Pilocarpine

“ Effects.—Pilocarpine, given subcutaneously in doses of about 32 mgrms. (1⁄2 grain) , causes within five minutes a profuse perspiration and salivation, the face becomes flushed, and the whole body sweats; at the same time, the buccal secretion is so much increased that in a few hours over a pint may be secreted. The tears, the bronchial secretion, and the intestinal secretions are also augmented; there are generally headache and a frequent desire to pass water; the pulse is much quickened, and the temperature falls from 1°·4 to 4°: the symptoms last from two to five hours. ”

“ I asked Craig as we parted from him and rode uptown.
"You saw that?" he smiled. "It was pilocarpine, jaborandi, a plant found largely in Brazil, one of the antidotes for stramonium poisoning. It doesn't work with every one. But it seems to have done so with him. Besides, the caffeine in the coffee probably aided the pilocarpine. Then, too, I made them smoke cigarettes without the dope that is being fed them. Lockwood's case, for some reason, hasn't gone far. But did you notice how the treatment contracted the pupils of Whitney's eyes almost back to normal again?" ”

“ In order to still further test the matter, he had injected muriate of pilocarpine into the ankle and into the supraclavicular region. The physiological effects of the drug (diaphoresis, salivation, etc.) were produced in both cases in about the same time, varying in different subjects from one and a half to four minutes ”

“ Pilocarpine has been used in a number of cases, but, with the exceptional case of a young man reported by Denis Dumont, all terminated fatally. The committee of the Paris Academy of Medicine reported in 1874 that in three experimental cases "it hastened death by the fits it brought on." Morphia is often of great value in calming the excitement and giving rest and sleep during the intervals of the paroxysms. Daturia and atropia, administered hypodermically, are somewhat less effectual. Inhalation of oxygen is said to arrest the convulsions and delirium, but not to retard death. ”

“ Its influence on the intestine is much like that of barium chloride. It causes violent contractions of the musculature of the gut and very active peristaltic movements. This is the case in whatever way the substance is administered. A few drops of a 1⁄10% solution of pilocarpine hydrochlorate in distilled water poured on the serous surfaces of the rabbit’s intestine brings about almost immediately violent peristaltic movements. In addition to this there is an increase in the amount of fluid secreted into the intestine, 20-30 c.c. gathering in the small intestine in an hour. ”

“ The gland cells themselves are unaffected. The nerves are so violently excited that direct stimulation of them by electricity adds nothing to the rate of salivary flow. The action is antagonized by atropine, which paralyses the nerve terminals. About 1⁄100th of a grain of atropine 105 antagonizes half a grain of pilocarpine. ”

“ Following the injection of atropine, the rise in uric acid output, that normally follows the ingestion of protein, was inhibited. But in sequence to pilocarpine, an excitant and not like atropine, a depressor of secretory activity, a marked increase in uric acid excretion followed. The contrast in response was naturally translated as striking evidence of the important rôle played by the digestive glands on uric acid excretion; in other words, it was held that the major portion of the endogenous uric acid was the reflex of such intensified glandular action. ”

“ In Pilocarpus they are largely distributed in the tissue covered on both sides of the leaf by the epidermis; the oil-cells are also abundantly met with in the petiole and in the bark of the stems and branches.
Chemical Composition—The active principle of Jaborandi is the alkaloid Pilocarpine, C23H35N4O4 + 4OH2, discovered in 1875 by Hardy. It is an amorphous soft mass, but yielding crystallized salts, among which the hydrochlorate and the nitrate are now more frequently used than the drug itself. The leaves afford about 1⁄2 per cent. ”

“ Pilocarpine: in tobacco and alcoholic abuse.
Potassium Bromide.
Potassium Iodide.
Rue: in minute doses in functional dimness of vision, e.g. hysterical amblyopia.
Salicylates.
Santonin: sometimes useful in later stages of iritis and chloroiditis, and in loss of power of optic nerve.
Seton: on temple; or blisters, along with iodide of potassium, in amaurosis coming on suddenly, and associated with tenderness of the eyeball on pressure; the disc is sometimes congested. ”

“ Death is to be averted by such measures as will keep the heart and lungs in action until the drug has been excreted by the kidneys. Inject stimulants subcutaneously; give coffee—hot and strong—by the mouth and rectum, or use large doses of caffeine citrate; and employ artificial respiration. Do not employ such physiological antagonists as pilocarpine or morphine, for the lethal actions of all these drugs exhibit not mutual antagonism but coincidence.
BELLAGIO, a town of Lombardy, Italy, in the province of Como, about 15 m. ”

“ Functional and organic affections should receive proper management, as they may prove to be the active cause of the disorder. If diuretics are called for, acetate of potassium will often best serve the purpose. The alkaline and laxative natural mineral waters are sometimes useful. In obstinate cases, especially in those in which no assignable cause can be detected, pilocarpine, atropia, tincture of belladonna, chloride of ammonium, bromide of potassium, and arsenic may be tried. Change of climate is at times advisable. ”

“ Active diaphoretics are among the best medicinal agents to be employed, their good effects being due to their derivative action and to the large discharge of fluid from the skin which they occasion, thus promoting the removal of what is effused in the lungs. The fluid extract of jaborandi in the dose of from 20 minims to a drachm, or the hypodermic injection of 1/8 to 1/6 grain of nitrate or muriate of pilocarpine, frequently causes prompt and profuse perspiration. ”

“ The qualitative test usually used consists in passing the gas-air mixture through a heated quartz tube, which liberates free chlorine. The chlorine may be detected by passing through a potassium iodide solution containing starch, or by the use of a heated copper wire gauze, when the characteristic green color is obtained.
An interesting physiological test has also been developed. The eye has been found to be very sensitive to chloropicrin. The gas affects the eye in such a way that its closing is practically involuntary. ”

“ If the black blood be not an excitant to the heart, it can only want such power, because it contains more carbon and hydrogen, than the red blood; [83] but if the heart of an animal, which has been killed expressly for the experiment, by lesion of the brain or of the lungs, has ceased to beat, it may, notwithstanding, be made to contract as long as it preserves its irritability, by throwing into the aortic ventricle either hydrogen gas, or carbonic acid gas. It follows, that neither hydrogen gas nor carbon can act as sedatives to the heart. ”

“ At room temperature it has a vapor pressure of 24 mm. of mercury. It thus lies, in persistency, between such gases as phosgene on the one hand, and mustard gas on the other, but so much closer to phosgene that it is placed in the phosgene group.
Chloropicrin is a very stable compound and is not decomposed by water, acids or dilute alkalies. The reaction with potassium or sodium sulfite, in which all the chlorine is found as potassium or sodium chloride, has been used as an analytical method for its quantitative determination. ”

“ Treatment? Let's see--an operation on the iris, delicate. That was it. Impossible, of course. But there was something else, a temporary expedient, until the surgeon could be reached--an undue expansion of the pupil----
"Why," shouted Kingozi aloud, sitting up in bed. "Pilocarpin, of course!"
What luck! He fervently blessed the shortage of phenacetin that had forced him to take pilocarpin as a sweating substitute for fever.
"Cazi Moto!" he called. Then, as the headman hurried up: "Get me the box of medicines, quick!"
He waited until he heard the little man reenter the tent. ”

“ The picrate of potassium has been given with advantage in intermittent fevers. A solution of picric acid in alcohol is an excellent test for potassa, if there be not too much water present, as it throws down a yellow crystalline precipitate with that alkali, but forms a very soluble salt with soda. Most of the picrates may be made by the direct solution of the carbonate, hydrate, or oxide of the metal, in a solution of the acid in hot water. The picrate of silver forms beautiful starry groups of acicular crystals, having the colour and lustre of gold. ”

“ Administered internally in solution, it has a power of quickening the action of the heart, and exciting the circulation generally. It is therefore particularly useful in the common case of fainting, or threatened syncope. This stimulant power is possessed only by the free alkali and its carbonates. And as the secretion of the stomach is acid, Dr. Pereira supposes that the free or carbonated Ammonia becomes neutralized before absorption; that it is therefore unable to act in the blood except as a salt, and can only operate as a Stimulant while in contact with the coat of the stomach. ”

“ First it gave off terrific clouds of chloropicrin gas; this is an agent that makes every soldier sicker than he was his first trip on the ocean. Naturally every man takes off his gas mask when he gets sick—chloropicrin gets through the mask—and that leaves him an easy mark for the phosgene. The latter gas comes from the mine five minutes after the chloropicrin. Since the inhalation of a microscopic quantity of phosgene is immediately fatal, taking off the masks at this time allows the phosgene to get in its deadly work. Most of the victims of chloropicrin are too sick to care, anyway. ”

“ Uses.—Petrolatum may be used alone, or as an excipient in the preparation of ointments, but does not aid the absorption of drugs (as do alcohol, glycerine, chloroform, animal oils and fats) , for it is not itself absorbed even when administered internally. Petrolatum exerts a demulcent action upon the mucous membrane of the alimentary tract, and may be prescribed in electuary or capsule in inflammation thereof. Liquid petrolatum is useful given internally in piles (dogs one-half ounce twice daily) to soften the feces. ”

“ If a person who has taken small doses of lead for a time be placed in a sulphur water-bath, or have his skin moistened with a 5 per cent. solution of sodium sulphide, the upper layer of the epidermis is coloured dark; but the perspiration excited by pilocarpin or other agency contains no lead.
§ 790. Fatal Dose— (a.) Sugar of Lead.—It may almost be said that it is impossible to destroy human life with any single dose likely to be taken or administered. In three cases an ounce (28·3 grms.) has been taken without fatal result. ”

“ Piperic acid differs from piperonylic acid by the group C4H4, and it was apparent that these carbon atoms must be attached to the carbon atom which appears in the carboxyl group of piperonylic acid, for if they were directly attached to the benzene ring polycarboxylic acids would result in oxidation. ”

“ So while the thyroid raises the energy level of the brain, and the whole nervous system, as a byproduct of its general awakening effect upon all the cells of the body, the pituitary probably stimulates the brain cells more directly, perhaps in the manner of caffeine or cocaine. ”

“ When a large excess of benzoic chloride is employed, no definite product is obtained.
Acetylpikrotin, C15H17O7Ac, crystallises from benzene, alcohol, or acetic acid in glistening plates melting at 244-245°, and is probably identical with the compound described by Paternò and Oglialoro as diacetylpikrotoxinin and melting at 227°. When pikrotin is allowed to remain in contact with acetic chloride for 24 hours at the ordinary temperature, and then heated until complete solution ensues, two compounds are obtained. ”

“ A digitalis stupe may be made to have the effect of a vapor bath: a large one is placed on the abdomen and the body is covered with blankets, which results in the production of abundant sweating. The vapor bath is applied in the ordinary way, so that no explanation is needed. If there be no contraindication in the state of the heart, pilocarpin salts can be injected in sufficient quantity to induce active diaphoresis. These measures proving inadequate, an attempt should be made to dispose of the fluid by acting on the kidneys and promoting diuresis. ”

“ Excitation of these nerves may excite to renewed efforts an excised heart which has just ceased to 2 beat after withdrawal of the supply of nutritive solution. Hence it is thought by some, that the accelerator nerves tonic ally exert a sustaining influence on the heart.
The alkaloid atropin paralyses the vagal nerve endings in the heart, while nicotine paralyses the ganglion cells. Muscarin obtained from poisonous fungi slows and finally arrests the heart. Adrenalin, the active principle of the medulla of the supra-renal glands, augments its power. ”

“ If the patient is very pale and anæmic, one drachm of the carbonate, or two drachms of the citrate or pyrophosphate of iron, may be advantageously added to each bottle of the "Favorite Prescription." If the carbonate be employed, as it is insoluble, the bottle should be well shaken every time before using. The functions of the skin should be kept active by frequent baths, and the patient, if able, should walk or ride in the open air, and freely expose herself to the sunshine. If the invalid be too weak to exercise much, she should go out in warm weather and sit in the open air. ”