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Autonomic nervous system

This article provides an overview of cholinergic transmission and its role in the autonomic nervous system. It explains the synthesis, release, and inactivation of acetylcholine, as well as the two types of cholinesterase. It also discusses the actions of acetylcholine on different receptor types and its effects on the heart, blood vessels, gastrointestinal tract, urinary bladder, respiratory tract, and eyes. Additionally, it covers cholinergic agonists and anticholinesterase agents.

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Autonomic nervous system

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  1. Autonomic nervous system

  2. Parasympathetic nervous system CHOLINERGIC TRANSMISSION: • Acetylcholine is synthesized by the enzyme choline acetyltransferase (ChAT). • Release of acetylcholine occurs by exocytosis with the influx of calcium ions. • Inactivation by acetyl cholinesterase is the major mechanism for termination of action of Ach.

  3. Autonomic nervous system • Acetylcholine is hydrolyzed by the enzyme Cholinesterase There are two types of cholinesterase – • Acetyl cholinesterase(true)– present at all neuromuscular junction. It hydrolyses specifically Acetylcholine. • Butyryl Cholinesterase(Pseudo)– present in plasma and liver. It hydrolyzes procaine and suxamethonium.

  4. Autonomic nervous system

  5. Parasympathetic nervous system Acetylcholine acts on two types of receptors: • Nicotinic receptors. • Muscarinic receptors.

  6. Autonomic nervous system Types of nicotinic receptors:

  7. Autonomic nervous system Types of muscarinic receptors: M1, M2, M3, M4, M5

  8. Autonomic nervous system ACETYLCHOLINE: HEART: M2 RECEPTORS • Decrease in the heart rate • Decrease in the conduction • Decrease in the contraction BLOOD VESSELS: M3 • Vasodilation via the release of nitric oxide

  9. Autonomic nervous system ACETYLCHOLINE : GIT: M1/M3 • Increase the tone and peristalsis. • Increase the secretion of the GIT glands and lacrimal gland. • Relax the sphincter. URINARY BLADDER: M3 • Contraction of detrusor. • Relaxation of trigone and sphincter.

  10. Autonomic nervous system • ACETYLCHOLINE : RESPIRATORY TRACT : • Constriction of bronchus • Increases the secretions of the respiratory tree.

  11. Autonomic nervous system ACETYLCHOLINE : EYE : • IRIS has parasympathetic innervation and acts on muscarinic receptors present on Circular or Sphincter muscle and Ciliary muscle (M 3 receptors ) • Radial muscle has alpha 1 receptors.

  12. Autonomic nervous system

  13. Autonomic nervous system

  14. Autonomic nervous system

  15. Autonomic nervous system ACETYLCHOLINE : • EYE : It causes the spasm of accommodation by contraction of ciliary muscle which causes the zonula to relax, thus allowing the lens to become more convex . • Thus vision is fixed for near objects.

  16. Autonomic nervous system Nicotinic action of Acetylcholine : • Autonomic ganglia ( N N ) – both parasympathetic and sympathetic are stimulated . • Skeletal muscle ( N M ) : Contraction of the fibers.

  17. Autonomic nervous system CHOLINERGIC AGONISTS • CHOLINE ESTERS– Acetylcholine, Methacholine, Carbachol, Bethanechol • CHOLINOMIMETIC ALKALOIDS– Pilocarpine,muscarine • ANTICHOLINESTERASES • Reversible : physostigmine, neostigmine, rivastigmine . • Irreversible(Organophosphurus compounds) : Malathione, parathione, tabun , sarin

  18. Autonomic nervous system Choline esters– Acetylcholine, Methacholine, Bethanechol • poorly absorbed from the stomach • poor lipid solubility • poor BBB penetration

  19. Autonomic nervous system • CHOLINE ESTERS: • Methacholine and Bethanechol have no nicotinic actions • Methacholine has prominent CVS action • Carbachol and Bethanechol acts on GIT and Urinary bladder. • Carbachol and Bethanechol are resistant to the hydrolysis by AchE

  20. Autonomic nervous system CHOLINOMIMETIC ALKALOIDS– Pilocarpine • Pilocarpine – stimulates only muscarinic receptors • Used in chronic simple glaucoma, acute congestive glaucoma and as miotic.

  21. Autonomic nervous system ANTICHOLINESTERASES AGENTS • These agents inhibit the AchE present in the synaptic regions . • Thus they prolong the existence of Ach released from the nerve endings. • These are of two types Reversible Anti - ChE Irreversible Anti - ChE

  22. ANS • Irreversible Anti-ChE agentsare insecticides and nerve gas poisons • Insecticides– Organophosphorus compounds - Parathion, Malathion, Diazinon (TIK-20), Echothiopate • Nerve gas poisons – Soman, Sarin, Tabun

  23. ANS ANTICHOLINESTERASES AGENTS • Reversible : Edrophonium ,Neostigmine, Physostigmine, Pyridostigmine, Tacrine

  24. ANS ANTICHOLINESTERASES

  25. ANS ANTI-CHOLINESTERASES AGENTS • Mechanism of action :Acetyl cholinesterase (AchE) is an enzyme withanionicand esteratic site. • Acetylcholine (Ach ) involves attraction of the positive charge N+ of Ach and anionic site; acetylation of serine leading to the acetylated enzyme. • The acetylated enzyme reacts with the water to produce acetic acid and free enzyme within milliseconds.

  26. ANS CHOLINESTERASES

  27. ANS Physostigmine : • Naturally occurring alkaloid. • Tertiary amine. • Oral absorption is good. • CNS action is present. • Used in glaucoma and as antidote in atropine poisoning.

  28. ANS Neostigmine : • Synthetic • Quaternary amine • Poor oral absorption • CNS action absent • Prominent action on skeletal muscles • Used in ileus, urinary retention, myasthenia gravis.

  29. ANS USES OF CHOLINOMIMETIC DRUGS: • Open / Wide angle glaucoma. • Miotics • Myasthenia gravis • Retention of urine • Drug poisoning – Atropine. • Alzheimer's disease – Donepezil, Galantamine, Rivastigmine, Tacrine

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