Reprinted from the North American Journal of Homceopathy, April, 1894. SOME CONSIDERATIONS BEARING UPON PRACTICE WITH DYNAMIC ANTAGONISTS.' IN CASES OF DRUG- POISONING.* By CHAS. S. MACK, M.D., Professor of Materia Medica and Therapeutics in the Hoirfoeopathic Medical College in the University of Michigan. THE dynamic property in a drug I should define as that by which the drug acts immediately upon vital processes, modifying their quality. Under this definition I should not include pure stimulants or pure depressants (if pure depressants exist), for such stimulants and depressants I picture as modifying the force, but not the quality of vital processes. I take it that when modification of vital processes is among the effects of chemical properties in a drug, immediate chemical changes (in tissues, secretions, or excretions) precede such modification ; and that physical or chemical changes caused by a drug's dynamic properties are secondary to its immedi- ate effect upon vital processes. We can conceive of two kinds of dynamic antagonism, the one quite distinct from the other. For present purposes let us call the one superficial antagonism, and the other radical By superficial antagonism we mean an antagonism patent in the tissues or functions of the body, but an antagonism between drugs which operate through respectively different (either partly different or wholly different) channels. By radical antagonism we mean an antagonism not only apparent in the tissues or functions of the body, but one between drugs which act through respectively (in all partic- ulars) the same channel. We shall presently question whether really there be such a thing as radical antagonism. Let us first, however, consider whether the immediate effect either of superficial or of radi- cal antagonism could be a normal condition. Any positive, pure, dynamic effect of a drug (by which 1 mean a dynamic effect producible in health, and not the dynamic modifica- tion of disease effects) is abnormal. J A view which I would urge is * Written especially for the North American Journal of Homceopathy. j- In this paper we shall not consider what might be called the dynamic antago- nism between health and disease. On this subject one may see my little book, "Philosophy in Homceopathy," (published by Gross & Delbridge, 48 Madison Street, Chicago), pp. 43 to 45, and 81 to 87, where the claim of contraria to being the law of cure is under discussion. 'J The fact that in medical literature positive, pure, dynamic effects of a drug are very frequently called physiological (instead of pathogenetic'}, or are described under the heading physiological action, seems in part a result of, and in part re- 2 Papers in Medicine. that the immediate resultant of two opposing dynamic drug forces can never be intrinsically the same as a condition found in health,- that, though this resultant may look like what obtains in health, the same it is not. To illustrate : Take a normal pupil; dilate it with a mydriatic, and then contract it with a myotic ; this pupil may now look as it did before your experiment began, but is a pupil normal when its condition is the immediate resultant of antagonism between two drugs ? I think not. Indeed, may it not be that this pupil is farther from normal than it would be under the influence of either one alone of these drugs, even though it would then be dilated or else contracted? If the views here expressed or implied are correct, it follows that in rational practice any benefit which we can reason- ably expect from dynamic antagonism (whether that antagonism be radical or superficial), must be something else than a direct reestab- lishment of normal conditions.* To some it may seem axiomatic that there is no such thing as radical antagonism, and superfluous to discuss whether there is ; but much of medical literature seems to me to have been written from the standpoint of a belief in such antagonism. That he who first formu- lated contraria contrariis opponenda used the incomparable adjective contrarius seems to imply that he believed in radical antagonism (this thought will again be touched upon in this paper), and I suspect that many adopting that formula have also believed in such antagonism. I think that radical antagonism does not obtain-that could we, be- ginning with an antagonism patent on the surface in any one func- tion or organ, trace the action of drugs indefinitely far toward the prime cause of their surface effects, we should always find them failing of the requirements necessary to radical antagonism, full and complete. But the question of radical antagonism seems to me one of opinion, and perhaps not capable of conclusive demonstration by purely inductive methods. Whatever links in the modus operandi of a dynamic drug may have been recognized in an inductive investiga- sponsible for, a lack of recognition of the fact that such effects are not normal, but abnormal. Is not the science of drug pathogenesy as distinct from the science of physiology, as is the science of pathology ? Is it not as confusing to call patho- genetic effects physiological, as it would be to call pathological effects physiological ? * By a rational practice in this connection I mean one in which we induce the pathogenetic effect of a dynamic drug, in the expectation, based upon some a pri- ori reason not law, of benefiting the patient. One wishing to do so may find in the North American Journal of Homceopathy for January, 1892, an article upon "Empiricism, Rational Practice, and Practice under Guidance of Law," in which I attempted to give a complete definition of rational practice. Drug Poisoning: Mack. 3 tion, there always must be, it seems to me, unrecognized links be- yond. Let us again draw our illustration from mydriatics and my- otics : To find that through these muscle fibres, or through those muscle fibres, the condition of the pupil under a given drug is deter- mined, is not to get at the root of the matter; nor is the root reached when we fix upon this or upon that nerve, or even nerve-centre, as the one through which the muscle fibres are affected. To demon- strate radical antagonism full and complete between a mydriatic and a myotic would be to show them operating through respectively (in all particulars) one and the same channel. The word all in this con- nection includes some minutiae which we may still hope to discover, and, I think, some which we shall never discover. A characteristic of science is that it can never exhaust the minutiae of any phenomenon. We have simply expressed the opinion that radical antagonism does not obtain, and given a reason for thinking that its existence could not be inductively demonstrated. One who agrees to this reason may still think that such antagonism exists, even though undemon- strable.* In the present paragraph we shall have regard only to superficial antagonism in rational practice; not to radical antagonism or to prac- tice under guidance of law. Perhaps we may in some circumstances reasonably expect to ameliorate a patient's condition, or even to save his life, by effecting superficial antagonism in a function or organ necessary to life (e. g., the respiration or the heart) ; but it seems possible to attach an entirely false significance to the fact of super- ficial antagonism in some function or organ not necessary to life. To illustrate I still again cite drug effects upon the pupil. Bartholow says he agrees with Schmiedeberg " that no example of physiological antagonism could be more exact " than that afforded by muscarine and atropine. Leading up to the statement that "viewed from all sides, these agents are exactly antagonistic," he is citing points of antagonism between them when he says : "On the eye, the con- tracted pupil of muscarine, due to stimulation of the circular fibres innervated by the third nerve, is opposed by the dilated pupil of atro- * In this foot-note we depart for the moment from strict adherence to our defi- nitions. Those definitions were not formulated with a view to specially consider- ing whether antagonism radical in kind may obtain in one organ or function, and not in all those affected by any two antagonistic drugs ; nor were they formulated with a view to specially considering whether an antagonist acting less deeply than another may still be in kind radical. The difficulty (or impossibility) of demon- strating radicalness of antagonism at any point would be such as I have just indi- cated. My opinion is that there is no such thing as radical antagonism between drugs at any point or in any degree. 4 Papers in Medicine. pine, produced by stimulation of the radiating fibres, innervated by the sympathetic.* If, in treating one poisoned by muscarine, our immediate object were (as in the common ophthalmological practice with mydriatics) simply to dilate the pupil, it might be of no moment whether it was through paralysis of the third nerve and circulatory fibres, or through stimulation of the sympathetic nerve and radiating fibres, or through a combination of these, or in still some other way, that the dilatation was effected. But in poisoning by muscarine the contraction of the pupil is not what harms the patient, and there is no advantage in merely dilating the pupil. If it is true that the contraction from mus- carine is effected through a channel other than that through which the dilatation from atropine is effected, it may fairly be doubted whether this contraction and this dilatation have any bearing upon the question whether atropine will benefit a patient poisoned with muscarine. We tend, then, to the conclusion that, in the rational treatment of those seriously poisoned, while it may sometimes be useful to establish superficial antagonism in a function upon which life depends (as that of respiration), the establishment of superficial antagonism in a function or organ not essential to life (e. g., the pu- pil) may be useless. Up to this point our discussion has been upon giving in rational practice to those seriously poisoned dynamic antagonists. It may be that in contraria contrariis opponenda we have a law of nature, and practice under guidance of law I should not classify as (technically) rational practice. If contraria be law, considerations quite different from those bearing upon rational practice present themselves. A law of nature speaks from the true centre of things, and to us, who as inductive scientists observe surface facts, it states what relation between those facts must be established to a given end. It may be, then, that, if contraria is law, antagonism in an organ not necessary to life (e. g., the pupil) is significant as an indication, and that the contrariety between muscarine s myosis and atropine s mydriasis, are facts between which that law states the relation, though the contra- riety it demands might be more satisfactory between muscarine and some mydriatic, both of which, as far as we could trace them, we found operating (on muscle fibres in the iris, on nerves, etc.) through respectively one and the same channel. My use here of the word contrariety is perhaps incorrect, and will presently be referred to. If out of regard for contraria as law we are to use dynamic antag- onists in case of drug poisoning, and if I am mistaken in supposing * Bartholow's "Hypodermatic Medication," Fifth edition, pp. 311, 312. Drug Poisoning: Alack. 5 that no such thing as radical dynamic antagonism between drugs exists, we must, I think, fix either upon radical antagonism or else upon superficial antagonism-one or the other-as that which con- traria. exacts. It seems to me that there is an essential difference between these two kinds of antagonism (if radical exists at all), and that one and the same law (if contraria be law) docs not speak indis- criminately of them both. In writing of homoeopathy's claim and of isopathy's, I have re- garded as significant the facts that similis is a comparable adjective, and that idem is incomparable.* A drug may be in greater or less degree a similar, i. e., maybe more or less homoeopathic. One who is disposed to accord any place to isopathy among medical systems must, I think, admit that, idem being an incomparable adjective, iso- pathic treatment (excepting with drugs which themselves were pro- ducts of disease, or in case of poisoning by drugs) would be entirely impracticable, even if in theory correct; for in any given case one drug only could be isopathic,-in selecting the isopathic drug no latitude could be allowed,-a drug could not be more or less isopathic. Thoughts analogous to those suggested by the compara- bility ot similis and the incomparability of idem may suggest them- selves to one considering whether the contrariety afforded in radical antagonism or that afforded in superficial antagonism is the contra- riety which contraria would exact. If I am mistaken in thinking that radical antagonism between dynamic drugs does not obtain, it still appears that to any given dynamic drug there could be but one radi- cal antagonist. Contrarius is an incomparable adjective, and a radi- cal antagonist would meet the demands of contraria ; but I think it would be as impracticable to comply with a law which exacted a radical antagonist (contrarius being incomparable) as it would be to practise isopathy, excepting with drugs which themselves were pro- ducts of disease, or in case of drug poisoning (idem being incompar- able). Though contrarius is incomparable, we may by agreement regard it in contraria contrariis opponenda as predicating what we may agree to call comparable contrariety ; such contrariety is afforded to super- ficial antagonism ; superficial antagonism of greater or less degree may obtain. I take it that, notwithstanding the incomparability of contrarius, comparable contrariety has often been regarded as satis- fying the demands of contraria. When, in the third paragraph back from this point, I said that the contrariety demanded by con- traria might be more satisfactory between muscarine and some my- ,* See p., 43 of Philosophy in Homoeopathy." 6 Papers in Medicine. driatic other than atropine (than between muscarine and atropine}, j spoke as if contrarius were comparable, which it is not. 1 suppose that any drug worth considering as a dynamic antago- nist in case of drug poisoning, is itself capable of producing serious poisoning. In passing I simply allude to the generally recognized possibility of seriously, even fatally, embarrassing one function or organ with a drug used for the sake of antagonism in some other function or organ. While this possibility is, as I say, generally recognized, the recognition is, I think, more cordial in theory than in practice. I think that often due caution is not observed in at- tempts to relieve with dynamic drugs persons seriously poisoned. Conclusions to which this paper tends are : ist, That radical an- tagonism (dynamic) between drugs does not obtain. 2nd, That in rational practice upon those poisoned with drugs there is no use in attempting superficial antagonism (dynamic) in functions or organs not necessary to life. 3rd, That in rational practice we should not without the greatest cautidn attempt to dynamically antagonize dy- namic drug poisons. 4th, That if contraria is law and applicable in the treatment of those poisoned with dynamic drugs, the contrariety it exacts must be such as is afforded in superficial antagonism. 5 th, That, if contraria is law, we should not without the greatest cau- tion attempt under that law to relieve with dynamic antagonists those seriously poisoned by drugs, unless cause can be shown for thinking that under contraria doses which would in themselves be harmless are efficient.