Pilocarpine

INTRODUCTION:
  • Pilocarpine: is alkaloid with 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 penetrate the CNS at therapeutic doses. 
  • Pilocarpine exhibits muscarinic activity and is used primarily in ophthalmology. 
  • Actions of pilocarpine and atropine on the iris and ciliary muscle of the eye
  • Drug contraindicated in iridocyclitis is pilocarpine
MECHANISM OF ACTION:
  • Pilocarpine binds to muscarinic receptor - Activates receptor binds G-protein - Removal of GDP and addition of GTP to G-protein - Dissociation of G-protein from muscarinic receptor - Separation of G-protein into alpha and beta-gamma subunits - Alpha subunit interacts with and activates Phospholipase C - Phosphatidyl inositol biphosphate (PIP) complex - Phospholipase breaks down PIP into inositol 1,4,5-triphosphate (IP3)and diacylglycerol (both 2o) - IP3 interacts with ER membrane which releases Ca2+
  • Muscle Action - Ca2+ binds to calmodulin forming a complex - This complex binds to caldesmon - When caldesmon is bound by Ca2+/calmodulin complex this allows myosin-actin interactions to occur -The muscle (pupil)contracts Marieb 
INDICATION:
  • Dry mouth (xerostomia), particularly in Sj√∂gren's syndrome, but also as a side effect of radiation therapy for head and neck cancer.
  • It has also been used in the treatment of chronic open-angle glaucoma and acute angle-closure glaucoma. It acts on a subtype of muscarinic receptor (M3) found on the iris sphincter muscle, causing the muscle to contract -resulting in pupil constriction (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.
  • Reduce the possibility of glare at night from lights when the patient has undergone 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. 
  • Combination of pilocarpine and epinephrine use in glaucoma treatment may inhibit Pigmented pupillary cyst
  • Pilocarpine is shown to be just as effective as apraclonidine in preventing intraocular pressure spikes after laser trabeculoplasty.
  • 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.
ADVERSE EFFECT:
  • Pilocarpine has been known to cause excessive salivation, sweating, bronchial mucus secretion, bronchospasm, bradycardia, vasodilation, and diarrhea. 
  • Eye drops can result in brow ache,Accomodative spasm,Blurred vision and miosis.
  • Punctate stenosis,Follicular conjunctivitis & Posterior synechia 
  • Systemic injection of pilocarpine can compromise the blood brain barrier allowing pilocarpine to gain access to the brain which can lead to chronic epilepsy.
  • "Scoline apnea" is a serious complication. In that condition, patient is unable to resume normal muscle function and spontaneous respiration after the administration of the depolarising muscle relaxant succinylcholine (scoline), which is used to induce short lasting muscle relaxation during general anaesthesia.
  • Acquired nasolacrimal duct obstruction 
  • Myopia
Exam Question of:
  • Acquired nasolacrimal duct obstruction is caused by Pilocarpine
  • Pilocarpine is used to treat glaucoma by Improving drainage of aqueous humor
  • Pilocarpine is used to treat glaucoma
  • Drug used in acute congestive glaucoma is Pilocarpine 
  • Punctate stenosis,Follicular conjunctivitis & Posterior synechia are the Side effects of Pilocarpine
  • Drug of choice for acute congestive glaucoma is 1-2% pilocarpine
  • Cause of anisocoria may be due to Pharmacological blockage
  • In primary open-angle glaucoma pilocarpine eye drops lowers the intraocular pressure by its direct action on the Longitudinal fibres of the ciliary muscle/Sphincter pupillae muscle
  • Pilocarpine is not used in young adults as it causes Myopia
  • Combination of pilocarpine and epinephrine use in glaucoma treatment may inhibit Pigmented pupillary cyst
  • Drug contraindicated in iridocyclitis is pilocarpine
  • Pilocarpine is used in Primary, Open Angle Glaucoma,Acute Angle Closure Glaucoma & Chronic Synechial Angle Closure Glaucoma
  • Pilocarpine acts on trabecular meshwork and affects the aqueous outflow
  • Accomodative spasm,Blurred vision,Miosis are side effects of topical pilocarpine solution
  • Alcohol, salicylates and pilocarpine can be used as Diaphoretics

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