Cholinergic Drugs (direct acting) Part-2

(3) CARBACHOL (Carbamylcholine)

• Carbachol is is an ester of carbamic acid and poor substrate for AChEsterase. It is biotransformed by other esters at very slow rate.

• Carbachol has both Muscarinic and Nicotinic actions.

Functions

(i) Actions :

• Carbachol has profound effects on both Cardiovascular system and GI system.

• It has ganglion stimulating activity and it may first stimulate and then depress these systems.

• It can cause release of epinephrine from adrenal medulla by its nicotinic functions.

On Eye :

• It cause miosis

• It cause spasm of accomodatiom in which the ciliary muscle of the eye remains in a constant state of contraction.

• Carbachol is also used to stimulate micturation by contraction of detrusor muscle.

(ii) Therapeutic uses:

• Carbachol has high potency, receptor non-selectivity and relatively long duration of action.

• Carbachol is rarely used.

• Carbachol administered ocularly to induce miosis to reduce the intraoccular pressure in the treatment of glaucoma.

(iii) Adverse effects :

• Few adverse effects occur with opthalmologic use, due to lack of systemic penetration.

• Side effects include accomodation spasm, pupillary constriction, headache, conjuctival hypermia.

(4) PILOCARPINE

• Alkaloid pilocarpine is tertiary amine and is stable to hydrolysis by AChEsterase.

• When campared with ACh and its derivatives, it is far less potent but it is unchanged and can penetrates the CNS at therapeutic doses.

• Pilocarpine exhibit muscarinic activity & is primarily used in opthalmology.

(i) Actions :

• Pilocarpine produce rapid miosis, contraction of ciliary muscle and spasm of accomodation.

• Pilocarpine is most potent stimulators of secerations such as sweat, tears, amd saliva.

(ii) Therapeutic uses:

• Pilocarpine is used for the treatment of glaucoma and is drug of choice for emergency lowering in intraoccular pressure in both open angle and closure angle glaucoma.

• Pilocarpine is extremely effective in opening in Trabecular meshwork around the Schelem canal, cause an immediate drop in intraoccular pressure(IOP) because of increase drainage of aqeous humor. This action occurs wiyhin few minutes and last for 4-8 hours.

• The topical carbonic anhydrase inhibitors, such as : dorzolamide and B-adrenergic blockers are effective in treating glaucoma but are not used for emergency lowering of IOP.

• The miotic action of Pilocarpine is also useful in reversing mydriasis due to atropine.

• This drug is useful in promoting salivation in patients with Xerostomia (Dry mouth resulting from reduced or absence of saliva flow & it also occurs due to irridation of head&Neck).

• Sjögren syndrome, which is characterized by dry mouth and lack of tears, is treated with oral pilocarpine tablets.

(iii) Adverse effects:

• Pilocarpine can cause :

-Blurred Vision

- Night blindness

- Brow Ache (Pain behind or around the eye brow)

• Poisonong with Pilocarpine is characterized by: profuse sweating(diaphoresis) and salivation.

• Parental atropine, at doses that can cross the blood-brain barrier , is administered to counteract the toxicity of pilocarpine.

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