Pilocarpine

-3.03

1.1

OIL OR CRYSTALS

NEEDLES

FREELY SOL IN ETHANOL; INSOL IN DIETHYL ETHER /HCL/

SOL IN WATER, ALC, CHLOROFORM; SPARINGLY SOL IN ETHER, BENZENE; ALMOST INSOL IN PETROLEUM ETHER

SOL IN ETHANOL, DIETHYL ETHER

2.07e+00 g/L

195-205

34 °C

34 °C

HYGROSCOPIC. /HCL/

SENSITIVE TO LIGHT.

STABLE IN AIR BUT AFFECTED BY LIGHT. /NITRATE/

151.18 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；139.67 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；145.44 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；148.74 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

WHITE CRYSTALS; SLIGHTLY BITTER; MP: 195-198 °C; ALSO GIVEN AS 204-205 °C; 1 G DISSOLVES IN 0.3 ML WATER, 3 ML ALCOHOL, 366 ML CHLOROFORM; INSOL IN ETHER; /HCL/

ODORLESS, FAINTLY BITTER CRYSTALS; SOLN ACID TO LITMUS; PKA1= 6.8, PKA2= 1.3 /HCL/

MP: 173.5-174.0 °C DECOMP; SPECIFIC OPTICAL ROTATION: +77 DEG TO +83 °FOR D (SODIUM) LINE (10%); 1 G DISSOLVES IN 4 ML WATER, 75 ML ALCOHOL; INSOL IN CHLOROFORM, ETHER /NITRATE/

SOL ARE ACID TO LITMUS /NITRATE/

WHITE POWDER OR CRYSTALS FROM ALC /NITRITE/

Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]；H330: Fatal if inhaled [Danger Acute toxicity, inhalation]

P260, P264, P270, P271, P284, P301+P316, P304+P340, P316, P320, P321, P330, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

IMAP assessments - 2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-, (3S-cis)-: Human health tier I assessment；IMAP assessments - 2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-, (3S-cis)-: Environment tier I assessment

Acute Tox. 2 (100%)；Acute Tox. 2 (100%)

Acute toxicity - category 2；Acute toxicity - category 2

Acute toxicity (Oral) - Category 1；Acute toxicity (Dermal) - Category 1；Specific target organ toxicity - Single exposure - Category 1 (nervous system)

Acute Tox. 2 *；Acute Tox. 2 *

Overdosage should be treated with atropine titration (0. 5 mg to 1. 0 mg given subcutaneously or intravenously) and supportive measures to maintain respiration and circulation. Epinephrine (0. 3 mg to 1. 0 mg, subcutaneously or intramuscularly) may also be of value in the presence of severe cardiovascular depression or bronchoconstriction. (L1712)

As the drug acts as a cholinergic agonist, pilocarpine may propagate muscarinic side effects, particularly when used in the oral form. The muscarinic receptors are present in nearly all major organ systems, and muscarinic medications can mediate autonomic function wherever the receptors are present. Due to the receptor's role in mediating the response of the parasympathetic nervous system, stimulation of the receptors will cause "rest and digest" functions throughout the distribution of M1-M5 receptor locations: the neuronal, cardiac, musculoskeletal, pulmonary, digestive, and urinary systems.；Due to the location of the M3 receptors in blood vessels, vasodilation will occur, resulting in decreased blood pressure and flushing. When postganglionic muscarinic receptors are activated, sweating and diaphoresis can occur. Other toxicity symptoms may include miosis or excess lacrimation (especially when using the ocular form), hypersalivation, vomiting, bradycardia, bronchospasm, urination, and diarrhea. Sweating is the most common side effect in those on the oral dosage form and even more common in patients on higher doses of daily oral pilocarpine.

It is essential to monitor for side effects of excessive stimulation of the muscarinic receptors, as previously due to the systemic effects of the oral preparation. Fortunately, pilocarpine is not among the narrow therapeutic index medications. However, there is no known antidote for treating these side effects, and care should still be taken by the healthcare team to monitor doses and weigh the pros and cons of treatment. If a patient is unable to tolerate the side effects of pilocarpine, they should notify their healthcare team, who may either decrease the dose or discontinue the treatment.

Pilocarpine is a cholinergic parasympathomimetic agent. It increase secretion by the exocrine glands, and produces contraction of the iris sphincter muscle and ciliary muscle (when given topically to the eyes) by mainly stimulating muscarinic receptors.

PILOCARPINE IS CHIEF ALKALOID OBTAINED FROM LEAFLETS OF SOUTH AMERICAN SHRUBS OF GENUS PILOCARPUS. ...IT WAS LONG KNOWN BY NATIVES THAT CHEWING OF LEAVES OF PILOCARPUS PLANTS CAUSED SALIVATION, 1ST EXPT WERE...PERFORMED IN 1874 BY BRAZILIAN PHYSICIAN NAME COUTINHOU.

FROM PILOCARPUS JABORANDI HOLMES, RUTACEAE: PETIT, POLANOVSKI, BULL SOC CHIM (3) 17, 557, 702 (1897).

LOCAL IRRITATION, ALLERGIC REACTIONS, & SYSTEMIC EFFECTS ARE UNCOMMON. 1 CASE OF MALFUNCTION IN EUSTACHIAN TUBE & DISTURBANCE IN MIDDLE EAR HAS BEEN REPORTED AFTER USE OF 4% SOLN /OF PILOCARPINE/.

HAZINESS OF CORNEAL EPITHELIUM & SUPERFICIAL CORNEAL VASCULARIZATION WITH REDNESS OF CONJUNCTIVA HAVE BEEN OBSERVED...IN 2 PT AFTER LONG-CONTINUED USE OF PILOCARPINE EYEDROPS.

ADVERSE SIDE EFFECTS FROM TOPICAL USE ON EYE ARE FEW, CONSISTING OF SENSATION OF DIMNESS OF VISION...ENFORCED ACCOMMODATION FOR NEAR, CAUSING PSEUDOMYOPIA & IMPROPER FOCUSING...BY PEOPLE BELOW AGE OF PRESBYOPIA. ACHING DISCOMFORT IN EYE FROM CONTRACTION OF CILIARY MUSCLE...@ START OF TREATMENT WITH...EYEDROPS.

SALIVARY, LACRIMAL, GASTRIC, PANCREATIC, & INTESTINAL GLANDS, & MUCOUS CELLS OF RESP TRACT ARE...STIMULATED BY.../PILOCARPINE/. ...AFTER PILOCARPINE, COMPOSITION OF SALIVA TENDS TO APPROACH...ULTRAFILTRATE OF PLASMA. ... GASTRIC GLANDS...SECRETE JUICE...ESP ABUNDANT IN PEPSIN & MUCIN...

For more Human Toxicity Excerpts (Complete) data for PILOCARPINE (12 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Pilocarpine

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

ALL PARASYMPATHOMIMETIC DRUGS, IN TOXIC DOSES, STIMULATE ALL SECRETIONS & PRODUCE SEVERE GI COLIC & DIARRHEA & DYSPNEA; IRIS IS MARKEDLY CONSTRICTED; HEART RATE IS 1ST INCR & THEN SLOWED. DEATH MAY BE DUE TO RESP PARALYSIS OR HEART BLOCK. /PARASYMPATHOMIMETIC DRUGS/

...INJECTION OF PILOCARPINE INTO CEREBRAL VENTRICLES OF...RABBIT PRODUCED VARIETY OF AUTONOMIC & SOMATIC MOTOR EFFECTS...PILOCARPINE...BEEN FOUND TO EVOKE CHARACTERISTIC CORTICAL AROUSAL OR ACTIVATION RESPONSE IN CATS FOLLOWING IV INJECTION OF RELATIVELY SMALL DOSES...

◉ Summary of Use during Lactation；Limited information indicates that maternal use of ophthalmic pilocarpine did not adversely affect the breastfed infant. If ophthalmic pilocarpine is used during breastfeeding, monitor the infant for signs of cholinergic excess (diarrhea, lacrimation, and excessive salivation or urination), especially in younger, exclusively breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.；Because no information is available on the use of oral pilocarpine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.；◉ Effects in Breastfed Infants；A woman with glaucoma used a pilocarpine insert (Ocusert; strength not specified) in one eye while nursing (extent not stated) her newborn infant for 9 weeks. No adverse reactions were noted in the infant.[1]；A mother who was taking pilocarpine eye drops (concentration not stated) twice daily as well as 2 drops of timolol 0.5% eye drops daily and acetazolamide 250 mg orally twice daily and delivered a preterm infant at 36 weeks of gestation. The infant began 5 months of exclusive breastfeeding at 6 hours after birth. On day 2, the infant developed electrolyte abnormalities consisting of hypocalcemia, hypomagnesemia, and metabolic acidosis. The infant was treated with oral calcium gluconate and a single dose of intramuscular magnesium sulfate. Despite continued breastfeeding and maternal drug therapy, the infant's mild metabolic acidosis disappeared on day 4 of life and the infant was gaining weight normally at 1, 3 and 8 months, but had mild hypotonicity. The authors considered the metabolic effects to be caused by transplacental passage of acetazolamide that resolved despite the infant being breastfed. The infant gained weight adequately during breastfeeding, but had some mild, residual hypertonicity of the lower limbs requiring physical therapy.[2]；◉ Effects on Lactation and Breastmilk；Relevant published information in nursing mothers was not found as of the revision date. In animals, cholinergic drugs increase oxytocin release,[3] and have variable effects on serum prolactin.[4] Other centrally acting cholinergic drugs increase serum prolactin in humans.[5][6] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

S01EB01

S - Sensory organs；S01 - Ophthalmologicals；S01E - Antiglaucoma preparations and miotics；S01EB - Parasympathomimetics；S01EB01 - Pilocarpine

N - Nervous system；N07 - Other nervous system drugs；N07A - Parasympathomimetics；N07AX - Other parasympathomimetics；N07AX01 - Pilocarpine

QN - Nervous system；QN07 - Other nervous system drugs；QN07A - Parasympathomimetics；QN07AX - Other parasympatomimetics；QN07AX01 - Pilocarpine

QS - Sensory organs；QS01 - Ophthalmologicals；QS01E - Antiglaucoma preparations and miotics；QS01EB - Parasympathomimetics；QS01EB01 - Pilocarpine

S01EB01

Pilocarpine is a muscarinic agent that mediates diaphoretic, miotic, and central nervous system effects. Pilocarpine stimulates the secretion of various exocrine glands, such as sweat, lacrimal, salivary, and gastrointestinal glands. Following oral administration, pilocarpine increased the mean salivary flow rate by 2- to lO-folds than placebo. Its peak levels were maintained for at least one to two hours. Pilocarpine increases smooth muscle tone, contracts the pupillary and iris sphincter muscles, and induces miosis. Because pilocarpine may affect all five muscarinic receptor subtypes, it is associated with parasympathetic side effects.

The muscarinic M3 receptor is expressed in various endocrine and exocrine glands, including the gastric and salivary glands. It is also found in smooth muscle cells in pupillary sphincter and ciliary bodies. The M3 receptor is a G_q-protein-coupled receptor that activates phospholipase C and upregulates inositol trisphosphate and intracellular calcium. M3 receptor activation has been implicated in smooth muscle contraction and the stimulation of salivary glands. Pilocarpine is an agonist for M1 and M2 receptors, and is a full and partial agonist at the M3 receptor.

...ACT PRIMARILY @ MUSCARINIC RECEPTORS OF AUTONOMIC EFFECTOR CELLS, GANGLIONIC EFFECTS CAN ALSO BE OBSERVED. THIS IS PARTICULARLY TRUE OF PILOCARPINE, ALTHOUGH ITS GANGLIONIC ACTION ALSO INVOLVES STIMULATION OF MUSCARINIC RECEPTORS...

...AFTER TOPICAL INSTILLATION, MIOSIS BEGINS IN 15 TO 30 MIN & LASTS 4 TO 8 HR. REDUCTION OF INTRAOCULAR PRESSURE IS MAXIMAL IN 2 TO 4 HR, WHICH CORRELATES WITH MAX DECR IN OUTFLOW RESISTANCE. EFFECT ON INTRAOCULAR PRESSURE OUTLASTS EFFECT ON OUTFLOW FACILITY...PILOCARPINE...MAY DECR AQUEOUS PRODUCTION.

...PILOCARPINE /HAS AS/...PRINCIPAL ACTION STIMULATION OF SAME AUTONOMIC EFFECTOR CELLS AS THOSE ACTED UPON BY CHOLINERGIC POSTGANGLIONIC NERVE IMPULSES.

...PILOCARPINE...PRINCIPAL ACTION STIMULATION OF SAME AUTONOMIC EFFECTOR CELLS AS THOSE ACTED UPON BY CHOLINERGIC POSTGANGLIONIC NERVE IMPULSES. IN THIS RESPECT...RESEMBLE CHOLINE ESTERS...

There is limited information available about the metabolism of pilocarpine in humans. Inactivation of pilocarpine can occur at neuronal synapses and probably in plasma. Pilocarpine is reported to undergo CYP2A6-mediated 3-hydroxylation to form stereoisomers of 3-hydroxypilocaripine. Pilocaripine also undergoes hydrolysis mediated by paraoxonase 1, a calcium-dependent esterase in plasma and the human liver. Pilocarpic acid is a possible metabolic product of hydrolysis. Pilocarpine metabolites are reported to possess negligible or no pharmacological activity.

Pilocarpine has known human metabolites that include 3-hydroxypilocarpine.

Possibly occurs at the neuronal synapses and in the plasma Half Life: 0.76 hours

01MI4Q9DI3

PILOCARPINE

Mechanisms of Action [MoA] - Cholinergic Agonists

Mechanisms of Action [MoA] - Cholinergic Muscarinic Agonists

Established Pharmacologic Class [EPC] - Cholinergic Receptor Agonist

Pilocarpine is a Cholinergic Receptor Agonist. The mechanism of action of pilocarpine is as a Cholinergic Agonist and Cholinergic Muscarinic Agonist.

Agents causing contraction of the pupil of the eye. Some sources use the term miotics only for the parasympathomimetics but any drug used to induce miosis is included here.

Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.

Following oral administration of pilocarpine 5mg three times daily in healthy male subjects, peak plasma drug concentrations of 15μg/L were reached in 1.25 hours. At the dose of pilocarpine 10mg three times daily, peak plasma drug concentrations of 41μg/L were reached in 0.85 hours. The rate of absorption is increased when taken with food. Following ophthalmic administration in healthy subjects, the overall median Tmax was 2.2 hours. The mean (SD) Cmax and AUC0-t were 897.2 (287.2) pg/mL and 2699 (741.4) hr x pg/mL, respectively. In patients with presbyopia, the mean Cmax and AUC0-t,ss values were 1.95 ng/mL and 4.14 ng x hr/mL, respectively. The median Tmax was 0.3 hours postdose with a range from 0.2 to 0.5 hours post-dose.

Pilocarpine and its degradation products are eliminated predominantly in the urine.

There is no information available.

There is no information available.

LITTLE DEFINITIVE INFORMATION IS AVAIL ON FATE & ELIMINATION OF PILOCARPINE. IT IS PARTLY DESTROYED IN BODY, BUT LARGER FRACTION IS EXCRETED IN URINE IN COMBINED FORM.

PILOCARPINE PENETRATES EYE WELL; AFTER TOPICAL INSTILLATION...

MEDICATION (VET)

MEDICATION

Use (kg; approx.) in Germany (2009): >75；Consumption (g per capita; approx.) in Germany (2009): 0.000916；Calculated removal (%): 75.1

For the treatment of radiation-induced dry mouth (xerostomia) and symptoms of dry mouth in patients with Sjögrens syndrome.

TOTAL ALKALOIDS ARE EXTRACTED FROM...SUITABLE PILOCARPUS SPECIES, WITH ALC CONTAINING SMALL AMT OF HYDROCHLORIC ACID. SOLVENT DISTD OFF...RESINS ARE ALL DEPOSITED. ...FILTERED...EVAPORATED TO SMALL BULK. AMMONIA IS ADDED IN EXCESS & FREE ALKALOIDS EXTRACTED WITH CHLOROFORM.

PREOBRASHENSKI ET AL, BER 66, 1187 (1933); SAMOKH ALOV, MED PROM SSSR 11, NO 2, 10 (1957)...

ADSORBOCARPINE (BURTON, PARSONS)...ALMOCARPINE (AYERST)...ISOPTO CARPINE (ALCON)...MI-PILO (BARNES-HIND)...MISTURA P (LEDERLE)...PILOCAR (SMP)...PILOCEL (SOFTCON PRODUCTS)...PILOMIOTON (SMP)... /HCL/; PV CARPINE LIQUIFILM (ALLERGAN)...PILOFRIN LIQUIFILM (ALLERGAN)... /NITRATE/

OCUSERT PILO-20, PILO-40 /(ALZA)/

2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-, (3S,4R)-: ACTIVE

/PILOCARPINE/ HAS CIS CONFIGURATION; ISOPILOCARPINE IS TRANS: ZAV'VANOL, DOKLADY ADAD NAUK SSSR 82, 257 (1952). ABSOLUTE CONFIGURATION: HILL, BARCZA, TETRAHEDRON 22, 2889 (1966).

INCOMPATIBILITIES: SILVER NITRATE, MERCURY BICHLORIDE, IODIDES, GOLD SALTS, TANNIN, CALOMEL, POTASSIUM PERMANGANATE, ALKALIES.

/OCUSERT/...IS ELLIPTICALLY SHAPED UNIT...OF PILOCARPINE-CONTAINING RESERVOIR SURROUNDED BY PERMEABLE MEMBRANE. FOLLOWING PLACEMENT BY PT, DIFFERENT FORMS OF UNIT ARE DESIGNED TO RELEASE PILOCARPINE @ RATE OF EITHER 20 OR 40 UG/HR FOR 1 WK. INTRAOCULAR PRESSURE IS REDUCED CONTINUOUSLY...WITH...LESS TOTAL DRUG...

PILOCARPINE HYDROCHLORIDE & PILOCARPINE NITRATE ARE OFFICIAL IN USP BOTH AS SALTS & AS OPHTHALMIC SOLN. AVG ORAL OR HYPODERMIC DOSE OF PILOCARPINE, NOW RARELY USED, IS 5 TO 10 MG. DEVICE FOR ACHIEVING SUSTAINED RELEASE OF PILOCARPINE INTO CUL-DE-SAC OF EYE IS ALSO AVAIL (OCUSERT).