pilocarpine

[New Latin Pīlocarpus, jaborandi genus (Greek pīlos, wool, felt + Greek karpos, fruit; see -carp) + -INE².]

Key Terms: Exocrine, Sialogogue.

Definition

Pilocarpine is a medicine used to treat xerostomia, or dryness of the mouth, caused by a decrease in saliva production following radiation or due to Sjögren's syndrome, a disorder of the immune system characterized by the failure of the exocrine glands. Pilocarpine is also known as pilocarpine hydrochloride or Salagen.

Purpose

Pilocarpine is used to treat side effects arising from radiation treatment for head and neck cancers. It alleviates dryness of the mouth and throat and aids in chewing, tasting, and swallowing. It may also be given to treat dryness of the eyes resulting from cancer treatment.

Pilocarpine is also used in the form of eye drops or eye gel to treat glaucoma; it works by lowering the pressure of the fluid inside the eye.

Description

Pilocarpine is a naturally occurring substance found in the leaflets of Pilocarpus jaborandi, a South American shrub.

Pilocarpine works by stimulating the function of the exocrine glands, including the glands that produce saliva, sweat, tears, and digestive secretions. It also stimulates smooth muscles, such as those found in the bronchus, gallbladder, bile ducts, and intestinal and urinary tracts.

Pilocarpine was approved by the United States Food and Drug Administration as a sialogogue, or medication to increase the flow of saliva, in 1994. Pilocarpine was effective in relieving xerostomia symptoms after twelve weeks in over half the patients studied; however, the medication may not work for everyone.

Recommended Dosage

Pilocarpine is taken orally. It is available in round white tablets containing 5 mg. Different patients may require different dosages of the drug. The usual dose for adults is five milligrams taken three times a day. If necessary, the physician may increase the dosage to 10 mg, three times a day. Since increasing the dose increases the likelihood of side effects, the lowest dose that is effective should be used for treatment.

Pilocarpine begins to act 20 minutes after ingestion. It will continue to act for three to five hours, with the maximum effect taking place one hour after ingestion. Twelve weeks of regular use may be required for an improvement of symptoms.

If a dose is missed, it should be taken as soon as possible; however, if it is almost time for the next dose, only the next dose should be taken.

Precautions

Patients may wish to take this medication with a meal to avoid stomach upset; however, pilocarpine will have reduced effectiveness if it is taken with a meal that is high in fat. Patients should drink plenty of water to avoid dehydration due to increased sweating. Alcohol and antihistamines should not be used while taking pilocarpine. Due to the possibility of visual disturbances or dizziness, people using this medication should avoid driving or operating machinery, particularly at night. Patients should continue to see a dentist regularly during treatment even though symptoms may be improved, since xerostomia may increase the likelihood of tooth decay and other dental problems.

Studies have not been done to test the safety of pilocarpine use in pregnant or nursing women; very high doses of the drug may cause birth defects in animals. Studies have also not been done to test the use of pilocarpine by children.

Pilocarpine should not be taken by people who are sensitive to it or who have uncontrolled asthma, or such eye problems as inflammation of the iris or angle-closure glaucoma. It should be used with caution by people with breathing problems, gallbladder disease, kidney problems, peptic ulcer, psychological disturbances, retinal disease, or heart or blood vessel disease.

Side Effects

The most common side effect of pilocarpine use is increased sweating. Other less common side effects are as follows: nausea and vomiting, irritated nose, chills, flushing, frequent urination, dizziness, weakness, headache, difficulty with digestion, increased tear production, diarrhea, bloating, abdominal pain, and visual problems.

Symptoms of overdose include irregular heartbeat, chest pain, fainting, confusion, stomach cramps or pain, and trouble breathing. Unusually severe or continuing side effects such as diarrhea, headache, weakness, trembling, visual difficulties, nausea, and vomiting may also indicate overdose.

Interactions

Pilocarpine may interact with other medications, reducing or increasing their effects or, sometimes, increasing the side effects of the other medications. Pilocarpine may also be less effective as a result of interaction with other medications. The following drugs may cause interactions:

• amantadine
• anticholinergics
• antidepressants
• antidyskinetics
• antihistamines
• antimyasthenics
• antipsychotics
• beta-adrenergic blocking agents
• bethanecol
• buclizine
• carbamazepine
• cyclizine
• cyclobenzaprine
• disopyramide
• flavoxate
• glaucoma medications
• ipratropium
• meclizine
• methylphenidate
• orphenadrine
• oxybutynin
• physostigmine
• procainamide
• promethazine
• quinidine

Pilocarpine may also interact with alcohol, cocaine, and marijuana.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Dentistry in Medicine." Section 9, Chapter 103 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Periodicals

Bruce, S. D. "Radiation-Induced Xerostomia: How Dry Is Your Patient?" Clinical Journal of Oncology Nursing 8 (February 2004): 61–67.

Gorsky, M., J. B. Epstein, J. Parry, et al. "The Efficacy of Pilocarpine and Bethanechol upon Saliva Production in Cancer Patients with Hyposalivation Following Radiation Therapy." Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 97 (February 2004): 190–195.

—Racquel Baert, M.Sc.; Rebecca J. Frey, Ph.D.

An alkaloid that causes parasympathetic effects (e.g., secretion of salivary, bronchial, and gastrointestinal glands). It stimulates the sweat glands and also causes vasodilation and cardiac inhibition.

Brand names: Adsorbocarpine®Adsorbocarpine® 4%Akarpine®Isopto® CarpineOcu-Carpine®Ocusert® Pilo-20Pilocar®Pilopine HS®Piloptic®Pilostat®Salagen®

Chemical formula:

Drug Forms:
• Pilocarpine Hydrochloride Ophthalmic drops, solution (below)
• Pilocarpine Hydrochloride Oral tablet
• Pilocarpine tablets
• Pilocarpine eye solution, gel, or system
• Pilocarpine Hydrochloride Ophthalmic gel

Español:
• Clorhidrato de Pilocarpina, Solución para gotas oftalmicas
• Clorhidrato de pilocarpina, Tableta oral
• Tabletas de pilocarpina
• Solución, gel o sistema ocular de pilocarpina
• Clorhidrato de pilocarpina, Gel oftálmico

Pilocarpine Hydrochloride Ophthalmic drops, solution

What is this medicine?

PILOCARPINE is used in the eye to decrease pressure in certain kinds of glaucoma. It is also used to prepare the eyes for surgery.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•asthma, bronchitis
•glaucoma
•heart disease
•inflammation or damage in the eye
•wear contact lenses
•an unusual or allergic reaction to pilocarpine, sulfites, other medicines, foods, dyes, or preservatives
•breast-feeding
•pregnant or trying to get pregnant

How should I use this medicine?

This medicine is only for use in the eye. Do not take by mouth. Follow the directions on the prescription label. Wash hands before and after use. With your middle finger, apply pressure to the inside corner of your eye for 1 to 2 minutes. Tilt your head back slightly and pull your lower eyelid down with your index finger to form a pouch. Try not to touch the tip of the dropper to your eye, fingertips, or other surface. Squeeze the prescribed number of drops into the pouch. Do not blink for 30 seconds. Close your eye gently for 1 to 2 minutes to spread the drops.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

•atropine

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

This medicine can make your vision blur. You may find it is difficult to see, especially at night. Do not drive, use machinery, or do anything that requires clear vision until you know how this medicine affects you. This medicine may make your eyes more sensitive to light. Wear dark glasses in bright sun, or under any bright lights.

Do not wear contact lenses while you are using this medicine.

You can get dehydrated if you sweat a lot while taking this medicine. Make sure you drink enough fluids in order to stay hydrated.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•eye irritation, burning, or itching
•difficulty breathing
•irregular heartbeat
•nausea, vomiting

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•blurred vision
•dizziness
•headache
•sensitivity of the eyes to light
•weakness or tiredness

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Do not freeze. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

A cholinergic alkaloid from leaves of Pilocarpus jaborandi and P. microphyllus; used as an ophthalmic miotic in the form of its hydrochloride and nitrate salts.

This article may require copy-editing for grammar, style, cohesion, tone or spelling. You can assist by editing it now. (August 2009)

Pilocarpine
Systematic (IUPAC) name
(3S,4R)- 3-ethyl- 4-((1-methyl- 1H-imidazol- 5-yl) methyl)dihydrofuran- 2(3H)-one
Identifiers
CAS number	92-13-7 54-71-7 (hydrochloride)
ATC code	N07AX01 S01EB01
PubChem	5910
DrugBank	APRD00382
ChemSpider	5699
Chemical data
Formula	C11H16N2O2
Mol. mass	208.257 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	0.76 hours (5 mg), 1.35 hours (10 mg)
Excretion	urine
Therapeutic considerations
Pregnancy cat.	C
Legal status	℞-only(US)
Routes	gtts, p.o.
Y(what is this?)  (verify)

Pilocarpine is a muscarinic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist^[1] in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its topical application^[2], e.g., in glaucoma and xerostomia.

Contents 1 Clinical uses 2 Scientific uses 3 Trade names 4 Adverse effects 5 References

Clinical uses

Pilocarpine has been used in the treatment of chronic open-angle glaucoma and acute angle-closure glaucoma for over 100 years.^[3] It acts on a subtype of muscarinic receptor (M₃) found on the iris sphincter muscle, causing the muscle to contract and produce miosis. Pilocarpine also acts on the ciliary muscle and causes it to contract. When the ciliary muscle contracts, it opens the trabecular meshwork through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the eye to decrease intraocular pressure.

Pilocarpine is often used as an antidote for Scopolamine, Atropine and Hyoscyamine poisoning.

In ophthalmology pilocarpine is also used to reduce the possibility of glare at night from lights if the patient underwent implantation of phakic intraocular lenses; the use of pilocarpine would reduce the size of the pupils, relieving these symptoms. The most common concentration for this use is pilocarpine 1%, the weakest concentration.

Pilocarpine is also used to treat dry mouth (xerostomia) that can occur for example as a side effect of radiation therapy for head and neck cancers. Pilocarpine stimulates the secretion of large amounts of saliva and sweat.

Pilocarpine is used to stimulate sweat glands in a sweat test to measure the concentration of chloride and sodium that is excreted in sweat. It is used to diagnose cystic fibrosis (CF).

PREPARATION: the drug and powdered leaf of pilocarpin microfelixis are subjected to extracted forotoal alkaloid with ethanol acidified with HCL with solvents removed under reduced pressure and resultant aqueous residue is neutralized with ammonia and kept aside till all the resin is settled down completely. It is filtered and concentrated by sugar solution to a small volume made alkaloid with ammonia and finally extracted with chloroform. The solvent is removed under reduced pressure.

Scientific uses

Pilocarpine is used to induce chronic epilepsy in rodents, commonly rats, as a means to study the disorder's physiology and to examine different treatments. Smaller doses may be used to induce salivation in order to collect samples of saliva, for instance, to obtain information about IgA antibodies.

Trade names

Pilocarpine is available under several trade names such as: Diocarpine (Dioptic), Isopto Carpine (Alcon), Miocarpine (CIBA Vision), Ocusert Pilo-20 and -40 (Alza), Pilopine HS (Alcon), Salagen (MGI Pharma), Scheinpharm Pilocarpine (Schein Pharmaceutical), and Timpilo (Merck Frosst).

Adverse effects

Use of pilocarpine may result in a range of adverse effects, most of them related to its non-selective action as a muscarinic receptor agonist. Pilocarpine has been known to cause excessive sweating, excessive salivation, bronchospasm, increased bronchial mucus secretion, tachycardia, hypertension, browache (when used as eye drops) and diarrhea. It can also result in miosis when used chronically as an eye drop. Systemic injection of Pilocarpine can compromise the blood-brain barrier allowing the pilocarpine to gain access to the brain. This can lead to chronic epilepsy.

The therapeutic uses of pilocarpine are limited by its adverse effects.

References

Fabene, P.F. et al. 2008 Nature Med 14, 1377-1383

1. ^ Spalding et al. 2002
2. ^ Pharmacology, (Rang, Dale, Ritter & Moore, ISBN 0443071454, 5:th ed., Churchill Livingstone 2003) Page 144
3. ^ Rosin, A.. "Pilocarpine. A miotic of choice in the treatment of glaucoma has passed 110 years of use". Oftalmologia (Romania) 35 (1): 53–55. PMID 1811739. 

4 Ashutosh Kar (Medicinal chemistry)

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