Physostigma.
The dried, ripe seed of Physostigma venenosum, Balfour (Nat. Ord. Leguminosae). A climbing perennial, native of Calabar, in the Gulf of Guinea, on the western coast of Africa, and around the sources of the river Coma, near Gabon. River banks. Dose, 1 to 3 grains.
Common Names: Calabar Bean, Ordeal Bean, Ordeal Bean of Calabar.
Chief Constituents.—Physostigmine or eserine, a very poisonous base; calabarine, less, poisonous and probably a decomposition product of the former; eseridine, eseramine, all of which are alkaloids; and phytosterin, closely resembling animal cholesterin.
Preparation.—Specific Medicine Physostigma, 1/30 to 5 drops. (For specific purposes in nervous disorders the small fractional doses are preferred.)
Specific Indications.—Feeble and tremulous pulse, cool surface, cold. extremities, and contracted pupils; or pupils dilated, with small, rapid pulse; mental torpor in cerebro-spinal meningitis; difficult breathing with sense of constriction; meteorism.
Action and Toxicology.—Calabar bean is a spinal paralyzant, the brain being apparently unaffected by it. It is also probably a direct muscle poison, though this is doubted by Wood. The motor and reflex centers of the cord are depressed, and finally paralyzed by it when given in poisonous doses. It also acts upon some of the medullary centers. The nerves are apparently not much affected by it, though some contend that it first stimulates and then destroys the excitability of their terminals in the muscles. Unstriped muscular tissue and the glands are stimulated by it, and peristalsis greatly exaggerated and intestinal secretion increased. It lengthens the diastolic pause, thus slowing the heart-beat and increasing its power, probably through its action upon the heart-muscle itself, or by stimulating the vagal terminals and the cardiac ganglia. Arterial tension is first raised by it; then lowered. When dyspnea occurs it is thought to be due to the tetanic action of calabarine, which is present in variable proportions in commercial extracts of physostigma, thus rendering the latter undesirable preparations. Physostigma and its alkaloids are eliminated chiefly in the urine, the latter being then capable of producing poisonous effects when tested upon the eyes of animals. Physostigma kills by centric respiratory paralysis.
Physostigma (and physostigmine [eserine] more powerfully) reduces intraocular tension and strongly contracts the pupils, the myosis taking place in a few minutes and lasting from six to twelve hours, and sometimes to a lesser degree for several days. It temporarily increases the power of accommodation for close vision, which action may be followed by spasm of accommodation. These effects often cause severe pain, which may continue for hours. Much diversity of opinion prevails as to the manner in which the drug acts upon the eye. Wood believes its ocular effects are caused by "local peripheral influence;" "that there is a simultaneous stimulation of the oculo-motor nerve-ending and paralysis of the peripheral sympathetic nerve-ending." As the pupil is known, in overwhelming doses, in human poisoning, to dilate he concludes: "that when the alkaloid is in sufficient amount the primary oculo-motor stimulation is followed by oculo-motor palsy". The view that the drug acts by constricting the vessels of the iris, or the view of Schmiedeberg, that eserine acts directly by stimulation of the iris muscle, is no longer generally held, though Hare still maintains the latter view. In fact, the whole range of physiological action of physostigma and its alkaloids is discordantly voiced by experimental investigators.
Full doses in man produce extreme prostration and muscular weakness, loss of mobility, dizziness, slow, feeble and irregular pulse, nausea, and sometimes vomiting. Severe diarrhea often takes place and the pupils are usually contracted. If the alkaloid or the extract be applied to the conjunctiva close contraction takes place, even though atropine has previously produced dilatation; and the effects are confined only to the eye so treated. Poisonous doses increase the foregoing symptoms, with the addition of muscular tremors or fibrillary twitchings (confined only to portions of the muscle), the reflexes are abolished, respiration and circulation are extremely depressed and the victim dies of paralysis of the medulla-center of respiration.
The treatment of poisoning by physostigma and its alkaloidal salt consists in the hypodermatic administration of a full dose of atropine sulphate, the best-known physiologic antidote (prompt emesis and tannic acid if the poison has been swallowed), the application of external heat, and respiratory and cardiac stimulation by means of alcohol, ether, ammonia, digitalis, and strychnine. Wood suggests the availability of the antagonizing effect of pilocarpine (which by some is regarded equally as antidotal as atropine) in doses proportionate to the quantity of poison ingested.
Therapy.—External. Extract of physostigma for local use in ocular diseases has been entirely replaced by physostigmine.
Internal. Physostigma, in medicinal doses, has scarcely any effect upon the circulation, and but little on breathing. The secretions of the salivary, sweat, intestinal and mammary glands are increased by it. (See also Physostigminae Salicylas.) The drug is employed chiefly to reduce spasm and give tone to relaxed muscular walls of the stomach and bowels, and in the smaller doses in inflammatory diseases of the meninges. It has failed to sustain the reputation once accorded it in chorea, epilepsy, trismus neonatorum, and puerperal convulsions and reflex paralysis. In traumatic tetanus it has failed more often than it has benefited, but charity is held out in the view that probably inert preparations have been responsible for its failure, and the drug has not therefore had a fair trial. It is one of the suggested antidotes for strychnine poisoning, the alkaloid being preferred. For all of the above purposes the physiological doses have been advised.
In minute doses, however, physostigma gives favorable results in certain diseases of the brain and spinal cord. The usual prescription for this purpose is: Rx Specific Medicine Physostigma, 5 drops; Water, 4 fluidounces. Mix. Sig.: Dose, one teaspoonful every two to four hours. The indications are a cool skin, cold extremities, feeble tremulous pulse, and contracted pupils. Occasionally the dilated pupils will guide if associated with a rapid, small and tense pulse. It is one of the few agents which has exerted a favorable influence in cerebro-spinal meningitis, the dull intellect, pupillary contraction, and small, weak pulse leading to its selection.
Physostigma, in the form of the extract or the specific medicine, may be used in weakened states of the gastro-intestinal canal, when giving rise to dilatation, visceral ptosis, and flatulence. Thus it is indicated in gastric and intestinal dilatation, fecal accumulation, and sometimes in tympanites, catarrh of the intestines and bladder, and constipation, with hard, dry feces. Nux vomica aids its action in intestinal atony, a state present in all of the above-named disorders. On account of its action upon the smooth muscular fibres of the intestines it is sometimes an ingredient of pills for the treatment of constipation. Owing to its stimulant action upon the bronchial muscular fibres it may be used in chronic bronchitis with bronchial dilation, with dyspnea, bronchial asthma and emphysema, to assist by its contractile force in expelling mucus. For the respiratory disorders quite full doses are required, and other agents, more kindly in action, are preferred in Eclectic practice as stimulating expectorants. From 1/20 to 1/10 grain of the extract is sufficient for the effect upon the bronchial and intestinal musculature. The same, or eserine (1/60 grain) has been used for excessive sweating, as in the night sweats of phthisis. Wood reports a case of phantom tumor, associated with intestinal dyspepsia, asserted to have been cured by it.
