The nitrate of an alkaloid obtained from extract of jaborandi.

Preparation. - By shaking the extract with chloroform and a little alkali, evaporating the chloroformic solution, neutralising the product with nitric acid and purifying by recrystallisation.

Characters. - In white crystalline powder, or in acicular crystals.

Solubility. - Soluble in eight or nine parts of water at common temperatures, slightly soluble in cold, freely soluble in hot rectified spirit.

Reactions. - Strong sulphuric acid forms with it a yellowish solution which, on the addition of bichromate of potassium, gradually acquires an emerald-green colour. It leaves no ash when burned with free access of air. It causes contraction of the pupil of the eye.

U.S.P. Pilocarpinae Hydrochloras. Hydrochlorate of Pilocarpine. - The hydrochlorate of an alkaloid prepared from Pilocarpus. It should be kept in small, well-stoppered vials.

Characters. - Minute, white crystals, deliquescent, odourless, having a faintly bitter taste, and a neutral reaction.

Solubility. - Very soluble in water and in alcohol, but almost insoluble in ether or chloroform.

Dose.- 1/20 to 1/2 gr. internally or by subcutaneous injection. Uses. - Its action and uses are similar to those of Pilocarpus.

Action. - Jaborine has an action like that of atropine and antagonistic to that of pilocarpine. The amount of jaborine in the leaves is insufficient to antagonise the pilocarpine, so that the leaves have an action like that of pilocarpine. It is probable that some discrepancies between the statements of different observers regarding the action of pilocarpine may be due to the presence of more or less jaborine in the pilocarpine which they supposed to be pure.

Pilocarpine stimulates the peripheral terminations of efferent nerves going to glands, and first stimulates and then paralyses the efferent nerves going to structures composed of involuntary muscular fibre. In large doses it lessens but does not quite destroy the irritability of voluntary muscle and motor nerves.

It appears to have a certain action on the nerve-centres. It produces in Rana esculenta convulsions like those of picro-toxin. In Rana temporaria it only produces paralysis. Frogs poisoned by it croak, when stroked, in the same way as when the cerebrum is removed. In mammals it causes dyspnoea, convulsive twitching and shivering, and movements of rotation (p. 215; cf. also Apomorphine). These may, however, be partly due to the action of the drug upon the heart. It seems, however, to stimulate the centres of the salivary and sweat glands as well as the peripheral terminations of the secreting nerves.

From its stimulating action on secreting nerves it produces enormous secretion of saliva from the submaxillary, sublingual, and parotid glands, and enormous secretion of sweat from the sweat-glands, beginning either in the face or at the point of subcutaneous injection, and extending over the whole surface of the body. It produces, though to a less extent, secretion of tears from the lacrimal gland; of wax from the ears; of mucus from the nose and from the bronchial mucous membrane; of gastric juice from the glands of the stomach; probably of intestinal juice from the intestinal glands, and of urine from the kidney. The secretion of milk is sometimes but not always increased. It does not appear to increase the secretion of bile.

Its stimulating action on nerves supplying involuntary muscular fibre is observed in the eye, intestine, heart and vessels, bladder, uterus, and spleen. By stimulating the terminations of the third nerve in the eye it causes contraction of the pupil and spasm of accommodation, and indistinct vision. After this passes off there may be dilatation of the pupil. By stimulating the intestinal ganglia it causes increased peristalsis. By stimulating the vagus ends in the heart like nicotine, large doses of it cause the pulse to become slow in frogs and in mammals, and the blood-pressure to fall: In small doses its effect is more complicated, as will be afterwards noticed. In larger doses it paralyses the vagus ends (A, Fig. 106, p. 313), but not the inhibitory ganglia. By acting on the bladder it causes contraction, and may produce strangury and sometimes retention. It causes contractions of the uterus, which, in rabbits, begin at the openings of the Fallopian tubes and proceed to the os uteri. This depends also on a peripheral action of the drug, and is not arrested by destruction of the spinal cord. It causes contraction of the spleen in man both in its normal condition and when abnormally enlarged.

As vomiting is a complex movement demanding the cooperation of the abdominal muscles and diaphragm, it is evident that it would not ensue merely from increased contraction of the gastric walls. Jaborandi appears, however, to irritate the stomach, and often causes nausea and vomiting; and so does pilocarpine, though to a less extent, even when subcutaneously injected.

It is probable that even when injected subcutaneously it is eliminated by the mucous membrane of the stomach in the same way as tartar emetic, morphine, atropine, quinine, and strychnine, and that it thus acts as a local irritant to the gastric nerves (Fig. 5, p. 39).

Its action on the circulation is a complicated one, as the direct effect of the drug on the heart and vessels is probably much modified by the reflex action from the stomach, intestines, etc, which have been stimulated by it. The vessels usually become much dilated at first, the carotids pulsating violently, the pulse becoming rapid, and a feeling of heat being perceived over the body. When perspiration sets in there is sometimes a feeling of cold and shivering. The blood-pressure usually falls a little at first, with quicker pulse, then rises with slower pulse (p. 272), and finally falls greatly from vaso-motor paralysis.

Respiration. - There is sometimes a feeling of slight dyspnoea just after the dose has been given, but this only lasts for a few moments. Poisonous doses cause in animals dyspnoea and convulsions, which, as already mentioned, probably depend in some measure on cardiac failure. In animals the abundant secretion into the bronchi and pulmonary oedema produced by large doses also lead to dyspnoea.

The temperature rises when the patient is shivering and falls during sweating (p. 440). The secretion of sweat usually lasts for two or three hours, and is so copious that the body loses one or two pounds and sometimes as much as eight pounds from it and the salivation together. Sweating does not occur in every patient who takes pilocarpine, and even salivation is not a constant symptom.

After the sweating is over there is usually a feeling of debility, languor, and thirst.

Pilocarpine is excreted unchanged by the urine. It does not appear in the saliva.

The injurious effects sometimes produced by it are, in addition to the dimness of vision and vomiting already mentioned, sudden collapse, swelling of the salivary glands and tonsils, hiccough, diminished secretion of urine, albuminuria, strangury, bleeding from the vagina, and anticipation of the menstrual flux.

Atropine antagonises pilocarpine very completely, preventing its action if administered before it, and removing its effects if given after it. Sudden collapse ought therefore to be treated by the subcutaneous injection of atropine.

The nausea and vomiting generally yield easily to morphine.

Uses. - As its action is a peripheral rather than a central one, it affects the eye more powerfully when applied locally than when taken internally. It has been employed in chronic catarrh, in iridocyclitis, intraocular haemorrhage, turbidity of the vitreous humour, in separation of the retina, in albuminuric retinitis, and instead of physostigmine in glaucoma, etc. (vide Myotics, p. 225). It has been used with a certain amount of success in deafness depending on disease of the labyrinth, especially when it is syphilitic.1 In some skin diseases it is very useful, especially in prurigo and chronic urticaria and in baldness; also in cases of Hebra's prurigo and psoriasis. In small doses it relieves thirst in chronic renal disease, and has been used for a similar purpose in fever (vide Refrigerants, p. 360).

It has been used in diseases of the throat, especially tonsillitis and diphtheria, but its utility in the latter disease is uncertain. In . bronchitis, asthma, and whooping-cough it sometimes gives relief, though it is not so useful as might be expected (p. 254). From its action on the uterus it has been used as an oxytocic to induce premature labour. As a diaphoretic it may be used in small doses to induce diaphoresis and prevent or relieve coryza, bronchial catarrh, or rheumatism consequent on a chill (p. 330).

1 Politzer, Med.-Chir. Rundschau, viii. 1885.

It has been employed to remove pleural and peritoneal effusions, and has been used in cardiac dropsy when digitalis failed, but great care is then requisite in its use.

Its chief use, however, is in dropsy, and especially in uraemia depending on disease of the kidneys; it may be given subcutaneously as the nitrate in 1/6-1/3 grain doses. In renal dropsy it not only removes water from the body but it removes urea and possibly other products of tissue-waste. Some of the urea is excreted in the sweat, and a considerable amount appears in the saliva. Probably the removal of these products from the body is the reason why pilocarpine cuts short uraemic convulsions. In puerperal eclampsia it is not so successful as in convulsions depending on kidney disease. Pilocarpine has also been used to eliminate other poisons from the body, and has been used in syphilis and chronic poisoning by lead, mercury, and arsenic.

Contra-indications. - Fatty heart, and impeded pulmonary circulation from valvular disease, emphysema, or pleurisy. These conditions do not absolutely prohibit the use of the remedy, but it must then be given with care and the patient watched. It may be combined with alcoholic stimulants, and atropine should be ready for subcutaneous injection if necessary.