Cholinomimetic Drugs

 

3.5. Indirect-acting Cholinomimetic Drugs

Characteristics:

anticholinesterase drugs ie. inhibitors of ACh metabolism-similar effects to direct-acting cholinomimetics

Mechanism:

-normally ACh is rapidly degraded in the cholinergic synapse (T1/2=40ms)

-indirect-acting cholinomimetics block the enzymatic hydrolysis of acetylcholine ----> increases local concentrations of Ach

- effect of ACh is amplified, leading to muscarinic or nicotinic effects, depending on the organ.

- the effect can be therapeutic or life-threatening

 classification:

A) Reversible Inhibitors

-all are poorly absorbed from conjunctiva, skin & lungs except physostigmine which is well absorbed from all sites-is used topically in the eye-more commonly used clinically than organophosphates

Carbamate esters -2 step hydrolysis like ACh-but the covalent bond of carbamylated enzyme is more resistant to hydration (T1/2=30-60 min)eg neostigmine, physostigmine Clinical use:

Primary target organs of anticholinesterase drugs:

§ eyes

§ skeletal muscles

§ neuromuscular junctions

§ gastrointestinal tract

§ urinary tract

§ respiratory tract

§ heart

-effects are similar to direct-acting cholinergic agonists

Major uses in the treatment of:

a) Glaucoma) Myasthenia gravies) Stimulation of gastrointestinal and urinary tract motility (eg. neostigmine)                                         - same effects as with agonists) Reversal of neuromuscular blockade) Atropine poisoning

a) Glaucoma:

-an ocular disease caused by increased intraocular pressure due to inadequate drainage of aqueous humor at filtration angle ----> damage to the retina & optic nerve.-intraocular pressure is determined by the balance between fluid input & drainage out of the globe. -aqueous humor produced by ciliary epithelium and drained at the filtration angle of the anterior chamber.