected by the antagonist, sixteen were examples PHYSIOLOGICAL ANTAGONISM. 
213 
of preponderating dilatation. From these facts, 
it must he concluded that the state of the pupil 
cannot always serve as a guide for the further 
administration of the antagonist. 
The next point for consideration is—the antag- 
onistic influence of opium and belladonna on the 
heart. That opium, in full doses, acting alone, 
slows the heart, and that belladonna quickens it, 
are unquestionable facts. Observers are by no 
mejJhs agreed as to the influence reciprocally ex- 
erted by these agents when administered simul- 
taneously, Mitchell, Morehouse, and Keen find 
that “ morphia has no power to prevent atro- 
pia thus influencing the pulse, so that as regards 
the circulation they do not counteract one an- 
other.” Harley maintains that morphia, here as 
elsewhere, increases the effect of atropia. “ If, 
however,” he says, “ the dose of atropia is small, 
and the morphia produce considerable derange- 
ment of the vagus, the rapidity of pulse is not 
greater than when the atropia is administered 
alone. In my own observations I have invaria- 
bly seen that the acceleration of pulse produced 
by atropia is lessened by morphia, and vice versa, 
and this is the conclusion derived from a study 
of the reported cases of poisoning. The effect 
of the atropia, however, preponderates. The 
result of the combined effect is not the mean of 
the two, but is nearer the standard of atropia 
than of morphia. As wakefulness and active 
delirium increase the pulse-rate, and stupor with MORPHIA AND ATROPIA. 
absolute repose lessens it, these factors must also 
be considered in estimating the relative share of 
opium and belladonna in the result. The experi- 
ments on animals have usually demonstrated an 
antagonistic action as regards the heart.” Har- 
ley’s experiments on dogs certainly show that 
the accelerating effect of atropia on the heart is 
remarkably lessened by combination with mor- 
phia. In the careful experiments of Heubach, 
the same result is shown; the increased pulsations 
caused by atropia are diminished by morphia, 
but the general level of effect is above the mean 
considerably. We must, therefore, conclude that 
the effects of morphia are antagonistic to those 
of atropia on the heart to a limited extent, but 
that the effects of atropia preponderate, and, 
hence, the result of the combined effects is a rate 
of movement greater than the mean. 
Without doubt, the most important point in 
the whole range of the antagonism of morphia 
and atropia is the opposed action on the respira- 
tory function. Less difference of opinion exists 
on this than on any other point connected with 
the subject. In general terms, it may be said 
that opium is a respiratory depressant, and atro- 
pia a respiratory stimulant. The cause of death 
in opium narcosis is failure of respiration, the 
action of the heart ceasing after respiration. 
Atropia counteracts this tendency, and maintains 
the activity of the respiratory function. All the 
cases of poisoning teach this lesson. As the PHYSIOLOGICAL ANTAGONISM. 
215 
opium narcosis deepens, the respiratory acts be- 
come less and less frequent and more and more 
shallow; the quantity of oxygen admitted to the 
blood lessens, and the oxidation processes decline; 
the surface becomes cold, and, carbonic acid 
accumulating, carbonic-acid narcosis is added to 
the toxic coma. Atropia counterbalances these 
effects by raising the number and increasing the 
depth of the respiratory acts, hence more oxygen 
is admitted to the blood, the chemical inter- 
changes are more extensive and speedy, and ex- 
cretion is facilitated. The improvement is repre- 
sented by a flushed face, a warm and dry skin, and 
a more active circulation generally. 
Atropia proves fatal by exhausting the irrita- 
bility of the motor ganglia of the heart and of 
the general vaso-motor system, and also of the 
respiratory centres. Morphia, by lessening the 
work of the heart and of the lungs, opposes 
these effects of atropia. The facts presented in 
the 120 cases of poisoning generally support this 
view of the antagonism. In some of the cases, 
it is true, the narcosis was too profound to permit 
any new impression to be made; but, in those 
suitable for the action of the antagonist, nothing 
could be more striking than its favorable influ- 
ence on the respiration. Dr. Johnston, of Shang- 
hai, whose experience of opium-poisoning has 
reached to hundreds of cases, says that the effect 
of the atropia is simply marvellous in stimulating 
the respiratory function and removing the car- 216 
MORPHIA AND ATROPIA. 
bonic-acid narcosis. In the fatal case of atropia- 
poisoning narrated by Dr. Gross, the injection of 
morphia induced stertor. I have already sug- 
gested that the more gradual introduction of the 
morphia influence would have prevented this ac- 
cident, which seems to have been an idiosyncrasy, 
rather. In a case narrated by Dr, Fothergill,* 
the influence of the antagonist on the respiratory 
function is most conspicuous. A woman had 
taken, at 11 a.m., laudanum containing from 12 
to IT grains of opium. At 2 p.m. the respiration 
was almost gone, but the pulse, though small, was 
rhythmical and regular. One grain of sulphate of 
atropia was then injected subcutaneously. In a 
half-hour the respiration was becoming well es- 
tablished, and, in an hour and a half after the in- 
jection, was going on steadily, 13 to the minute, 
and long and deep. Ho further use of the antag- 
onist was necessary to overcome the effects of the 
poison. It is probable, indeed, that the quantity 
of atropia used was rather in excess, as an emetic 
had caused the discharge of some opium, and the 
subsequent account shows a preponderating action 
of atropia. An equally instructive case, as show- 
ing the power of atropia to overcome the respi- 
ratory depression caused by morphia, is narrated 
by Dr. McGee.f A stout, muscular man of 40 
* The Antagonism of Therapeutic Agents. Philadelphia, 
H. C. Lea, 1878, p. 132. 
f Am. Jour, of the Med. Sci., July, 1869, p. 282. PHYSIOLOGICAL ANTAGONISM. 
217 
years swallowed 30 grains of opium in 10 or 12 
ounces of whiskey. He became profoundly com- 
atose. In two hours an eighth of a grain of 
atropia was injected, and, this having no effect, 
in half an hour the same quantity was repeated. 
The respirations were then nearly suspended, the 
face being livid, but under the influence of the 
atropia the respirations increased greatly; the 
pulse rose to 140, the pupils became widely di- 
lated, and consciousness was so far restored that 
the patient could be roused. He then slept pro- 
foundly for a number of hours, but his pulse con- 
tinued at 81, with the respirations full and deep, 
and Dr. McGee, wisely trusting to the antagonis- 
tic action, did not exhaust his patient by ambula- 
tion, flagellation, artificial respiration, and other 
ingenious devices for keeping awake those who 
need the restorative effects of sleep and quiet, I 
might narrate many examples from the collection 
of cases made for this study, showing the impor- 
tance of the antagonism exerted on the respiratory 
functions. There is no difference in the lesson 
taught us in the cases of opium narcosis. The 
cases of atropia-poisoning treated by morphia are 
not less instructive. Various examples come to 
us with the authority of such names as Graefe,* 
Schmidt,f Fronmliller,| Cohn,§ and others, oc- 
* Schmidt’s Jabrbucher, vol. cxxv. p. 350. 
f Ibid., vol. cxxiv. p. 167. J Ibid., vol. cxxvi. p. 282. 
| Berlin, klin. Woch., 11, 16, 1865. 218 
MORPHIA AND ATROPIA. 
curring in ophthalmic practice. Some of these 
were probably not lethal, although characteristic 
and violent symptoms were produced; yet the 
antagonistic action of the morphia was not less 
conspicuously displayed. 
If we now pass from the clinical evidence to 
the results of experimental research on man and 
on animals, we are greatly surprised with the 
differences in the conclusions drawn. Mitchell, 
Morehouse, and Keen conclude that “ the influ- 
ence of atropia on the pulse and respiration is in 
no way altered by the use of full doses of mor- 
phia, so that in this particular their supposed 
antagonism does not exist,” In some experi- 
ments of my own, made on a medical student, 
I found that morphia modified to a considerable 
extent the effects of atropia on the pulse and 
respiration,—a fact clearly exhibited in the graphic 
representation of the results.* Harley expresses 
himself with decision against the supposed an- 
tagonism of these agents on the respiratory func- 
tion, hut he indicates conditions under which they 
may he used in opposition with advantage,—a 
singular contradiction between his facts and his 
opinions. “ Belladonna is powerless to obviate 
the chief danger in opium-poisoning, viz., the 
depression in the respiratory function.” But, in 
another place, he says, “ in the treatment of bella- 
donna-poisoning, our efforts must he directed to 
* See the tracings on another page. PHYSIOLOGICAL ANTAGONISM. 
219 
sustain the breathing. Opium must be used, not 
as an antidote, but as a means of calming the 
nervous agitation when it is excessive,” etc. 
It is impossible to find any meaning in such ex- 
planations. Again, he says, “ when the heart 
shows indications of failing power, the subcuta- 
neous injection of grain of sulphate of atro- 
pia, at intervals of two hours, must be practised.” 
The facts of Dr, Harley admit of very different 
interpretation from those which he has advanced; 
they prove that atropia exerts a distinct stimu- 
lant action on the respiratory organs, and are in 
conformity with clinical experience. We may 
now regard it as settled that atropia antagonizes 
the depression caused by morphia on the respira- 
tory function, notwithstanding the adverse opin- 
ions just quoted. 
The antagonistic action of atropia and mor- 
phia is further exhibited in the control of the 
former over the nausea, depression, and actual 
syncope caused by the latter. This antagonism 
is exhibited in ordinary medicinal doses, and 
clinical experience justifies the remark of Har- 
ley, that morphia should not be administered 
alone unless its action on the subject is known, 
but always with atropia. The explanation of 
the utility of atropia in preventing the nausea 
and depression caused by morphia consists in 
the counterbalancing action of these agents on 
the cerebrum. While the depression—ofttimes 
the syncope—is thus prevented, the nausea may 220 
MORPHIA AND ATROPIA. 
occur, for atropia also excites nausea in some 
subjects. The coldness of the surface and the 
clammy sweat caused by morphia are removed 
by atropia. The importance of this fact is con- 
siderable. The first effect of morphia is to raise 
the arterial tension and to energize the cardiac 
movements, but this is followed by decline in 
the tension and by slowing of the movements. 
The peripheral vessels become relaxed, and the 
blood current becomes slow; the sweat glands 
act freely, and the functional interchanges be- 
tween the blood and tissues are suspended. The 
action of atropia brings about an important 
change; the peripheral vessels contracting in 
their vermicular manner, and more blood being 
received from the heart, the surface grows warm 
and dry, and the function of metamorphosis of 
tissue is resumed. The effect of this resumption 
of activity at the periphery on the condition of 
the cerebrum is only less important than the 
renewal of hsematosis at the lungs. 
Atropia stimulates the action of the kidneys 
somewhat, and morphia checks the flow of urine. 
They both act to render the emission of urine 
more difficult, but it is an error to suppose that 
they act in the same way. Morphia dulls the 
sensibility of the mucous membrane and dimin- 
ishes the contractile energy of the muscular coat 
of the bladder: atropia stimulates the sphincter 
to more energetic contraction, so that the volun- 
tary efforts at relaxation are opposed. PHYSIOLOGICAL ANTAGONISM. 
221 
Having now indicated the points of antago- 
nism, and examined into the opinions for and 
against the belief in its existence, we are pre- 
pared to ascertain how a lethal dose of the one 
can overcome the effects of a corresponding dose 
of the other agent. It is evident that very rarely 
is a lethal dose of one agent counterbalanced by 
the other in animals. The reason apparently is 
the difference in the extent and variety of the 
cerebral structures in man, as compared with 
the inferior animals. The physiological actions 
are the same in animals as in man, except the 
difference in degree, to employ the words of the 
illustrious Bernard, but when we reach the brain, 
we find that in animals the force of the poison is 
expended on a few comparatively simple organs, 
whereas in man it is diffused over much more 
extensive and complicated structures. 
Experience has demonstrated that the quantity 
of poison which can be antagonized successfully 
and a fatal result averted is comparatively lim- 
ited. Very considerable quantities, as we have 
seen, were taken in some of the successful cases, 
but they did not exceed a certain limit, and the 
stomach-pump and emetics were freely used, so 
that the actual amount entering the blood was 
far less than that taken into the stomach. What 
disposition of the poison is effected ? There is 
no chemical union of the antagonist, to destroy 
the toxic power. It is simply opposed until 
elimination is accomplished. The tendency to 222 
MORPHIA AND ATROPIA. 
destroy life by overwhelming the functions of 
particular organs is opposed and held in check, 
and gradually the poison is eliminated. Further- 
more, the separation of the poison from the 
blood and its excretion by the usual channels 
are greatly promoted by the action of the antag- 
onist in maintaining the functional activity of the 
organs depressed by the poison. The rate of 
elimination and the means of promoting it be- 
come, therefore, important elements in the man- 
agement of these eases, and, I may also add, are 
usually wholly neglected. The principal route 
of excretion is by the kidney, but the skin and 
intestinal canal also convey oft' some of the poi- 
son. In a few minutes after the alkaloids are 
swallowed, traces of them are discoverable in the 
urine. Free action of the kidneys should there- 
fore be maintained by the use of diluents. An- 
other practical point of high importance is the 
removal of the urine as fast as it accumulates in 
the bladder. Brown-Sequard has shown that 
absorption of alkaloids takes place from the 
mucous membrane of the bladder, and he pro- 
poses to make use of this fact by injecting mor- 
phia solutions into this viscus. It is probable 
that alkaloids contained in the urine may diffuse 
into the blood again from the bladder. The 
action of the bowels should be free, and the 
skin should be stimulated,—in fact, all the 
channels of excretion should be kept freely at 
work. THERAPY. 
223 
No absolute rule can be laid down as to the 
quantity of the antagonist to be used. Taking 
morphia-poisoning as the type, the quantity of 
atropia must be determined by the efleets. What 
are the guides ? The pupils ? No. For, al- 
though they may react in the usual way to the 
antagonist, it must be remembered that the 
action of atropia preponderates, and in some 
instances they do not react normally. The true 
guides are the state of the respiration and that 
of the circulation. If the breathing is deep and 
rhythmical, and the pulse is full and strong, 
the state of the pupil and the depth of the 
narcotism are of little moment. When the 
amount of the antagonist administered suffices 
to establish the respiration and circulation in 
their proper condition, the quantity is sufficient, 
whether or not it may be theoretically. As a 
rule, it is better to give the antagonist in small 
quantity, frequently repeated, until the amount 
required has been given. Large doses, as is 
evident in some of the cases, produce unpleasant 
effects, and may be in excess of the real require- 
ments. In some actual trials, I found that 
grain of atropia was about equal in toxic power 
to a grain of morphia. In deciding on the dose 
of the antagonist, the amount of the poison 
probably eliminated must be taken into consid- 
eration. 
Therapy,—lt would be a waste of space to 
repeat the therapeutical applications of morphia 224 
MORPHIA AND ATROPIA. 
and atropia already given with considerable ful- 
ness in the preceding sections. Nevertheless, 
it is necessary to indicate the circumstances re- 
quiring or permitting their conjoined adminis- 
tration. A general rule may be formulated fis 
follows: 
Whenever the hypodermatic injection of mor- 
phia is proper and necessary, atropia should he 
combined with it unless contraindicated. 
In the 'psychical disorders, in which power is in 
excess, the conjunctivse injected, the temperature 
high, morphia should be used alone. When 
power is deficient, the tendency being to de- 
pression, atropia should be combined with it. 
This is the rule, also, for other affections of the 
brain in which the subcutaneous injection is in- 
dicated. 
For the relief of insomnia, or to procure sleep, 
the combination of morphia and atropia is to be 
preferred. The reader should not forget that an 
excess of atropia, or an amount of atropia suffi- 
cient to antagonize the cerebral effects of the 
morphia, will prevent sleep. They should he 
used in the proportion of T|y to grain of atro- 
pia to I grain or | grain of morphia. As the 
susceptibility to atropia varies immensely, the 
precise quantity to be employed in any case must 
he regulated accordingly. 
In the treatment hypodermatically of the vari- 
ous convulsive disorders, morphia and atropia should 
be combined. THERAPY. 
225 
The neuralgias are best treated by the combined 
morphia and atropia solution. There are several 
reasons for this: 
Much larger doses of morphia may in this way 
be injected without danger to the patient; and 
the larger the quantity, as Brown-Sequard has 
shown, the greater the curative power. 
Morphia and atropia combined are more effec- 
tive than either singly. 
The systemic effects during the time of maxi- 
mum narcosis, and also after the narcosis has 
disappeared, are much less unpleasant and de- 
pressing when the two agents are combined than 
when morphia is used alone. 
Sometimes atropia is better borne than mor- 
phia, and vice versa: in this case the agent whose 
effects are least unpleasant should be in excess. 
In sciatica atropia is often more effective than 
morphia: the proportions in which they should 
be used are as follows: to of a grain of 
atropia, \to \ grain of morphia; here the physi- 
ological effects of atropia predominate, but the 
toxic effects are guarded by the morphia. 
In neuroses of the respiratory and circulatory or- 
gans morphia and atropia should be used together. 
This is especially the case in angina pectoris and 
asthma, with the caution I have already given as 
to the use of atropia in certain diseases of the 
heart. Morphia alone is to be preferred in 
pleuritis. 
In the diseases of the digestive apparatus, requiring 226 
MORPHIA AND ATROPIA. 
hypodermatic medication, morphia and atropia 
should be used together. 
As a general rule, in diseases of the urinary and 
genital organs, the two agents should he combined. 
For some purposes atropia should he in excess, 
as in spermatorrhoea, when the more decided 
anaphrodisiac effect of this agent is indicated. 
In cases of pelvic and uterine pain, atropia should 
he proportionally in larger amount than mor- 
phia. 
Acute rheumatism, rheumatic gout, muscular rheu- 
matism, and myalgia are best relieved by a combi- 
nation of morphia and atropia, the latter being 
in excess, as respects its physiological action, 
of the former. The injection of atropia, thus 
guarded by morphia, exerts in these diseases an 
action beyond the relief of pain, how desirable, 
soever, that may be: it modifies, in a way not 
now understood, the morbid process. The prog- 
ress of research renders it more and more prob- 
able that rheumatism is an expression of disorder 
in the nervous system, rather than an affection 
per se of the fibrous structures. Besides relieving 
in some way this centric disturbance, atropia 
favors the excretion from the blood of products 
(the urates) representing the active but imperfect 
tissue-change occurring in these diseases. 
In surgical disorders of various kinds, the 
combined use of morphia and atropia has most 
important and varied applications : to prevent and 
relieve shock ; to cure pain ; to relax spasm ; to facili- THERAPY. 
227 
tale surgical operations. Whenever, in surgical 
practice, the hypodermatic injection of morphia 
and atropia is indicated, the following rule should 
regulate the relative proportion in which they 
are employed: 
If the action of the heart he feeble, the surface 
cold, and the vital powers depressed, atropia 
should be in excess as respects the physiological 
effects. 
Treatment of Toxic Symptoms caused by 
Morphia or Atropia.—l may assume, notwith- 
standing the objections of Harley and the results 
of experiments on animals by Brown-Sequard, 
that the physiological antagonism of morphia 
and atropia has been amply demonstrated by 
cases of poisoning occurring in man. 
In treating cases, the difficulty of precisely 
regulating the amount necessary to overcome the 
toxic symptoms is not easily surmountable. I 
ascertained, in the case which occurred to myself, 
that one-twenty-fourth of a grain of atropia was 
equal in toxic power to one grain of morphia. 
The state of the pupil affords valuable but not 
unerring indications; atropia possesses more 
power, relatively, over the movements of the iris 
than morphia. 
In a case of morphia-poisoning, subcutaneous 
injections of atropia should produce the following 
results: 
Dilatation of the pupil. 
Flushing of the face succeeding to pallor. 228 
MORPHIA AND ATROPIA. 
Dryness and warmth of the skin succeeding to 
a cold and clammy sweat. 
Rise in the pulse-rate and temperature. 
Return of reflex movements of eyelids and 
fauces. 
The dilatation of the pupil should he slightly 
maintained, and should not be carried to the ex- 
aggerated degree sometimes thought necessary. 
The mistake should not he made of confounding 
the sopor produced by morphia and atropia with 
morphia coma. This caution is the more neces- 
sary because this sleep is often considered a con- 
dition of danger requiring renewed administra- 
tion of the antidote, and the patient is at length 
poisoned by atropia. Sufficient atropia should 
he administered to maintain the action of the 
heart and the respiration. So long as these con- 
tinue good, no danger is to be apprehended from 
sleep merely. 
Atropki, relatively considered, does not equal 
morphia in toxic activity. Severe physiological 
effects do not necessarily imply a condition in 
which life is endangered. It is to be remem- 
bered that the toxic effects of atropia endure 
much longer than those of morphia, and hence 
repeated applications of the physiological anti- 
dote may be required. DUBOISIA. 
Duboisia is the alkaloid of Duboisia Myopo- 
roides, a member of the Solanacese. 
The Solution.—The salts of the alkaloid, or 
active principle, are freely soluble in water, and 
hence the solutions for hypodermatic use are 
readily prepared. The following formula will 
be found useful: 
R Duhoisise muriat. vel sulph., gr. i ; 
Aquae destil., %i. M. 
Sig.—Eight minims contain -fa of a grain. 
The Dose.—The amount administered will 
depend on age, idiosyncrasies, habit, etc. For 
an adult the dose will range from yly to y grain. 
Eight minims of the above-mentioned solution 
will produce characteristic physiological effects, 
but a much larger quantity can be administered 
without causing dangerous symptoms. 
Physiological Effects.—Dryness of the mouth 
and fauces, difficulty of deglutition, and a husky 
voice are experienced in a few minutes; simulta- 
neously there is a sense of fulness in the head, 
tinnitus, and vertigo; the action of the heart is 
accelerated, the pulse gains in tension, the face 
flushes, the pupils dilate, and the vision for near 230 
DUBOIS lA. 
objects is blurred and indistinct; the sense of 
fulness in tbe head is followed by headache, es- 
pecially of the frontal region, the vertigo im- 
pairs the locomotion, and the voluntary muscles, 
especially of the lower limbs, become paretic. 
During the time of the maximum effect of a full 
medicinal dose there is considerable excitement 
of mind, an intense restlessness, but apparently, 
no sensations of a pleasurable kind, but rather 
anxiety and dread. With the subsidence of the 
more active symptoms, notably the decline in 
the circulation and the diminished excitement, a 
more quiet condition of the mind, a feeling of 
somnolence, comes on, followed by sound sleep. 
Dreams and visions disturb the sleep somewhat. 
In animals (dogs) large doses produce a high 
degree of excitement, apparently hallucinations 
and delirium. No corresponding experiences 
have thus far occurred or been noted in man. 
The effects of duboisia are very nearly the 
same as those of atropia. Instilled into the eye, 
the pupil dilates, but more readily than from 
atropia, and the dilatation ceases earlier. Duboi- 
sia is less irritating to the mucous membrane, 
hence it will probably supersede atropia in oph- 
thalmic therapeutics. As duboisia seems to have 
more decided calmative and hypnotic effects than 
atropia, it will also probably supersede the latter 
in hypodermatic employment, if the quantity to 
be obtained and the price will justify the change. 
Therapy.—Duboisia may be substituted for THERAPY. 
231 
atropia in all the conditions of disease in which 
the latter is now employed. Duboisia is to he 
preferred probably in all cases; but recent expe- 
riences justify me in the expression of my con- 
viction that it is much more effective in psychical 
disorders than atropia. The indications for the 
administration of these agents are the same. HYOSCYAMIA. 
THE ALKALOID OF HYOSCYAMUS NIGER. 
The alkaloid of commerce exists in two forms, 
—as a brown, soft solid; as a white, crystallized 
substance. Both found in the shops are, as a 
rule, prepared by Merck, of Darmstadt. The 
amorphous preparation is generally preferred, 
owing to its comparative cheapness and to its 
activity. A solution of this is made in the 
proportion of one grain to twenty minims,— 
eight minims of alcohol, six minims of ether, 
and six minims of water (Prideaux). This may 
he diluted by equal parts of alcohol and water. 
A solution of the acetate may be formed ex- 
temporaneously by dissolving one grain of the 
amorphous hyoscyamia in two drachms of 
water acidulated with thirty minims of acetic 
acid. When solution is effected, it should be 
carefully neutralized by ammonia, and after- 
wards filtered. 
The crystallized alkaloid in the form of a salt 
—the sulphate most usually—is more readily 
prepared for hypodermatic use. When its isola- 
tion shall he readily effected, we can hardly 
doubt it will be found more uniform in its effects 
232 THE DOSE. 
233 
and more active than the extract containing it. 
The following is the formula proposed by Seguin : 
R Hyoscyamise (Merck’s cryst.), gr. ii; 
Glycerinse, 
Aquae destil., aa, rr\,c ; 
Acid, carbol., gr. ss. M. 
Filtra. ' 
Sig.—One minim contains t|q grain. 
The dose of hyoscyamia is variously stated, 
and indeed ranges from grain to two or three 
grains. As this extraordinary variation is plainly 
due to differences in the quality of the prepara- 
tion, care must be used. The specimens of soft 
extract containing the alkaloid are not, in respect 
to any two specimens, alike as to the quantity. 
Some of them probably are not more active than 
good specimens of the ordinary extract. It is 
necessary to proceed with caution, since violent, 
even dangerous symptoms have been noted by 
Gill,* Empis,f and others. In using the crystal- 
lized alkaloid, the dose should not exceed one- 
one-hundredth of a grain for the initial trial. 
Gill had violent symptoms from gL grain. When 
the strength of any given preparation is known, 
the dose will he determined by the character of 
the case and by the quantity needed to produce 
physiological effects, which varies much in indi- 
viduals and in diseases. 
* The Practitioner, February, 1878, p. 84. 
f Annuaire de Therapeutique, 1881, p. 31, et seq. 234 
HYOSCYAMIA. 
Physiological Effects.—Whilst hyoscyamia 
corresponds closely in action to atropia and du- 
boisia, there are differences. Hyoscyamia is less 
excitant and deliriant, and more calmative and 
hypnotic. In respect to the mechanism of the 
action on the heart and circulatory system, on 
the respiration, on the pupil, and on the brain, 
there is no difference between these several alka- 
loids of the Solanacese. 
Therapy. Within a few years past much 
clinical experience has been’ published show- 
ing the value of hyoscyamine in mental dis- 
orders. Prideaux* makes the important ob- 
servation that it acts differently as respects 
promptness and efficiency under varying condi- 
tions of insanity. Thus, in acute mania charac- 
terized by depression, one-sixteenth grain will 
have a decided effect, whilst in the condition of 
excitement of chronic mania larger doses are ne- 
cessary, reaching as high as one-tenth grain sub- 
cutaneously, which he regards the preferable 
mode of administration. In mania with intense 
motor excitement and destructive tendencies, 
Prideaux regards hyoscyamine as “ the most 
rapid and reliable narcotic we possess.” In epi- 
leptic mania, delusional insanity, and in chronic de- 
mentia, it does good in many cases. 
Dr. C. Keinhard | has used hyoscyamine in 
* The Lancet, 1879,—Sept. 27, Oct. 4 and 11. 
f Archiv fur Psych, und Nervenkrankheilen, Band xi. THERAPY. 
fifteen insane and twelve epileptics. In eight of 
the insane it produced calmative effects and did 
good, and in five epileptics with maniacal attacks 
it diminished their number and severity. Men- 
del* has also used hyoscyamia in various psy- 
choses with advantage, those improved being 
characterized by high motor excitement. In 
active delirium the crystallized alkaloid prepared 
by Merck has been used-by FronmiiHerf with 
good results. To these observations showing the 
value of this remedy in disorders of the mind 
may be added the reports of Pearse,| Grill ,§ and 
Lawson,||—all confirming the utility of hyoscy- 
amia in mania with high motor activity. More 
recently, Seguin has made an exhaustive study 
of the actions and uses of this agent. lie finds 
that in mania it produces sleep more certainly 
even than chloral, and without bad after-effects. 
It has produced a positive cure in a case of delu- 
sions of persecution, and has done more than 
any other remedy in paralysis agitans, as respects 
relief to the trembling. In chorea, mercurial trem- 
bling, senile trembling, etc., in spasmodic cough, lar- 
yngismus, hiccough, etc., hyoscyamia has been used 
* Allg. Zeitscbr. f. Psych., xxxvi., 1879. 
f Memorabilien. Quoted in Virchow u. Hirsch’s Jahres- 
bericht for 1877. 
X Lancet, Sept. 1876, p. 319. 
§ The Practitioner, Feb. 1878, p. 8L 
|| Ibid., Aug. 1878. 
]f Archives of Medicine, June, 1881. 236 
HYOSCINE. 
with success as a palliative in numerous instances, 
occasionally with curative results. (Oulmont.*) 
Ladenhurg has prepared from hyoscyamus 
secondary alkaloids such as had been previously 
obtained from atropia. Hyoscine was so derived. 
A crystallizahle salt is formed by combination of 
hydriodic acid with hyoscine. Its physiological 
effects correspond to those of hyoscyamia, hut 
are less powerful. It causes less dryness of the 
mouth, and less disturbs accommodation, and is 
more decidedly sedative. In the clinical trials, 
one-half of the cases of whooping-cough were re- 
lieved, and it did good in all the cases of asthma, 
six in number, in which it was used. Hyoscine 
also relieved the pain of enteralgia. There is 
much to be hoped from further experience with 
this interesting remedy. 
HYOSCINE. 
* Bull. Gen. tie Therap., vol. Ixxxiii. p. 481. STRYCHNIA. 
ALKALOID OF STRYCHNOS NUX VOMICA. 
History.—Strychnia was probably the first 
agent submitted to systematic examination by 
the physiological method. Magendie, having as- 
certained its properties, suggested that “ medi- 
cine would perhaps derive great advantage from 
the knowledge of a substance whose property is 
to act on the spinal cord, for we know that many 
severe diseases have their seat in this part of the 
nervous system.” Causing muscular rigidity, he 
supposed it might be used with good effects in 
the condition of paralysis, and it was not long 
before Fouquier subjected the suggestion to the 
test of experiment, and treated cases of paralysis 
successfully. The first application of strychnia 
hypodermatically in the treatment of disease was 
made by Dr. Behier, of Paris, but the observa- 
tions of Mr. Charles Hunter really initiated the 
clinical experience since continued so success- 
fully. 
The Solution.—The following solutionis con- 
venient : 
R Strychnise sulpbatis, gr. i ; 
Acid, carbolic., gr. i; 
Sig.—Ten minims contain jL grain 
Aqua 3, £i. M. 238 
STRYCHNIA. 
As a solution of strychnia will long remain free 
from a penicilium, the addition of carbolic acid 
is necessary only when the solution is intended 
to be kept several months. Although one grain 
will dissolve in an ounce of water entirely, at the 
ordinary temperature, it tends to crystallize out; 
hence before taking out the required amount the 
bottle should be placed in a vessel containing 
some hot water. The sulphate, in larger relative 
proportion, and other salts, as the nitrate, have 
been proposed, but from a mistaken notion of the 
solubility. The sulphate is the most soluble of 
the salts of strychnia, but not more freely than 
in the proportion of the above formula. By the 
aid of heat, two or more grains will dissolve in 
an ounce of water, but on cooling the surplus 
will crystallize out. On the other hand, the 
solution containing one grain to the ounce will 
remain a perfect solution for some time, and not 
until after several months will some minute 
crystals form on the glass. 
The dose of strychnia subcutaneously has been 
variously given. Lorent employed from one- 
twenty-fifth to one-tenth of a grain, and Eulen- 
berg has given up to one-eighth. Hunter admin- 
istered from one-ninetieth to one-twenty-fourth 
of a grain. Echeverria produced toxic symptoms 
in a boy, which, however, were readily recovered 
from, by one-thirtieth of a grain. From five to 
ten minims of the solution recommended will 
be suitable quantities under the varying circum- PHYSIOLOGICAL EFFECTS. 
239 
stances of cases. Half a grain is the smallest 
fatal dose recorded. 
Physiological Effects.—lt is important to note 
the effects produced by the hypodermatic injec- 
tion of medicinal doses. Unfortunately, until 
toxic symptoms are excited, the disturbance is too 
vague for characteristic description. Some facts 
can be stated, however, from clinical observation. 
When a solution of strychnia of the usual 
strength is injected under the skin, a sensation 
of heat and smarting persists for some time in 
the part. The skin also becomes red in the 
neighborhood of the puncture; a subjective sen- 
sation of warmth is perceived in the limb, and 
an actual rise in temperature may be noted. At 
the same time erection of the hair-follicles [cutis 
anserina) takes place. 
In a few seconds pain or distention is felt in 
the abdomen, intestinal movements and loud bor- 
borygmi occur, just as is the case so frequently 
after the hypodermatic injection of the narcotic 
alkaloids. Next the pupils dilate, deep-seated 
pain and throbbing are felt in the brain, and an 
unpleasant giddiness renders the erect posture 
painful, and standing or walking uncertain. 
Ringing in the ears, detonation, anxiety, a feeling 
of dread, and flashes of light before the eyes are 
also quite commonly experienced. The counte- 
nance of the patient affords some indication of 
the cerebral disturbance, appearing anxious and 
distressed. 240 
STRYCHNIA. 
The foregoing symptoms are more severe if 
larger doses be administered, and in addition 
there occur some stiffness of the jaws, jerking of 
the extensor muscles, and sharp pains like elec- 
tric shocks shooting through the limbs. Dr. 
Echeverria has so well described these severe 
symptoms that I transcribe his account. My 
own observations supply no further experiences 
than those I have just detailed. 
“ I injected first the right thigh, and about two 
minutes after, the left. In two minutes more the 
boy commenced to sigh, and have a meaningless 
smile, with stiffness in the jaws, soon passing into 
real trismus. The pupils were largely dilated, 
the face congested, and tetanic spasms of the res- 
piratory and cervical muscles followed. Every 
attempt to articulate a word awoke a.spasm. He 
could neither speak nor be touched without being 
seized with a jerk, and the whole surface of the 
body was in a perspiration.”* In another case 
Dr. Echeverria had similar experiences. He 
thus describes them: “In about eight minutes 
she complained of giddiness, and was soon seized 
with trismus and opisthotonos. The tetanic 
spasms were not violent, and were accompanied 
by general perspiration, congestion of the face, 
and enlargement of the pupil.” Other impor- 
* Treatment of Paralysis by Hypodermic Injections of 
Strychnine. Medical Communications of the Connecticut 
State Medical Society, 1808. PHYSIOLOGICAL EFFECTS. 
241 
tant observations were made by Dr, Echeverria. 
“ The temperature of the limbs was always raised 
after the injection. The frequency of the pulse 
was also augmented. The capillary circulation 
was rendered more active in the limbs, exhibit- 
ing large red patches, more intense in the vicinity 
of the punctured region. This condition would 
last three and even four days after the operation. 
The injections were attended with perspiration 
of the head and limbs, more profuse with the 
girl than with the boy. The pupils were always 
dilated, and gurgling of the bowels would persist 
some minutes after the puncture. Another very 
perceptible result was the fibrillar contractions, 
or twitching of the muscles in the limbs, lasting 
for a minute or two, and which I have found pro- 
longed for more than an hour in other similar 
cases/’ 
When we come to analyze the symptoms pro- 
duced by the subcutaneous injection of strych- 
nia in full medicinal doses, we observe that the 
effects are exerted on the nervous system of ani- 
mal life, and to some extent on the sympathetic 
system. 
In small quantity strychnia does not affect the 
irritability of the motor and sensory nerves, as 
Klapp* and Spitzkaf have shown, but in large 
* The Journal of Nervous and Mental Diseases, vol. v., 
1878, p. 619. 
f Ibid., vol. vi., 1879. 242 
STRYCHNIA. 
doses it does appear to have this effect, as Yul- 
pian * and others have demonstrated. The op- 
posing observations on this point are reconciled 
by the fact, discovered by Martin-Magron et 
Buisson, that the action of strychnia on the 
nerves is local, and therefore greatly influenced 
by the quantity reaching them. 
Strychnia causes a rise in pressure of the blood 
by stimulating the vaso-motor centre in the me- 
dulla, and by inducing contraction of the arte- 
rioles, as has been experimentally demonstrated 
by Mayer,f Spitzka,| and others. It also, in 
medicinal doses, stimulates the intra-cardiac gan- 
glia, thus increasing the heart’s rate of move- 
ment. Clinical observation has seemed to be 
conclusive as to the power of strychnia to stimu- 
late the respiratory organs and to increase the 
depth and force of inspiration. 
In a lethal dose the effect follows immediately 
almost on the administration of the poison. The 
head feels powerfully distended; a shudder passes 
over the body, with a catch in the breathing; a 
pain deep in the epigastrium shooting to the spine 
occurs at the same time; the jaws are clinched; 
electric-like shocks fly through the limbs; the 
muscles of extension of the extremities and the 
muscles of the abdomen become rigid and start 
* Archives de Physiologic Norm, et Path., 1870, p. 116, 
et seq. 
f Archiv f. experiment. Pathologic u. Pharmacol., Band 
11, p. 458. t Supra. THERAPY. 
243 
up in sudden strong contraction; the face is pale 
and distorted by a grim smile [risus sardonicus); 
the pupils are dilated; the pulse is quick; the 
breathing jerking. With the progress of the 
action the sensibility of the reflex centre becomes 
so acute that the minutest peripheral impression— 
a breath of air, a touch, a gleam from a mirror— 
will excite a spasm, in which general extension 
of the voluntary muscles takes place, the breath- 
ing is suspended, the hands are clinched, the 
toes incurvated, the head bent backward, and the 
body so arched that the heels and the occiput are 
the only points of support. During the parox- 
ysm the face grows dusky, and the skin gener- 
ally dark and perspiring. Death ensues by the 
fixation of the respiratory muscles, but rarely 
occurs in the first paroxysm, and may be delayed 
to the third or later. The mind is unaffected 
until carbonic-acid narcosis comes on. Much 
soreness is felt in the muscles after the paroxysm, 
but they are not rigid. The paroxysms increase 
in number and violence to the end, which occurs 
usually within two hours. 
Therapy.—The original suggestion of the use 
of strychnia in the treatment of paralysis was 
made, as has been shown, by Magendie, after his 
course of experiment demonstrating the nature 
of its actions. Dr. Behier, of Paris, was, it ap- 
pears, the first physician to employ strychnia by 
the hypodermatic method, and afterwards Prof. 
Courty, of Montpellier, used it with complete 244 
STRYCHNIA. 
success in three cases of facial 'paralysis. Not- 
withstanding these, and some other authorita- 
tive statements regarding the curative effects of 
strychnia thus administered, it was not until 
Mr. Charles Hunter’s paper—“ On Strychnia Hy- 
podermically administered in Paralytic Affec- 
tions”*—appeared that professional attention 
was strongly directed to this subject. Echever- 
ria’s paper also revived the interest in this coun- 
try, continued by cases occurring in the practice 
of Hr, Hammond, of New York, which were 
reported by Hr, Reuben A. Yance.f These were 
cases of hemiplegia, paraplegia, and local paral- 
ysis. As might have been expected, the local 
paralyses were most decidedly benefited, hut all 
were improved in a marked degree. The forms 
of paralysis which have been treated in this way 
are the following: 
Hemiplegia. 
Paraplegia. 
Infantile paralysis. 
Local paralyses. 
Progressive muscular atrophy. 
Progressive locomotor ataxia. 
Mr. Hunter reports three out of four cases of 
hemiplegia cured by the injections of strychnia. 
Two of the cases were respectively of six and 
two and a half years’ duration. This statistical 
statement should not mislead the reader. Suc- 
* British and Foreign Medico-Chirnrgical Review, April) 
1868. 
f Journal of Psychological Medicine, vol. iv. p. 867, et seq. THERAPY. 
245 
cess like this cannot he expected in the treatment 
of paralysis of cerebral origin; the cases of Mr. 
Hunter were evidently very favorable cases for 
treatment by this method. Nevertheless, the 
hypodermatic injection of strychnia, in many 
cases, is decidedly curative. As Hr. Echeverria 
has well remarked, “ the effects of strychnia are 
widely different when administered hypodermat- 
ically or by the mouth. By the latter method 
the quantity may he repeated and increased, un- 
successfully, as manifested in the cases of Hun- 
ter, and in those here related; and yet a smaller 
dose of the substance, exhibited hypodermatic- 
ally, he capable of regenerating at once the lost 
muscular power.” 
We should possess clear notions, then, as to 
the circumstances in which it may be proper to 
use the hypodermatic injection of strychnia in 
hemiplegia, for, manifestly, a remedy of such 
power may prove to he as harmful when indis- 
creetly employed as it is unquestionably useful 
in suitable cases. 
In my own experience it has not been useful 
in old cases characterized by contractions of the 
palsied limbs. 
It is contraindicated in recent hemiplegia. 
It has been exceedingly useful in old cases of 
hemiplegia in subjects not very advanced in life, 
the paralysis being partial as to motility, and the 
limbs not wasted. 
The hypodermatic injection of strychnia has 246 
STRYCHNIA. 
been used in spinal paraplegia by Eehier, Courty, 
Euppaner, Hunter, Ecbeverria, and others, with 
success. The rules for its administration are 
similar to those I have given for hemiplegia. 
It is not proper in acute cases involving struc- 
tural alterations of the spinal cord. 
In cases of paraplegia due to softening or 
tumor in the spinal canal it will do harm. 
It wrill be beneficial in cases of reflex paraple- 
gia, in paraplegia due to anaemia of the cord, in 
hysterical paraplegia, and in those cases of pare- 
sis of the muscles of the inferior extremities due 
to concussion of the cord, but after the acute 
symptoms have subsided. 
It is certainly true, however, that Mr. Hunter 
obtained advantage from it in a case the symp- 
toms of which indicated myelitis. Dr. Echever- 
ria’s Case I, may be classed in the same category, 
—the patient complaining of formication and 
numbness, and being paralyzed both as to motion 
and sensation. 
The hypodermatic injection of strychnia has 
proved an exceedingly valuable adjunct to the 
treatment of infantile paralysis. If the electro- 
muscular contractility to the continuous or in- 
duced current be not lost, very beneficial results 
may be expected from this treatment. The in- 
jection promotes the capillary circulation, and 
increases the growth and power of the muscles. 
In various local paralyses the hypodermatic 
injection of strychnia is even more decidedly THERAPY. 
247 
curative. Courty* cured facial paralysis by in- 
jecting strychnia over the course of the facial 
nerve. Pletzer, Lorent, Sacmann, and Eulen- 
herg had good results from the same treatment.f 
In a case of paralysis of the vocal cords with 
aphonia, Heudorfer failed, hut in a similar case 
Waldenburg succeeded with the strychnia injec- 
tion. 
In the 4‘drop wrist” of lead-poisoning—paral- 
ysis of the extensors—it is a very important addi- 
tion to the other means of treatment of this very 
obstinate affection. It is more successful than 
any other agent in writer’s cramp. Palsy of single 
muscles or groups of muscles, following cold or 
rheumatism, is generally curable by this means. 
The injection also increases much the contractile 
power in cases of palsy following injury of nerve 
trunks. 
Paralysis of the bladder, with dribbling of urine, 
and paralysis of the sphincter ani not due to mye- 
litis, are much benefited and frequently cured by 
this means. 
In progressive muscular atrophy it has been used 
with great advantage in cases in which the 
electro-muscular contractility was not lost. 
In paralysis of cerebral or spinal origin, with- 
out wasting of the muscles, the injection may be 
made under the skin. The dose of strychnia will 
vary, with the age of the subject, from to of 
* Eulenberg, p. 243. 
f Ibid. 248 
STRYCHNIA. 
a grain. In local paralyses, in infantile paralysis, 
in progressive muscular atrophy, the injection 
must be made into the affected muscles. If the 
electro-contractility be not lost, the following 
effects may be expected: 
Rise in temperature of the limb, and increase 
of capillary circulation. 
Increase in muscular power with growth of 
muscles. 
Cure of the paralysis. 
If, however, the electro-muscular contractility 
to the galvanic current is lost, fatty degeneration 
has so far proceeded that the injection of strych- 
nia will be useless. 
The method of practising the injection into 
the muscles is as follows: 
The affected muscle or group of muscles is 
grasped with the left hand and made prominent, 
and with the right the needle is plunged quickly 
and boldly into the muscular tissue. When in- 
serted as far as necessary, the needle is with- 
drawn a short distance to clear any vessel it may 
have penetrated, at the same time moving the 
point about, and then the fluid is slowly injected. 
It is important, of course, to avoid the blood- 
vessels, and to insert the needle into the para- 
lyzed muscles. The pain of this operation is not 
greater than the subcutaneous injection, and little 
danger of deep-seated abscess is to he feared. 
Muscular tissue, as is well known, does not read- 
ily take on the morbid action called inflammatory. THERAPY. 
249 
The systemic effects do not follow so quickly 
nor are they as powerful after injection into the 
muscular tissue as after the subcutaneous injec- 
tion. Both local and systemic effects are pro- 
duced ; hut it is chiefly the local effects which 
are desired in cases of local paralysis. Some 
cases of local paralysis of the bladder cannot he 
reached in this way. In paralysis of the sphinc- 
ter ani the needle may readily be thrust into this 
muscle. 
The subcutaneous injection of strychnia has 
been used in progressive locomotor ataxia, but with 
a negative result. In my own experience I have 
observed no decided influence for good or evil. 
Neuralgia. The hypodermatic injection of 
strychnia has been used by Dr. Anstie in gastral- 
gia and cardiac neuralgia, with advantage. “My 
decided opinion is, at present,” says Dr. Anstie, 
“ that there is no such remedy for gastralgia as 
strychnia subcutaneously injected in doses of yt& 
to -g of a grain.” Although I cannot speak so 
positively as Dr. Anstie on this subject, I can 
say that I have observed good effects from the 
strychnia injection in the class of cases to which 
he refers. 
Amaurosis and Amblyopia.—According to Eu- 
lenberg, Fremineau was the first to employ the 
hypodermatic injection of strychnia for the cure 
of a case of amaurosis following typhus. Sac- 
mann soon after reported a cure of amaurosis by 
the same means, and Spaeth one of amblyopia,— 250 
STRYCHNIA. 
“ functional paralysis of the retina.” Dr. La- 
cerda,* of Lisbon, employed the hypodermatic 
injection of strychnia with success in a case of 
“ amaurotic amblyopia.” Talko, of Tiflis,f also 
succeeded in curing amblyopia by repeated injec- 
tions, ranging in strength from fa to % of a grain. 
The most important contributions to our knowl- 
edge of this subject have been made by Prof. 
Nagel, of Tubingen, who reports cures, of am- 
blyopia and amaurosis, and even cases of the 
latter in which there was white atrophy of the 
optic disks.| 
Weinow§ employs the nitrate, fa grain, in- 
jected into the temple every two or four days. 
If no improvement occur after three injections, 
he discontinues the practice. In an excellent 
paper on the subject, Bull || gives a resume of 
Nagel’s observations, and follows with an account 
of twenty-four cases. He concludes that in func- 
tional amblyopia we may expect good and per- 
manent results from strychnia; and even in some 
cases of organic origin, provided there be no ex- 
tensive atrophy of the nerve structures, some 
* Gazette de Lisboa, xi., 1867, and Schmidt’s Jahrbucher 
der gesammten Medicin, vol. cxliii. p. 67. 
f Ibid., vol. cxlv. p. 74. 
% Berliner klinische Woebenscbrift, viii. p. 6, 1871. Also, 
Dr. Nagel’s special treatise, which, however, I have not had 
the opportunity to consult. 
$ Quoted in the London Medical Record, vol. i. p. 156. 
11 The American Journal of the Medical Sciences, 1872, THERAPY. 
251 
improvement is obtained from the use of the 
remedy. If actual atrophy of the nerve exists, 
he thinks strychnia useless. All authorities are 
agreed that it is in alcohol and tobacco amauro- 
sis, especially the latter, that the injection of 
strychnia renders such important service. It is 
conceded that the remedy will do no good if no 
improvement has occurred after three or four 
injections. 
To these must be added the amblyopia of dis- 
use, of hysteria, and allied states.* 
The Antagonisms of Strychnia.—The discovery 
of chloral hydrate and the subsequent announce- 
ment of strychnia as its physiological antago- 
nist, made by Liebreich, have been followed by 
numerous researches, monographs, and clinical 
reports. Liebreich demonstrated that animals 
in a deep stupor from chloral intoxication, the 
dose administered being lethal, were aroused, 
and death was averted by strychnia. If, for ex- 
ample, two rabbits of equal weight—say three 
pounds—receive grain of strychnia sulphate, 
a fatal dose, and to one of them fifteen grains of 
chloral be also given, the former will die in te- 
tanic convulsions in ten minutes, while the latter 
will sleep two hours or more quietly, and will 
wake up in a normal state. Such a striking ex- 
hibition would seem to be conclusive, but other 
observations are necessary. The most important 
* L. De Wecker, Therapeutique Oculaire, p. 640. 252 
STRYCHNIA. 
and elaborate research, undertaken to determine 
the supposed antagonism of chloral and strych- 
nia, is that of the Committee of the British Med- 
ical Association, Dr. J. Hughes Bennett, Chair- 
man.* The Committee first, rightly, settled the 
lethal dose of each agent; they next ascertained 
the result of the simultaneous administration of 
chloral and strychnia; and then the result of the 
administration, at varying intervals, of one sub- 
sequently to the lethal dose of the other agent. 
Their general conclusions are as follows: “1. 
That, after a fatal dose of strychnia, life may he 
saved by bringing the animal under the influence 
of chloral hydrate; 2. That chloral hydrate is 
more likely to save life after a fatal dose of 
strychnia than strychnia is to save life after a 
fatal dose of chloral hydrate; 3. That, after a 
dose of strychnia producing severe tetanic con- 
vulsions, these convulsions may he much re- 
duced, both in force and frequency, by the use 
of chloral hydrate, and consequently much suf- 
fering saved; 4. That the extent of physiological 
antagonism between the two substances is so 
far limited that (1) a very large fatal dose of 
strychnia may kill before the chloral has had 
time to act; or (2) so large must be the dose of 
chloral hydrate to antagonize an excessive dose 
of strychnia that there is danger of death from 
the effects of the chloral hydrate; 5. Chloral 
* Brit. Med. Jour., Oct. 8, 1874, p. 437, et seq. THERAPY. 
253 
hydrate mitigates the effects of a fatal dose of 
strychnia by depressing the excess of reflex ac- 
tivity excited by that substance, while strychnia 
may mitigate the effects of a fatal dose of chloral 
hydrate by rousing the activity of the spinal 
cord; but it does not appear capable of remov- 
ing the coma produced by the action of chloral 
hydrate on the brain.” 
A careful investigation of the supposed antag- 
onism of chloral and strychnia has been under- 
taken by Husemann.* He holds that chloral is 
an antidote to strychnia, prevents the spasms, 
and averts death, and that it has a corresponding 
effect in the case of the strychnia bases sold 
under the name of brucin. One of the earliest 
attempts to ascertain whether the antagonism 
existed was that of Hajewski,f who found that 
chloral prevented or relieved the cramps caused 
by strychnia, and also to a certain extent the 
cardiac depression, but that strychnia was not in 
the same degree an antagonist to chloral. In a 
memoir on the treatment of poisoning by chloral, 
ErlenmeyerJ holds that, while chloral is useful 
to oppose some of the effects of strychnia, the 
converse does not hold good, and strychnia is 
not useful in chloral-poisoning. The influence 
which Erlenmeyer’s opinion might otherwise 
* 11 Antagonistische und antidotarische Studien.” Arch. f. 
exp. Pathol, und Pharmacol., vi. p.’345. 
f Centralbl. f. d. med. Wissensch., 17, 1870, p. 261. 
J Prakt. Arzt, xiv. p. 11. Quoted in The Practitioner. 254 
STRYCHNIA. 
have is decidedly weakened by a statement made 
in this connection, intended to illustrate and en- 
force his views, that, while morphia is an antag- 
onist to atropia in poisoning by the latter, atropia 
is not an antagonist in poisoning by morphia. 
Arnould,* who has also investigated this ques- 
tion experimentally, regards the antagonism as 
more limited in scope than Liebreich has main- 
tained. This question has also been studied 
by Prof. Ore, of Bordeaux,f who concludes that 
strychnia rather promotes than prevents the poi- 
sonous action of chloral. 
What is the teaching of clinical experience? 
I have found recorded seven cases of strychnia- 
poisoning, in which chloral was the chief or only 
means of treatment employed. An equal num- 
ber of cases I find in which chloroform inhala- 
tions were practised successfully. Although the 
latter do not come within the range of the 
present subject, yet, as the effects of chloral are 
attributed by Liebreich to the disengagement 
of chloroform in the blood, they may serve to 
illustrate and confirm the former. Of the seven 
cases of strychnia-poisoning, in which chloral 
was the chief or only agent used, all proved 
successful, ISTo facts could be stronger. lam 
unable to find any cases of chloral-poisoning in 
* Presse Med. Beige, 1870, No. 9, p. 69. Quoted by Huse- 
mann. 
f Bull. Gen. de Therap., Ixxxiii. p. 403, et seq. THERAPY. 
255 
which strychnia was properly and adequately 
used, as it is in animals. 
If we now sum up the evidence, we cannot 
fail to be convinced of the antagonistic action of 
chloral and strychnia; hut chloral is an antagonist 
to strychnia-poisoning, rather than strychnia is 
an antagonist to chloral-poisoning. The expe- 
rience on rabbits shows that grain of strychnia 
is equivalent to fifteen grains of chloral. In 
the cases of poisoning in man, thirty grains of 
chloral subcutaneously was sutficient to allay 
the spasms and avert death from four grains of 
strychnia. But no absolute rule can be laid down, 
since the susceptibility to the action of these 
poisons varies greatly in different individuals. 
As in the published cases emetics were used, and 
in many instances the quantity of strychnia was 
merely estimated, no positive conclusions can be 
drawn from them. Artificial respiration mate- 
rially retards the action of strychnia, and warmth, 
as Brunton* has shown, exercises a remarkable 
influence in lessening the effect of chloral. Thus, 
“ Br. Brunton found that an animal wrapped in 
cotton-wool recover perfectly from a dose of 
chloral which is sufficient to kill it when exposed 
to the cooling action of the air, and that recovery 
from the narcotic action is much quicker when 
the temperature is maintained in this way, and 
still more rapid when the animal is placed in a 
f Jour, of Anat. and Physiol., May, 1874, No. 14. 256 
STRYCHNIA. 
warm bath, provided this is not excessive.” 
Heat would therefore seem to be an antagonist 
to chloral, and for an obvious reason, for heat 
increases the action of the heart, and thus opposes 
the depression of the heart, which is a main factor 
in the toxic effects of chloral. In the treatment 
of the toxic effects of strychnia by chloral, the 
amount of the latter administered should be de- 
termined by the symptoms. Sufficient chloral 
should be given to suspend the strychnia spasms, 
for the danger consists in the stoppage of respi- 
ration by tetanic fixation of the respiratory mus- 
cles. The amount required for this will, doubt- 
less, vary within considerable limits, as I have 
already intimated. In the case of the Sioux 
Indian, treated by Hr. Turner,* the quantity of 
strychnia was not known, but the return of the 
spasms from time to time required repeated doses 
of chloral, one hundred and five grains in all 
being given within five hours. When strychnia 
is used against chloral-poisoning, the objects to 
be accomplished are different. By stimulating 
the cardiac and respiratory centres with strych- 
nia, the tendency to cardiac and respiratory 
failure is prevented. The quantity required will 
be determined by the effects; but it is probably 
much less than theory indicates. The initial dose 
may be -g grain, and each succeeding dose T|~g- 
grain, which may be repeated every half-hour, 
* Med. and Surg. Eeporter, June 15, 1872. THERAPY. 
257 
or more frequently, until an approximation to 
the maximum is reached. 
Chloral and strychnia can hardly be regarded 
as antagonistic in their actions on the functions 
of the brain, since chloral suspends them, and 
strychnia does not affect them in any way. In 
one respect they have opposed effects,—chloral 
producing cerebral anaemia and strychnia rather 
increasing the intra-cranial circulation. On the 
spinal cord the antagonism is very complete,— 
chloral suspending the reflex and motor functions 
of the cord and strychnia exalting both. Strych- 
nia stimulates the respiratory and vaso-motor 
centres in the cord, and thus opposes and coun- 
teracts the most dangerous tendency of chloral 
narcosis. The chief danger from strychnia— 
the tetanic fixation of the muscles of respiration 
due to the exalted reflex function—is removed by 
the action of chloral. This antagonism is more 
certain and effective than the opposite one, or 
the stimulation of the chloralized spinal cord by 
strychnia; whence it follows that chloral is a 
more useful antagonist in strychnia-poisoning 
than is strychnia in chloral-poisoning. 
An antagonism has been demonstrated between 
strychnia and bromide of 'potassium. Notwith- 
standing the difference in the rate with which 
they act, bromide of potassium has been used 
successfully in several instances to counteract 
the toxic effects of strychnia. The doses admin- 
istered must be large and must be frequently 258 
STRYCHNIA. 
repeated. One drachm may be given every half- 
hour, sufficiently diluted in water. The limita- 
tion of the doses will he determined by the effect 
on the spasms. Bromide may also be used in 
conjunction with other remedies,—with those 
more prompt, but evanescent in effect, as ether 
or chloroform inhalations. 
Strychnia as a Stimulant of the Respiratory Func- 
tion.—The importance of atropia as a special 
stimulant of the respiratory function has been 
frequently alluded to. The resemblance in the 
spinal actions of atropia and of strychnia has 
been manifest in the study of these agents, 
Atropia, in therapeutical works, is sometimes 
suggested as an opponent and antagonist of 
strychnia; it is so placed in Guhler’s “ Commen- 
tary on the French Codex.” Hardly any state- 
ment could be more fallacious. In some experi- 
mental investigations made some years ago, I 
found that atropia intensified the effects of strych- 
nia, and hastened death by contributing to the 
tetanic fixation of the muscles of respiration. 
We find that strychnia stands njext to atropia as 
a stimulant to the respiratory function. Through 
the heightened reflex activity of the spinal cord 
and of the respiratory centres in the medulla, 
strychnia causes death by spasm of the respira- 
tory muscles and asphyxia. It must therefore 
antagonize those agents which, like acrmite, 
cause death by paralysis of the respiratory mus- 
cles. This supposition is confirmed by experi- THERAPY. 
259 
ment. In an interesting series of experiments 
to test this antagonism, Dr. Fothergill found that 
a lethal dose of aconitine was entirely overcome 
by a quantity of strychnia twice as great as the 
lethal. The animals given the aconitine alone 
died; the same animals receiving the aconitine 
with the strychnia, in previous experiments, re- 
covered. The existence of the antagonism is, 
O / 
therefore, undoubted. 
An opposition of actions has been determined 
to exist between strychnia and nitrite of amyl. 
These substances act in an opposite manner on 
the nervous system of animal life and on the 
sympathetic system. Amyl nitrite suspends the 
reflex function of the spinal cord and causes 
paralysis of the muscular system, and death en- 
sues from paralysis of the respiratory muscles. 
The most characteristic effects are those on the 
heart and the arterial system. It depresses the 
arterial tension to the lowest point, and increases 
greatly the action of the heart, a necessary result 
of the enormous dilatation of the peripheral ves- 
sels. The reflex and spinal effects, the cardiac 
and arterial disturbance, are the opposite of those 
produced by strychnia. From the physiological 
stand-point, then, an antagonism must be pre- 
sumed to exist between them. An experimental 
research by Dr. Gray,* of Glasgow, strongly 
supports this view. Thus, he found that one- 
* Glasgow Med. Jour., 1871, p. 188. 260 
STRYCHNIA. 
fourth of a grain of strychnia proved fatal usually 
to the rabbits which he used for experiment. 
He was able to administer half a grain of strych- 
nia and ten drops of the nitrite of amyl simulta- 
neously, by subcutaneous injection, without any 
marked disturbance following. Of course, fur- 
ther investigations are necessary, hut sufficient is 
now known to justify the inhalation of nitrite of 
amyl in cases of strychnia-poisoning. COOTA. 
THE ALKALOID OF CONIUM MACULATUM. 
The Solution.—When this alkaloid was first 
used subcutaneously, the only preparation avail- 
able was the alcoholic solution. The following 
formula, proposed by Burman, is an advance on 
previous attempts: 
II Coniae, 3'iii, rr\^xii; 
Acidi acetici fort., ppii, ; 
Spts. vini rect., gi; 
Aquae destillatae, ad gii. M. 
Sig.—One minim of this solution is a sufficient dose to begin 
with. Five minims contain one minim of conia. 
As the alkaloid conia readily undergoes de- 
composition and varies greatly in strength, prep- 
arations made from commercial samples must he 
very unequal in power. It follows, therefore, in 
beginning a new solution care is necessary to 
determine its strength. The salts of conia, con- 
sisting of the hydrohromate, hydriodate, and 
tartrate, are, on the other hand, more permanent. 
These salts crystallize in large, transparent, vit- 
reous crystals, those of the tartrate being espe- 
cially fine. Solutions prepared from the tartrate 262 
CONIA 
of conia will, no doubt, prove more advantageous 
in all respects. 
Physiological Effects.—The local effects of 
the injection are the same as those of other 
alkaloids. In the largest dose which can be 
safely administered, it induces sleepiness, vertigo, 
coldness of the surface, diminished sensibility, 
and weakness of the inferior extremities. The 
respiration becomes slower and less full. The 
pulse diminishes in number and force, falling so 
much as thirty to forty beats per minute. 
In a case of poisoning carefully observed by 
Hr. Bennett,* weakness of the legs and stagger- 
ing were first noticed. Loss of all power of 
voluntary movement next followed. He became 
unable to swallow, and completely lost his power 
of vision. “ His pulse and breathing were per- 
fectly natural,” but at the expiration of a half- 
hour after this, paralysis of the muscles of respi- 
ration had taken place, the action of the heart 
continuing, but was “very feeble.” Meantime 
his intelligence was preserved, but he was with- 
out power of articulation. 
The mode in which conia produces these effects 
has been elaborately examined by Kolliker and 
Guttman. The last-named observer has shown 
that conia does not act on the spinal cord, nor 
does it destroy the irritability of muscle, but par- 
alyzes the peripheral terminations of the motor 
* Clinical Medicine, p. 413, Am. ed. THERAPY. 
263 
nerves. Death is produced by asphyxia—paral- 
ysis of the muscles of respiration—and not hy 
cessation of the heart’s movements, for these 
continue after respiration has ceased. 
Therapy.—The therapeutical applications of 
conia hy the hypodermatic method are neither 
numerous nor important. 
It has been used in the treatment of asthma by 
Pletzer. Although it appears to be a rational 
remedy, paralyzes the muscles of respiration, and 
in this way may be supposed to antagonize that 
condition of things which exists in asthma, expe- 
rience is not in its favor, and a careful examina- 
tion of its physiological effects discloses the fact 
that the influence which it exerts on respiration 
is a toxic action only. In the treatment of asthma 
it is not at all equal to morphia and atropia; 
nevertheless, in cases in which these agents dis- 
agree, or in which it is undesirable to use them, 
it may he tried. 
Erlenmeyer procured relief, hy the hypoder- 
matic injection of conia, to the difficult breath- 
ing of emphysema. The same authority reports 
having cured a case of angina pectoris by two 
injections of conia. He therefore recommends 
it in these affections. 
Lorent, influenced by theoretical considera- 
tions,—the action of conia on the pulse and 
respiration,—has employed this agent hypoder- 
matically in pneumonia and pleuritis, with the 
effect to reduce decidedly the pulse-rate. It does 264 
CONIA 
not appear that this treatment is worthy of seri- 
ous consideration. In the spasmodic affections 
of the thoracic viscera, Lorent has had expe- 
riences with conia similar to those of Erlen- 
meyer. 
Conia is also one of the numerous remedies 
proposed for the cure of tetanus. Successful cases 
have been reported, cured by conium adminis- 
tered internally; hut we may he permitted to 
distrust these, since Harley has shown that the 
extract is entirely devoid of conia, and therefore 
innocuous. For the treatment of tetanus, the 
hypodermatic injection of conia may he used 
with a reasonable expectation of benefiting the 
patient. 
As conia produces motor paralysis, it has been 
held to be antagonistic to strychnia ; but since it has 
been shown by Guttman that conia paralyzes the 
peripheral terminations of the motor nerves, and 
does not act upon the cord, this view must be 
abandoned. Besides clinical experience is want- 
ing. 
In a careful course of investigation, Burman * 
has studied the combined effects of conia and 
morphia on the condition of mania. He finds 
the combined remedies very useful to allay the 
excitement of acute mania. The indications are 
intense motor activity and wakefulness as con- 
comitants of mania. 
* The West Hiding Lunatic Asylum Eeports, vol. ii. p. 1, etseq. WOORARA OR CURARA. 
The Solution.—The strength of the solution 
usually employed for hypodermatic use is one 
per centum,—one grain to one hundred minims 
of water. The dose is of a grain, or ten 
minims of the solution. The repetition of the 
dose will depend on the effects produced, and on 
the character of the malady for which it is pre- 
scribed. 
The active principle—woorarin or curarin— 
may he employed in place of woorara. In the 
form of sulphate it is readily soluble in water. 
The dose is to grain. The solutions 
should he carefully filtered, especially those of 
the crude drug, as it contains a great many im- 
purities. 
Physiological Actions.—The actions of woo- 
rara have been investigated in the most thorough 
manner by Bernard, Kolliker, Kuhne, and others. 
It is a necessary part of the equipment of a 
physiological laboratory since Bernard* made 
his historical observations on its action. 
Woorara is locally an irritant. If the solu- 
tions are carefully prepared, no little pain and 
* Letjons sur la Physiologie et Pathologie du Systeme Ner- 
veux. Tome i. p. 196. 
265 266 
WOORARA OR CURARA. 
smarting are felt at the point where the injection 
is made,—inflammation follows, an abscess forms, 
and an ulcer remains. This is not an invariable, 
but a very frequent result, and should be men- 
tioned before the injections are practised. 
Applied to the unbroken skin or mucous mem- 
brane no effect follows. Introduced into the 
stomach it rarely produces any toxic symptoms, 
although it is probable slow absorption may take 
place, and ultimately characteristic effects appear. 
Applied to a denuded surface, or subcutaneously, 
diffusion into the blood is rapid. It is a paralyzer 
of the nervous system of animal life. An early 
symptom is disturbance of vision, strabismus, 
double vision, ptosis,—the upper eyelids falling 
well over the eyes. Next, weakness of the lower 
extremities (paresis) comes on, extending ulti- 
mately to all the voluntary muscles. Death 
ensues from paralysis of the respiratory function. 
The paralyzing action of woorara is not in the 
muscles, for they retain their Hallerian irritabil- 
ity, but in the terminations of the nerves in the 
muscles,—the end-organs of the motor nerves. 
It is this complete paralyzing action, involving 
the nerves only, and leaving the muscles intact, 
that renders woorara such an important agent in 
physiological research. 
The careful experiments of Hammond and 
Mitchell* on two varieties of woorara—carroval 
* The American Journal of the Medical Sciences, July, 1859. THERAPY. 
267 
and veto—throw some important light on the 
subject of the action of woorara. The two vari- 
eties were similar in mode and character of ac- 
tion, but differed in power,—vao being much 
feebler. In their experiments, death was caused 
by paralysis of the heart, its muscular tissue 
having lost contractility. 
According to the observations of MM. Yoisin 
and Lionville,* when woorara is injected subcu- 
taneously, a state of shivering and feverishness, 
trembling, a rapid and weak pulse, sweating, 
quickly follow. In a few minutes the paralysis 
begins, and extends to all the voluntary system. 
If pressure by a ligature is made above the point 
wdiere the poison is inserted, its entrance into the 
general mass of the blood is impeded. If artifi- 
cial respiration is maintained in animals, death 
may be averted, even when a lethal dose has 
been given, so rapidly is it eliminated by the 
urine, which, indeed, may be actively poisonous. 
Distinct traces of sugar are also found in the 
urine, whence the condition is entitled “ curara 
diabetes.” f 
Therapy.—When the first publications were 
made, setting forth its peculiar action, very con- 
fident hopes were entertained that a specific for 
tetanus had been discovered. It failed in the 
hands of Follin, Gintrac, Cornoz, and Richard, 
* Archives General de Medecine, Oct. 1866. 
f L. Hermann, Lehrbuch der experimentation Toxicologic. 
Berlin, 1874, p. 305. 268 
WOORARA OR CVRARA. 
and was successful in the hands of Gherini, 
Demme, Lochner, and Spencer Wells.* In most 
of the successful cases it was used endermically 
as well as hypodermatically. Of twelve cases 
treated by the hypodermatic injection, four ter- 
minated favorably. According to the statistics 
of Demme, of twenty-two cases treated by woo- 
rara, administered in either mode, eight recov- 
ered. Prof. Busch treated eleven cases of tetanus 
by woorara, and six recovered; hut, as the profes- 
sor thinks this agent is adapted only to the more 
chronic cases, our estimate of its value must not 
be too high, for chronic cases often terminate in 
recovery under the most diverse methods of treat- 
ment. 
In the successful cases, large doses of woorara 
were administered. Spencer Wells injected one- 
twelfth of a grain at a dose. The dose ranges 
from one-sixtieth to one-thirtieth of a grain. 
The frequency of administration will be governed 
by the effects upon the spasms. 
Woorara has also been used in strychnia-poison- 
ing, hut without sufficient success to justify its 
employment in this class of cases. It does not 
hear the relation of a physiological antagonist to 
strychnia, and hence should not he used against 
the toxic symptoms caused by this agent. 
Although the reports are contradictory in re- 
spect to the utility of woorara in epilepsy, it yet 
* Eulenberg, op. cit. THERAPY. 
269 
deserves a more careful trial than has been 
accorded it hitherto. Kunze * advocates its use, 
and reports that in many cases marked improve- 
ment followed its administration. He practised 
the injections once a week, using two and a half 
grains each time, and this quantity he says pro- 
duces no distinct physiological effects. Of 13 
old epileptics, 3 were cured by this treatment. 
Hr. "Watson f reports a case, which he diagnos- 
ticated hydrophobia, an opinion in which Prof. 
Flint concurred, in which recovery ensued after 
the hypodermatic injection of woorara. The first 
dose was grain, and subsequently 1 grain and 
i grain were injected. The details of the case 
are well and accurately told, and the conclusion 
seems entirely justified. 
Very recently an Italian ease of hydrophobia 
has been reported cured by curara. Injections 
of morphia and inhalations of chloroform had 
been used without success. Then curara was 
used until paralytic symptoms occurred, when it 
was suspended. Then the symptoms of hydro- 
phobia occurring, curara was used again with 
like success.;}: 
* Deutsche Zeitschrift. fur prakt. Med., 1877, No. 1. 
f Am. Jour, of Med. Sciences, July, 1876. 
JLa France Medicale, Aug. 1879, p. 541. From Indipen- 
dente. FTICOTIA. 
THE ALKALOID OE NICOTIANA TABACUM. 
The Solution and Dose.—Erlenmeyer recom- 
mends the following formula; * 
R Nicotise, gr. ss ; 
Aquae destil., spj. M. 
Four drops (minims) of this contain one-sixtieth 
of a grain,—a suitable dose. The official Vinum 
Tahaci may he used as a substitute for the al- 
kaloid. The dose will range from one to five 
minims. 
Physiological Effects.—Mcotia is one of the 
most deadly poisons, ranking in this respect with 
prussic acid. In its local action it is somewhat 
irritant. In its remote or systemic action it 
strongly depresses the nervous and vascular sys- 
tems. At first respiration is slightly accelerated, 
and is accompanied by a bruit, produced, accord- 
ing to Bernard, by a very abrupt contraction of 
the diaphragm. Slowness and feebleness of res- 
piration soon succeed to this acceleration. The 
* Die subcutanen Injectionen, op. cit., p. 85. 
270 THERAPY. 
271 
pupils dilate, and convulsive phenomena make 
their appearance in the eyes and extremities, 
partly of a clonic, and partly of a tonic or tetanic 
character. Complete adynamia supervenes, ac- 
companied by muscular trembling; the action of 
the heart becomes exceedingly feeble, and death 
takes place by failure of the circulation (paralysis 
of the heart).* 
Therapy.—Mcotia has been employed with 
success in the treatment of tetanus. About one- 
half of the traumatic cases treated with it get 
well,—a proportion of recoveries greater than 
with any other remedy except physostigma. 
Prof. Houghton, of Dublin, who was probably 
the first to employ this agent in tetanus, ascer- 
tained experimentally that it is a physiologica. 
antagonist to strychnia. 
iNieotia is indicated in spasmodic asthma, certain 
cases of angina 'pectoris, colic, strangulated hernia, 
etc., but I know of no instance in which it has 
been used for the relief of these conditions. 
Cases of obstinate convulsive tic, “ histrionic 
spasm” and local muscular spasm are of a nature, 
theoretically speaking, to be benefited by the 
subcutaneous injection of nicotia. 
* Gubler, Commentaires du Codex Med., op. cit., p. 347. HYDROCYANIC ACID. 
The Solution and Dose.—The Acidum Hydro- 
cyanicum Dilutum of the IT. S. Pharmacopoeia is 
the preparation which I have employed for hypo- 
dermatic use. The maximum quantity which I 
have used is four minims, hut this amount is 
hardly safe in many cases. It should not he for- 
gotten that the action of hydrocyanic acid is so 
rapid that a toxic dose introduced under the skin 
would infallibly destroy life before any measures 
could be employed for relief. Por ordinary pur- 
poses, two minims of the official solution will 
he sufficient for hypodermatic use. As its effects 
are quickly expended, it may he repeated fre- 
quently,—as often as every two hours. 
Physiological Effects.—Locally, the effects 
are somewhat irritant, but are not more so than 
a solution of morphia. A metallic taste, slight 
salivation, faint nausea, giddiness, and sighing 
respiration are the only systemic effects which 
I have observed from the doses I ventured to 
administer. 
Therapy.—The good effects sometimes pro- 
duced in mental disorders by prussic acid, when 
administered by the stomach, are more conspic- 
272 THERAPY. 
273 
uously exhibited when the remedy is injected 
under the skin.* It is adapted to acute cases, in 
which power is in excess. Cases of mania or 
melancholia, in which the subcutaneous injec- 
tion of morphia proves hurtful, are benefited by 
prussic acid, and vice versa. 
I have used hydrocyanic acid hypodermatically 
in spasmodic asthma, but without moderating 
the paroxysms. It is indicated in angina pectoris, 
and other cardiac neuroses, but I am not aware 
of any instances in which it has been tried. 
As a remedy for gastralgia when a simple neu- 
rosis of the stomach, it is undoubtedly useful. 
In nausea and vomiting due to functional disturb- 
ance, and especially those cases in which morphia 
and atropia disagree, it may be used with a con- 
fident expectation of affording relief. But, as a 
general practice, the subcutaneous injection of 
prussic acid in those stomach disorders is, in re- 
spect to promptness and efficiency, greatly inferior 
to morphia and atropia. 
The injection may be practised over the epigas- 
trium in cases of vomiting. 
W. Preyer,f who has carefully investigated 
the physiological action of prussic acid, affirms 
that atropia is a physiological antidote. His re- 
searches have conducted him to the conclusions 
that prussic acid acts by depriving the blood of 
* McLeod, Medical Times and Gazette, March, 1863. 
f The Practitioner, vol. i. p. 106. 274 
HYDROCYANIC ACID. 
its oxygen, and that in very large doses it para- 
lyzes the heart. He considers atropia the antag- 
onist to this action by maintaining the action of 
the heart. I have carefully repeated the experi- 
ments of Preyer, and am unable to confirm 
them.* I find that animals (cats) fully under the 
influence of atropia are speedily destroyed by 
poisonous doses of prussic acid,—just as speedily, 
indeed, as if atropia had not been administered. 
If administered simultaneously, or atropia soon 
after prussic acid, the result is the same. 
* Prize Essay of American Medical Association, for 1869, 
on Atropia. PHYSOSTIGMA—ESERIYE. 
The Solution.—The extract of physostigma 
was formerly the only preparation available for 
hypodermatic use. Recently the active principle 
—the alkaloid eserine—has been substituted. The 
existence of two alkaloids possessed of different 
properties seems to be established, but that which 
is known as eserine is now universally 
in place of the crude drug and its preparations. 
The muriate or hydrochlorate is the salt generally 
used. 
1J Eserine muriat., gr. iv ; 
Aquas destil., M. 
Sig.—Two minims contain of a grain. 
Eserine is now also added to disks of gelatine 
in proper proportion. One may be dissolved in 
water when required for use. 
The dose of the alkaloid ranges from grain 
to yV grain. 
The extract may also be used hypodermatic- 
ally : it is simply rubbed up with distilled water 
and then filtered. From one-fourth to one-half 
a grain is the ordinary dose of the extract, 
but in tetanus a much larger quantity can be 
injected. It is highly important to obtain a 
275 276 
PHYSOSTIGMA—ESERINE. 
genuine preparation, otherwise disappointment 
must ensue. 
Physiological Effects.—The effects of phy- 
sostigma and eserine are the same in what mode 
soever they may be administered, hut are more 
rapid and pronounced by the subcutaneous areo- 
lar tissue. When a full dose is administered, 
giddiness, a sense of weakness and fatigue, and 
difficulty in maintaining the vertical position and 
in walking are experienced. The action of the 
heart and the arterial tension are lowered for a 
brief period at first, but in a short time the ten- 
sion rises, and the heart-beats become more vig- 
orous. Toxic doses in man cause death by pa- 
ralysis of respiration and of the heart, the whole 
muscular system, including the sphincters, being 
in a state of complete muscular relaxation, but 
the consciousness is preserved until carbonic acid 
poisoning clouds the mind. It is a paralyzer, 
but before complete resolution occurs, the volun- 
tary muscular system is agitated by tremors, 
which consist, in alternate muscular contraction 
and relaxation. The contractility of the muscles 
is not destroyed, nor even impaired.* The pe- 
ripheral nerves (end organs) and the trunks of 
the nerves are not concerned in the paralysis, 
but it is spinal entirely. Physostigma heightens 
rather than impairs the sensibility of the sensory 
* Fraser; from Transactions of the Royal Society of Edin- 
burgh. W. Laschkewich, Yirchow’s Archiv, Band 35, p. 291. THERAPY. 
277 
nerves. After merely lethal doses have been 
administered, the action of the heart continues 
after respiration; but, as already stated, large, 
toxic doses paralyze the heart in the diastole, and 
this organ is found after death flaccid, not at 
all or very feebly responding to galvanic excita- 
tion.* 
Contraction of the pupil is a constant result of 
the action of physostigraa, whether instilled into 
the eye or introduced into the general system. 
This result is doubtless due to paralysis of the 
sympathetic fibres and to stimulation of the third 
nerve. 
As respects the intestinal canal, the effects of 
physostigma are not very distinctive. It in- 
creases secretion somewhat, and therefore the 
number and density of the alvine discharges. 
Therapy.—The applications of physostigma 
in the treatment of disease are directly deduci- 
ble from its physiological action. Its principal 
effect being on the cord, destroying its reflex 
function, obviously it is adapted to the treatment 
of conditions in which the reflex function is ab- 
normally excited, as in tetanus, hydrophobia, strych- 
nia-poisoning, etc. A great many cases of teta- 
nus have been treated, chiefly by the extract, and 
the average proportion of recoveries to death is 
one-half. The result in many more cases would 
* Arnstein u. Sustschinsky, Abstract in Schmidt’s Jahr- 
biicher, vol. cxlii. p. 286. 278 
PH YSOS TIG MA—ESERINE. 
have been favorable if a better mode of admin- 
istration had been followed and a purer drug 
obtained. In tetanus, the ability of the patient 
to swallow and the absorption powers of the 
stomach are alike impaired. Hence the hypo- 
dermatic method should always be adopted in- 
stead of the stomachal. Furthermore, the qual- 
ity of the extract used in many of the cases was 
poor, and the quantity prescribed was too seldom 
governed by the effects produced. Eserine hy- 
podermatically and in quantity sufficient to keep 
the spasms in check, so that the nourishment of 
the patient can be efficiently carried on, is the 
proper mode of treatment. I know of no cases 
of hydrophobia treated by physostigma. 
Although theoretically a very perfect antag- 
onism exists between strychnia and physostigma, 
in actual trial, according to the report of the 
British Association committee, “ although the 
symptoms produced by either substance were 
modified considerably by the action of the other, 
there was no instance of recovery from a fatal 
dose.” 
A very perfect antagonism, through almost the 
whole range of their effects, has been demon- 
strated by Fraser * to exist between atropia and 
physostigma,—only, however, in respect to lethal 
doses, and not to large toxic doses. The com- 
* An Experimental Eesearch on the Antagonism between 
the Actions of Physostigma and Atropia. Edinburgh, 1872. THERAPY. 
279 
mittee above referred to admits tbat this antag- 
onism exists to a “ slight extent,” but is “ more 
limited than even Dr. Fraser has indicated.” 
This committee has also shown that “ chloral 
hydrate modifies to a great extent the action of 
a fatal dose of Calabar bean (physostigma), and 
in some instances saves life from a fatal dose.” 
The use of physostigma in epilepsy and chorea, 
based on theoretical grounds, has not been sat- 
isfactory. In progressive paralysis of the insane 
the results obtained by Browne, although dis- 
credited by Williams, justify further trials by the 
subcutaneous injection of eserine. Agents act- 
ing decidedly as paralyzers of the respiratory 
function, as conium, gelsemium, lobelia, etc,, 
have long been known to act favorably in bron- 
chitis, pulmonary congestion, and pneumonia, and to 
them must now be added physostigma, which is 
reported to have good effects in these diseases. 
Next to the use of eserine in tetanus, its most 
important applications in the treatment of dis- 
ease are in the field of ophthalmic practice. It 
is now largely used to counterbalance the effects 
of atropia on the pupil; in iritis to break away 
or prevent the formation of adhesions; in ulcer- 
ation and suppuration of the cornea; after ex- 
traction of cataract to prevent suppuration, and 
in the operation of iridectomy. The curative 
influence of eserine in these cases is due to its 
action in lowering the intraocular tension, in 
diminishing the conjunctival secretions by con- 280 
PH YSOS TIGMA—ESERINE. 
tracting the blood-vessels, and in checking the 
migration of the white blood-corpuscles.* To 
effect these important purposes, eserine is used 
chiefly hy the subcutaneous areolar tissue. 
* Weeker on Eserine, Pilocarpine, and Atropine in Oph- 
thalmic Diseases, Bull. Gen. Therap. PILOCARPINE. 
Pilocarpine is the active principle of Pilocar- 
pus pinnatus,—a member of the Rutacese,— 
commonly known as Jahorandi. 
The Solution.—The alkaloid is freely soluble 
in water. The nitrate is the salt usually found 
in the market, but the sulphate, acetate, phos- 
phate, chlorhydrate, and bromhydrate have been 
prepared. 
B Pilocarpin. nitratis, gr. xvi; 
Aquse destillat., M. 
Sig.—Five minims contain J of a grain. 
As pilocarpine is expensive, and the solutions 
spoil in a short time, a small quantity may be 
readily prepared, when required, in the propor- 
tions of the above formula. 
The Dose.—Children are proportionally less 
susceptible to the action of pilocarpine than 
adults. Hypodermatically, the dose ranges from 
iof a grain to J grain. Rarely is it necessary to 
exceed of a grain. 
Physiological Effects.—Within a few min- 
utes (2 or 3) after the injection a subjective sense 
of heat, accompanied by a feeling of fulness of 
the head, is experienced, followed speedily by a 
flush extending over the face, forehead, ears, and 282 
PILOCARPINE. 
neck. Simultaneously tke action of the heart 
increases, hut there occurs at the same time a 
general fall of the blood-pressure. The most 
characteristic effect is the increase of the perspi- 
ration and the secretion of the salivary glands. 
As the flushing of the face takes place the sa- 
liva begins to flow plentifully, a profuse perspi- 
ration breaks out over the whole surface of the 
body, the nasal and bronchial mucus and the 
tears are also increased, and sometimes a profuse 
watery diarrhoea occurs. The amount of perspi- 
ration discharged from the skin is enormous, and 
the salivary flow is measured by pints. It some- 
times happens that the amount of saliva is im- 
mense and the perspiration small, and vice versa, 
but usually both secretions are very greatly in- 
creased. A distinct fall of temperature—from 
0.5°-2° Fahr.—takes place when the sweating 
occurs, and is maintained for about four hours. 
Pallor of the face succeeds to the flushing, the 
pulse becomes weak, drowsiness, an extreme 
degree of languor, and chilliness of the surface * 
are experienced. These effects of pilocarpine 
are due to the action of this agent on the vaso- 
motor nervous system.f Paresis of this system 
causes dilatation of the arterioles, increased 
* Albert Robin, Etude Physiologique et Therap. sur la 
Jaborandi. Journ. de Therap. for 7 nos., 1875. 
f Kahler u. Soyka, Kymographische Untersuchungen iiber 
Jaborandi, Cent. f. med. Wissenschaft., 31, 541. PHYSIOLOGICAL EFFECTS. 
283 
afflux of blood to them, whence the flushing and 
the increased action of the heart. The sphygmo- 
graphic and kymographie tracings show a con- 
siderable lowering of the vascular tension, and 
to this diminution of the vaso-motor tonus is the 
increased secretion of saliva and sweat due,—for 
Prevost has demonstrated that ablation of the 
spheno-palatine ganglion is followed by an enor- 
mous effusion from the Schneiderian mucous 
membrane. The reduction of temperature is 
referable to the discharge of fluid from the sali- 
vary glands and skin, the evaporation from the 
surface cooling the adjacent tissues, and a portion 
of the heat of the body converted into another 
mode of motion. 
Pilocarpine contracts the pupil, and the ac- 
commodation is impaired. In the language of 
Mr. Tweedy,* when pilocarpine is instilled into 
the eye it causes “ contraction of the pupil, 
tension of the accommodative apparatus of the 
eye, with approximation to the nearest and 
farthest points of vision, and amblyopic impair- 
ment of vision from diminished sensibility of the 
retina.” 
In consequence of the great loss of fluid by 
the skin the urinary secretion is diminished in 
amount, and, as more or less urea and salts are 
contained in the sweat, the urine is pale and 
watery. The bladder is irritable, and pain is felt 
* Lancet, 11, 1875. 284 
PILOCARPINE. 
along the urethra during the action of the pilo- 
carpine. 
Therapy.—ln mumps and acute affections of 
the parotid, submaxi llary, and sublingual glands, 
and in acute tonsillitis, jaborandi has been used 
with success.* When the metastasis of mumps 
takes place it is said to afford great relief. Ob- 
stinate hiccough, which had resisted ordinary 
means, yielded to pilocarpine hypodermatically. 
Hoarseness (acute catarrh of larynx), bronchitis, 
hronchorrhoea, are cured or relieved by this agent. 
The asthmatic paroxysm has been promptly ar- 
rested by the hypodermatic injection of pilocar- 
pine. The paroxysms of difficult breathing 
accompanying emphysema are often quickly re- 
lieved by the same agent. In cardiac dropsy it 
is often beneficial by removing the surplus fluid. 
It is more especially adapted to the dropsy of 
acute albuminuria, and in the treatment of 
eclampsia, but the warning given us by Barker 
ought to be heeded. In all cases of disease in 
which there is a weak heart, pilocarpine must be 
used with caution, if at all. A further caution is 
necessary in respect to pregnancy, but it is doubt- 
ful if it possesses any real abortifacient property. 
* Besides the references already mentioned, the following 
should be consulted: Einger and Gould, Lancet, 1875; Linger 
and Murrell, Brit. Med. Jour., 1875; Hardy et Eochefon- 
taine, Gaz. Med. de Paris, 25, 1875 ; De I’Action des Alka- 
loidos du Jaborandi sur les Secretions des Glandes ; Carville, 
Ibid., i. p. 9; Eosenbach, Berl. klin. Woch., 23, p. 315. THE RAP ¥. 
285 
It is especially serviceable in the case of effu- 
sion into cavities and to effect the removal of 
recent products of inflammation. The good ef- 
fects are conspicuous in the case of inflammatory 
effusions into the eyes. 
The very important observation has recently 
been made,* that the hypodermatic use of pilo- 
carpine has the power to abort an impending 
ague chill. If given at chill time, just at or near 
the paroxysm, the sweat is induced and no febrile 
stage occurs. It appears further that in a con- 
siderable proportion of cases, the paroxysms are 
suspended permanently. Further experience is 
necessary to determine the actual value of this 
new expedient, but if it accomplish no more than 
abort single paroxysms of ague, it is a valuable 
addition to our resources. If a paroxysm has 
been prevented, but recurrences take place in the 
multiples of the regular periods (so-called sep- 
tenary periods), it seems important to administer 
the pilocarpine in anticipation of, and without 
waiting for, such periods. 
* Medical Record, August 16, 1879. Dr. Caspar Griswold, 
House Physician to Bellevue Hospital. AMYL NITRITE. 
Actions and Uses.—Being an extremely vola- 
tile and diffusible substance, it is difficult to pre- 
serve and use amyl nitrite. When administered 
in vapor by inhalation, the usual mode of giving 
it, the form of perl, or of solution in alcohol, is 
sufficiently convenient. For subcutaneous injec- 
tion the agent itself is used,—from two to five 
drops being given at a time. 
The effects of amyl nitrite, when given by the 
hypodermatic method, are similar to hut less 
rapid than by inhalation. The effects are uni- 
formly the same. Increased action of the heart; 
lowering of the arterial tension; flushing of the 
face; fulness and distention of the head, and 
headache sometimes very violent; singing in the 
ears; vertigo, confusion of mind, and even un- 
consciousness, result from the inhalation of the 
vapor. Whilst these effects occur as the inhala- 
tion is proceeding, when thrown under the skin 
an interval of appreciable duration is observed 
before the action begins. The dilatation of the 
vessels, a result of the paralyzing action exerted 
by amyl nitrite on the vaso-motor system, is the 
central fact of its physiological powers, for on 
286 ACTIONS AND USES. 
287 
this depend all the other phenomena. The ap- 
plications of the remedy are based on this prop- 
erty. Although inhalation is a convenient mode 
of administration, it is not practical when the 
respiration is ceasing. Consequently, the subcu- 
taneous injection of amyl nitrite may be of im- 
mense utility in failure of the heart and of the 
respiration, in cases of angina pectoris, chloroform 
narcosis, surgical shock, cholera asphyxia, and allied 
states. The indication is to take off the vascular 
tension, and the result is the heart is freed from 
restraint. Dr. F. A. Burrall, of Yew York,* 
states that he has “ a record of nine cases, in 
all of which impending death from chloroform 
seems to have been averted by nitrite of amyl” 
administered hypodermatically. 
* The New York Medical Record, March 25,1882, p. 335. CHLOROFORM. 
The injection of chloroform is not practised 
by the ordinary subcutaneous method, for the 
action is local and not systemic. It is not, there- 
fore, adapted to the treatment of internal mala- 
dies, and is only useful in external neuralgise so 
situated that the injected chloroform may act on 
the nerve-trunk or on the peripheral distribu- 
tion of the nerve. I have therefore entitled the 
method the “ Deep Injection of Chloroform,” in 
the articles I have written calling attention to 
the efficiency of this plan in the class of cases to 
which it is adapted.* 
The needle is inserted deeply, in the case of 
the infra-orbital division of the fifth, underneath 
the lip, passing up so that its point is in the 
neighborhood of the nerve at its point of emer- 
gence; in the case of the sciatic, passed down 
near the trunk of the nerve at its exit from the 
pelvis. In the case of any superficial neuralgia 
the same plan is pursued,—the needle inserted 
deeply, so that its point rests in the neighbor- 
hood of the affected nerve. lam the more dis- 
* The Clinic, 1873, vol. v. p. 145; The Practitioner (Lon- 
don), 1874, vol. xiii. p. 9, 
288 PHYSIOLOGICAL EFFECTS. 
289 
posed to reiterate this instruction because it is 
too often supposed that the treatment consists in 
the subcutaneous injection of chloroform. This 
practice was long ago condemned or regarded as 
improper, owing to the violent local inflamma- 
tion which follows its introduction into the sub- 
cutaneous areolar tissue. Thus, Dr. Anstie,* in 
an article on the “Hypodermic Injection of Rem- 
edies,” says of chloroform, that it is “ an agent 
entirely unfit to be used in that way.” Hunter,* 
after some trials with it, had made a similar dec- 
laration : “ The injection of chloroform is not to 
be recommended for the human subject.” This 
remark is all the more noteworthy because Hun- 
ter was one of the earliest and most enthusiastic 
advocates of the hypodermatic method. Eulen- 
bergf simply repeats the remark of Hunter, and 
mentions an experience of Sandras, in which ten 
drops of chloroform were injected. 
Physiological Effects.—The effects produced 
by the injection of chloroform into the areolar 
tissue are these : vaporization of the chloroform, 
and consequent gaseous distention of the sur- 
rounding parts, painful swelling, inflammation, 
and, occasionally, the formation of an abscess. 
The pain experienced by the patient at the mo- 
ment of injection is also considerable, and as the 
needle is withdrawn the chloroform acts ener- 
getically on the wounded skin. These are very 
* Op. cit. f Hypoder. Injectionen, supra. 290 
CHLOROFORM. 
serious and almost insuperable objections to the 
hypodermatic injection of chloroform. They are, 
to a large extent, obviated in the method of deep 
injection. It is true, in the latter method, consid- 
erable pain is felt and swelling arises, but the 
pain soon subsides and the inflammation rarely 
proceeds to suppuration. The pain is felt at the 
moment of injection and for some minutes sub- 
sequently, but this disappears and is succeeded 
by a feeling of numbness and anaesthesia of the 
parts into which the chloroform diffuses. A 
puffy swelling quickly forms at the site of the in- 
jection, and an induration of variable size forms, 
which is afterwards slowly absorbed. The numb- 
ness persists for a week or more. Systemic, or 
rather cerebral, sensations are felt usually only 
when the injection is inserted into the deeper 
parts of the face, and then are very transient, 
consisting only of a little giddiness followed by 
drowsiness. Indeed, the results, so far as sys- 
temic effects are concerned, may be regarded as 
absolutely free from danger. So much swelling 
and induration occurring at the site of an injec- 
tion must occasion apprehension of the formation 
of an abscess. Thus far this untoward result 
has not happened in any of my cases or in any 
of the reported cases, with one exception. This 
was a man suffering from tic douloureux, in whom 
repeated injections were made about the supra- 
and infra-orbital foramina, a locality unsuited for 
repeated injections. PHYSIOLOGICAL EFFECTS. 
291 
To ascertain more satisfactorily than is possi- 
ble from patients the degree of suffering which 
attends the deep injection of chloroform, and the 
extent and duration of the resulting numbness, I 
practised an experiment on myself by injecting 
ten minims of Squibb’s chloroform deeply in the 
calf of the leg. The pain was by no means so 
severe as I had anticipated, and could easily, in- 
deed, be borne. Considerable swelling resulted, 
and an induration as large as a filbert continued 
for two weeks, when it was absorbed entirely. 
Immediately after the injection numbness was 
experienced about the site of the injection; it 
then extended downwards, and on the following 
day had reached the bottom of the foot. A 
space in which the sense of touch and the appre- 
ciation of pain and temperature were decidedly 
diminished existed from the point at which the 
chloroform was inserted to the hollow of the 
foot, although somewhat irregular in shape, at 
least two inches in transverse diameter at any 
point. This condition of altered sensibilit}’ per- 
sisted for several weeks. 
It is obvious, from the foregoing considera- 
tions, that chloroform injected into a part modi- 
fies the conductivity of the nerves. As pain 
means an irritation of a nerve or nerves, the 
perception by the centres of consciousness of this 
impression, and its reference outwardly to the 
peripheral distribution, we may assume, with 
some confidence, that chloroform causes an in- 292 
CHLOROFORM. 
terruption in tlie route or circuit of transmission. 
It has long been known that swelling of a part, 
the seat of a neuralgia, is a signal of the cessation 
of the pain. 
When the chloroform is injected into the deeper 
parts of the face, it comes into relation to vessels 
having an intimate connection with the intra- 
cranial circulation. It is, of course, perfectly 
well known that the facial vein communicates 
with the pterygoid plexus and the cavernous 
sinus. This anatomical fact explains the greater 
cerebral effect of an injection of chloroform in 
the deeper parts of the face as compared with 
the same injection elsewhere. 
Therapy.—Since the publication of my origi- 
nal cases of tic douloureux, various cases of neural- 
gia—of the fifth, cervico-brachial, sciatic—have been 
treated by me successfully by the chloroform in- 
jection. This method is especially adapted to the 
treatment of sciatica. I have had under treatment 
since 1874 twelve cases of sciatica, all of great 
severity and all chronic, in which I used the chlo- 
roform injections, and of these eight were cured, 
two improved, and two received no benefit. Ido 
not include in this summary those cases of sciatica 
which were symptomatic of spinal or cerebral 
disease. Other cases have been reported in this 
country and abroad in which this method suc- 
ceeded after other approved methods had failed.* 
*Dr. de Cerenville, La Tribune Medicale, August 20, 1876; 
Dr. Collins, The Clinic, 1875. THERAPY. 
293 
One of the most remarkable cases demonstrating 
its utility is that reported by Dr. J. B. Matti- 
son,* in which not only was the neuralgia cured, 
but also the opium habit with which it was com- 
plicated. 
Strictly localized spinal pain and coccydinia have 
been cured by me by injecting the chloroform 
deeply near to the point of emergence of the 
sensory branches, or, in case of the pain in the 
coccyx, as deeply as possible about the point of 
greatest pain. 
The official spiritus chloroform!, IT. S. P., has 
been substituted for pure chloroform with good 
results in cases of chronic sciatica coming to the 
Jefferson Medical College clinic. 
* Medical Record, New York, May, 1874. ETHER AKD ALCOHOL. 
Ether has been more or less used, in the past 
few years, subcutaneously, to procure its stimu- 
lant and anodyne effects. In cases of emergency 
various alcoholic liquors have, also, been in- 
jected. A practice has thus grown up which 
must receive some attention. 
Actions and Uses.—When ether is thrown 
under the skin, it causes an emphysematous 
swelling and an intense burning pain, fortunately 
of brief duration. Almost immediately the ef- 
fects are perceived, the pulse becomes stronger 
and fuller, the face flushed, and the skin warm 
and perspiring. In two or three minutes the 
odor of ether is observable in the breath. Ex- 
hilaration, inco-ordination of muscular move- 
ments, and sopor follow in the order named 
when full doses are repeated. The quantity 
given at one time varies from five minims to 
twenty, and as frequently as may be required. 
In cases of sudden depression of the powers 
of life, whiskey and brandy are sometimes in- 
jected subcutaneously. An ordinary syringeful 
—from 20 to 30 minims—may be administered. 
These remedies act similarly to ether, but less ACTIONS AND USES. 
295 
promptly, whilst, at the same time, their effects 
are more sustained. They cause the same local 
distress, and alike increase the organic move- 
ments, especially of the heart. Whiskey and 
brandy are more apt to be followed by local in- 
flammation, abscess, and sloughing than ether. 
An anaesthetic area is usually left about the site 
of the injection. 
In France bromide of ethyl has been proposed 
as a substitute for ether in subcutaneous medi- 
cation, hut it seems to me with doubtful propri- 
ety. Ether has also been used as a substitute 
for chloroform in the cases for which the latter 
has been employed successfully. After the au- 
thor had brought forward and demonstrated the 
utility of chloroform in certain painful states, a 
certain physician, without any reference to the 
remarkable results which had been achieved by 
chloroform, published some observations on the 
use of ether in the same group of cases, as if his 
idea and practice were novel! In the treatment 
of sciatica and other painful affections ether is less 
efficient and more painful than chloroform. 
Dr. Barth has employed subcutaneous injec- 
tions of ether in 'pneumonia with striking results. 
Of 14 cases of severe and adynamic pneumonia 
and broncho-pneumonia treated by the ether 
injections, there were 11 cures and 3 deaths.* 
* Gaz. Hebdom. de Med. et de Chirurg., Nos. 50, 51, and 
62, 1881. 296 
ETHER AND ALCOHOL. 
Very soon after the injection is practised, a grate- 
ful sense of stimulation is experienced, the res- 
pirations grow more easy, the pulse becomes 
fuller and stronger, the face gains in color, and 
the tongue moistens. The amount required at 
each injection is about 15 minims, and the num- 
ber of injections from two to four a day, accord- 
ing to the amount of depression present in each 
case. The same method has been pursued in the 
treatment of variola, by M. du Castel. It is prob- 
able that in various maladies characterized by 
sudden and profound depression of the powers 
of life the hypodermatic injection of ether will 
prove a valuable resource. Chloroform narcosis 
is, however, a condition which will he intensified, 
by ether injections, and also by injections of al- 
coholic liquids. The depression caused by the 
bites of venomous snakes, surgical shock, cholera Asi- 
atica and cholera morbus, the passage of biliary or 
renal calculi, the action of arterial sedatives, as ac- 
onite, veratrum viride, etc., and cardiac failure from 
hemorrhage are alike conditions in which the 
prompt action of ether may be a most precious 
resource. 
If it is necessary to give repeated injections, 
the administration should not be practised at the 
same site even twice, but should be at distant 
points. 
Whiskey and brandy are given subcutaneously 
when the patient is unable to swallow the stimu- 
lant, or the urgency will not admit of the delay ACTIONS AND USES. 
297 
necessary for absorption by the stomach. The 
depression caused by hemorrhage is the particu- 
lar state justifying this practice. I must reiterate 
the injunction against the use of alcoholic stimu- 
lants in chloroform narcosis. When the stimu- 
lant action of alcohol is desired, it must be given 
in small doses. CHLORAL HYDRATE, AND CHLORAL 
AND MORPHIA. 
The Solution.—Crystallized chloral only is 
suitable for the preparation of solutions for hy- 
podermatic use. A saturated solution in water 
contains 50 per centum of chloral. Although this 
is rather irritating to the tissues, a weak solution 
may he more objectionable, as two punctures 
will be necessary to introduce the required 
amount. 
R Chloral, hydratis, gss; 
Aquae destil., %i. M. 
Sig.—Thirty minims contain 15 grains of chloral. 
The Dose.—Chloral diffuses into the blood 
more rapidly from the subcutaneous areolar tis- 
sue than from the stomach. Under ordinary 
circumstances, ten grains will be a sufficient 
quantity for an adult; but special conditions 
may require more. 
Physiological Effects.—Very great pain and 
smarting are felt at the point of puncture, and it 
persists, unfortunately, for a half-hour or longer. 
Considerable swelling, an erythematous blush, 
and urticaria-like eruption take place about the 
puncture. A hard nodule, very prone to suppu- 
298 PHYSIOLOGICAL EFFECTS. 
299 
rate, usually forms. Especial pains are necessary 
to avoid penetrating a vein, for, although Ore 
has proposed the operation of intra-venous injec- 
tion for the purpose of inducing anaesthesia, the 
direct admission of chloral to a vein is consid- 
ered so hazardous that the proposed expedient is 
almost universally condemned. The production 
of sleep is the result of the chloral injection, and 
this follows promptly, usually without any dis- 
turbance of function. In some subjects, how- 
ever, just as when taken into the stomach, a 
period of excitement, with headache, precedes 
sleep, or, it may be, prevents it altogether. If 
the dose be sufficient, sleep is very sure to follow, 
and the drowsiness comes on within live minutes 
after the injection is practised. The sleep of 
chloral is very like that of natural sleep, and 
there are no after-disturbances,—no headache, 
nausea, nor constipation. 
Administered subcutaneously, chloral possesses 
distinct pain-relieving power, differing in this 
respect from the effects of its stomach absorp- 
tion. 
A weak heart, especially a fatty heart, is an 
important contraindication to the hypodermatic 
injection of chloral, still more than to its admin- 
istration by the stomach. Numerous deaths have 
resulted from its incautious use in cases of weak 
heart when taken by the stomach ; the danger is 
greater, of course, when it is thrown under the 
skin. 300 
CHLORAL HYDRATE. 
Therapy.—So unpleasant is the local action of 
chloral that its use by the hypodermatic injec- 
tion is restricted, usually, to cases in which the 
stomachal administration is prevented by the 
condition of that organ, or by the inability or 
the unwillingness of the patient to swallow. 
Vomiting, not controlled by the ordinary means, 
may sometimes, frequently indeed, be arrested by 
the injection of five to ten grains of chloral in 
the epigastric region. Obstinate hiccough, not 
amenable to the usual treatment, may also be 
stopped in the same way. In violent cholera mor- 
bus and in true cholera excellent results are ob- 
tained from the chloral treatment, better, in the 
author’s experience, than from any other treat- 
ment. In the cholera epidemic at Riga in 1871, 
the injections were remarkably successful.* Sim- 
ilar successes attended the practice of Mr. Hall, 
an English army surgeon, at Kheri, Oudh, India,f 
of Hepven,J and others. During a short epidemic 
of cholera in Cincinnati in 1873, I had the most 
convincing proofs of its efficiency. When the 
cramps are severe and the algid state well ad- 
vanced, very considerable doses must be used. 
In one very formidable case, in which there 
seemed but little hope, sixty grains were admin- 
istered hypodermatically in two hours, with the 
* O. Liebreich, Berliner klinische Wochenschrift, 1871, p. 
408. Letter from Dr. y. Keichard. 
f The Practitioner, July, 1875. 
J Gaz. Med. de Paris, September 13, 1873. THERAPY. 
301 
effect to stop the cramps, restore warmth, and to 
remove, indeed, all unfavorable symptoms. 
In asthma decided relief is produced hy the 
injection of chloral. Other neuroses of the chest 
organs are equally benefited; hut the utmost 
circumspection is needed lest a fatal result fol- 
low, by paralysis of a weak heart. 
The hypodermatic injection of chloral is indi- 
cated and may he employed in all cerebral disor- 
ders in which chloral is so much prescribed by 
the stomach: to procure sleep, to allay the ex- 
citement of mania, and to prevent convulsive 
attacks. The remedy is employed in this group 
of cases hypoderraatically, when the patient can- 
not or will not swallow it in the usual way. In 
superficial neuralgice the local use of chloral may 
he substituted for the deep injection of chloro- 
form. 
Chloral and Morphia.—ln most of the cases for 
which chloral is directed in the preceding para- 
graphs the combination with morphia is to he 
preferred, generally speaking, to the chloral 
alone. As is perfectly well known, the pain- 
relieving power of chloral is greatly inferior to 
that possessed by morphia. A combination of 
the two makes an anodyne and hypnotic of the 
highest order of excellence; that which is want- 
ing in one is supplied hy the other, and in re- 
spect to their special properties each adds to the 
power of the other. In a paper read before the 
Hew York Neurological Society, I showed that 302 
CHLORAL AND MORPHIA. 
whilst morphia increased the physiological effects 
of chloral in all other respects, it prevented the 
depression of the heart’s action caused by the 
latter, and thus obviated the chief danger from 
its administration. The combination is ren- 
dered still more efficient by the addition of atro- 
pia. The following formulae are intended to 
illustrate and embody the above principles, and 
may be employed for the hypodermatic injection 
of these remedies: 
B Chloral hydrat., sjiij ; 
Morphia sulph., gr. iv ; 
Aquae destil., gi. M. 
Sig.—Twenty minims contain 7J grains of chloral and £ 
grain of morphia. 
B Chloral hydrat., giij ; 
Morphias sulph., gr. iv ; 
Atropiae sulph., gr. ; 
Aquae destil., gi. M. 
Sig.—Twenty minims contain grains of chloral, £ grain 
of morphia, and grain of atropia. CAFFEIK 
The Solution.—The preparation now used is 
the citrate, and as it is soluble in water, can he 
dissolved in that menstruum for hypodermatic 
use. 
R Caffeine citratis, gr. xxiv ; 
Sig.—Twenty minims contain 1 grain. 
Aquaj, 51. M. 
The Dose will range from ten to twenty min- 
ims of the above solution, or from one-half to 
one grain. 
Physiological Effects.—The local effects are 
similar to those produced by other alkaloids. 
Slight drowsiness is an immediate effect, hut this 
is quickly followed by stimulation of the brain 
and the other animal functions. In very large 
doses it produces decided excitement of the ner- 
vous and vascular systems, violent palpitation of 
the heart, with frequency, irregularity, and some- 
times intermittence of the pulse, oppression and 
pain in the head, disorders of the senses, ring- 
ing in the ears, flashes of light before the eyes, 
priapism, and delirium. 
Therapy.—Caffein has been used hypodermat- 304 
CAFFE IN. 
ically for the relief of neuralgia. Eulenberg 
found it useful in a case of occipital neuralgia. 
Dr. Anstie says with regard to it: “In one case 
of severe neuralgia of the superficial branches 
of the circumflex in the shoulder, two successive 
injections of caffein (over the biceps) appeared to 
cut short the malady altogether. In a case of 
dorso-costal neuralgia, attending shingles, the 
patient was injected daily, for five or six days, 
with the effect of notably mitigating the pain on 
each occasion.” Lorent used the hypodermatic 
injection of caffein in hysterical headache and mi- 
graine. Dr. Anstie relieved by it the insomnia 
attendant upon chronic alcoholism without delir- 
ium. In these affections, as Anstie suggests, caf- 
fein will probably be found a valuable remedy. 
Caffein is indicated in simple melancholy, in 
hysterical paroxysms, in certain cases of delirium 
tremens; but our knowledge is not yet sufficient 
to pronounce positively on these points. It has 
also been used with success against opium narco- 
sis; in this state it is certainly inferior to atropia, 
yet, as there is no therapeutical incompatibility, 
these agents may be used simultaneously in the 
same case. APOMORPHIA. 
—becoming greenish and unfit for use,—it should 
be kept in powder and the solution made when 
required. The dose for an adult by the subcuta- 
neous areolar tissue is y1 grain, and for children a 
proportional amount. As very serious symptoms 
have been produced by full doses, it is necessary to 
be circumspect, especially in the case of children. 
As a solution of apomorpliia rapidly changes, 
Physiological Effects.—ln a few minutes 
after the injection is made some nausea, giddi- 
ness, and headache are experienced, and vomiting 
occurs abruptly and thoroughly in from five to 
twenty minutes. At the first effort the stomach 
is well emptied; but the vomiting recurs a few 
times at intervals of a quarter to a half hour. 
Such is the ordinary course of action of a suffi- 
cient but still small dose. If a full dose is given 
by the subcutaneous areolar tissue, there occur 
headache, vertigo, nausea, a cold sweat, a quick, 
small, feeble pulse, depression and drowsiness, 
and profuse vomiting, followed by prolonged 
sleep. 
A very alarming condition of depression—a 
state of collapse, indeed—has been caused in 306 
A POM OR PHI A. 
children and inebriates by the hypodermatic 
injection of a full dose. Toxic doses in animals 
cause at first great excitement, vomiting, fol- 
lowed by muscular trembling, paralysis, and 
convulsions.* It does not seem to affect the 
blood-pressure,f nor the motor and sensory 
nerves; the respirations at first greatly increase 
in number, but ultimately become more shallow 
and infrequent, death occurring from paralysis 
of the respiratory function. J 
Therapy.—The use of apomorphia hypoder- 
matically is confined to the production of vomit- 
lt is the most useful of all the emetics for 
narcotic poisoning. The evidence is convincing 
that profound insensibility hinders the emetic 
action, but an increase of the dose suffices to 
overcome this. If then in the treatment of poi- 
soning by narcotic substances the usual dose 
does not have the desired effect, it must be re- 
peated until vomiting does occur. It is highly 
probable that very much larger doses can, be 
administered in the condition of insensibility 
from poisons than in ordinary cases of disease. 
It is extremely questionable to employ apomor- 
* E. Harnack, Archiv f. exp. Path. u. Pharmacologie, vol. 
ii. p. 291. 
f Dr. Vincent Siebert, Untersuchungen iiber Apomorphia. 
Abstract in Schmidt’s Jahrbiicher, vol. civ. p. 14, et seq. 
J Harnack, supra. 
$ Gee, Note on Apomorphia, etc., St. Bartholomew’s Hos- 
pital Reports, vol. v., 1869. THERAPY. 
307 
phia in opium-poisoning, since this agent has an 
effect on the cerebrum, and causes death by 
paralysis of respiration. If the patient is too 
profoundly narcotized for the action of emetics, 
the stomach-pump is an available and effective 
resource, and should unquestionably he preferred 
to the subcutaneous use of apomorphia. 
In capillary bronchitis, to free the tubes of their 
contents, and in croup, to dislodge the false mem- 
brane, apomorphia is used to obtain the mechan- 
ical effect of powerful emesis. In common with 
other emetics it is supposed to possess expec- 
torant properties, hut it is never used hypoder- 
matically for this purpose. ERGOTIK 
The Solution.—The Ergotin, so called, em- 
ployed in medical practice is not the supposed 
active principle, hut an aqueous extract. Per- 
fectly good ergotin is now to be obtained from 
various manufacturers, but the aqueous extract 
prepared by Squibb, of Brooklyn, for hypoder- 
matic injection is an excellent preparation,—the 
best, doubtless, to be obtained at present. This 
“ extract of ergot is almost entirely soluble in 
cold water, and represents good rye ergot in the 
proportion of one grain of extract for five grains 
of ergot. Sixty grains of this extract dissolved 
in two hundred and fifty minims of water—the 
solution filtered and made up to three hundred 
minims by passing water through the filter to 
wash it and the residue upon it—makes a solu- 
tion which represents ergot in the proportion of 
minim for grain, and is of the same strength as 
the fluid extract of ergot, but is free from alcohol 
or other irritant substance.” Such are Squibb’s 
instructions for the preparation of a solution. A 
much more concentrated solution can be prepared 
from Squibb’s extract, wdiich is soluble in water 
in the proportion of grain to minim, by simply THE SOLUTION. 
309 
rubbing up the extract witb distilled water until 
saturated,—then filter. Of this solution, so pre- 
pared, from five to fifteen minims may be injected, 
—the largest quantity in cases of great urgency 
and danger. The following formula may be used 
as a guide in the preparation of a solution: 
R Ergotin (aq. ex.), £ij ; 
Aquae destil., 
M. Filter. 
Sig.—From five to twenty minims at each injection. 
Dragendorff and Podwissotzky propose their 
newly-discovered sclerotinic acid, in aqueous so- 
lution, for hypodermatic injection, but at present 
this substance is too difficult to procure and too 
expensive to be used. Furthermore, the conclu- 
sions of these experimental physiologists are not 
yet well established in professional opinion, and 
may prove to be erroneous; nevertheless they 
assert with confidence that “ the special, active 
substances in ergot are sclerotinic acid and scle- 
romucin.” * 
As solutions of ergotin undergo important 
changes in a short time, it is desirable to pre- 
vent them, if this result can be accomplished 
without impairing the quality of the material. 
The addition of one per cent, of carbolic acid 
* Archiv fur experimen. Pathologic u. Pharmakologie, vol. 
vi. p. 153. Ueber die wirksamen und einige andere Bestand- 
theile des Mutterkornes. 310 
ERGOTIN. 
will prevent any change for several months, and 
this rather increases than lessens the therapeu- 
tical power of the solution. 
Physiological Effects.—Considerable pain, 
lasting for several minutes, attends the injec- 
tion, and a tumefaction, subsequently sometimes 
hardening into a firm nodule, forms at the site 
of the puncture. It is rare, however, for sup- 
puration to occur, if proper care is exercised 
in the preparation of the solution, and in in- 
jecting. 
If a moderate dose is injected, there may he 
no symptoms whatever produced. Frontal head- 
ache, transient giddiness, more or less dilated 
pupils, are produced by full doses in from fifteen 
minutes to a half-hour. In a somewhat longer 
time,—an hour or two after the injection,—some- 
times quite severe rhythmical pains come on, 
referrible to the region of the uterus, and un- 
doubtedly uterine in seat. Women experienced 
in the sensation, spontaneously, liken the pains 
to those of the first stage of labor. In a case of 
uterine fibroid expelled from the cavity by the 
action of ergotin hypodermatically used, severe 
rhythmical pain always came on in a half-hour 
after the injection. That these pains are uterine 
seems highly probable, not only in respect to the 
examples cited above, hut because of the unques- 
tionable action of ergot on the parturient uterus. 
The cases are parallel, for when subinvolution 
exists, or when a fibroid is contained in the PHYSIOLOGICAL EFFECTS. 
311 
uterine cavity, the muscular development of the 
organ is sufficient to permit the action of ergotin 
to take place. On the other hand, ergot un- 
questionably affects the muscular fibre of the 
intestine, hut in the examples of pain above re- 
ferred to there was no increased intestinal action. 
When considerable daily doses of ergotin are 
injected, the patients complain of a sense of 
pressure, with pain and numbness in the museles 
of the thighs and legs. They also complain of 
fatigue on slight exertion, of a sense of coldness 
of the limbs at night, especially, and muscular 
cramps of varying severity and persistence. The 
bladder, too, or, rather, the sphincter, is kept in 
a state of spasm when daily doses are adminis- 
tered, so that micturition becomes slow, difficult, 
or impossible, the catheter becoming necessary 
in rare instances. 
The actions of ergot have been studied by 
many observers, and their reported observations 
differ widely, and are often, indeed, diametri- 
cally opposed. Faulty methods are frequently 
responsible for discordant and contradictory 
views. Thus, attempts have been made to ar- 
rive at a knowledge of the influence of ergot on 
the blood-pressure by injecting a quantity of the 
infusion or fluid extract into the jugular vein. 
We are told, with a remarkable naivete, that 
under these circumstances the blood-pressure at 
first falls and then rises remarkably. Prof. 
Wood confirms what Dr. Holmes has asserted 312 
ERGO TIN. 
with regard to this experiment. Brown-Sequard 
long ago demonstrated that ergot had the power 
to contract the vessels, and this fact has since 
been confirmed by a number of observers at dif- 
ferent periods,* and he also asserts that which in 
itself has a high degree of probability, that the 
vaso-motor spasm which first comes on is fol- 
lowed by vaso-motor paralysis. The results of 
the very numerous experiments made are nearly 
uniform in proving that ergotin causes a rise in 
the blood-pressure, a necessary sequence of the 
contraction of the arterioles. The particular 
constituents of ergotin effecting this result have 
been ascertained by recent investigations. Koh- 
ler devoted himself especially to determine the 
physiological effects of the “ Ergotin” of Bon- 
jean, and of the “ Ergotin” of Wiggers,—the 
former being an aqueous extract merely, and the 
latter a conjectural active principle. His re- 
searches proved that the former possessed the 
properties belonging to ergot, the latter exhib- 
* Among those who have demonstrated the narrowing of 
the vessels caused by ergotin are the following : Dr. H. Koeh- 
ler. Yergleichend-experirnentelle Untersuchungen iiber die 
physiologischen Wirkungen des Ergotin Bonjean und des 
Ergotin Wiggers. Virchow’s Archiv, vol. lx. p. 381. M. 
Laborde, Gazette des Hopitaux, March 10,1877. Dr. A. Wer- 
nich, Beitrag zur Kenntniss der Ergotinwirkungen. Vir- 
chow’s Archiv, vol. Ivi. p. 505. This research was in part 
determined by some experiments of Handelin, made under 
the direction of Schmiedeherg,—these experiments having 
shown that ergotin causes the blood-pressure to fall. PHYSIOLOGICAL EFFECTS. 
ited powers of a different kind. The most re- 
cent and valuable contribution to our knowledge 
of this subject is the research of Podwissotzky 
on sclerotinic acid, a new product of ergot, a 
knowledge of which we owe—as has been shown 
—to Dragendorff and Podwissotzky.* These 
experiments have demonstrated (apparently) that 
this new substance is the true active principle, as 
the discoverers had previously affirmed. Sclero- 
tinic acid is tasteless, odorless, freely soluble in 
water, and without any irritating effect on the 
tissues when injected, so that it is perfectly 
adapted for hypodermatic use. It is much to be 
desired that it shall prove to be all that its dis- 
coverers claim for it. 
It is said that sclerotinic acid has been largely 
used in Germany by Prof. Von Holst, in solution 
in water, the dose being one-half to three-quar- 
ters of a grain hypodermatically. This substance 
appears to possess a high degree of activity. 
Ergot exerts an influence on the heart in ac- 
cordance with that on the arterioles,—it dimin- 
ishes the number and lessens the power of the 
heart-beats. A toxic dose arrests the heart in 
the diastole, not by reason of a poisonous action 
on the cardiac muscle, but through the agency 
of the pneumogastric nerves, for when these 
nerves are divided the heart is not arrested by 
* St. Petersburger med. Wochensclirift, Aug. 27 and Sept. 
8, 1876. 314 
ERGO TIN. 
the same or a larger toxic dose.* Paralysis not 
due to an action on the motor nerves or on the 
muscles, and therefore centric in origin, is a result 
of the poisonous action of ergot on the lower ani- 
mals, Convulsions are also produced by it. An 
explanation of these symptoms is afforded in the 
extreme cerebral anaemia induced in animals by 
the large quantity of the drug administered. 
The following is a summary of the symptoms 
of acute ergotism in man: nausea, vomiting, ab- 
dominal pain, dryness of the throat, thirst, an- 
orexia, itching of the extremities, numbness, 
lassitude, vertigo, dilatation of the pupils, drow- 
siness, delirium, and stupor, diminution of the 
force and frequency of the pulse (rarely the op- 
posite state), with tendency to syncope, pallor 
and lividity of the face, etc. 
Chronic ergotism, witnessed occasionally on a 
large scale by reason of the consumption of dis- 
eased lye as food, exists in two forms,—convulsive 
and gangrenous. Generally the convulsive form 
begins by vertigo, disorders of vision, tinnitus 
aurium, numbness of the fingers and toes, and 
afterwards of the whole integument. Tetanoid 
cramps follow,—of the fingers, of the forearms, 
on the arms, and of the arms against the chest; 
of the toes, on the palmar surface of the foot; 
of the leg, on the thigh. The muscles of the 
* Eberty, Abstract in Schmidt’s Jahrbiicber, vol. clviii. 
p. 120. PHYSIOLOGICAL EFFECTS. 
315 
thorax, abdomen, and diaphragm are also at- 
tacked, making respiration difficult and painful, 
and inducing attacks like asthma. Cramps of 
the same character attack the intestine,—the 
muscular layer,—and pains like colic and diar- 
rhoea ensue, hut the appetite continues ravenous. 
Usually, or at least frequently, the uterus be- 
comes affected, expulsive pains come on, and 
abortion takes place. The action of the heart is 
weak and slow, the pulse feeble, the surface cold. 
At first the spasms are occasional, but they be- 
come more frequent, ultimately continuous, re- 
sulting in opisthotonos or emprosthotonos. Com- 
plete anaesthesia of the whole surface succeeds 
to the tetanoid attacks, and gangrene in spots of 
small extent may occur. The organs of sense 
lose their power to react to their physiological 
stimuli, and taste, hearing, and smell are abol- 
ished. The pupils are dilated, sometimes un- 
equal, and various disturbances of vision ensue. 
Epileptiform attacks may occur as well as the 
spasms; delirium sets in, and the poor victim 
passes into a state of complete insensibility. 
The convulsive and gangrenous forms, al- 
though clinically separable, are not pathologi- 
cally very different. The gangrenous form sets 
in by tingling, numbness, formication, an insup- 
portable sense of fatigue in the members, an 
earthy hue of the skin, coldness of the surface; 
nausea, vomiting, and diarrhoea then occur; 
muscular contractions take place; an eruption of 316 
ERGOTIN. 
vesicles filled with a dark ichorous fluid appears 
on one or more extremities; and gangrene, dry 
or moist, quickly destroys the toes, the legs, the 
nose, or other parts. Doubtless, not unfrequently, 
owing to the contraction of the arterioles in front, 
a weak heart behind, and blood containing a 
great excess of fibrin, sudden coagulation of the 
blood in a large vessel takes place, and gangrene 
of a member is the result. These are the factors 
probably concerned in the formation of gangren- 
ous spots of greater or less size. 
To enter so largely in the consideration of 
these topics may seem an unnecessary elabora- 
tion, but at the present time so freely is ergotin 
used, and in such large doses, that any details in 
regard to the results of its administration should 
not be omitted. 
Therapy.—The therapeutical uses of ergot are 
based on the modern conception of its physiolog- 
ical actions. 
One of the most effective remedies against 
hemorrhage in any situation not remediable by 
surgical means is the hypodermatic injection of 
ergotin. Originally used against uterine hemor- 
rhages, it has become generalized in its applica- 
tion to the treatment of hemorrhage in general. 
Not to enter into tedious details, it will suffice to 
state that the hypodermatic injection is the most 
effective way of treating all cases of uterine 
hemorrhage to which ergot is adapted. 
Subinvolution of the uterus, a state of things fruit- THERAPY. 
317 
ful of mischief, is most effectively treated by a 
daily hypodermatic injection of ergotin.* The 
same treatment used persistently, about twice a 
week, will cure the so-called chronic metritis. Lo- 
cal thickening and hypertrophy of the uterine wall 
just developing into, or well-formed, intra-mural 
fibroids can he cured in a large proportion, and 
are being cured since the beneficent discovery of 
Hildebrandt f was announced. The relative pro- 
portion of cures to cases cannot be stated in 
numbers, notwithstanding the enormous experi- 
ence now accumulated. Selecting out of a mass 
of reports, probably no better or more accurate 
can be found than that of Prof. Byford, of Chi- 
cago. Of his group of 101 cases, 22 were cured, 
and all the rest, except 21, were more or less 
ameliorated. Various modes of introducing the 
agent were employed, and probably not all were 
treated by the best method, or by ergotin of the 
best quality. Besides the arrest or diminution 
in the growth, it is, as Prof. Hildebrandt re- 
marks, “ of great significance that those distress- 
ing symptoms, the profuse hemorrhages, the 
debilitating serous discharges, and the harassing 
pains, totally disappear.” 
Hypodermatic injections of ergotin are also 
used to effect the expulsion of polypi from the 
* Keating, Amer. Journal of Med. Science, July, 1873. 
| Berliner klinisclie Wochensclirift, June 17, 1872. 318 
ERGO TIN. 
uterine cavity. The hydatid mole may be most 
effectively expelled by the same agent. 
Hypertrophied prostate, as Prof. Langenbeck has 
shown, may be reduced in size by the subcuta- 
neous injection of ergotin. I have succeeded 
better, I think, by injecting the lobes of the 
prostate through the rectum, an expedient which 
is easily practised. A bivalve rectal speculum 
must be first introduced ; then vessels felt for, 
and the point for puncture selected, when the 
needle may be introduced and some five minims 
inserted. The utmost care must be exercised 
in regard to each detail, for inflammation and 
suppuration of the prostate would be a serious 
addition to the sufferings and hazards of the 
case. Hemorrhoids that are recent, not previ- 
ously inflamed, and bleeding in consequence of 
increase of pressure in the portal system, can be 
relieved greatly by ergotin injections. 
Varicocele, if not too far advanced in respect to 
the size of the vessels and atrophy of the testis, 
may be cured by the injection of ergotin. The 
needle must be inserted between the vessels, and 
entrance into a vein avoided,—a fact which must 
be ascertained with absolute certainty,—and the 
fluid must be sufficient in amount to diffuse 
among the vessels. Great pain attends the oper- 
ation, so great that the patient may faint or suf- 
fer considerable shock, and there will be subse- 
quently a good deal of inflammation and swelling, 
with the usual concomitants of feverishness and THERAPY. 
319 
pain. An injection of ergotin on the dorsum of 
the penis in the neighborhood of the dorsal vein 
is an efficient expedient to promote the vigor of 
the erections when they are not well maintained. 
Injections in the perineum once a week is an 
excellent remedy in cases of spermatorrhoea with 
feeble erections and a discharge of mucus from 
the urethra. 
Probably the most efficient means we now 
possess for the arrest of haemoptysis is the hypo- 
dermatic injection of ergotin. It acts promptly, 
and does not interfere with the simultaneous use 
of other means of treatment, hut the injection is 
usually sufficient of itself. Numerous cases of 
haemoptysis have been reported in the treatment 
of which ergot was the principal or only agent 
employed, hut the most careful recorded and in- 
structive series of cases which have come under 
my observation are those of Dr. Anstie.* His 
conclusions are as follows : 
“We have now established the facts (a) of the 
direct action of ergot in the cases which I have 
recorded; (6) of its superiority in several of these 
cases to other styptics that had been tried; (c) 
the probability, from physiological analogies, that 
ergot would act more universally as a checker of 
haemoptysis than the routine remedies with which 
we are familiar; (d) also, that it is perfectly safe 
for the purpose in view, and in this respect is 
* The Practitioner (London), vol. x. p. 279 320 
ERGO TIN. 
superior to digitalis, which otherwise resembles 
it a good deal.” These good effects were ob- 
tained by the stomachal administration, hut Dr. 
Anstie makes a remark which has been abun- 
dantly confirmed since,—“ For getting the best 
results, I can scarcely doubt that the hypoder- 
mic injection of ergotin is a decidedly superior 
method.” 
Scarcely less important than Hildehrandt’s dis- 
covery of the value of ergotin in uterine fibroids 
is the observation of Langenbeck with cases 
showing the curative power of the ergotin injec- 
tions in aneurism.* Soon after the cases of Lan- 
genheck were reported, Plagge,f of Darmstadt, 
published a case of traumatic popliteal aneurism, 
in which the ergotin injections were signally ben- 
eficial. In a case of femoral aneurism, Schnei- 
der has succeeded by the ergotin injections, and 
Dutoit in one of the subclavian.J I have myself 
seen remarkable diminution in size and great 
improvement in condition in a case of aneurism 
at the transverse arch of the aorta, death being 
due to other causes entirely. After death the 
walls of the aneurism were very thick and firm 
by deposition of successive layers of fibrin, and 
rupture was not possible. In Langcnheck’s and 
* Berliner klinische Wochenschrift, No. 2, 1869. 
f Betz’s Memorahilien. Quoted in London Medical Record, 
vol. ii. p. 87. 
| Berliner klinische Wochenschrift, 1872, p. 115. Quoted 
from Langenheck’s Archiv, Band xii. THERAPY. 
321 
other successful cases the aneurisms treated were 
on superficial arteries, except that of Dutoit. It 
has heen asserted that these injections are idle in 
the case of aneurism of the aorta, since this vessel 
possesses hut rudimentary elements of the or- 
ganic muscular fibre to he acted on by such an 
agent as ergot. Such critics overlook the fact 
that ergot, by slowing the heart and raising the 
tension at the periphery by contracting the arte- 
rioles, offers the most suitable conditions for se- 
curing the coagulation of blood in the aneurismal 
sac. 
In varicose veins, Yoit * has proposed and has 
used successfully injections of ergotin in the im- 
mediate neighborhood of the diseased vessels. 
Enlarged spleen has been cured by the injection 
practised at any indifferent point,f but preferably 
under the integument of the abdomen. 
The disease leukaemia, which is closely con- 
nected pathologically with a condition of the 
spleen, has been cured by Dr. Da Costa, and ex- 
ophthalmic goitre benefited by the same treatment. 
Brown-Sequard was undoubtedly the first to 
use ergot systematically, and from the stand- 
point of a correct appreciation of the nature of 
its action, in disease of the brain and nervous 
system. It has heen used with advantage, hypo- 
* Berliner klinische 'Wochenschrift, supra. 
f Dr. Miller, N. Y. Med. Kec., April 15, 1876, and Dr. Da 
Costa, who was the first, in Amer, Jour. Med. Sci., Jan. 1875. 322 
ERGOTIN. 
dermatically, in the treatment of the acute affec- 
tions of the meninges of the brain and spinal cord, 
and in cerebrospinal meningitis. It is highly ser- 
viceable in these affections if used at the proper 
time—during the stage of excitation—and before 
depression comes on, when it is harmful. It 
ought to be serviceable in those cases of cerebral 
hemorrhage in which the escape of blood occurs 
slowly and there is a gradually deepening coma. 
In the congestive form of migraine—flushed 
face, injected conjunctive, quick pulse, severe 
pain, coincident with each arterial pulse—the hy- 
podermatic injection of ergotin is highly useful, 
and often affords immediate relief. In ordinary 
headaches of the congestive variety, but not in 
the headaches of anemia, it is equally efficient 
and curative. The most ardent and comprehen- 
sive advocate for the use of the subcutaneous 
injection of ergot is Dr. Marino,* who finds it 
superior to all remedies in sunstroke, tic douloureux, 
and hemicrania. In sciatica, the results of its use 
are sometimes “brilliant/’ but it often fails with- 
out apparent cause. 
* Quoted in London Medical llecord, vol. v. p. 456. QUINTA. 
The Solution.—Opinions are divided in re- 
spect to the proper solution of the sulphate, and 
as to the salt of quinia which should he used for 
the hypodermatic injection. Since the last edi- 
tion of this monograph was published, and very 
recently, important recommendations have been 
made in respect to the particular salt which 
should be employed. As the sulphate has been 
chiefly used, I first submit to the reader the best 
formula with which I am acquainted for the ad- 
ministration of this salt hypodermatically : 
R Quinise di-sulph., gr. 50; 
Acid, sulphuric, dil., rq, 100 
Aquae font., ; 
Acid, carbolic, liq., rq, 5. 
Solve. 
“ Place the quinine and water in a porcelain 
dish over a spirit-lamp ; heat to the boiling-point, 
and add the sulphuric acid, stirring with a wooden 
spatula. Filter at once into a bottle, and add the 
carbolic acid. This gives six grains to the drachm. 
Even this solution will deposit some crystals at a 
temperature of 50°, and, of course, at or below 
323 324 
QUINIA. 
that temperature requires to be warmed before 
using.”—Lente.* 
Kin ate of quinia is soluble in the proportion 
of one to four of water. It can readily be ob- 
tained by a reaction between solutions of kinate 
of barium and sulphate of quinine. At Guy’s 
hospital, the strength of the solution used is one 
to four, prepared according to the following pro- 
cess : “ Put into a beaker svi of distilled water 
and sij of kinate of quinia, and heat until the salt 
dissolves, which it does almost immediately, and 
then add enough distilled water to make up to 
Si.” 
The use of so concentrated a solution of kinate 
of quinia is attended with some difficulty, as the 
neck and stopper of the bottle become encrusted 
with a deposit of the kinate, and the syringe 
used to make the injection must be frequently 
cleaned. 
Lactate and sulpho-vinate of quinia have also 
been recommended for hypodermatic use. By 
Prof. Gubler the hydrobromate of quinia was 
preferred to all other salts. 
R Quiqiae hydrobromat., gr. 48; 
Aquas destillat., giv. 
M. Dissolve, if necessary, by heat. 
Sig.—Twenty minims contain 4 grains. 
Very recently a new compound salt of quinia 
* The New York Medical Journal, March, 1874. ACTIONS AND USES. 
325 
lias been introduced for hypodermatic injection, 
and it seems to possess very distinct advantages 
over all other preparations hitherto proposed. 
It has been “ termed quinta bimuriatica earbami- 
data, and is formed by Drygin from a combina- 
tion of twenty parts of muriate of quinia, twelve 
parts of muriatic acid, and three parts of urea. 
The resulting salt is soluble in equal parts of 
water.* The trials that have been made of it at 
Hamburg have proved so successful that it is 
highly desirable it should be known more widely. 
A 50 per cent, solution has always been employed, 
and the quantity injected has varied from a half 
to three syringefuls. The local irritation was 
in most cases very slight, and at the worst con- 
sisted in a circumscribed burning pain, without 
redness or swelling.” 
Actions and Uses.—Beside the local irrita- 
tion, little is to be said respecting the physiologi- 
cal effects of quinia. The solutions of quinine, 
when injected beneath the skin, excite consider- 
able burning and a zone of more or less intense 
redness for some distance around the puncture. 
If care be not used in the preparation of the 
solution, inflammation will follow at the site of 
the puncture, matter will form, and possibly a 
diffuse inflammation of the areolar tissue will 
ensue. Before I had learned the necessity for 
* Centralbiatt f. d. med. Wiss., June 14, 1879. Quoted in the 
Medical Times and Gazette, July 12, 1879. 326 
quiNiA. 
caution, accidents of this kind occurred in my 
own hands, and lately some very had cases have 
been reported as occurring in New Orleans, 
where, it is said, a mixture of quinia sulphate and 
water was injected under the skin. Some cases 
of tetanus have been reported caused by subcu- 
taneous injection of quinine, but there must have 
existed a peculiar state of the nervous system, 
in which, as is well known, very slight injuries 
may be followed by this malady. But little sys- 
temic effect follows the subcutaneous injection 
of quinia. The actions are similar in character 
to those produced by the stomach administration, 
and, as they are so well known, require no de- 
scription here. 
Dr. Chasseaud published, in 1862, an account 
of the great success Avhich he had obtained in the 
treatment of malarial fevers, in the hospital at 
Smyrna, by the subcutaneous injection of quinine. 
He ascertained that this agent, administered in 
this way, had a more decidedly curative power, 
without occasioning its usual physiological effects, 
than when given by the stomach. This practice 
has since been continued with undiminished suc- 
cess at the same hospital by Dr. J. McCraith. 
Dr. Moore, of the Bombay Medical Sendee, re- 
peating these experiences, concludes “ that four 
or five grains of quinine injected beneath the 
integument are equal to five or six times that 
amount taken into the stomach.” 
Not only is the immediate therapeutic effect of A CTIONS AND USES. 
327 
the quinine given in this way greater, but more 
permanent cures thereby result. In one hundred 
and fifty cases treated in this way, Dr. Chasseaud 
had but a single relapse. Such has been my own 
observation. 
From five to ten grains, injected under the 
skin, will suffice to cure an ordinary intermittent. 
Fevers of the remittent type, and pernicious 
fevers, will require a larger amount. In those 
deadly malarial attacks, known as 'pernicious, is 
the efficacy of this treatment most conspicuous. 
Much depends, as everybody knows, upon bring- 
ing the patient promptly under the quinine influ- 
ence; the subcutaneous injection is the quickest 
and most powerful means of accomplishing this 
object. 
Recent malarial fevers may be aborted at the 
beginning of the cold stage by a full injection, 
but it is better to anticipate the attack by an 
hour or two, in order to procure the physiological 
effects before the onset of the expected paroxysm. 
It is true that the injection may be administered 
at any time during the febrile movement, but it 
is better to anticipate and prevent it. The ulti- 
mate cure will depend upon the amount of quinia 
received by the patient, and not upon the period 
at which it was administered. 
The subcutaneous injection is much more effec- 
tive also against chronic malarial poisoning than the 
stomach administration, but here we meet with 
new conditions, requiring other management 328 
QUINIA. 
than the use of quinine. We may confidently 
expect to prevent the febrile movements hy fre- 
quent repetition of the injection; hut we do not 
thereby cure the disease, for the changes induced 
by the long-continued action of malaria, in the 
liver, spleen, gastro-intestinal mucous membrane, 
cerebro-spinal axis, must he corrected if we would 
arrest the objective phenomena of fever and cure 
the patient. 
Dr. Eulenberg sums up bqs conclusions in 
regard to the cases in which the subcutaneous 
injection of quinia in malarial fevers may be 
desirable as follows: 
In intermittents complicated with gastric dis- 
order. 
In children in whom the disagreeable taste and 
the large doses necessary produce strong aversion 
and stomach derangement. 
In poor and hospital practice, where economy 
in the use of the drug is desirable. 
These conclusions seem to the writer well 
founded. But he has omitted chronic malarial 
poisoning, in which the subcutaneous injection 
of quinia has undoubted utility. 
The antipyretic effects of quinia are constantly 
made use of in the treatment of continued fevers, 
as all the world knows, the administration being 
by the stomach; but Dr, Ravicini* urges the 
* Revista Clinica di Bologna. Quoted in the London Medi- 
cal Record, vol. ii. p. 824. ACTIONS AND USES. 
329 
hypodermatic use of quinia in typhoid. He com- 
bines a minute quantity of morphia with it. He 
gives three injections daily, making in the aggre- 
gate about 70 grains, and this practice he contin- 
ues for several days. The results are most favor- 
able : the sordes disappear from the mouth and 
teeth, the headache, meteorism, and gurgling in 
the right iliac fossa are greatly diminished, the 
spleen is reduced in size, and the countenance 
becomes more composed. The disease, although 
not cut short, is much abbreviated, as nearly all 
convalesce at the end of the second week, or, at 
most, of the third. The morphia, he thinks, 
affects the nervous phenomena favorably. If 
these statements can be relied on, nothing can 
be more satisfactory than this mode of treating 
typhoid. By using the new compound—muriate 
of quinia and urea—there need be no apprehen- 
sion, which otherwise might be felt as to the 
effect of an irritant on the tissues of a typhoid 
fever patient. 
Mr. Hall,* of the British army, serving in 
India, reports remarkable success in the treat- 
ment of heat-apoplexy (sunstroke) by the hypoder- 
matic injection of quinine. He reports in all 
seven cases of a severe type in which this treat- 
ment proved uniformly and invariably successful. 
He refers also to the experience of Mr. Waller, 
of Calcutta, which was equally favorable. 
* The Practitioner, March, 1876. 330 
QUINIA. 
In some cases of neuralgia good results have 
been obtained by quinia, subcutaneously. One 
notable example of ovarian neuralgia, accompa- 
nied by, or caused by, menorrhagia, has been 
reported, and I can confirm from personal obser- 
vation the special utility of quinia under these 
circumstances. CAEBOLIC ACID. 
The Solution.—The following formula is a 
suitable one for the preparation of a solution of 
carbolic acid for hypodermatic use : 
R Acid, carbolic, purif., gr. x ; 
Aquae destil., %i. M. 
Sig.—Two ■per centum solution of carbolic acid. 
The Dose.—From fifteen to thirty minims— 
even as much as 5i—of the above solution may 
be injected, but not more than the largest amount 
once in six hours. The minimum dose may be 
administered very frequently, until the maximum 
amount prescribed is reached. The quantity at 
each injection and the frequency of repetition will, 
however, depend on the character of the case. 
Physiological Effects.—Some smarting at- 
tends immediately, but declines rapidly, and is 
replaced by a local anaesthesia and analgesia ex- 
tending for some distance around the puncture. 
Usually very little irritation is produced, and it 
is rare for an inflammatory induration and sup- 
puration to follow. Uo change occurs in the 
feelings and condition of the patient, due to the 
carbolic acid. Elimination takes place by the 
331 332 
CARBOLIC -ACID. 
bronchial mucous membrane to a slight extent, 
also by the skin, but chiefly by the kidneys. 
If the injections have been practised frequently 
and in considerable quantity, the characteristic 
changes in the appearance and reaction of the 
urine are observed. A slight smoky appearance 
may be disregarded, but if the urine becomes 
persistently blackish, the administration should 
be lessened or suspended. 
Therapy.—lmportant results have been ob- 
tained from the subcutaneous and parenchyma- 
tous injection of carbolic acid. The original 
conception suggesting its employment was the 
supposed relation of certain morbific ferments to 
diseased processes. Influenced by these notions, 
Kunze,* of Halle, employed it in these maladies 
(Infectionskrankheiten), notably in erysipelas, and, 
as it proved, with excellent results. Some ex- 
perience of my own is quite confirmatory. By 
injecting five minims of a two per cent, solution 
just at the margin of the inflammation, and at 
several points, two or three times a day, a very 
favorable influence on the case is at once appa- 
rent. Kunze found the same practice very bene- 
ficial in pleuro-pneumonia. The injections had the 
effect to lower the temperature and the pulse- 
rate. Aufrechtf has repeated the same practice 
and confirmed the results of Kunze. 
The practice has been greatly extended by 
* Schmidt’s Jahrbucher, vol. clxiv. p. 147. f Ibid. THERAPY. 
333 
Hiiter,* under the title of “ parenchymatous in- 
jections,”—Form parenchymatbser Einspritzungen, 
—and applied to the treatment of synovitis, white 
swelling, adenoma, bubo, fibroma, etc. A two per 
cent, solution is thrown into the cavity of the 
joint every day or two, and into the substance of 
the abnormal growths. In some cases remark- 
able results of a curative kind follow, as I have 
ascertained by actual trial. In several instances 
I have seen ulcers of the face, which had all the 
external signs and appearances of epithelioma, heal 
and cicatrize permanently under the influence 
of carbolic acid injections so practised that the 
medicament came into contact with the tissues 
immediately adjacent to the diseased tissue. 
The needle was entered in the sound tissue just 
at the margin of the disease, and passed well 
under the ulcer, so that the carbolic acid solution 
could diffuse thoroughly through the parts. If 
necessary, two or more punctures can he made 
at one sitting. 
In acute rheumatism decided relief has been 
produced by these injections about the affected 
joints; they are still more efficient in chronic 
rheumatism, and also do good in myalgia. Super- 
ficial neuralgm may not unfrequently be promptly 
cured by deep injections of the two per cent, 
carbolic acid solution instead of chloroform. 
* Schmidt’s Jahrbiicher, vol. clxiv. Also Dr. Kothe, Die 
Carbolsilure in der Medicin, Berlin, 1875, p. 40, et seq. MERCURY. 
The Solution and Dose.—Applying the rules 
already given, I reject all insoluble preparations 
of mercury. Scarenzio* used in 1864 a mix- 
ture of calomel, glycerine, and water. Hebraf 
injected a solution of sublimate,—gr. i to Sss 
water. Hill, of England, made use of a solu- 
tion of sublimate containing of a grain to the 
dose. Lewin,| who first submitted this practice 
to systematic examination, employed a weak so- 
lution of corrosive sublimate. The following is 
a suitable formula for hypodermatic injection of 
mercury ; 
R Hydrarg. chlor. corrosiv., gr. i; 
Aquas destil., §i. M. 
Ten minims of this contain of a grain. As 
Lewin, and especially Liegeois, have shown that 
concentrated solutions are not desirable and that 
large doses are not necessary, this formula will 
* Eulenberg, op. cit., p. 307. 
f Ibid. Also, Bulletin de Therapeutique, vol. i., 1869, p. 
297. De I’Application de la Methode hypodermique au Traite- 
ment de la Syphilis par les Preparations mercurielles. Par le 
Dr. E. Bricheteau. Ibid., vol. ii., 1869, p, 158, by M. Liegeois. 
% Ibid. 
334 THE SOLUTION AND DOSE. 
335 
be strong enough for ordinary purposes. Recog- 
nizing the fact that induration of the tissue, and 
frequently unhealthy and sloughing ulcers, were 
produced by these injections of sublimate, Briche- 
teau requested M, Bouilhon, a Paris pharmaceu- 
tist, to prepare a salt of mercury soluble and free 
from irritant properties. M. Bouilhon suggested 
the double iodide of mercury and sodium as sup- 
plying the conditions required. 
R Hydrarg. et sodii iodid., gr. xxiv ; 
Aquae destil., M. 
Fifteen minims of this contain of a grain. 
Ten minims, or of a grain, will generally be 
sufficient for an injection. “ This salt,” says M. 
Bouilhon, “fulfils perfectly the object; it intro- 
duces into the economy only the active substance 
combined with a small quantity of a salt of soda.” 
But as this salt is difficult to prepare, and as the 
corrosive chloride is more readily procured, the 
latter will generally be employed. With suita- 
ble precautions, abscess will not frequently result 
from its use. Thus, Lewin, who used his solu- 
tion—which is stronger than that I have recom- 
mended—many hundred times, found small ab- 
scesses to occur in the proportion only of two to 
three for one hundred injections. 
The formula of M. Liegeois * is as follows: 
* Bulletin General de Therapeutique, 30 Aout, 1869, p. 158. 336 
MERCURY. 
R Hydrarg. chlor. corrosiv., gr. iij ; 
Morphias sulph., gr. iss ; 
Aquae destil., M. 
Fifteen minims of this solution contain of a 
grain, the quantity recommended by Liegeois for 
a single injection. It will be perceived that this 
solution contains the same quantity of sublimate 
as the formula I have proposed, but only about 
one-third of that used by Lewin. In two cases 
only has Liegeois observed abscess and eschar 
follow his injection. This comparative immunity 
from ill effects is to be attributed, unquestion- 
ably, to the small proportion of sublimate. The 
injection is preferably inserted under the skin of 
the back. 
Physiological Effects.—The injection of the 
corrosive chloride is accompanied by severe burn- 
ing pain and considerable local heat and redness. 
If the solution be concentrated it will produce 
induration of the areolar tissue, inflammation 
and abscess, and sometimes a dry eschar, leaving 
an ulcer slow to heal. The intensity and per- 
sistence of the pain will depend upon the quan- 
tity of sublimate injected; weak solutions do 
not occasion much distress; the pain of any so- 
lution may be much mitigated by the conjoined 
use of morphia, as in the solution of Liegeois. 
Salivation is frequently produced, according to 
Lewin, who had fifty-one cases of mercurial 
stomatitis in one hundred and forty-four men 
treated in this way. On the other hand, Li - THE RAP F. 
337 
geois found salivation an “ exceptional” occur- 
rence, there being only four in one hundred and 
ninety-six subjects, and these were mild cases. 
The difference in result here is plainly due to the 
difference in the strength of the respective solu- 
tions. It is a curious and important circum- 
stance that this physiological effect has no rela- 
tion to the therapeutical results in syphilis, for 
Liegeois’s cures are even more numerous, pro- 
portionally, than Lewin’s. 
The subcutaneous injection of sublimate does 
not impair any of the functions, but increases 
the activity of the digestion, and assimilation, so 
that decided increase in weight takes place in 
most of the cases in which it is employed. 
Therapy,—The therapeutical applications of 
mercury by the hypodermatic method are con- 
fined to the treatment of syphilis, in which re- 
sults of the greatest value have been obtained. 
It is applied to the treatment of primary (in- 
fecting chancre), secondary (constitutional), and 
tertiary forms of this disease. I have used it 
with great advantage in the tertiary, but have 
not had the opportunity to give it sufficiently 
numerous and prolonged trials to enable me to 
pronounce as to its utility in primary and secon- 
dary syphilis. I therefore avail myself of the 
very full reports and statistical evidence pub- 
lished by George Lewin, of Berlin, and M. Lie- 
geois, of Paris. The following are the statistics 
of Lewin: 338 
MERCURY. 
Cases* treated exclusively by injections of 
sublimate, 107; relapses 24, or 22 in 100. 
“ Cases treated by injections of sublimate, after 
sarsaparilla decoction and sweating, 58; relapses 
19, or 30 in 100. 
“ Cases treated simultaneously by injections of 
sublimate, sarsaparilla decoction, and sweating, 
24; relapses 7, or 83 in 100. 
“ Cases treated by injections of sublimate and 
iodide of potassium, 60; relapses, 14, or 23 in 
100. 
“ Cases treated by injections of sublimate and 
chloride of potassium, 60; relapses 14, or 23 in 
100.” 
To sum up—3s6 patients have been treated by 
injections of sublimate, either singly or joined 
to other means; the relapses have been 89, or 25 
in 100. 
With tbe ordinary means of treatment, tbe re- 
lapses are 81 in 100 cases.f 
The conclusions arrived at by Lewin,| as a 
result of his large observations, are the follow- 
ing; 
1. The syphilitic phenomena disappear quickly, 
and with a rapidity proportional to the quantity 
of sublimate daily injected. 
* These statistics are based upon cases of constitutional 
syphilis. 
f Bulletin de Therapeutique, vol. i., 1869, p. 300. Abstract 
of Lewin’s researches by Bricheteau. 
t Ibid. THERAPY. 
339 
2, Certainty and precision of the method, as 
ascertained by nine hundred observations made 
during two years and a half. 
3, Lessened number of relapses, aud those that 
occur are light. 
4. Facility of execution. 
The statistics of Liegeois are even more favor- 
able. Thus, of 196 cases of constitutional syph- 
ilis, treated by injections of sublimate, 127 were 
cured, and 69 were ameliorated. For the cured, 
the number of injections were 68; for those 
ameliorated, 50. The number of relapses in 
those noted as cured were 12 (9.45 in 100); for 
those noted as ameliorated, 14 (20.30 in 100). 
The greater number of injections, and the in- 
creased length of time required by Liegeois’s 
method as compared with LewiiTs, are due to 
the small quantity injected, but these disadvan- 
tages are more than counterbalanced by the 
greater proportional number of cures. The pro- 
duction of salivation, then, is unnecessary in 
order to secure the best results from the hypo- 
dermatic injection of mercury. The longer the 
constitutional symptoms have existed, the greater 
the number of injections required to effect a 
cure. 
In practising the injection, the back should be 
selected for the site of the puncture. Two in- 
jections, of eight minims each, may be practised 
at one sitting, one on each side. This quantity 
should be inserted daily. If the symptoms be 340 
MERCURY. 
not urgent, if time is of little consequence, and 
if it be desirable to avoid salivation, the daily 
quantity may be much less. 
With the view to avoid the irritation produced 
by subcutaneous injections of corrosive sublimate 
in the ordinary way, and also to administer it in 
larger doses, Dr. Staub conceived the idea of 
using it in the form of an albuminous solution 
in alkaline chlorides. He prepared his solution 
as follows ; 
Corrosive sublimat., 1 gr. 25. 
Chloride of ammonium, 1 gr. 25. 
Chloride of sodium, 4 grs. 15. 
Water, 1 gr. 25. 
After filtration this solution is added to an 
albuminous solution (white of one egg to 125 
parts of water). Twenty drops of this contain 
5 milligrammes of sublimate. It produces no 
irritation when injected under the skin. The 
results of treatment with this solution have been 
very favorable in the hands of M. Staub. He 
reports 44 observations, the treatment varying 
from 17 to 34 days, and the amount injected 
being 1 centigramme daily. He observed no 
relapses.* 
The subcutaneous use of the albuminous so- 
lution of mercury is greatly extending. Within 
the past two years especially, numerous reports 
have been published, showing the rapidity and 
* Archives Generales de Medecine, Juillet, 1872. THERAPY. 
341 
permanence with which cures have been effected. 
It has also been established by the recent expe- 
rience in the hypodermatic treatment of syphi- 
lis, that relapses are much less apt to occur by 
this method than by the stomachal or epidermal 
administration. ARSENIC. 
The first actual trial of arsenic subcutane- 
ously was made by Dr. C. B. Radcliffe, in a case 
of chorea, and the announcement of this fact is to 
be found in the article on chorea in Reynolds’s 
“ System of Medicine.”* As an interesting sub- 
ject historically, I quote those paragraphs con- 
cerned with this topic: 
“ This patient had suffered for nine years with 
a distressing choreal affection of certain muscles 
of the neck, by which the head was kept contin- 
ually turning and bobbing. At different times 
various modes of treatment had been tried, in- 
cluding the hypodermic injection of morphia 
and atropia, without the least benefit. . . . The 
idea of injecting arsenic hypodermically oc- 
curred to me on the 12th of January, 1866, and 
was carried out the same day. Fowler’s solution 
was chosen, and the part selected was the most 
tender point over the contracting muscle.” Com- 
mencing with three minims, the quantity injected 
was finally raised to fourteen minims. “ Before 
the fourth injection was practised, a marked 
* Yol. ii. p. 133, et seq. 
342 THERAPY. 
343 
change for the better had taken place; before 
the eighth, the choreal movements were almost 
at an end, and a change for the better had gone 
on steadily from the beginning.” Dr. Rad- 
elitfe reports another case in which amelioration, 
equally as great, was produced by the hypoder- 
matic injection of arsenic, the patient being a 
lady sixty years of age. He has also employed 
u with results more or less satisfactory the hypo- 
dermic injection of arsenic in certain cases of 
neuralgia, epilepsy, and other affections of the 
nervous system.” 
In the choreal cases above referred to, Dr. Rad- 
cliffe’s “ object in introducing the arsenic hypo- 
dermically was not to escape gastric irritation, 
but to produce some local change in the nerves 
of the parts which were the seat of the disorder, 
as well as to bring about some more general 
change in the system.” 
Dr. Radcliffe employed for these injections at 
first the undiluted Fowler’s solution, but as con- 
siderable local irritation followed, he afterward 
diluted it by one-half water. This proved much 
less irritant. It is probable, I think, that the 
Liquor Sodce Arseniatis will be found much better 
for hypodermatic use than Fowler’s solution. 
This being a higher oxide than the arsenite of 
potassa, is less irritant in its local action and less 
apt to produce arsenical poisoning. Moreover, 
it is a clear solution, possessed of a considerable 
degree of osmotic power. The solution of the 344 
ARSENIC. 
arseniate of soda maybe injected in quantities of 
five to ten or even fifteen minims. Every alter- 
nate day is sufficiently often in ordinary cases to 
make the injection. It will be found advisable 
not to insert the solution frequently in the same 
neighborhood. 
Dr. Radcliffe’s example has been followed 
with success. Hot only local but severe general 
chorea has been treated with good results. Suc- 
cessful cases have been reported by Perroud, 
Garin, Hammond, and others. 
Remarkable results have been obtained from 
the hypodermatic injection of arsenic in lympha- 
denoma by Billroth and Czerny. Fowler’s solu- 
tion is used, and the injection made into the 
substance of the enlarged glands. The quantity 
depends somewhat on the susceptibility of the 
patient, and therefore varies,—from 5 to 10 min- 
ims of the official solution being injected daily. 
The same practice has been followed with good 
results in enlarged spleen and in splenic leucocythe- 
mia. 
M. Lipp* has proposed to use arsenic sub- 
cutaneously in cases of psoriasis and chronic 
eczema. He reports three eases thus treated 
successfully. He injected from one to two 
centigrammes of arsenious acid. The general 
symptoms produced by these injections were 
elevation of temperature, acceleration of pulse, 
* Archiv fur Dermatologie und Syphil., No. 3, 1869. THERAPY. 
345 
diminution of appetite, increased thirst and diu- 
resis, nervous excitement, headache, vertigo, 
cough, redness of conjunctiva, etc. The advan- 
tages which M. Lipp claims are the smallness of 
the dose, the shorter duration of the treatment, 
and the absence of injury to the digestive organs. 
Excellent results have since been obtained in 
numerous instances of cutaneous diseases of an 
obstinate character by this practice, in the hands 
of dermatologists, in all parts of the world. 
The class of cases benefited by arsenic sub- 
cutaneously is the same as those heretofore 
treated by the stomachal administration of the 
same agent. AQUAPOTCTURE. 
The method now designated aquajpuncture 
consists merely in the subcutaneous injection of 
water at ordinary temperature. A special in- 
strument has been invented by M. Guerard for 
the simultaneous introduction of a number of 
tine streams of water (douches jiliformes), but an 
ordinary hypodermatic syringe will answer the 
purpose very well by making a number of punc- 
tures within a certain area. 
The immediate effect of the sudden introduc- 
tion of a fine jet of water is a sense of burning, 
which lasts a few minutes, a feeling of distention 
and warmth lasting longer, for about the point 
of puncture considerable swelling takes place, 
presenting the appearance of a wheal of urtica- 
ria. The immediate effect of the introduction 
of cold water is to cool the nerve-filaments; of 
hot water to raise their temperature, and the dis- 
tention of the parts stretches the nerve-filaments. 
Undoubtedly, therapeutical effects are produced 
by such impression. What difference of physio- 
logical or therapeutical effects will follow the in- 
troduction of very warm or very cold water, or 
346 AqUA PUNCTURE. 
347 
greater or less stretching of nerve-fibres, re- 
mains to be determined by further investigations. 
The method of aquapuncture has been used in 
fourteen cases of various forms of neuralgia by 
Servajan,* with the result of a cure in all but 
one. Among these were examples of facial, 
sciatic (5), lumbar (3), and other forms. 
The injection of water has been gravely pro- 
posed f as a substitute for morphia in the treat- 
ment of painful affections, and a medical eccen- 
tric has propounded the extraordinary theory 
that the systemic effects of a solution of morphia 
are due not to the morphia, but to the water ! 
If this was not intended as a practical joke, if 
the author is really sincere in his proposition, it 
is a curious example of that morbid desire for 
notoriety which is indifferent to the means em- 
ployed to secure it. 
Water injections have been used with success 
to deceive the patient in cases of morphia habit 
of a few days’ or few weeks’ duration; but an- 
cient and experienced morphia-takers cannot be 
so deceived, for they quickly realize the differ- 
ence in the amount of effect produced. In 
making an effort to cure them, it is never useful 
to practise any deceit; their co-operation must 
be sought and their confidence gained. If water 
merely is to be injected, let them be informed, 
* De I’Aquapuncture, par J. Servajan, Paris, 1872, p. 41. 
f Lafitte, Union Medicale, No. 113, 1875. 348 
AQUAPUNCTURE. 
but do not commit tbe professional error (not to 
speak of moral wrong) of being concerned and 
caugbt in an attempt to deceive. 
I have had excellent results from tbe injection 
of water into paralyzed and wasting muscles : it 
promotes their nutrition, and contributes indi- 
rectly to tbe regeneration of voluntary power. 
In the various cases to which the aquapuncture 
is applicable, the quantity injected will range 
from thirty minims to a drachm. When the first 
injection does not relieve in two minutes, another 
should be inserted. As far as practicable the 
“ painful points,” or the tissue in which the pain 
is felt, should be the site of the injection. IRRITANT INJECTIONS. 
Dr, Luton,* of Rlieims, under the singular 
designation “ parenchymatous substitution,” de- 
scribed a method of treating neuralgias, new 
formations, hypertrophies, etc. This method 
consists in the injection into the substance of 
the affected part of such irritants as tincture of 
iodine, nitrate of silver, chloride of sodium, etc. 
The term applied to this process was intended 
to express the theoretical views of its author in 
regard to the nature of the therapeutical action 
which takes place. The pain and irritation set 
up in the part were assumed to be substituted for 
the morbid process. 
Dr. Ruppaner imitated this method of Luton 
in the treatment of sciatica and other neuralgias. 
Dr. Bertin (de Gray) also, attracted by the results 
obtained by Luton, practised the method for 
several years and then published the results.f I 
have had myself a limited experience with this 
method. 
The substances employed in this way are chiefly 
the following; 
* Archives Generates de Medecine, Oct. et Nov. 1863. 
t Ibid., Avril, 1868, p. 444. 
349 350 
IRRITANT INJECTIONS. 
A solution of iodine. 
A saturated solution of common salt. 
A solution of the nitrate of silver. 
The tincture of cantharides. 
The following is the solution of iodine em- 
ployed hy Berlin: 
R Potassii iodidi, gr. xv ; 
Tinct. iodinii, ; 
Aquae destil., M. 
The quantity of tincture of iodine may be in- 
creased to v. 
The tincture of iodine is sometimes employed 
alone and undiluted. 
The following is a suitable formula for the 
nitrate of silver solution : 
R Argenti nitrat., gij ; 
Aquae destil., §i. M. 
To illustrate at the same time the class of cases 
to which this method is applicable, and its thera- 
peutical power, I subjoin the statistics of Berlin ; 
1. Tumors formed by development of the thyroid gland 8 
Cured 5 
Ameliorated 1 
Failed 2 
2. Lymphatic ganglions 3 
Cured 8 
3. Bursae.... 1 
Cured 1 IRRITANT INJECTIONS. 
351 
4. Neuralgias ... 7 
Old sciaticas treated by injection of nitrate of silver 2 
Cured 2 
Old sciaticas treated by solution of common salt.. 2 
Cured 0 
Eecent sciaticas treated by solution of common salt 2 
Ameliorated 2 
Eecent sciaticas treated by injection of nitrate of 
silver 1 
Cured 1 
Euppaner employed the nitrate of silver in- 
jection in one case of cervico-hrachial neuralgia, 
and in four cases of sciatica; two cases were 
ameliorated, and three cases of sciatica were 
cured. 
As respects neuralgia, this method of treatment 
seems specially adapted to cases of sciatica,—ob- 
stinate cases in which structural alterations have 
probably taken place in the neurilemma. In 
order to he effectual, the injection—five drops of 
the nitrate of silver solution—should be thrown 
into the vicinity of the nerve. It produces great 
pain and burning, and is followed by consider- 
able inflammation, not diffused, but localized to 
the site of the injection. Abscesses, of course, 
frequently happen from this practice, and, in- 
deed, sufficient irritation to result in this way 
seems necessary to produce the best effects. It 
is probably true that the irritation, and not the 
agent, is the principal factor in the curative 
process. 
Injections of the iodine solution have been 352 
IRRITANT INJECTIONS. 
practised with success in goitre. The tincture of 
iodine may he thrown into the substance of an 
enlarged thyroid without producing violent irri- 
tation. Five minims of the tincture will be suf- 
ficient for this purpose, and it may be repeated 
every other day. Recent cases are quickly cured 
by this treatment. I have seen excellent results 
from the same application in those cystic and 
glandular tumors so frequently found in the cervi- 
cal region. After evacuating the cyst with a tro- 
car, the tincture of iodine may be freely thrown 
into the sac, and the solid parts of the tumor 
injected by the hypodermatic syringe, the needle 
point being well introduced into the substance of 
the growth. 
Mdarged bur see are best treated by the same 
means; evacuate the contents and inject the so- 
lution of iodine. Slight inflammatory action fol- 
lows, the tumor becomes indurated, and finally 
disappears. 
Solid tumors may be destroyed by injecting 
such irritants into them as will give rise to vio- 
lent inflammatory action and sloughing. Into 
the substance of cancerous new formations vari- 
ous corrosives may be injected; but this practice, 
although rational, has not hitherto proved satis- 
factory,—a remark equally true of Dr. Broad- 
bent’s method of injecting dilute acetic acid,— 
of the success of which such confident expec- 
tations were at first entertained. Solutions of 
chloride of zinc of varying strength have lately IRRITANT INJECTIONS. 
353 
been proposed for “ interstitial injection” as a 
means of curing certain cystic tumors. It is as- 
serted that when the air is excluded eschars are 
not produced. The strength of the weaker solu- 
tion is about five grains of the chloride of zinc 
to the drachm of water, and of the stronger 
solution about a half-drachm to a drachm. The 
method consists in introducing an aspirator and 
withdrawing some part of the contents of the 
cyst, and then injecting from five to twenty drops 
of the zinc solution. 
Recently* considerable success has been claimed 
for the treatment of tumors by the injection into 
their intimate structure of gastric juice. As this 
practice is devoid of danger in suitable cases, 
and as the gastric juice is not difficult to obtain 
from the stomach of the pig, it is desirable to 
have further experience in order to form decided 
opinions as to its utility. 
The natural digestive fluid, the juice of Carica 
papaya, has been used successfully to effect the 
solution of morbid growths, in the same way as 
pepsin. It deserves further investigation. 
It would be foreign to my purpose to speak of 
such uses of the iodine solution as the injection 
in hydrocele, in hydrothorax and empyema, in 
cystic disease of the ovary, etc., and of the use ol 
perch!oride and persulphate of iron in ntevus. 
Injection of Ammonia into the Veins.—As 
* Bulletin General de Therapeutique, Aout 15, 1869. 354 
IRRITANT INJECTIONS. 
the hypodermatic syringe is the instrument em- 
ployed in this operation, it may he proper to in- 
clude in my account of hypodermatic medication 
some references to the injection of ammonia into 
the veins. We owe to Prof. Halfourd, of Mel- 
bourne, Australia, the introduction of this im- 
portant means of relief. He used it to overcome 
and remove the lethal effects of the poison of 
venomous snakes. A number of successful cases 
have now been reported occurring in the prac- 
tice of Prof. Halfourd and others. The solution 
used consists of one part of aqua ammonias, fortior 
and two parts of distilled water. By means of 
an ordinary hypodermatic syringe this solution 
is injected into a vein. The quantity is deter- 
mined by the effect; one or more syringefuls 
may be injected. Care must be used to prevent 
the introduction of air. The operation appears 
to be devoid of danger, and to be free from ulte- 
rior bad effects. 
The injection of ammonia is indicated not only 
in the case of poisoning by venomous snakes, 
but in various conditions in which the danger to 
life consists in depression of the heart’s action. 
In poisoning hy hydrocyanic acid it may be used 
with a good prospect of success. The report of a 
case of poisoning by chlorodyne has lately come 
to us from Australia, in which life was saved by 
the injection of ammonia. In cases of danger 
from thrombus of an important vessel, as, for 
example, thrombus of the pulmonary artery, a IRRITANT INJECTIONS. 
355 
cause of sudden deatli after delivery, this mode 
of treatment is strongly indicated. In failure of 
the heart’s action during the chloroform narco- 
sis, the injection of ammonia should be promptly 
practised. 
Recent experiences by Brunton and Fayrer 
have demonstrated that the intravenous injection 
of ammonia is not effective against the poison- 
ing by the venomous snakes of India, and grave 
doubts are now entertained in respect to the same 
practice in the poisoning by Australian snakes, 
the apparent cures heretofore reported being in- 
stances of the post rather than the propter hoc. INDEX. 
Abdominal neuralgia, morphia in, 111. 
Accidents from morphia injections, 71. 
Aconite and atropia, antagonism of, 189. 
Affections of the bladder and urethra, morphia in, 112. 
After-pains, 113. 
Agents for hypodermatic injections, 47. 
Alkaloids of opium, 55. 
Ammonia, injection of, 353. 
in bites of venomous snakes, 354. 
cardiac depression, 353. 
Amyl nitrite, 286. 
in angina pectoris, 287. 
chloroform narcosis, 287. 
cholera asphyxia, 287. 
Aneurism, ergotin in, 320. 
Angina pectoris, 104. 
Antagonism of atropia and aconite, 189. 
hromal hydrate, 188. 
morphia, 192. 
muscaria, 183. 
physostigma, 161. 
pilocarpine, 173. 
quinia, 187. 
Apomorphia, 305. 
effects of, 305. 
in capillary bronchitis, 307. 
narcotic poisoning, 806. 
Aquapuncture, 346. 
in neuralgia, 347. 
morphia habit, 347. 
Arsenic, 342. 
in choreal affections, 343. 
lymphadenoma, 344. 
skin diseases, 344. 
Asthma, atropia in, 155. 
chloral in, 301. 
357 358 
INDEX. 
Asthma, morphia in, 101. 
pilocarpine in, 284. 
Atropia, 140. 
physiological effects, 142. 
therapy of, 150. 
in cerebral diseases, 150. 
ataxia, 150. 
chronic meningitis, 151. 
chronic myelitis, 161. 
delirium tremens, 151. 
epilepsy, 154. 
mental disorders, 151. 
neuralgia, 153. 
dysmenorrhcea, 158. 
sciatica, 153. 
tic douloureux, 153. 
in disorders of digestive system. 158 
cholera, 158. 
colic, 158. 
vomiting, 158. 
in genito-urinary diseases, 158. 
dysuria, 159. 
enuresis, 159. 
spermatorrhoea, 159. 
in respiratory and cardiac diseases, 155. 
asthma, 155. 
cardiac depression, 157. 
restraint neuroses, 157. 
Bladder, affections of, 112. 
spasm of, 112. 
Bromal hydrate and atropia, 188. 
Caffein, 303. 
in migraine, 304. 
neuralgia, 808. 
opium narcosis, 304. 
physiological effects of, 303. 
Carbolic acid, 831. 
in adenoma, 332. 
bubo, 332. 
erysipelas, 332. 
fibroma, 333. 
rheumatism, 333. 
physiological effects of, 331. 
therapy of, 331. 
Cardiac neuroses, atropia in, 157. 
morphia in, 104. INDEX. 
359 
Catarrh, morphia in, 103. 
Cerebral diseases, atropia in, 150. 
morphia in, 77. 
morphia and atropia in, 224 
Cerebro-spinal meningitis, morphia in, 84. 
Cholera, atropia in, 158. 
chloral in, 300. 
morphia in, 108. 
Chloral hydrate, 298. 
in asthma, 300. 
cerebral disorders, 301. 
cholera, 300. 
neuroses of the chest, 300. 
physiological actions of, 298. 
solutions of, 298. 
therapy of, 299. 
Chloral and morphia, 301. 
Chloroform, 288. 
deep-injection of, 290. 
in neuralgise, 292. 
physiological effects of, 289. 
Codeia and its salts, 118. 
Colic, 110, 158. 
Conia, 261. 
and morphia, 264. 
in emphysema, 268. 
tetanus, 263. 
physiological actions, 261. 
Convulsions, atropia and morphia in, 224. 
chloral and morphia in, 301. 
hyoscyamia in, 235. 
Cough, morphia in, 101. 
Curara, 265. 
in epilepsy, 267. 
hydrophobia, 268. 
tetanus, 267. 
physiological effects of, 265. 
therapy, 266. 
Cystitis, atropia in, 159. 
morphia in, 112. 
Delirium tremens, atropia in, 151, 
chloral in, 301. 
morphia in, 82. 
Duboisia, 229. 
in psychical disorders, 231. 
physiological effects of, 229. 
Dysmenorrhcea, atropia in, 153. 360 
INDEX. 
Dysmenorrhoea, morphia in, 113. 
Dyspepsia, 107. 
Dysuria, 159. 
Eclampsia, atropia and morphia in, 224. 
chloral and morphia in, 301. 
hyoscyamia in, 235. 
morphia in, 88. 
Emphysema, atropia in, 155. 
morphia in, 102. 
Enuresis, atropia in, 159. 
Epilepsy, atropia in, 121. 
morphia in, 86. 
Epistaxis, ergotin in, 316. 
Ergotin, 308. 
in aneurism, 320. 
fibroids, 317. 
haemoptysis, 319. 
hemorrhages, 319. 
hypertrophy of the uterus, 317. 
prostate, 818. 
leucocythemia, 321. 
meningitis, cerebral and spinal, 322. 
varicocele, 318. 
its source, 308. 
solutions, 309. 
Ether, 294. 
in adynamic states, 296. 
chloroform narcosis, 296. 
cholera, 296. 
pneumonia, 295. 
variola, 296. 
False pains, morphia in, 113. 
Fractures, morphia in, 115. 
Gastralgia, 107. 
Gastric ulcer, 107. 
Genito-urinary diseases, morphia in, 112. 
morphia and atropia in, 226. 
Hernia, morphia in, 115. 
morphia and atropia in, 226. 
Hiccough, 103. 
History of the hypodermatic method, 17 
Homotropine, 190. 
Hydrocyanic acid, 272. 
in angina pectoris, 273. INDEX. 
361 
Hydrocyanic acid, in gastralgia, 273. 
nausea, 273. 
physiological effects of, 272. 
therapy, 272. 
Hyoscine, 236. 
Hyoscyamia, 232. 
in chorea, 235. 
mental diseases, 234. 
paralysis agitans, 236. 
physiological effects of, 234. 
solutions of, 234. 
Hypodermatic method, 30. 
history of, 17. 
solutions for, 31, 34. 
syringes, 36. 
tablets, 38. 
Hysteria, 85. 
Injections, hypodermatic, mode of, 43. 
dangers of, 44, 71. 
local effects of, 53. 
systemic effects of, 53. 
Insanity, atropia in, 152. 
duhoisia in, 231. 
hyoscyamia in, 234. 
morphia and atropia in, 224. 
morphia in, 77. 
Insomnia, morphia and atropia, 224. 
Instrument for hypodermatic injections, 36. 
Irritant injections, 349. 
in neuralgia, 351. 
tumors, 352. 
substances used for, 349. 
Laryngismus stridulus, 100. 
Local effects of remedies, 53. 
Localization of injections, 25. 
Malarial fever, 325. 
Mercury, 834. 
in syphilis, 337. 
physiological elfects of, 336. 
solutions of, 334. 
Metrorrhagia, ergotin in, 317. 
Migraine, 95, 322. 
Morphia, 55. 
Moaphia and atropia, 192. 
chloral, 298. 362 
INDEX. 
Morphia habit and its treatment, 120. 
and atropia, solutions of, 56. 
tablets, 59. 
therapy of, 77. 
in abdominal neuralgia, 111. 
asthma, 101. 
cardiac neuroses, 104. 
catarrh, 103. 
cerehro-spinal meningitis, 84. 
cholera, 108. 
chorea, 90. 
delirium tremens, 82. 
dysmenorrhoea, 113. 
dyspepsia, 107. 
eclampsia, 88, 89. 
emphysema, 102. 
epilepsy, 86. 
fractures, 115. 
hernia, 115. 
hysteria, 85. 
muscular cramp, 92. 
myalgia, 111. 
neuralgia, 93. 
obstetric operations, 113. 
peritonitis, 110. 
pleuritis, 104. 
psychical disorders, 77. 
scirrhus, 108. 
sunstroke, 85. 
surgical diseases, 115. 
syphilis, 114. 
tetanus, 90. 
vomiting, 109. 
Muscaria and atropia, 183. 
Neuralgia, atropia in, 152. 
caffein in, 303. 
morphia in, 93. 
morphia and atropia in, 225. 
Nicotia, 270. 
in angina pectoris, 271. 
asthma, 271. 
colic, 271. 
hernia, 271. 
muscular spasms, 271. 
source of, 270. 
therapy of, 270. INDEX. 
363 
Obstetric practice, morphia in, 113. 
Opium alkaloids, 55. 
Opium narcosis, atropia in, 192. 
caffein in, '304. 
Ovarian neuralgia, atropia in, 153. 
Palpitation of the heart, 105. 
Paralysis, strychnia, 244. 
Penicilium in solutions, 34. 
Physiological antagonists of aconite, 189. 
of atropia, 161. 
of hromal hydrate, 188. 
of muscaria, 183. 
of quinia, 187. 
Physostigma, 275. 
and atropia, 161. 
in bronchitis, 279. 
chorea, 279. 
ophthalmic diseases, 279. 
paralysis (general), 279. 
strychnia-poisoning, 277. 
tetanus, 277. 
physiological antagonists, 161. 
physiological effects, 276. 
solutions of, 275. 
therapy of, 277. 
Pilocarpine, 281. 
and atropia, 173. 
in asthma, 284. 
ague, 285. 
bronchitis, 284. 
cardiac dropsy, 284. 
eclampsia, 284. 
effusions, 284. 
hoarseness, 284. 
mumps, 284. 
tonsillitis, 284. 
physiological actions, 281. 
solution, 281. 
therapy, 284. 
Pleuritis, morphia in, 103. 
pilocarpine in, 284. 
Pneumonia, morphia in, 103. 
Post-partum hemorrhage, ergotin in, 316. 
Psychical disorders, atropia in, 151. 
duhoisia in, 231. 
morphia in, 77. 
and atropia in, 224. 364 
INDEX. 
Quinia, 323. 
and atropia, 187. 
in malarial fevers, 326. 
thermic fever, 329. 
physiological effects of, 325. 
solutions, 323. 
Remedies used hypodermatically, 47 
Remote effects of injections, 53. 
Respiratory neuroses, 100. 
Rheumatism, atropia in, 159. 
carbolic acid in, 333. 
Sciatica, atropia in, 153. 
morphia in, 93. 
Scirrhus, carbolic acid in, 333. 
morphia in, 108. 
Scleromucin, 313. 
Sclerotinic acid, 313. 
Stricture, spasmodic, 113. 
Strychnia, 237. 
antagonists of, 251. 
and aconite, 258. 
bromide of potassium, 257. 
chloral, 251. 
nitrite of amyl, 259. 
solutions of, 237. 
actions of, 239. 
in amaurosis, 249. 
amblyopia, 249. 
hemiplegia, 244. 
infantile paralysis, 246. 
neuralgia, 249. 
paralyses, 244. 
poisoning by, treatment of, 251. 
Syphilis, mercury in, 337. 
morphia in, 114. 
Tetanus, atropia in, 154. 
curara in, 267. 
morphia in, 91. 
nicotia in, 271. 
physostigma in, 277. 
Tic douloureux, 95. 
Vomiting, atropia in, 158. 
chloral in, 300. INDEX. 
365 
Vomiting, hydrocyanic acid in, 273. 
morphia in, 109. 
Wine of tobacco, 270. 
Woorara (curara), 265. 
effects of, 265. 
in epilepsy, 268. 
hydrophobia, 269. 
strychnia-poisoning, 268. 
tetanus, 267. 
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