Cholinergics 2022-2023 University of Baghdad PDF

University of Baghdad College of Medicine 2022-2023 Title: Cholinergics Grade: 2nd Grade Module: PP(Principles of Pharmacology) Speaker: Assistant Proff. Dr.Mohammed Qasim Al Atrakji Date:9/11/2022 University of Baghdad/ College of Medicine 2022-2023...

University of Baghdad College of Medicine 2022-2023 Title: Cholinergics Grade: 2nd Grade Module: PP(Principles of Pharmacology) Speaker: Assistant Proff. Dr.Mohammed Qasim Al Atrakji Date:9/11/2022 University of Baghdad/ College of Medicine 2022-2023 Dr.Mohammed Qasim 2022-2023 2nd Grade  University of Baghdad/ College of Medicine 2022-2023 CHOLINERGIC SYSTEM Acetylcholine [Ach] an choline ester, is a neurotransmitter of parasympathetic system. Nerves which synthesize, stores & release Ach are known as ‘Cholinergic”  University of Baghdad/ College of Medicine 2022-2023 SITES OF ACTYLCHOLINE RELEASE: GANGLIA- All pre-ganglionic fibers of ANS.[Both in sympathetic & parasympathetic ganglia.] POST GANGLIONIC PARASYMPATHETHIC nerve endings SWEAT GLANDS: Sympathetic postganglionic nerve endings supplying sweat glands SKELETAL MUSCLES- Somatic nerve endings supplying skeletal muscles ADRENAL MEDULLA CNS- brain & spinal cord University of Baghdad/ College of Medicine 2022-2023  University of Baghdad/ College of Medicine 2022-2023 ACETYLCHOLINE (Ach) Is major neurotransmitter autonomic & somatic site Hemicholinium block choline uptake in axoplasm Transport of Ach into synaptic vesicle is blocked by vesamicol Botulinum toxin inhibit Ach release relieve spasm in spastic disorder, facial wrinkles  University of Baghdad/ College of Medicine 2022-2023 Termination of action of Ach A specific Acetylcholineesterase present in all cholinergic sites hydrolyses ester bond choline in μs (very fast) Location: All cholinergic sites, RBC, Gray matter Nonspecific Butrylcholinesterase (Pseudo) present in plasma hydrolyses Ach slowly Location: Plasma, Liver, Intestine, White matter  University of Baghdad/ College of Medicine 2022-2023 Cholinergic receptor Muscarine alkaloid mimic the effect of parasympathetic nerve discharge but not in autonomic ganglia Nicotinic alkaloid stimulate autonomic ganglia, neuromuscular junction but not other autonomic effector cells  University of Baghdad/ College of Medicine 2022-2023 Classification M-cholinoceptors can be classified into subtypes according to their molecular structure, signal transduction, and ligand affinity in the M1, M2, M3 subtypes, etc. M1-receptors are present on nerve cells, e.g., in ganglia, where they mediate a facilitation of impulse transmission from preganglionic axon terminals to ganglion cells and in Gastric parietal cells M2-receptors mediate acetylcholine effects on the heart. Opening of K+ channels leads to slowing of diastolic depolarization in sinoatrial pacemaker cells and a decrease in heart rate.  University of Baghdad/ College of Medicine 2022-2023 M3-receptors are found in the glandular epithelia (which respond with activation of phospholipase C and increases secretory activity) and in smooth muscle. In smooth vessels, the relaxant action of ACh on muscle tone is indirect, because it involves stimulation of M3-cholinoceptors on endothelial cells that respond by liberating NO. In the CNS, where all subtypes are present, cholinoceptors serve diverse functions, including regulation of cortical excitability, memory, learning, pain processing, and brain stem motor control.  University of Baghdad/ College of Medicine 2022-2023 Characteristic of Nicotinic receptors NM-cholinoceptors Location: neuromuscular junction Function: depolarization of muscle end plate and contraction of skeletal muscle NN-cholinoceptors Location: autonomic ganglia Function: depolarization postganglonic membrane (in adrenal medula –catecholamine release)  University of Baghdad/ College of Medicine 2022-2023 Cholinergic Drugs Choline esters Acetylcholine Bethanechol Carbachol Methacholine Alkaloid Muscarine Arecoline Pilocarpine  University of Baghdad/ College of Medicine 2022-2023 Acetylcholine (Prototype) Orally destroyed, given iv destroyed by pseudocholinesterase in plasma & at the site of action by cholinesterase Nonspecific in action Not used therapeutically Physiology of Ach & action in vitro University of Baghdad/ College of Medicine 2022-2023 preparation Eye-(M3) Sphincter muscle of iris-contraction(miosis) Ciliary muscle-contraction for near vision University of Baghdad/ College of Medicine 2022-2023  University of Baghdad/ College of Medicine 2022-2023 Blood vessels (M3) Vasodilatation is primarily mediated through endothelium derived relaxing factor(EDRF) which is nitric oxide In vivo parasympathetic stimulation effects appears as fall in BP and flushing esp. in blush area of face which has cholinergic innervation University of Baghdad/ College of Medicine 2022-2023  University of Baghdad/ College of Medicine 2022-2023 Bronchial smooth muscle constrict bronchoconstriction  University of Baghdad/ College of Medicine 2022-2023 Detrusor muscle contract while bladder trigone & sphincter relax- Voiding of urine Glands Glands- sweating, salivation, lacrimation  University of Baghdad/ College of Medicine 2022-2023 Skeletal muscle(NM) Ach to muscle end plate causes contraction of fibre High dose can cause twitching & fasciculations  University of Baghdad/ College of Medicine 2022-2023 Ach substitute Effective orally, more selective in their action Methacholine – Less susceptible to acetylcholinesterase, totally resistant to pseudocholinesterase Carbachol, Bethanechol resistant to hydrolysis of both true and pseudocholinesterase Bethanechol(M3)have negligible effects on CVS (M2),no nicotinic action  University of Baghdad/ College of Medicine 2022-2023 CARBACHOL Ester of carbamic acid Has both muscarinic and nicotinic actions Muscarinic actions are prominent on eye, GIT & urinary bladder DOA more than 30 min Therapeutic uses: Glaucoma  University of Baghdad/ College of Medicine 2022-2023 METHACHOLINE Has methyl group in its structure Has both muscarinic and nicotinic actions (very mild nicotinic actions ) Muscarinic actions are prominent on CVS Longer DOA as compared to ACh Therapeutic uses: given SC for the relief of paroxysmal atrial tachycardia BETHANECHOL University of Baghdad/ College of Medicine 2022-2023 Structure related to Ach, acetate is replaced by carbamate & choline is methylated Has no nicotinic actions Muscarinic actions are prominent on eye, GIT & urinary bladder Prolonged DOA Therapeutic uses: Post operative Gastric distension Paralytic ileus Bladder atonia  University of Baghdad/ College of Medicine 2022-2023 Adverse effects Extension of pharmacological action Flushing, salivation, sweating, bradycardia, bronchospasm, hypotension Uses Post-operative paralytic ileus, Urinary retention, abdominal distension Bethanechol is preferred drug due to specific action & wider margin of safety