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The dried leaflets of (1) Pilocarpus Jaborandi, Holmes; or (2) Pilocarpus microphyllus, Stapf (Nat. Ord. Rutaceae). Brazil and Paraguay. Dose, 20 to 60 grains.
Common Names: Jaborandi, (1) Pernambuco Jaborandi, (2) Maranham Jaborandi.

Principal Constituents.—The powerful liquid alkaloid pilocarpine (C11H16N2O2); a colorless, viscid oil, isopilocarpine; a volatile oil chiefly pilocarpene (C10H16); and pilocarpidine (C10H14N2O2) in Pilocarpus Jaborandi only.
Preparation.—Specific Medicine Jaborandi. Dose, 1 to 60 drops.

Derivatives.—Pilocarpina Hydrochloridum, Pilocarpine Hydrochloride. Translucent, colorless and odorless crystals of a feebly bitter taste; hygroscopic in the air. Very soluble in water and alcohol, less soluble in chloroform, and not at all in ether. Dose, 1/12 to 1/6 grain by mouth; 1/24 to 1/8 grain (hypodermatically).

Pilocarpinae Nitras, Pilocarpine Nitrate. Permanent, shining, odorless crystals, very soluble in water and less so in alcohol; insoluble in chloroform and ether. Dose, 1/12 to 1/4 grain (by mouth); 1/24 to 1/8 grain (hypodermatically).

Specific Indications.—Deficient secretion; marked dryness and heat of skin and mucosa; muscular pain; muscular spasms; pain with puffiness of tissues; urinal suppression, the urine being of high specific gravity and deep color; pulse full, hard, sharp and strong, with deficient secretion; increased temperature with dry skin and membranes; sthenic forms of fever; marked restlessness due to lack of secretion; ptyalism, with stomatitis; inflammatory rheumatism, with swollen and painful parts, and dry membranes and skin; soreness and stiffness of joints in subacute rheumatism; dry, harsh cough; tenacious sputum; renal dropsy with deficiency of urine; uremia; uremic poisoning, with convulsions; itching, with jaundice; increased ocular tension; deafness due to deficient aural secretion; alopecia; poisoning by atropine or belladonna; colliquative sweating (minute dose).

Action and Toxicology.—Jaborandi and its alkaloid, pilocarpine, are the most powerful excitants of the secretions of the peripheral secretory glands known. In full doses they cause an enormous outpouring of sweat and saliva, and to a lesser degree stimulate the lachrymal, nasal, faucial, and bronchial secretory apparatus, and to a still lesser extent those of the stomach and intestines. Even the modified secretory organs of the aural canal are indirectly affected by them and the quantity of cerumen increased. The growth of hair and intensification of its color are stimulated by their internal action as well as when locally applied. By most pharmacologists the effect of these drugs upon peripheral secretion is attributed to the direct action upon the terminals of the peripheral nerves and not to any impression per se upon the epithelial secretory cells. This they prove by completely checking them with atropine, known to act upon the same parts but in exactly an opposite manner. Cushny declares that both act upon an intermediary receptor interposed between the nerve and cells at the myocellular junction, and that neither the nerve nor the cells are directly impressed. These bodies are stimulated by pilocarpine and muscarine (agaricine) and depressed or paralyzed by atropine. It is generally conceded that while atropine is the complete antagonist of pilocarpine, which chiefly acts in the manner described and to a very limited extent upon the central nervous system, on the other hand pilocarpine is, therefore, not a complete antagonist of atropine. The action of pilocarpine upon the involuntary muscles is caused in the same manner as upon the sudoriferous glands—by impressing the myo-neural receptors.

Moderate doses of these drugs have scarcely any effect upon the central nervous system, and pilocarpine is less apt than jaborandi to cause gastric and intestinal discomfort. Both, however, appear to increase peristalsis and in full doses may cause a persistent watery diarrhea, with straining or tormina after the diarrhea ceases. Upon the eye myosis is produced by both the local and internal use of them, and spasm of the accommodation also occurs. In large doses they are cardiac depressants, probably affecting the heart muscle and to some degree vagal inhibition. The extent to which the vaso-motor system participates in first causing increased and then lowered blood pressure is not satisfactorily known. Full doses cause cardiac arrhythmia, and increase the number of heartbeats greatly, but render them weaker. The uterus, spleen, and bronchi contract under the influence of these drugs. Temperature, though at first considerably increased, falls when sweating has become well established. This action is more marked during fevers than in health. After the termination of sweating temperature regains its normal status, usually at once, but is sometimes delayed for several hours. As a rule, the secretion of milk is believed to be unaffected by pilocarpine, but contrary to what might be anticipated, where there is a diminished lacteal secretion, it apparently increases the supply.

One or two drachms of powdered jaborandi infused in a cupful of boiling water and taken at one dose will in about ten to twenty minutes cause a tingling of the skin with marked redness of the surface. This sensation is first experienced in the face, but soon extends to the whole surface of the body, and is quickly followed by an abundant perspiration, which is apt to last for four or five hours. Almost simultaneously with the sweating the secretion of saliva increases to such an extent as to greatly embarrass speech, the person being obliged to assume an inclined position that the escape of saliva may be facilitated. During this stage from one to two pints of saliva and even more may be secreted, and usually there will be in addition an augmentation of the bronchial and lachrimal flow. The saliva contains an abundance of ptyalin and salts and readily converts starch into sugar. At times the mucous glands of the intestines are so stimulated and peristalsis so increased as to cause diarrhoea, and it is not a rare circumstance that the submaxillary glands enlarge and become painful. Nausea and vomiting (less likely with pilocarpine), vertigo, hiccough, heaviness of the head, and contraction of the pupils may take place. From the commencement of perspiration the face becomes pale, the pulse temporarily fuller and more frequent; the pulsations become irregular, and with persons laboring under cardiac affections, a kind of asystole is observed. The effects of these drugs occur more readily in adults than in children, the latter in fact standing their action much better than adults. In using these medicines to produce diaphoresis it is not necessary to use warm drinks or other usual aids toward facilitating the sweating. During the sudorific action of jaborandi the quantity of urine is lessened, to a greater or lesser extent, and micturition frequently proves painful. As urea exists to a large extent in the saliva and sweat caused by jaborandi (no uric acid being found), a diminution of it occurs in the urine voided; but, after sweating, it gradually returns to its normal figure in the urine. It would appear that the drug does not increase combustion in the body. Dryness of the mouth and throat, with a sense of fatigue and depression, most usually follows the cessation of its active effects. Administered in divided doses, jaborandi, instead of acting as a diaphoretic and sialagogue, becomes an active diuretic. The conclusions then are that jaborandi and its alkaloid exert a strong special influence upon the sudoriferous and salivary glands, and (in small doses) upon the renal glomerules, which stimulates their functional activity.

Pilocarpine, the active principle of jaborandi, has an action nearly identical; however, it causes less salivation, less vomiting, and is more certain in its effects. The hydrochloride and the nitrate of this alkaloid are used; they may be employed internally, or by subcutaneous injections. In poisoning by jaborandi or pilocarpine, death is not apt to result except where an existing grave cardiac disease renders the patient a victim to exhaustion. Atropine is the physiologic antagonist to its sudoriferous and muscular effects; morphine overcomes the nausea and diarrhoea and pain; strychnine, caffeine and digitalis may be required to support the heart.

Therapy.—External. Externally applied pilocarpus and pilocarpine are accredited with the rather singular effect of causing the hair to become darker in color, and to stimulate the growth of that appendage it is frequently employed in alopecia. The specific medicine, fluidextract, or the alkaloid, may be used in lotions with soap liniment and cologne; or the latter, with or without cantharides, may be incorporated with a lanolin base. The specific medicine may be applied in dry eczema, and to allay inflammation in erysipelas, mumps, mastitis, orchitis, epididymitis, and swollen and painful joints. Pilocarpine, being a strong myotic, is coming to be preferred to physostigmine (eserine) in eye affections, though acting slower and less profoundly than the latter, but with less irritation. In fact, it is a most valuable myotic in all conditions of the eye in which there is increased intraocular pressure. Locally used pilocarpine lessens pain from excessive use of the eyes, and alleviates congestive conditions. By some it is preferred to eserine in glaucoma. After traumatism, with increased ocular tension, the latter as well as pain is relieved by the local use of pilocarpine hydrochloride. Instilled in the eye it is also useful in keratitis and phlyctenular conjunctivitis, both in the early stage.

Internal. Jaborandi is diaphoretic, sialagogue, myotic, sedative, diuretic and antispasmodic, according to the manner of employing it. The keynote to its therapy is arrest of secretion whether it be of the glands of the skin, the glands of special ferments, or the glands of the mucous tracts. Oversecretion due to weakness of the glands is also corrected by it, and the debilitating or unhealthful outpour controlled. In other words, like many other drugs having a single though apparently a double action, it tends to stimulate normal secretion by correcting faulty functioning as manifested in either deficiency or hypersecretion. It is also of value in the early stage of acute inflammations, particularly of the skin, respiratory organs, and in acute rheumatism. When given too freely in the latter it may produce vomiting and excessive sweating. Then it should be discontinued. As the regulation of abnormal secretion has ever been a cardinal feature of Eclectic therapeutics, the adoption of pilocarpus has given us a remedy capable of great good, but one which, on account of its depressing action on the heart and the debility occasioned by excessive diaphoresis, must be used with judgment and care.

Pilocarpus was once used for many purposes for which it is now discarded. Among these were dropsies of various origin. At the present day its eliminative powers are sought only in dropsy of renal origin, not to cure the disease producing it, but to unburden the system of watery accumulation and to some extent of poisonous and convulsive irritants. Occasionally it is used in the attempt to remove pleural effusions, but other agents are better. Owing to its depressing action upon the heart and the danger of inducing pulmonary edema it should not be employed in dropsies of cardiac origin. Such deaths as have occurred from pilocarpus and its alkaloid have been caused by these two accidents. While it is generally advised that it is safe in the early stages of acute Bright's disease, most clinicians are extremely cautious or do not use it at all in chronic parenchymatous nephritis nor in any advanced form of nephritis, especially in those past middle life. Pilocarpine is the one great theoretical and apparently practical drug for uremic convulsions, relieving the kidneys of their burden by placing it upon the skin, whereby a large amount of fluid together with urea and toxins are eliminated. In this condition it is expedient to quicken its action by hot drinks, heat to the surface of the body, and the aid of enveloping blankets. One-twelfth to one-sixth grain of pilocarpine nitrate may be given hypodermatically.

Since these earlier and still established uses for pilocarpus the drug has come into prominence in Eclectic practice chiefly through the writings of Webster, Ketchum, and Foltz. Added to its diuretic and sudorific qualities, jaborandi is sedative and antispasmodic, many preferring it to veratrum for the former purpose, and to lobelia or gelsemium for the latter. The indications for this drug, specifically considered, may be summed up as follows: It is a remedy for sthenic conditions, and must be avoided, or its use carefully guarded, in weakened conditions of the heart. Jaborandi is efficient in disorders exhibiting a dry, hot skin, with febrile reaction, especially when accompanied by acute suppression of the secretions; dry, parched mouth; full, strong, hard, and sharp pulse; deficient renal activity with deep-red urine, scanty in quantity and of high specific gravity; restlessness, and, with any of these symptoms, pain. jaborandi is claimed by Webster to be adapted to almost any febrile or inflammatory condition, sthenic or asthenic, with or without a dry skin. Most observers, however, prefer to limit its use to sthenic conditions only.

As a remedy for pain and inflammation jaborandi has been highly endorsed in mammitis, with dry skin and suppressed lacteal secretion, in acute articular inflammation and acute articular rheumatism, the joint being extremely painful and swollen. In erysipelas with dry skin and elevation of temperature it is especially valued, and is also locally applied. Webster declares that in cerebro-spinal meningitis it has no equal. This view has not been universally endorsed. In rheumatic affections its value is enhanced by its power to eliminate urea and uric acid from the system. Jaborandi is indicated by stiffness, soreness, and swelling of the joints, whether the parts show redness or pallor. Many declare it one of the most important agents to use in the early stage of acute inflammatory rheumatism. One of its chief indications in such disorders is puffiness of the tissues. Its action should not be carried to extremes, however, and the ever-present danger of cardiac depression should be kept in mind. Jaborandi has proved a useful drug in exanthematous diseases with tardy appearance or tendency to retrocession of the eruption, and by this action has been thought to avert the danger of post-scarlatinal dropsy. For acute (preferably) or chronic muscular pain, pleurodynia, lumbago, and muscular spasm, it sometimes proves a most efficient drug. The specific indications must, of course, be observed.

Jaborandi is recommended for cough when the throat is very dry and secretion checked. It is well recommended in bronchial asthma and whooping-cough with dryness of the respiratory passages. Small doses relieve "winter cough," and the cough of chronic bronchitis with lack of secretion, and dry, irritable, hoarse cough. In the early stage of bronchitis, and in the congestive stage of pneumonia, it rapidly relieves the local inflammation, and reduces the fever if it be given in diaphoretic doses. Some employ it in the attempt to abort acute lobar and lobular pneumonias, and sometimes it is effective at least in limiting the damage done by a violent sudden invasion. Here again the caution concerning the heart depression and the danger of pulmonic edema must be remembered, and the drug used with extreme good judgment. In respiratory troubles it does best service when associated with other indicated remedies, as bryonia, asclepias, lobelia, etc. In acute tonsillitis with secretion of tenacious pharyngeal mucus it serves an excellent purpose. Foltz valued it highly in pharyngitis sicca. When exudation has taken place in pleurisy, jaborandi is one of the best agents to effect the removal of the fluid and promote resolution. Some value it to increase secretory activity. It finds also a place in the treatment of dry croup and laryngismus stridulus. In laryngeal diphtheria (so-called membranous croup), if the child is strong, jaborandi may be administered in doses sufficient to increase the secretions of the throat, and thus loosen the false membranes. Many, however, cannot stand its action, and only in the sthenic cases, and never in the debilitated, should it be attempted. The well-known toxic effect of diphtheria in inducing cardiac and vaso-motor paralysis renders the use of any possible circulatory depressant inadvisable. And this is true of jaborandi in the doses necessary to induce free secretion.

Jaborandi has given good service in metastatic and gonorrheal orchitis, ovaritis, and metritis, the specific indications for it being present. Both internally and locally it sometimes alleviates in parotitis (mumps).

Jaborandi is one of the most useful of agents in properly selected cases of la grippe or epidemic influenza, and of catarrhal fever. In fact the drug acts admirably as a non-stimulating diaphoretic and sedative in many inflammatory and febrile conditions, provided the stomach is not too irritable to retain the medicine. It is sometimes used like gelsemium to prepare the system for the kindly action of quinine in intermittent fevers. It should never be used in adynamic fevers, such as typhoid fever.

Small doses of pilocarpus restrain excessive secretion. This is well exhibited in its successful use in controlling some cases of polyuria (diabetes insipidus), colliquative night sweats, and ptyalism and the consequent aphthous stomatitis induced by the latter. In the first named its action is enhanced by ergot.

Acting upon the theory that the act of parturition is favored by free diaphoresis, jaborandi and its alkaloid have been successfully used in cases of tedious labor due to a rigid, hard os uteri. In these cases the pains are severe yet ineffectual, the skin dry, pulse full, sharp, and hard, and there is some febrile reaction. These conditions are rectified by diaphoretic doses of the drug. They are, however, rarely employed for this purpose.

Rarely in diaphoretic doses, it may do good in the albuminuria of pregnancy.

Many skin disorders of a dry character appear to be benefited by the internal (and external) use of jaborandi. Among these are eczema, pruritus, particularly when occurring in a jaundiced skin, prurigo, hyperhydrosis pedum and psoriasis. (See also External Uses.)

The late Dr. Foltz was an enthusiastic advocate of the use of jaborandi in eye, ear, nose, and throat disorders, particularly where there is a lack of the natural secretions of these parts. Full doses of jaborandi contract the pupils, impair accommodation, diminish intraocular tension, and increase secretion. Locally applied, the action is similar, the effects upon the pupil, however, being much less pronounced when the drug is internally administered. Foltz praised it in rheumatic iritis, and for the absorption of "non-organized vitreous opacities". In iritis he always used it, and believed that it shortened the duration of the disease, and if adhesions were present, assisted in their absorption. Optic neuritis, retinal detachment, choroiditis, episcleritis, tobacco and alcoholic amblyopia, and atrophy of the optic nerve are also conditions in which he advised its use. Others have advised it in hemorrhages and plastic exudations of the retina, hemorrhage into the vitreous humor, floating bodies in the vitreous, glaucoma, and corneal opacities. For ocular affections Foltz advised as a dose from three to ten drops of specific medicine jaborandi, every two or three hours; and as a collyrium, one to two grains of pilocarpine hydrochloride to two fluidounces of water. In ear disorders jaborandi improves by increasing the secretions of the aural cavities and canals. Unhealthy cerumen is frequently restored to its natural condition by the continued use of small doses of jaborandi. Jaborandi is the best remedy in non-suppurative inflammation of the middle ear, of the proliferous type (Foltz), and it proves a good drug for nervous deafness, deafness following scarlet fever and diphtheria, and with appropriate adjunct specific treatment, in inner ear diseases of syphilitic origin (Foltz). The alkaloidal salts (1/3 to 1/6 grain subcutaneously) have been employed in these disorders, but the specific medicine jaborandi is to be preferred in doses of three to ten drops every three or four hours.

Pilocarpus and its alkaloidal salts have been used to counteract the poisonous effects of belladonna, atropine, stramonium, daturine, and poisonous bites or stings, and in ptomaine poisoning from canned fish and meats. In the latter instances it has no antidotal power, but favors elimination of the offending material. While failing to completely counteract the toxic effects of atropine, it nearly always relieves the unpleasant dryness of tissues following the use of that alkaloid or of belladonna.

Where depressing effects are produced by jaborandi, as sometimes occurs where there is valvular disease or fatty degeneration of the heart, or morbid pulmonic circulation, strychnine hypodermatically may sustain the heart-action. Digitalis, cactus, caffeine, or strophanthus may also be used. The profuse sweating may be checked by atropine. When pilocarpine acts like atropine, such effects are probably due to contaminating jaborine. In cases where the internal exhibition of jaborandi by mouth occasions nausea or vomiting, this may be avoided in giving the dose by rectal enema. Coffee is also said to prevent its nauseating effect.

The dose of jaborandi in infusion (45 grains to 2 fluidounces of water) is 1 fluidounce, which may, if necessary, be repeated every ten or fifteen minutes; of the fluidextract, from 10 drops to 1 drachm; of specific medicine jaborandi, 1 to 30 drops; of pilocarpine or its salts, internally, from 1/4 to 3/4 grain; by subcutaneous injection, 1/20 to 1/4 grain, in solution.

Pilocarpine.—The alkaloid pilocarpine is used in the forms of hydrochloride and nitrate in the same diseases as the infusion and alcoholic preparations of the leaves. The effects of the alkaloid are said to be more certain than when the leaves are used, and the tendency to nausea and vomiting is greatly diminished. Pilocarpine may be used in many of the aforementioned disorders, although jaborandi is generally preferred by the Eclectic physicians.

The Eclectic Materia Medica, Pharmacology and Therapeutics, 1922, was written by Harvey Wickes Felter, M.D.

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