Picrotoxinum

Picrotoxin

Picrotoxin—is not an alkaloid, although allied to this group of substances. It does not combine with acids to form salts. It is neutral, crystallizable, forming needle-shaped, stellar, or foliaceous crystals. It is soluble in 240 parts of cold and 25 parts of warm water, and in alcohol, and dissolves freely in alkaline solutions. It is unaffected in solution by the metallic salts, tannin, etc., and is not precipitated by the tests for the alkaloids. It may be administered in pill-form, and can be combined with any of the usual so-called nervine tonics. Picrotoxin may be administered subcutaneously, in solution in water— one grain to oz ss—the dose ranging from 1/60 of a grain to 1/40 of a grain. By the stomach it may be given in from 1/60 of a grain to 1/20.

Antagonists

The carefully - conducted researches of Browne show that chloral is its physiological antagonist in rabbits and Guinea-pigs, and probably will prove to be of value in cases of poisoning in man. The anaesthetics, and the motor depressants in general, are antagonistic in respect to its power to produce spasm.

Synergists

All the remedies of this group, notably strychnine, brucine, and ergot, increase the effects of picrotoxin.

Physiological Actions

The taste of picrotoxin is bitter. It increases the flow of saliva. In what form soever administered, more or less nausea is produced, when the quantity given is sufficient to cause cerebral effects. It is not an irritant to the gastro-intestinal mucous membrane; it increases secretion, and promotes peristalsis, but no hyperaemia of the mucous membrane has been observed after death from a toxic dose. The secretions of the glandular appendages of the mucous membrane, probably also of the pancreas and liver, are decidedly increased, the stools becoming soft and more copious. Administered at any point, picrotoxin diffuses readily into the blood, but nothing is known at present of the changes which it induces, if any, in the composition of the blood. After death the right side of the heart is distended, and the left side incompletely emptied and flaccid. The action of the heart varies with the stage of the effects, and doubtless also more or less according to the size of the dose. At first the cardiac movements are slowed, the arterial tension somewhat elevated; during the convulsions the action grows rapid, but, succeeding the convulsions, and during the stage of coma, the pulse becomes slow again. According to Planat, by small doses, the cardiac pulsations are slowed before the convulsions come on; then the muscular excitement induces rapid action, to be succeeded again by the retarding effects of the remedy, increased by the coma. Roeber also finds that the cardiac contractions are retarded, and the walls of the heart dilated and flaccid. The respiration is also accelerated, and there occurs strong inspiratory dilatation, because of spasm of the glottis—effects which are due to stimulation of the pulmonary portion of the vagus, and which cease on division of this nerve (Roeber). When the convulsions cease, the respiration becomes slower and more shallow. No engorgement of the lungs is found after death (Browne).

The pupils are not specifically affected. During the convulsions they dilate somewhat, when the tonic spasms come on, and contract again during the clonic spasms. The fundus of the eye, examined by the ophthalmoscope, exhibits considerable hyperaemia.

The cerebral effects of picrotoxin are variously interpreted. Drowsiness, stupor, some muscular trembling, are observed in cold- and warm-blooded animals, and have also been experienced in man. A heavy, stupid intoxication, with vertigo, incoordination, and diminished sensibility, followed by after-headache, depression, and nausea, are symptoms ascribed to the action of cocculus Indicus in beer sophisticated by this drug. Restlessness, unsteady gait, and weakness of the hind extremities, also precede the convulsions in animals. Twitching of the ears, shaking of the head, and spasms in the eyelids, eyebrows, lips, and fore-paws, now come on. Then follows a distinct tonic convulsive stage, with opisthotonos, or emprosthotonos, tetanic fixation of the muscles of respiration, cyanosis, and stertor. This tetanic stage is succeeded by the general clonic convulsions, and the seizure is terminated by a temporary paralysis and coma. In the order and succession and character of phenomena, a remarkable similarity in the actions of picrotoxin to the epileptic paroxysm must be discerned. By Roeber the convulsions are referred to the effects of the poison on the medulla. He finds that, after destruction of the brain, the symptoms are the same as before; after destruction of the optic lobes, the convulsions are less violent; but when the medulla is removed the convulsions do not occur, and a large dose causes coma only. These facts indicate that picrotoxin acts on the spasm and vagus centers in the medulla, and on Setschenow's inhibitory center. Planat, Chirone, and Testa, also hold that this agent acts on the cerebellum, medulla, and spinal cord, and leaves the brain exempt. Against these opinions we have the carefully-considered but still hypothetical view of Browne, who finds in Ferrier's cortical centers the real seat of the action of picrotoxin. That the center, and not the periphery, is the place where the action of the poison is expended, seems proved by the studies of Roeber, who finds that the electrical reactions of nerve and muscle remain unaltered.

The action of the heart is arrested in the diastole, and, while the cavities are full, the capillaries at the periphery are empty. The vascular lesions,post mortem, are similar to those of epilepsy. That some of the poison is yet in the blood, is proved by the fact that flies eating it are poisoned. Elimination probably takes place by the various channels of excretion, but chiefly by the kidneys. The skin is powerfully acted on, and hence picrotoxin ranks among the most active diaphoretics. The urinary excretion is also increased, but more exact observations are needed on these points.

Therapy

Picrotoxin will, probably, be found very useful in cases of torpor of the intestines, dependent on deficient secretion and paresis of the muscular layer. In the night-sweats of consumption it has been used with great success by Murrell, who had but one failure in twenty cases. He finds that it is best to give the necessary dose at night—from 1/180 grain to 1/60. The effect lasts about ten days, when the sweating begins again, and the remedy must be repeated. Picrotoxin has been used with success in the treatment of epilepsy by Pla-nat, Dujardin-Beaumetz, Hurd, and by Hammond. It is more especially adapted to the weak and anaemic type. It has been also used with success in chorea, and with promising results in paralysis agitans. In a case of glosso-labio-laryngeal paralysis Gubler obtained a notable amelioration. Further experiences with these diseases are much needed. It is probable that this remedy may be applied with advantage to the treatment of other paralyses. According to Tschudi, it has been given in paralysis of the sphincters with good results. The tremors of chronic alcoholism have, it is said, been removed by it. One of the forms of sick-headache—that occurring at or about the menstrual period—is sometimes greatly relieved by its timely exhibition. An ointment of picrotoxin—ten grains to an ounce of simple ointment—has been applied with success to the treatment of parasitic skin-affections. Care is necessary, and abraded surfaces must be avoided.

A saturated tincture of cocculus Indicus might be employed in place of picrotoxin. Planat recommends a tincture composed of one part of the berries to four parts of alcohol, and of this one drop is the initial dose, morning and evening, increased daily by the addition of two drops, up to sixty or seventy drops for an adult, daily. In the diseases for which it is prescribed, it is necessary, to secure curative effects, that the physiological action be produced. Planat has used this tincture successfully in chorea, epilepsy, eclampsia (infantile), and in painful contractures of the extremities. Gubler advises the dose of a mille-gramme of picrotoxin for subcutaneous use. He has observed that indurated spots result from the injections, but they slowly disappear.

Authorities referred to:

Browne, Dr. Crichton. The British Medical Journal, vol. i, 1875, pp. 409, 443, 476, 540

Chirone and Testa. Annali. Univ. di Med. e Chirurg. Quoted in London Med. Record, October 15, 1880.

Dujardin-Beaumetz. Annuaire de Thérap. for 1876, p. 33.

Gubler, Prof. A. Bull. Général de Thérap., 1875.

Hammond, Dr. W. A. St. Louis Clinical Record, October, 1876.

Hurd, Dr. Michigan Med. News, February 10, 1881.

Kohler, Prof. Dr. Berl. klin. Wochenschrift, No. 47, 1867.

Murrell, Dr. William. The Practitioner, October, 1879, vol. xxiii, p. 241.

Planat, Dr. Bull. Gén. de Thérap., 1876. Also Annuaire de Thérap., 1876, p. 29.

Roeber, Dr. Archiv für Physiol., etc., for 1869, p. 30.