6/4/13

pilocarpine

The alkaloid pilocarpine [pye-loe-KAR-peen] is a tertiary amine and is stable to hydrolysis by acetylcholinesterase. Compared with acetylcholine and its derivatives, it is far less potent, but it is uncharged and will penetrate the CNS at therapeutic doses. Pilocarpine exhibits muscarinic activity and is used primarily in ophthalmology.

1. Actions: Applied topically to the cornea, pilocarpine produces a rapid miosis and contraction of the ciliary muscle. The eye undergoes miosis and a spasm of accommodation; the vision is fixed at some particular distance, making it impossible to focus  [Note the opposing effects of atropine, a muscarinic blocker, on the eye ] .


Figure:  Actions of pilocarpine and atropine on the iris and ciliary muscle of the eye.


Pilocarpine is one of the most potent stimulators of secretions (secretagogue) such as sweat, tears, and saliva, but its use for producing these effects has been limited due to its lack of selectivity. The drug is beneficial in promoting salivation in patients with xerostomia resulting from irradiation of the head and neck. Sjögren's syndrome, which is characterized by dry mouth and lack of tears, is treated with oral pilocarpime tablets and cevimeline, a cholinergic drug that also has the drawback of being nonspecific.


 2. Therapeutic use in glaucoma: Pilocarpine is the drug of choice in the emergency lowering of intraocular pressure of both narrow-angle (also called closed-angle) and wide-angle (also called open-angle) glaucoma. Pilocarpine is extremely effective in opening the trabecular meshwork around Schlemm's canal, causing an immediate drop in intraocular pressure as a result of the increased drainage of aqueous humor. This action lasts up to 8 hours and can be repeated. The organophosphate echothiophate inhibits acetylcholinesterase and exerts the same effect for a longer duration . [Note: Carbonic anhydrase inhibitors, such as acetazolamide, as well as the β-adrenergic blocker timolol, are effective in treating glaucoma chronically but are not used for emergency lowering of intraocular pressure.] 


3. Adverse effects: Pilocarpine can enter the brain and cause CNS disturbances. It stimulates profuse sweating and salivation



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  2. We sometimes administer pilocarpine to rabbits to mimic the effects of organophosphate poisoning... to see if our toxicology students can identify the symptoms of excessive muscarinic stimulation.

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  3. The joys of working in a Pharmacology Department, where one can reinforce theory with practicals.

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