Nitro-Glycerinum

Spiritus Glonoini

Spirit of Nitroglycerin

Glonoin

Properties

Nitro-glycerin is an oily liquid, colorless, or pale yellow, and has the specific gravity 1·60 at 59° Fahr. It burns quietly in the open air, but heated in a close vessel, or subjected to percussion, it explodes violently. It decomposes if long kept. It is very slightly soluble in water, but dissolves freely in alcohol and in ether. The best preparation for administration is the alcoholic solution—one part of nitro-glycerin to one hundred parts of alcohol. The dose of this ranges from one minim to many minims. As the susceptibility to this agent varies greatly, the initial dose should be the smallest. One minim of the one-per-cent solution will give some persons violent headache, while others may take a minim of the undiluted drug without any decided effect.

So much apprehension is felt by patients who have to take this remedy, that the names "glonoin" and "trinitrin" have been proposed for it, and have now come into general use.

Sodii Nitris

Sodium nitrite.

Potassii Nitris

Nitrate of potassium. These salts have been proposed and used as substitutes for amyl nitrite and nitro-glycerin. Dose, gr. iij—gr. viij.

Antagonists

All those agents which increase the reflex activity of the spinal cord and stimulate the vaso-motor system, as strychnine, ergot, digitalis, belladonna, etc., antagonize nitro-glycerin.

Synergists

Amyl nitrite acts very similarly, and the motor depressants in general promote the actions of nitro-glycerin.

Physiological Actions

The taste of nitro-glycerin is at first sweetish, but this impression is followed by aromatic pungency. In a few minutes—from three to five—after a small medicinal dose, there are suddenly experienced a feeling of giddiness, tension of the head, with fullness, languor, nausea, and sometimes stomach-pain. Such effects are experienced from a small dose, if the individual taking it is susceptible. It follows, then, that the quantity of nitro-glycerin causing such symptoms must vary in different patients. Dr. Harley experienced these effects after taking fifteen drops. Dr. Fuller experienced some fullness of the head, perspiration, intermittent pulse, and some after-headache, from a dose equivalent to fifty minims of a one per-cent solution, or a half-drop of the nitro-glycerin itself (Murrell). In some persons a drop or two of the one-per-cent solution will cause dizziness, faintness, a rapid and very weak pulse, perspiration of a rather clammy character; or, indeed, the symptoms may proceed to unconsciousness. Dr. Murrell applied the moistened cork of the bottle containing the solution to his lips, and in a few minutes experienced a tremendous action of the heart and arterial system; his pulse rose to 100 and higher, and he had "a splitting headache" for some time. There is no change in the temperature. Women and the feeble in constitution suffer more decided effects than the robust. Drowsiness comes on, with a feeling of languor, in those on whom the smallest dose acts kindly. With the rapid pulse is a considerable degree of dicrotism. The change in the character of the pulse begins in about six minutes after the dose is taken, and lasts on the whole about one hour. The sphygmographic tracings appended to Dr. Murrell's paper are remarkable for the extent of the excursions of the lever, the abrupt ascent, the sharpness of the summit, and the dicrotic rebound, indicating an extremely low state of the arterial tension. When the heart of a frog is put into a ·75-per-cent salt solution, and two drops of a ten-per-cent solution of nitro-glycerin are added, the heart acts more and more slowly, and presently stops. An alcoholic solution has no effect (Brunton). When injected into the jugular vein of a cat, the nitro-glycerin solution arrests the heart speedily. That the vagus is paralyzed, and the inhibition thus removed from the heart, is proved by the fact that galvanic excitation of the vagus has no effect in restraining the cardiac movements. Changes occur in the blood like those induced by amyl nitrite and the nitrites of soda and other nitrites; that is, the blood assumes a chocolate-color, and probably loses its power of absorbing and conveying oxygen; but its so-called ozonizing function may not be interfered with, since nitro-glycerin does not prevent the guaiac reaction, in which respect it agrees with the other nitrites. The change in the color of the blood is produced slowly when blood is shaken up with some nitro-glycerin outside of the body (Brunton).

In frogs nitro-glycerin causes weakness, tetanus, ending in paralysis; but, in warm-blooded animals, there are convulsive movements, as twitching of the muscles, hiccough, spasmodic breathing, etc. The tetanus in frogs, according to Brunton, is not due to a direct action of the poison on the spinal cord, thus opposing the assumption of Minor, who held that it acts on the medulla. The paralyzing effect of nitroglycerin appears to be due to an action on the muscles, and also on the motor nerves. When it is applied directly to the muscles, they quickly lose their contractility. The reflex function of the cord is extinguished first in the parts external to the cranium, the cerebral nerves preserving their power to transmit impressions until later. Sensation is destroyed by it as well as motility. Death is due to asphyxia —to paralysis of the muscles of respiration. Notwithstanding the activity of nitro-glycerin, the most serious symptoms are recovered from without detriment. Thus Dr. Murrell narrates several cases in which unconsciousness was produced without any ill results, except some temporary headache.

Therapy

Nitro-glycerin is adapted to the treatment of the maladies in which its congener, amyl nitrite, has proved so effective. It has the advantages over the latter of being more permanent, more readily administered, and more sustained in action. In sea-sickness, reflex vomiting, gastralgia, hepatic colic, and other painful and spasmodic affections of the digestive tube, it may afford very prompt relief. It was first employed in the treatment of angina pectoris, in which it gives as much relief as does amyl nitrite, but the latter should be preferred when the utmost promptitude of action is necessary. The form of the disease requiring this medicine is that characterized by high tension of the peripheral vessels, which is doubtless the condition in the genuine cases of angina pectoris. Very prompt relief may be given to attacks of hiccough by this medicine. Some cases of spasmodic asthma are much benefited by it. The less there is of structural alterations, the more certain the relief. As the secretions of the mucous membrane of the respiratory tract are increased by it, the cases with deficient secretion are those most certain to be benefited. It should be carefully tried in whooping-cough and in laryngismus stridulus. There is much to be expected from nitro-glycerin in diseases of the nervous system characterized by heightened reflexes. An attack of epilepsy may be aborted by its timely administration, and Hammond finds it as a remedy for this disease second only to the bromides. By preventing the spasm of the vessels and consequent sudden anaemia of the brain, the first and most important event in the series can not occur. It should be fairly tried in tetanus and hydrophobia. In neuralgia of the fifth nerve it has given immediate relief in numerous instances. It is the most appropriate remedy in that form of migraine, or sick-headache, in which the vessels are in a condition of spasm, but is not proper in those cases having a flushed face from dilated vessels.

The cold stage of an intermittent may be aborted by the timely administration of nitro-glycerin. It promises to be especially useful in the pernicious malarial diseases to prevent the dangerous depression of the cold stage. In these cases its administration should be so timed that the physiological effect of the remedy occur at the onset of the cold stage of the disease. The mechanism of its curative action is obvious. Remarkable results have lately been obtained from this remedy in acute and chronic Bright's disease (Robson)—results which the author is able, from personal observations, to confirm. It is well known, of course, that high arterial tension is present; but whether as causative of the renal changes, or a consequence of them, is not known. The apparently constant association of degenerative changes in the renal ganglia with the lesions of Bright's disease, discovered by Da Costa and Longstreth, would indicate that the state of the vessels is a factor in developing the structural alterations. The manner in which nitro-glycerin affords relief, and possibly effects a cure, is thus fully explained. Indeed, all of the curative results obtained from nitro-glycerin must be referred to its action on the vascular apparatus. The suggestions as to its therapeutical employment above made have been abundantly justified by the experiences gained since the publication of the last edition of this work. The author has now to submit some observations on the utility of trinitrin in cardiac affections. Pseudo-angina pectoris, fatty heart, and weak heart, are morbid states that appear from about forty-five onward. Degenerative changes, belonging to advanced life, underlie the attacks of pain with disordered function, and are also responsible, to some extent, for the other condition. Weak cardiac contractions, and damaged vessels, interfere with the nutrition of the body in general, including the muscular substance of the heart. Feebleness of the cardiac contractions lessens the force of the impulsion with which the blood enters the arterioles, and they contract on their lumen as the anaemia increases. Now, trinitrin opposes this state of things. Under its action, the heart contracts more frequently and energetically, the arterioles dilate, and thus the organs of circulation are helped in two modes: in facilitating the distribution of the blood by lessening the pressure in the arterioles at the periphery; and in improving the power of its own muscular tissue, by the increased amount of blood passing into it through the coronary artery. If we add to these good effects the permanent improvement of nutrition by a suitable diet and exercise, we have a satisfactory solution of some of the most difficult problems given us to solve. It should be understood, also, that the improvement of nutrition by increased alimentation is the more complete because, by the action of trinitrin, a much larger quantity of blood is obtained by the tissues, and hence more of the nutritious matters, than would otherwise be available. The author has availed himself of these facts, and has utilized trinitrin in the treatment of anaemia in its ordinary form, and in the pernicious variety. One of the most common of the therapeutical fallacies of the day is the giving of iron to cure anaemia, for in a large proportion of the cases the iron can not be assimilated. The organs concerned in blood-making may be in a pathological condition, or functionally torpid. Stomachal and intestinal digestion may be in such a state that the ordinary preparation of food-stuffs is too imperfectly performed for the materials to be utilized in blood-making. To cure anaemia, something more is requisite than to give iron. The functional or pathological states that interfere must be removed. When all the digestive and assimilative functions are restored, failure is still encountered by imperfect distribution of the blood. The heart may be feeble and act imperfectly, the peripheral arterioles may contract on their lumen, and thus hinder the passage of the blood. Such is the condition in a large proportion of the cases of anaemia. To bring about a proper activity of the nutrition, it is necessary to restore the organs of circulation, and admit the fullest nutrient supply to all the tissues. It is this function of trinitrin that places it in the front rank of remedies for anaemia, for by dilating the arterioles and energizing the heart's action the fullest supply of blood is sent to all the tissues of the body.

Authorities referred to:

Brunton, T. Lauder. St. Bartholomew's Hospital Reports, vol xii, p. 140. Preliminary Notes on the Physiological Action of Nitroglycerin.

Minor, Dr. A. J. Journal of Nervous and Mental Diseases, vol. iii, p. 355.

Murrell, Dr. William. The Lancet, 1879, pp. 80, 113, 225.

Robson, Dr. Mayo. The British Medical Journal, November, 1880, p. 803.