This section is from the book "Materia Medica: Pharmacology: Therapeutics Prescription Writing For Students and Practitioners", by Walter A. Bastedo. Also available from Amazon: Materia Medica: Pharmacology: Therapeutics: Prescription Writing for Students and Practitioners.
After a very brief period of increased activity from accelerator stimulation, the heart becomes slowed through prolongation of the diastolic pause, and there is diminished muscular contraction in systole, i. e., the heart does less work and has a longer resting period, and there is diminished output of blood and a gradual lowering of blood-pressure. This is the typical vagus effect; and it must be due to stimulation of the vagus center, for it does not occur if the vagi are cut or after atropine. This is followed by the same stages as result from digitalis.
As a matter of fact, in laboratory animals aconite produces effects which resemble so closely those of digitalis that one would think of the drugs as belonging to the same pharmacologic class. Following or accompanying the slowing there may be sinus arhythmia, heart-block, or one or other of the manifestations of increased irritability, normally inactive points in the heart taking on the power of originating stimuli (Cushny). (See Digitalis.) It was with aconite that Cushny discovered the phenomenon of reversed or retrograde rhythm, in which the auricular beat follows that of the ventricle instead of preceding it. In toxic amounts it also constricts the arteries by stimulation of the vasoconstrictor center.
In therapeutics it has been assumed that pure vagus stimulation might be obtained, as shown by a slowing of the rate and a fall in arterial pressure. But Mackenzie (1911) gave tincture of aconite, beginning with 5 minims every two hours, then 10 minims, then 15. Although the dose was given for several days in many cases, not the slightest effect could be detected. Then, at Cushny's suggestion, he got Price to try aconitine in cases of auricular fibrillation in which digitalis proved effective, and in cases of rapid heart due to fever and other causes. Price carefully pushed the drug until the patient felt tingling of the tongue and skin, but in not a single instance did he get any evidence of a reaction on the heart or blood-vessels. Rudolf and Cole (1912), in tests on 55 patients with and without fever, failed to get any change in the pulse-rate. They gave as much as 4 1/2 minims of the B. P. tincture, equivalent to 2 1/4 minims (0.14 c.c.) of the U. S. P. tincture, every ten to fifteen minutes for 8 to 10 doses.
On the other hand, W. H. Thomson (1915) considers that it has a special value in reducing the high arterial pressure in chronic interstitial nephritis. He uses up to 10 drops of the 35 per cent. tincture, equivalent to 35 drops or about 18 minims (1.1 c.c.) of the U. S. P. tincture. He finds the excretion of urea greatly increased, and states that both these effects have been corroborated by J. E. Welch. In a verbal communication, Welch informs me that he gets such results only from large and frequent doses of the strong tincture.
Laboratory experiments show that from therapeutic amounts there is no depression of any part of the vasoconstrictor mechanism; and the drug lowers arterial pressure, if at all, by pure cardiac depression and not by dilatation of the arteries.
From moderate doses there is stimulation of the respiratory center, with increased depth and frequency of respiration; but from doses beyond therapeutic there is early depression of the center, with slowing of the respiration, labored breathing, and lessening of the intake of air. In poisoning there may be also some stimulation of the sensory vagus endings in the lungs (for the accessory respiratory muscles contract vigorously), and a stimulation of the bronchoconstrictor nerve-endings, the result being bronchial spasm (Dixon). Death takes place from asphyxia due to paralysis of the respiratory center. If artificial respiration is maintained, the heart will continue to beat for some time after the respiratory center fails.
This is the last part of the nervous system to be affected, and consciousness is retained until the final stages of poisoning. The mind becomes dulled only when the patient passes into collapse.
The vagus center is stimulated, as already indicated; the vasoconstrictor center is stimulated by poisonous doses, but this stimulation soon passes into depression; the respiratory center is at first stimulated but very soon depressed, and through its paralysis death is produced. The vomiting center may be stimulated; the heat-regulating center may be affected so that temperature in fever is lowered. Convulsions may occur in the poisoning, and are due either to asphyxia or to stimulation of the reflex centers of medulla and spinal cord.
The peripheral ends of the sensory and secretory nerves we have already spoken of. They are strongly stimulated, and later depressed. This effect is observed not only on local application, but also after the drug is absorbed, for aconite is selective. From a poisonous dose taken internally the tingling, and later the numbness, become general. The ends of motor nerves are also somewhat stimulated and later depressed. The ends of the nerves conveying heat and cold sensations are affected in the poisoning, and cause chilly feelings regardless of any changes in the cutaneous circulation or in the body temperature.
From large amounts there is slight direct stimulation of cardiac muscle (already referred to) and of voluntary muscle, as indicated by its occurrence after curare. This is of no therapeutic importance.
Aconite is antipyretic, i. e., it tends to induce a fall of temperature in fever, but it is not strongly so. There seems to be a stimulation of the heat-regulating center, the center which sets going the mechanisms to bring an abnormal temperature to normal. (See Antipyretics.) The fall in temperature results from lessened production of heat, owing to diminished activity of the circulation, but there is also some increase of heat loss from a moderate dilatation of the skin vessels, and perhaps from sweating.
The saliva is increased, as already mentioned, partly reflexly from the mouth, and partly through stimulation of the secretory nerve-ends. The sweat is also increased, but free sweating is irregular and not marked.' It is believed to be due to stimulation of the nerve-endings in the sweat-glands, and slightly to dilatation of the skin vessels. At best, aconite is a mild and uncertain diaphoretic.
Poisoning from doses by mouth is readily recognized by the prompt tingling of mouth, lips, and tongue, followed by numbness. There may also be nausea, vomiting, diarrhea, and pain in the stomach. After absorption the tingling may become general over the whole surface of the body, being first noticed in the finger-tips. The pupil is dilated and the vision deranged, with mistiness of the sight or diplopia. Early in the poisoning there are the peculiar chilly sensations. The breathing may be asthmatic, labored, from constriction of the bronchi, and there may be cyanosis.
The circulatory changes we have spoken of. Blood-pressure is lowered, then raised, then again lowered, and collapse follows. Death takes place usually from asphyxia caused by respiratory paralysis, but perhaps also from ventricular fibrillation or heart-block. It takes about 0.2 mg. of aconitine per kilo to kill a rabbit (Eden).
The treatment of poisoning by aconite consists in washing out the stomach, keeping patient in absolute repose, keeping up bodily heat, and treating the condition of the heart as indicated under Digitalis. Atropine is said to be particularly antidotal, because it not only checks vagus activity, but also stimulates the respiratory center and depresses the constrictor endings in the bronchial muscles, thus overcoming the labored breathing.
Aconite is a drug that, in the light of recent research, has doubtful therapeutic value. Externally it is used in liniments to allay pain, as in neuralgia, lumbago, and muscular pains. It is applied to the gums in toothache. Internally its value may be considered problematic. It has been employed extensively to slow and quiet a heart which is overacting from any cause, for example, in nervous excitement or in sthenic fevers with quick pulse and high arterial pressure. Also to reduce arterial pressure when very high, as in chronic nephritis or convulsive conditions, as uremia or eclampsia.
In the fevers of children, and for adults at the onset of acute pharyngitis or tonsillitis or bronchitis, aconite has been employed empirically. Its supposed beneficial effects in these cases have been attributed to its antipyretic action, and perhaps to its power to quiet the rapid heart and lower the heightened blood-pressure which is associated with the onset of a cold. It is much less used in fever than formerly.
It is sometimes administered internally in trifacial neuralgia, with alleged relief of the pain.
For adults, a customary dose is 3 to 5 minims of the tincture given every hour for three or four doses. It is frequently given in tablets, each representing 3 minims (0.2 c.c.) of the tincture. For children the tincture may be added to the liquor ammonii acetatis to make a fever mixture. It is irrational therapeutics to administer atropine or belladonna at the same time as aconite, for atropine paralyzes the vagus endings and checks the vagus effect upon the heart.
Delphinium (larkspur) and staphisagria (stavesacre) are botanic and pharmacologic relatives of aconite, but they are limited in their therapeutic use to the destruction of pubic and head lice. A mixture of equal parts of the tincture of delphinium and ether is a favorite prescription. It should be specifically labeled "Poison." The poisonous symptoms are the same as those of aconite.