Cholinergic drugs

Nervous system CENTRAL NERVOUS SYSTEM PERIPHERAL NERVOUS SYSTEMS Sensory fiber motor fiber involuntary voluntary sympathetic parasympathetic

function Sympathetic and parasympathetic are complemantary Composition: pre,ganglion and post Chemicals are Ach and NA

Drugs produce similar effects to acetylcholine Cholinergic drugs Drugs produce similar effects to acetylcholine

Classification Direct cholinergic agents Indirect Cholinestrase reactivator

Effects of acetylcholine Muscarinic effects Contaraction of smooth muscle Peripheral vasodilation Increase secretion of saliva, exocrine Dcrease the contraction of the heart B. Nicotinic Stimulation of skeletal muscle tone

Trans acetylcholine active on muscarinic and nicotinic receptors

A. Direct cholinergic agents Mode of action Cholinomimetic alkaloid Choline esters Pilocarpine Methacholine Carbachol [Cholinomimetics & parasympathomimetics]

SAR Acetyl choline

Metacholine CH3 on beta carbon increase muscarinic Long duration Uses: Mythenia gravis, paroxysmal tachycardia

Synthesis

Carbachol Long duration Uses: glucoma Synthesis

Bethanicol Bioisoster of methacholine Long duration Mainly muscarinic Uses:abdominal distention,urinary distention

2. Cholinomimetic alkaloid pilocarpine Uses: glucoma, antagonises mydriatics

cevimeline For treatment of dry mouth in Sjogren’s syndrome Similar to pilocarpin

B.Indirect acting [anticholinesterase] Organophosphorus Carbamates Physostigmine Neostigmine methyl sulphate Pyridostigmine Neostigmine bromide(prostigmin) Edrophonium

Physostigmine acts by interfering with the metabolism of acetylcholine Physostigmine acts by interfering with the metabolism of acetylcholine. It is an inhibitor of acetylcholinesterase, the enzyme responsible for the breakdown of acetylcholine in the synaptic cleft of the neuromuscular junction. It indirectly stimulates both nicotinic and muscarinic receptors. (Find the structure and uses).

Neostigmine bromide(prostigmin)

Synthesis

Neostigmine methyl sulphate Uses Contraindication Bradycardia, cardiac disease, hypotension, parkinsonism.

Pyridostigmine bromide(mestinon)

Synthesis Uses: Mysthenia gravis

Edrophonium Chloride Short and rapid-acting cholinergic drug. Uses:myasthenia gravis , emergency treatment (short action) Side effects: bradycardiaa, hypotension,increase saliva

Cholinesterase reactivators 2-[(Hydroxyimino)methyl]-1-methylpyridinium chloride

Synthesis

Cholinergic blocking agents [Anticholinergic] Act at different sites Postganglionic of parasympathetic (Antimuscurinic) At ganglionia of sympathetic and parasympathetic (ganglion blockers) Neuromuscular junction of voluntry system (neuromuscular blocking agents)

I. Antimuscarinics [similar to Ach & alkaloid] There effects will be : Mydriatic Antispasmodic antisecretory

Antimuscarinics similar to Acetyl choline Antimuscarinic:aminoalcohol,aminoamides,papaverine derivatives. Aminoalcohols:esters,ethers,carbamates. Esters:solaneceous alk.,synthetic analouges,esters of other alc.

2. Alkaloid antimuscarinics Atropine, Hyoscin Uses of Antimuscarinics: Antispasmodic Antisecretory Antiparkinsonism mydriatics

Esters of other aminoalcohol Cyclopentolate Uses: mydriatic ,cycloplegic

Aminoalcohol ethers Orphenadrine Uses: Antihistaminic,antiparki-nsonism. N,N-dimethyl-2-(phenyl(o-tolyl)methoxy)ethanamine

Oxybutynin used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination Homework : find the structure and mechanism of action

Papaverine and related compounds. Vasodilator relax smooth muscle.(GIT,bronchi,uretures,biliary system).

Trihexyphenidyl Uses Parkinson’s disease

Ipratropium bromide Uses Bronchodilator

Ganglionic blocking agent Hexamethonium

Neuromuscular bloking agents Decamethonium bromide Assay :volhard

Neuromuscular blocking agents Uses