Physostigma

Calabar Bean

Calabar bean. The seed of Physostigma veneno-sum Balfour (Nat. Ord. Leguminosae, Papilionaceae). Féve de Calabar, Fr.; Kalabarbohne, Ger.

Extractum Physostigmatis

Extract of physostigma. Dose, gr. 1/6 —gr. ss—gr. j.

Tinctura Physostigmatis

Tincture of physostigma. Dose, τη v —τη xx.

Composition

Calabar bean contains two alkaloids, physostigmine or eserine and calabarine. These have been supposed to be the same, but they differ in physiological action; physostigmine paralyzes, "whereas calabarine has a tetanizing action. "Eserine" has been more used than "physostigmine" to designate the alkaloid.

Physostigminae Sulphas

Physostigmine sulphate. A white or yellowish-white microcrystalline powder. Very soluble in water and in alcohol. Dose, gr. 1/100 to gr.1/60.

Physostigminae, Salicylas

Physostigmine salicylate. In colorless, shining, acicular, or short columnar crystals, turning reddish on long exposure to light and air, odorless, having a bitter taste and a neutral reaction. Soluble in 130 parts of water, and in 12 parts of alcohol at 59° Fahr. Dose, gr. 1/100—gr. 1/60.

Antagonists and Incompatibles

The vegetable astringents, tannic acid, and the caustic alkalies, are chemically incompatible. As respects physiological actions, physostigma is antagonized in a limited part, but not in the whole of its actions, by atropine, and still more by chloral. Therapeutically, the tetanizing agents may be regarded as opposed to physostigma.

Synergists

The paralyzers, or depressors of the motor nervous system, conium, gelsemium, nitrate of amyl, etc., act in harmony with physostigma, increasing its effects in the whole range of its physiological influence.

Physiological Actions

The preparations of physostigma are apt to excite nausea. Increased secretion of the gastro-intestinal mucous membrane, and increased peristalsis, follow their administration. The active principles quickly diffuse into the blood. Physostigma does not impair the respiratory function of the blood, but, after death, loose coagula are found, the globules have undergone changes of shape, and rectangular plates of haemato-crystallin occur (Leven and Laborde). The action of the heart is affected by considerable toxic doses; it is paralyzed in the diastole, and is flabby, but it contracts lazily on electric stimulation. In less than lethal doses the action of the heart is slowed, and the arterial tension is, for a brief period, lowered, but soon rises considerably above the normal. As these effects are not due to an action on the inhibitory apparatus, and follow when the heart is separated from the vaso-motor center by division of the spinal cord, it is probable that the action consists in a stimulation of the cardiac ganglia, and a subsequent paralyzing action on the cardiac muscles. The same result may be due to a paralyzing action on the accelerator nerves of the heart (Köhler). The respiration is more powerfully affected than the circulation. When a lethal dose is administered the respiration becomes slower and shallower, and death ensues from arrest of the respiratory movements (asphyxia), the heart continuing in action for some time afterward.

Physostigma does not affect the centers of conscious impressions, and consciousness is preserved until the oxygenation of the blood is so far interfered with that carbonic-acid narcosis supervenes. Giddiness, vertigo, and a sense of muscular weakness and fatigue, are produced by considerable doses (Gubler). When a lethal dose is administered to an animal, its muscular system soon grows weak, and complete paralysis soon after ensues. The voluntary muscular system, however, before complete resolution occurs, is agitated by a succession of tremors—temporary tetanic contractions followed by entire relaxation. These muscular tremblings occur, but more feebly, after complete paralysis, and persist in a slight degree after death. The muscular contractility is not destroyed, not even impaired, by physostigma.

The irritability of the motor nerves is affected, if at all, to a very slight extent, and the sensibility of the sensory nerves is rather heightened. It follows from these facts that the paralyzing effect of physostigma is due to a direct action on the spinal cord.

As respects its effects on the eye, we find that it is eminently characteristic, and whether introduced directly into the eye, or taken into the stomach, or thrown under the skin, it contracts the pupil. This is a local and peripheral action, exactly corresponding, as to its seat, to the action of atropine. The end-organs of the sympathetic, or of the motor oculi, and it may be of both, are acted upon. By some it is held that the contraction of the pupil is due to a tetanic state of the circular fibers (Grünhagen, Rogow); by others, to a paralysis of the dilator system (Fraser, Hirschmann). It were probably safer to accept the conclusion that the nerves innervating both sets of fibers are acted on—the motor oculi stimulated (see case by T. Wharton Jones, "Practitioner," vol. iii), the sympathetic depressed—for we find that tetanic contraction of the muscular fiber of the intestine, followed by dilatation and a paretic state, can be experimentally produced by physostigma. The apparatus of accommodation is also affected; myosis begins in ten to fifteen minutes after eserine is inserted. Direct galvanization of the iris, contracted by physostigma, causes it to dilate (Engelhardt, Hermann).

Physostigma Therapy

The applications of physostigma to the treatment of disease are by no means so important as the elaborate study given to its physiological action, by various observers, would seem to indicate.

In torpor of the muscular layer of the intestine, combined with deficient secretion of the mucous membrane, this agent is often very serviceable. In some subjects fifteen minims of the tincture or a half-grain of the extract, taken at bedtime, will procure a morning evacuation, but it frequently fails. When the state to be relieved is such as is indicated above, a combination of physostigma, belladonna, and nux-vomica, is sometimes very effective: Rx Tinct. physostigmatis, tinct. nucis vomicae, tinct. belladonnae, āā 3 ij. M. Sig. Thirty drops in water, morning and evening. Rx Extract. physostigmatis, ext. belladonnae, ext. nucis vomicae, āā gr. v. M. Ft. pil. no. x. Sig.: One pill at bed-hour. Physostigma (gr. ¼ — gr. ss of the extract) is a useful addition to a cathartic pill. Rx Ext. physostigmatis, resinae podophylli, āā grs. iij. M. Ft. pil. no. vj. Sig.: One pill at bed-hour.

To the troublesome flatulence of women at the climacteric period, usually associated with a paretic state of the muscular layer of the bowel, very great relief is often afforded by the use of physostigma. With the relief to the flatulence there usually follows relief to the morbid fancies, the headache and vertigo connected with it.

The action of physostigma on the spinal cord, as a paralyzer, naturally suggested its use in tetanus. The evidence of its utility is discrepant. Moreover, tetanus, in many instances, manifests a tendency to spontaneous cure. It is difficult, therefore, to estimate the precise value of physostigma, but about one half of the cases treated with this agent recover—according to Watson, ten in eighteen; according to Roemer, twenty in forty-seven cases. A larger measure of success might have been achieved, had sufficient attention been paid to the quality of the extract used and to the mode of administration. The following remarks by Dr. Fraser, in regard to the treatment of tetanus by Calabar bean, are of great importance:

"I should myself feel inclined always to commence the treatment by subcutaneous injection, and to repeat such injection until the system is decidedly affected, and then to administer the remedy by the mouth in a dose three times as large as is found necessary by subcutaneous injection. Such a plan might be quite safely followed in a child of even nine years. If the remedial effects continue to be produced by administration by the mouth, it should be persevered with, for such administration has obvious advantages as far as the convenience of the practitioner is concerned. In the more severe cases, however, I believe subcutaneous injection should be alone employed. The distress and increase of spasm caused by swallowing, or the impossibility of introducing substances by the mouth, will render this necessary. I can not, also, too strongly urge that subcutaneous injection should always be used when severe and continued spasms occur, when a fatal result is imminent from the exhaustion caused by prolonged and frequent convulsions, and when apnoea threatens at once to close the tragic scene. By it we obtain the quickest and most powerful effect.

"From the preceding remarks it can not be expected that any arbitrary rules of dosage can be laid down. For an adult one grain of the extract by the stomach, or one third of a grain by subcutaneous injection, will generally be sufficient to commence with. This should be repeated in two hours, when its effects will usually have passed off, and the succeeding doses may be modified according to the experience that will be thus gained. . . . The great object is to produce as quickly as possible, and then to maintain, the physiological effect of physostigma in diminishing reflex excitability. The doses must, therefore, be continued in increasing quantities until this physiological effect is produced, or until the sedative action of the drug on the circulation is carried to a dangerous extreme, or until constant nausea and vomiting compel us to desist."