The leaflets of Pilocarpus jaborandi or of Pilocarpus micro-phyllus (Fam. Rutaceae), yielding, when assayed, not less than 0.6 per cent. of alkaloids. It is a Brazilian shrub.

Constituents

The alkaloid pilocarpine, also isopilocarpine and pilocarpidine, with similar action, and jaborine, which acts like atropine, but occurs in too minute quantity to have any effect.

Preparations And Doses

Pilocarpus, 0.6 per cent. alkaloid; dose, 30 grains (2 gm).

Fluidextract, dose, 30 minims (2 c.c.).

Pilocarpine hydrochloride and pilocarpine nitrate; dose, 1/6 grain (0.01 gm.), the former being readily soluble in alcohol and water, the latter in water but less readily in alcohol (1: 60).

Pharmacologic Action

Pilocarpine is directly antagonistic to atropine in its effects upon the ends of the secretory nerves, the ends of the nerves governing smooth muscle, the ends of the vagus nerves, and the ends of the third nerve in the internal eye. In strong solution it slightly stimulates the gland and muscle cells. It does not affect the sensory nerve-endings or the striated muscle or their motor end-plates. As with atropine, pilocarpine acts after nerve degeneration, and is presumed to affect a material which serves as receptor of nerve impulses. For practical purposes we can speak of its acting on the nerve-endings.

Secretion

The secretion chiefly affected is that of the sweat, pilocarpine being a very powerful diaphoretic. According to Edmunds and Cushny, a man may lose from 4 to 9 pounds in weight after a single dose; other observers also have estimated that the sweat may amount to a gallon, the solid as well as the liquid portion being increased in total quantity. The sweating takes place after the nerves to the glands have been cut peripheral to the ganglia, so the drug must act on the nerve-ending or the cell. The sweating is completely checked by atropine. As it takes much more atropine than normally, it is believed that pilocarpine stimulates the structures that atropine depresses, viz., the receptor substance between nerve-ending and muscle. There is some evidence that pilocarpine also acts slightly on the ganglia. The sweat is acid or neutral from the fatty acids of the sebaceous secretion, the sebaceous glands sharing in the stimulation.

The saliva and bronchial mucus are also considerably increased, and to some extent also the ear-wax and tears, the gastric, pancreatic, and intestinal juices, and all the mucous secretions. In very weak conditions the bronchial mucus may accumulate to such a degree as to interfere with the breathing and favor the development of edema of the lungs. All these secretory effects are prevented by atropine. The quantity of milk, of bile, and of urine are not directly affected. It is stated that the sugar in the blood and the sugar in the milk are increased in amount.

It is an interesting fact that, both from the local application of the drug to the scalp and its internal administration, the hair, in some cases, increases in abundance. This result is due, probably, to the increase of the scalp secretions. The new hair may beof a lighter shade and give a patchy appearance. As a test, Pringle (1908) injected 1/2 grain (0.03 gm.) of pilocarpine nitrate into the scalp, and got a growth of hair as the result.

Smooth muscle shows its increased activity only after poisonous doses, the chief manifestations being increased peristalsis in the alimentary tract and contraction of the bronchi, bladder, and pupil. The effects are due to stimulation of the nerve-endings, and are prevented by atropine. The arterial muscles are not affected, and probably not the uterus.

The Eye

A 0.5 to 1 per cent. solution, dropped in the eye, has the following effects:

(A) Pupil

There is stimulation of the third nerve-endings, with contraction of the pupil, the maximum contraction being reached in one-half to one hour, and lasting only three or four hours.

(B) Accommodation

The ends of the third nerve in the ciliary muscle are stimulated; hence this circular muscle contracts and causes bulging of the lens and fixation of the eye in accommodation for short distances. There may be a dull pain from the continued muscular contraction.

(C) Intraocular Tension

After a preliminary rise, lasting sometimes as much as half an hour, and probably brought on by increased secretion, the tension falls. The fall is more or less coincident with the pupil contraction, and results from the increased escape of fluid which follows the opening of the lymphatic outlets (spaces of Fontana) when the pupil contracts.

Circulation

From large doses the heart is usually slowed and slightly weakened, this action being due solely to stimulation of the vagus endings, and being preventable by atropine. From very poisonous doses, the vagus ends may become paralyzed, but the heart muscle itself is directly depressed, so that the beat continues slow. Sometimes the heart beats faster at first from vagus center depression. After toxic doses the arterioles are dilated by depression of the vasoconstrictor center, and blood-pressure falls.

Fig. 53.

Fig. 53. - Pilocarpine hydrochloride, 0.5 mg. per kilo, male dog. Upper tracing, auricle; middle, ventricle; lower, arterial pressure. The auricle almost ceases to beat. The ventricle loses tonicity and contractility (down-stroke, systole); the arterial pressure falls. The effect is due to vagus stimulation, the rate being slowed from 186 to 114. (Tracing made by Dr. C. C. Lieb.)

Pilocarpine is, therefore, a cardiac depressant, both vagus and direct, and in excessive doses an arterial dilator. Its margin of safety is small, and its administration in conditions of cardiac weakness has been followed in some cases by collapse and death. The author has seen two cardionephritic cases die from the combined effects of pilocarpine hydrochloride, 1/10 grain (0.006 gm.), and a hot-pack.

Respiratory Tract

Owing to the increased bronchial secretion and contraction of the bronchial muscles from stimulation of the ends of the bronchomotor nerves, the breathing in poisoning may be labored or asthmatic; at the same time there is depression of the respiratory center. These factors, joined to weakness of the circulation, tend to promote edema of the lungs, asphyxia, collapse, and death.

Nervous System

The mind remains clear in pilocarpine poisoning, but there is depression of the medullary centers and of the spinal reflexes, and there may be muscular weakness or paralysis.

Elimination

In the sweat, urine, and saliva.

Toxicology

As in physostigmine poisoning, there is prostration without loss of consciousness. There is at first excessive vagus action and depression of the vasoconstrictor center, with slowed or intermittent heart-beat (vagus standstill or vagus heart-block) and low blood-pressure. Later there is slow, feeble heart-beat and collapse.

The pupil is strongly contracted, the skin flushed and profusely sweating, and the saliva abundant. There may be nausea, vomiting, diarrhea, and abdominal cramps. The respiration may be labored, asthmatic, with the physical signs of increased bronchial mucus or edema over both lungs; there may be muscular relaxation, beginning in the lower limbs and ascending. Consciousness, though dulled, persists until near the end. Death takes place in collapse, with edema of the lungs.

The treatment is atropine hypodermatically, and the general treatment for collapse, especially artificial respiration. The atropine serves to overcome the asthmatic breathing, to lessen bronchial secretion, to diminish cramps in the abdomen, and to check excessive vagus action.

Therapeutics

The fluidextract is added to hair-washes, the pilocarpine salts being, as a rule, considered too expensive.

In the eye, a 1: 200 solution of pilocarpine hydrochloride is used in glaucoma, and to hasten contraction of the pupil after mydriatics.

Internally, it has been employed in chronic congestive conditions of the middle ear, in labyrinthine affections, and in congestive conditions of the eye. Its good effects seem to depend largely on the resulting diaphoresis. It has also been used as an expectorant in the dry stage of bronchitis, but it makes profuse sweating and salivation.

Its chief use is as a diaphoretic in nephritis with uremia and in dropsy. Tyson recommends 10 minims of the fluidextract three times a day, or a daily dose of 1/4 grain of pilocarpine hydrochloride. Because of its tendency to depress the heart or produce edema of the lungs, its effects must be watched; and it should not be employed if the heart is weak.