Page 47 - pharma 1 theoretical updated MNU_Neat

Clinical pharmacy 2024/2025 Level 3 Pharm D Pharmacology 1 (PO 502)

2- Indirect acting cholinergic agents (Anticholinesterase)
 Inhibit cholinesterase ➔ accumulation of large amount of Ach at different tissues ➔

response is potentiated & prolonged.
MOA: Cholinesterase has:
1. Anionic sites (have -ve charge) ➔ attract +ve charged N atoms of Ach.
+
2. Esteratic sites (have +ve charge) ➔ attract COOH group of Ach.
➔ So, the Esteratic site is acetylated & choline is released ➔ then, the acetyl group is
removed by water ➔ acetic acid & free enzyme.

➢ There are 2 types:

Reversible cholinesterase inhibitors: Irreversible cholinesterase inhibitors:

Combines with both sites ➔ but esteratic Combines with esteratic sites ➔
site is carbamylated ➔ carbamylated ester phosphorylation of the site ➔

➔ not readily hydrolyzed like Ach ➔ so, phosphorylated ester ➔ very slowly
enzyme remains inhibited for long time hydrolyzed or ever not hydrolyzed ➔
(4 -6 hrs.) prolonged inhibition of enzyme.

➢ Ex: physostigmine, neostigmine & ➢ Very long duration of action &
edrophonium. toxicity ➔ Used as insecticides e.g.
organophosphorus comp.

Reversible cholinesterase inhibitors

1) Neostigmine "Prostigmine"
Synthetic quaternary ammonium compound Uses:

a) Inhibit both true & pseudocholinesterase ➔ 1- Diagnosis & treatment of myasthenia
accumulation of Ach. gravis.
b) Has direct stimulation of cholinergic 2- ttt. of curare poisoning ➔ should be

receptors due to structure similarity to Ach. used with atropine to block muscarinic
c) Has direct action on skeletal muscles (not action.
related to cholinergic stimulation). 3- ttt. of paralytic ileus.
 Not cross BBB & not absorbed orally 4- ttt. of atonic urinary retention.

because it is a quaternary ammonium (urinary bladder is relaxed)
compound ➔ given IM. 5- ttt. of atrial tachycardia.

6- ttt. of Alzheimer disease

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