antimony are important for us, above all the potassium antimony tartrate, a double salt of tartaric acid. Tartarus stibiatus and tartarus emeticus, are other names for the same preparation. The other common antimony preparations are the naturally appearing sulphur compounds Sb2 S3 black or grey antimony our antimonium crudum and Sb2S5, red antimonium sulphide, our antimon, sulfurat, aurantiacum. Antimonium aresenicosum is a mixture of antimony pentoxide Sb2O5, with arsenic trioxide, As2O3. The variability of these preparations constitutes a great difficulty in deminitely establishing the characteristic antimony effect. In general potassium antimony tartrate is regarded as the compound which comes the nearest to approximating a true antimony effect, since the antimony binding here is very loose. Experimental investigations have also been made largely with it. Spiro assumes that the slighterobserved favorable effects from these.
This group is named after the first member of its group, nitrogen, but as in all chief groups, here the elements with the lowest ordinal number is the least characteristic of the group, because, as an element, nitrogen, in contrast to phosphorus and arsenic, is quite inert and its H as well as O compounds differ considerably from the other elements of the group. The H compounds of nitrogen, ammonia and its salts, do not come into consideration in comparison as drugs with the usual compounds of the other elements of this group, and they have already been discussed with the alkalies. The remaining elements of group V unfold their actions in or on the organism, especially in the various stages of oxidation. And if one compares the already oxidized compounds of nitrogen with the usual compounds of phosphorus and arsenic which are employed as drugs, then the group relationships will become more distinct. The actions on the vascular system, in particular on the capillaries, which give the essential note to the members of this group, naturally vary considerably in degree. And with the increase of metallic character of the elements with increasing atomic weight, the action sphere in this group narrows itself evermore in an organotropic sense. Nevertheless in the transition of medicinal preparations in the series from nitrogen, N, to phosphorus, P, Arsenic, AS, antimony or stibium, Sb, to bismuth, Bi, the red line can be easily followed which also traces out the group affinities of these elements.
NITRITES AND NITRATES
The point of departure in a pharmacologic consideration of nitrites and nitrates is the action on the vessels and blood pressure. It is not only the NO2 or better O. NO anion, the inorganic salts and organic esters of nitrous acid, but also a number of organic esters of nitric acid, as nitroglycerin, whose manner of action is characteristic. Also the inorganic nitrates, potassium and sodium nitrate, still work in the same sense so that one might assume a reduction to nitrites in the organism. Such a reduction by micro-organisms have the capacity for obtaining oxygen out of nitrates; the plants use nitrates for the building of protein, NH2 compounds, and here also a reduction must occur. It is important that the pharmacologic action of nitrates or nitrites appears only in the true salts or esters, that is, the nitrogen as an alkali metal or an organic radical through the intermediation of oxygen; in other words it must be inorganically bound; moreover, it must be as O. NO. In the nitro-bodies in which the nitrogens is bound directly, that is organically to the radical, the characteristic action is practically absent.
Best investigated experimentally of the nitrites is amyl nitrite; of the nitrates, nitroglycerin, the glonoin, of the homoeopathic materia medica. Even if amyl nitrite C5H11.O.N.O
is used only a little in homoeopathy, still one approaches nitrite action advantageously from it, because, it has been studied the best.
The transient alleviation which amyl nitrite as well as nitroglycerin gives in angina pectoris through widening of the coronary vessels is generally known. For homoeopathy it
is interesting as the first fact that the inhalation of vapors of only a few drops of amyl nitrite can produce very definite symptoms. The amount, certainly very slight, becomes effective with the mucous membranes of the respiratory organs acting as the portal of entry, and it is indeed exactly the great dispersion which favors this. The possibility that, by fine division, still other materials could be effective in this way, Hahnemann’s olfaction of the high potency, is not rejected without further consideration.
The second fact of decided interest is the particular relation of nitrites to the upper part of the body. If we find so frequently in homoeopathic literature reports acts from above down or from left to right then at first this seems absurd, but observation teaches it and requires explanation. And one so observed selection of a body region that appears free from objection occurs with amyl nitrite.
The immediate action on inspiration of the vapors of a few drops of amyl nitrite is the feeling of warmth in the head and neck, usually, a feeling of fullness and heaviness of the head; the arteries pulsate, vertigo and severe headache often appear. Face, head and neck are reddened; usually this reddening is limited to the head, neck and chest; only rarely does it reach the back or extend to the arms. The lower extremities are not involved in the widening of the blood vessels. The pulse becomes distinctly accelerated, often irregular. It is striking that in other cases the previously irregular pulse becomes regular. Therein one sees that a reversal of symptomatic effect of drug action can also lie simply in the diversity of the conditions, in the previously balanced or imbalanced state of the organism, and that it is not always the difference in dose which is responsible for such a reversal of the end result.
Severe toxic manifestations are represented by a type of intoxication with loquacity, at times nausea and vomiting, fainting and collapse; moreover, one will observe after marked and longer inhalations, indistinct vision or yellow vision, muscle twitching, local or general outbreak of sweat. According to pick, after a full dose of amyl nitrite objects appeared of a yellow color with a blue-violet halo surrounded with wavy borders.
The blood-vessel actions of the nitrites are the most important. They manifest themselves in widening of definite vascular fields, rapid sinking of the systolic and diastolic blood pressure, and acceleration of the pulse. The action occurs very rapidly (in a few seconds) after the inhalation, but has soon disappeared (after a few minutes). In men of middle age the action is more marked than in the very young and very old.
The fall in blood pressure, according to experimental results, is certainly to be ascribed to blood-vessel widening and not to an action upon the heart. An action immediately upon the vessels is established, but, in spite of a large number of refined pharmacologic experiments, it is still debated (between Brunton and others on the one side and Filehne on the other side whether the action of nitrites on the vessel is purely peripheral or also partly conditioned through central depression of the vasoconstrictors. For the participation of the centrum speaks an observation of Darwin that under nitrites exactly those parts are reddened which are also reddened by the feeling of shame a therapeutic indication, perhaps, for this symptom, if it is annoying through an excess. The numerous animal experiments, on the contrary, speak for a pure peripheral action on the vessel wall.
That many questions remained unsolved in this respect is shown by animal experiment when after compression of the carotid amyl nitrites is injected into the cranial end (the amyl nitrite in salt solution), it thereby effects an increase in blood pressure. Whether the peripheral-vessel action is excreted on the musculature or upon the nerve endings lying in it is still not determined.
Besides the ever again demonstrated vessel widening, the old observation of Gaspeys serve to show that bleeding from injured arteries begins again when amyl nitrite is administered. According to Lisin a wound of the intestine or the lip would bleed less by virtue of the lowering of blood pressure, but when the pressure returned to normal, the bleeding would be greater than before.
According to experiments of D.L. Brunton, the acceleration of cardiac action depends upon lessened activity of the vagus center; according to Dossin, however, also upon stimulation of the nervi accelerantes. In any case this action, at least partly, is the result of fall of pressure as in anemia and also an attempt at balance. As the tonus of the vagus center is greater during middle age, so the acceleration of the pulse in middle life is more marked in comparison to youth and to old age. But by single authors a direct action upon the heart is assured outside of central effects. Moreover, by inhalation of amyl nitrite a slowing of the heart is also observed through a reflex action on the respiratory passage. Outside of the acceleration of rhythm, still further proof of increased activity of the heart can be observed, as for example increased capacity of conduction and heightened contractility. The final weakening and paresis of the mammalian heart through enormous amounts can as well be a direct action as a result of asphyxia in consequence to alteration of the blood (methemoglobin formation). (The influence on respiration consists of irregularity at first after inhalation, this being a reflex irritant effect, also mild slowing, at the beginning: but on repeated inhalation, stronger acceleration follows the initial slowing, perhaps as action upon the vagus endings or upon the respiratory center, the acceleration like the cardiac increase probably being a compensatory attempt in consequence to the low blood pressure).
The vessel widening of upper part of the body is associated with an increase of the skin temperature and an increase of heat radiation. Consequently the internal temperature falls. In normal rabbits the decrease in body temperature is only slight. But when the temperature is made febrile by heat puncture, then amyl nitrate evokes a very distinct decrease. Here we have the same demonstration as with the antipyretics with central action, that the fall in temperature first comes distinctly to expression in disturbed temperature equilibrium.
To use the nitrites as antipyretics, where the radiation from the skin (without central involvement) is also desired, has experimental support. The increase temperature of the body surfaces determines this relationship according to the simile rule. Another is also the methodic indication from the symptoms to the therapeutic result; another, the possibility of explanation of the demonstrated result. If the direct result is the surest for the prospective way, then the indirect observation of the intermediate process is necessary or desirable for the retrospective explanation.
In connection with the nitrite headaches (obviously through vessel widening), the yellow vision (often with violet borders) seems to me worthy of note. This is a manifestation by no means rarely observed in migraine. Besides cina, which has this symptom of yellow vision as a very prominent one, a nitrite (or nitrate) is to be considered in those cases with this symptom.
Moreover, the action on the eye has been experimentally demonstrated. Filehne found in the frog eye the visual purple supply accumulated by a sojourn in the dark was not altered through nitrite poisoning. But the replacement of the visual red used by light is decidedly damaged under the influence of massive poisoning and the material provided is unstable. Atkinson asserts that sodium nitrite in small doses mildly widens the veins as well as the arteries of the retina, while after large doses a distinct narrowing is observed.
The relaxing action of nitrites on smooth muscle is known from the action on vessels but has also been demonstrated experimentally on other parts of organs, naturally not in general on the organs from nitrite inhalations. In this respect the use of nitrites, by inhalation as well as orally, in bronchial asthma depends on relaxation of the smooth muscle of the bronchi. The burning, of the well-known Charta nitrata also acts as nitrites which develop from the reduction of nitric acid. However, Trendelenburg found that sodium nitrite in Ringer’s solution produces a distinct increase in tonus on the surviving bronchial muscle. Such seeming contradictions are naturally riddles for those who do not take into consideration the method of introduction and the dosage associated with it. The demonstrations above satisfy us that under certain conditions nitrites act as tonus-increasing, under other conditions tonus- decreasing also on the bronchial muscle. The cases of asthma perhaps suitable for such medication will be selected not merely according to the viewpoint of muscle relaxation or constriction, but according to the totality of the immediately observable symptoms that, is the symptom dependencies (the modalities).
An action of nitrites has been experimentally demonstrated also on voluntary muscle. The direct influence of nitrite vapors on the resting frog muscles provokes a prolonged hardening with transition to rigidity. Leech found that in a solution of NaCl containing sodium nitrite (1:5000) a suspended muscle remained able to contract only for two hours and that amyl nitrite was just as damaging to it.
The end actions of amyl nitrite poisoning have little significance in this place. Chiefly they are the formation of methemoglobinemia with the accompanying glycosuria and asphyxia, with depression, weakness, and lethargy and the lethal ending affected through the blood alterations. Direct toxic actions on the central nervous system as they appear in the frog, as descending paresis, are not observed in mammals and man.
The nitrites of alkali metals (NaNO2 and KNO2), according to the studies of several investigators in general, are the same as amyl nitrite, only the salts orally are more persistently effective and they act more slowly. In particular the time of development and the duration of the blood pressure lowering are found to be greater. The headaches in man should be affected more easily than through the nitrite esters, because the circulatory alterations last much longer.
There is usually one impression which one generally gains: the compounds with organic fractions are more volatile than the inorganic compounds in which the action appears more slowly but is maintained longer.
Nitroglycerin, our glonoin (a shortening of glycerin, O.N.O) has clinically and experimentally almost the same action as the nitrites, nevertheless it is a nitrate and indeed the trinitrate of glycerin, the most simple of the trivalent alcohols, CH2.OH- CH.OH-CH2.OH, in that each OH group is replaced by a NO3 (more exactly O.NO2) group, that is C3H5(NO3)3 – (not, however, the impossible triglyceride of nitric acid, as it has entered homoeopathic literature through an error of H.Schulz). The extensive agreement of action with the nitrites is explained in that in the body the nitrites are formed from nitrates.
It has been shown by Hay that nitrites are formed in the blood from nitrates, which gives occasion for the formation of methemoglobin. Even in the test tube through alkali two thirds of the nitrates are reduced to nitrites. After small doses nitroglycerin appears chiefly in the form of nitrites in the urine, after, greater, for the most part unaltered.
To be noted as a minor deviation from the action of amyl nitrite is the feeling of heat in the larynx and in the throat and that the arteries in the neck pulsate especially strong. An exact description of the subjective head symptoms which undoubtedly are connected with the vessel widening are evident from the first American provings by Hering
Provings of glonoin are found in:
(1) C. Hering: American Arzneiprufungen, Bd. 1, 1857 (provings collected since 1847).
(2) Lembke: Zeitschr.f.hom. Klin, Bd.,2 1853.
(3) Eichhorn: Zeitschr. d. Verbascum hom. Aertze Oesterreichs, Bd. 2 p.18 1857.
(4) Demme: Schweiz. Zeitschr. f. Heilk., Bd. 1, 1862.
(5) Allg. Hom. Ztg., Bd. 63 pp. 119 and 128 1862; (Wood and Colby, according to the Brit. Jour. Hom., 1861.
(6) Leibinger: Deutsch. Zeitschr. f. Hom., p.194, 1926.
Soon after the discovery of glonoin in the year 1847 by Sobrere, C.Hering introduced this remedy into medicine. The provers observed: sensation of enlargement of the head, the chin seemed too long, the neck swollen, pressure in the eyeball, spots and flashes before the eyes, letters of a book became small on reading, well-known streets seemed strange. The headache was severe, there was a feeling of fullness with pulsation; movement, bending back and particularly shaking the head aggravate; mental work is difficult.
The acceleration of the pulse and lowering of blood pressure occurs (after about 1 mg.) later than after inhalation of amyl nitrite but also lasts considerably longer(2-3 hrs). If one perfuses nitroglycerin through the vessels of a frog, then, even in a dilution of 1:1 million, it increases the speed of perfusion considerably and one can recover nitrites from the fluid emerging from the veins even after the use of a solution of nitroglycerin 1:100,000. The vessel-dilating action is much more distinct in warm-blooded animals than in the frog. The severe toxic actions in man are nausea and vomiting, later delirium, loss of consciousness and coma.
There is a great individual difference of susceptibility for nitroglycerin and in persistent employment a strong, tolerance is established which is soon lost again after discontinuance of the medication.
GLONOIN IN ANGINA PECTORIS It should now be considered on the basis of the symptoms of the provings whether or not and how far the therapeutic use of nitroglycerin in angina pectoris is homoeopathic. Homeopathic authors, for example Dahlke and Stauffer and Bernauer (the last in Deutsch. Zeitschr.f. Hom, H. 3, p. 12, 1926) consider the non- homoeopathicity merely on the grounds that large doses, that is, about one milligram, widen the coronary vessels which would be characteristically the the opposite of the coronary narrowing in angina pectoris. I cannot recognize this argument as valid because the similarity or nonsimilarity in the homoeopathic method refers not to such intermediary processes and pathologic anatomic foundations, but to the symptomatic manifestations.
Now we find in the American provings of glonoin; constriction of the chest, restlessness, anxiety. Cardiac palpitation with pulsation in the carotids, unrest in the arms, numbness and fatigue in the left arm; the pulse is felt in the fingertips. One prover describes after one-third of a drop of the saturated alcoholic solution (three doses): “the activity of the heart proceeded laboriously with a peculiar sensation of oppression. I went into the open air and after a short time the severe symptoms diminished and there remained only a feeling of heaviness and an unpleasant sensation about the heart”.
From a proving of glonoin in Schwabia, the symptoms of the eleventh prover may be mentioned. Because of their struma parenchymatosa they seem to have special liability of the cardiovascular system, for they reported they had previously experienced “now and then very obvious cardiac action”. After five drops of the third decimal potency, which is also about one- fourth of the smallest dose used clinically under ordinary circumstances, these provers observed ever again: “After three to five minutes: transient feeling of anxiety. Feeling of oppression in the heat briefly, the cardiac pulsation unpleasantly obvious and the pulse seemed fuller, more powerful, not more rapid”.
In the sixth prover on the eight day of the proving with the fourth decimal potency was reported: “About 11 o’ clock in the morning cramplike pains in the left biceps in each movement particularly bending; it ceased immediately on rest; not sensitive to pressure. The pain increased up to noon and about this time passed over to the ulnar side of the arm. Diminished after about two hours and by evening it was only trifling”. On the twelfth day: In the morning about 11, paroxysmally for a few minutes, cramplike, constricting pain in the chest, particularly on inspiration. Coming, and going rapidly and lasted in all about one-half an hour”.
Such symptoms are, indeed, not an image of a completely developed case of angina pectoris but are still a very extensive approximation in the symptoms. The repeatedly observed pains in the left arm may be compared to the well-known radiation in angina pectoris and may be conceived as a viscero-sensory reflex. That one cannot produce a momentary occlusion of the coronary vessels and in the severely arteriosclerotic vessels, is certain, but still is not decisive for the question of the homoeopathic suitability. How does man react to angiospasm and how to glonoin? That is the question; with anxiety, sensation of oppression and cramp and radiating pain in the arm is the answer. And from this is yielded a certain probability under the homoeopathic viewpoint that glonoin is of use in angina pectoris; reversely if glonoin is helpful in angina pectoris, then this is a support of its proving symptoms.
The use of glonoin in angina pectoris would not be homoeopathic if it did not support the help of the organism in an attack but suppressed it. Now there is no doubt that in extreme angiospasm the self-regulation tends to vessel-widening and the symptoms are an expression for this and that glonoin supports this regulation in this sense. We must judge always according to observations, the symptoms, not according to ideas of intermediate events.
When further against the homoeopathic justification of glonoin
in angina pectoris is cited the brief action and the necessity of doses of about one milligram (also the 2-3 decimal potency), so this too is not valid. Glonoin is also a short and rapidly acting remedy, and so the remedy is suitable for the attack in respect to rhythm. That one cannot obtain lasting results with glonoin in the presence of high-grade structural alterations of vessels is no contradiction. Only if it could be demonstrated as has not been the case up to the present that the use of glonion favors the reappearance of the attack in the after effect, or that an afterstage of angiospasm existed, only then would it be palliative assistance in a case, although at times necessary and justified, to limit it to a minimum in the interest of the total circulation.