cholinergic & anti-choliesterase ppt.pptx

cholinergic & anti-choliesterase ppt.pptx

1. CHOLINERGIC TRANSMISSION A:- Precursor - Choline B :- Enzyme- Synthesizing - Choline Acetylase Degrading - A cetycholine Esterase (TRUE) - Butyrylcholine Esterase (PSEUDO) C :- 300,000 vesicles Quantum - 0.1 to 0.3 mv - 1mepp/sec

2. CHOLINERGIC TRANSMISSION (CONTD.) RECEPTORS N - Ligand gated ion channels N n & N m M - Through G- protein signalling systems M 1 – S tomach Glands - Release of hist. - Secretion of acid M 2 – (i) Myocardium - ↓ generation of impulses –SA - ↓ conduction of impulse – AV - ↓ contractility –Atria & Ventricle

3. CHOLINERGIC TRANSMISSION (CONTD.) (ii) Pre-synaptic ↓ Ach from cholinergic neurons ↓ NA Postgang . sym. Neurones M 3 - Smooth muscle – Contraction - Exocrine glands – ↑ secretion - Vascular Endothelium – ↑ NO secretion

4. CLASSIFICATION CHOLINE ESTERS - Acetylcholine - Methacholine - Carbachol - Bethanechol - Cevimeline NATURAL ALKALOID - Muscarine - Pilocarpine - Arecoline - Nicotine

5. ANTI- CHOLINESTERASES A) Reversible - Physostigmine - Neostigmine - Pyridostigmine - Edrophonium - Rivastigmine - Donepezil

6. ANTI- CHOLINESTERASES(contd.) B) Irreversible - Parathion (agricultural insecticides) - Malathion - Diazinon (Household) - Propoxur - Tabun - Sarin (Chemical warfare) - Soman

7. PHARMACOLOGICAL ACTIONS CVS (M 2 ) a ) Heart :- ↓ G/C /C in Myocardium (PR ↑ – AV) b ) Blood V essel(M 3 ) Dilatation – ↓ BP → Reflex tachycardia innervation is only on face to neck 2) Exocrine glands (M 3 ) Sweating > Salivation > Lacrimation = TBT secretion >> Gastric secretion

8. PHARMACOLOGICAL ACTIONS(contd.) 3 ) Smooth Muscle a ) G.I. – ↑ T one & Peristalsis b ) Urinary System – ↑ T one , Voiding c ) Bronchi – ↑ T one (Bronchial Asthma) 4) Eye- Cont. of circular mus. of iris → Miosis . - Cont. of ciliary mus.→ thickening of lens

9. PHARMACOLOGICAL ACTIONS(contd.) 5 ) Skeletal muscles (N M ) Twitching & fasciculation 6 ) Autonomic ganglia( Nn ) Both Ad & Ch - unpredictable 7 ) CNS (M+N ) Rapid destruction + min. entry →unpredictable response. 8 ) Stomach (M 1 ) – ↑ acid+ Pepsin

10. USES OF CHOLINE ESTERS 1) Cardiac – PSVT – Methacholine 2) Intestinal – Paralytic ileus , M egacolon ( carbachol / bethanechol ) 3) Urinary - Retention of urine ( carbachol / bethanechol ) 4) Lacrimal Secretion & Sialogogue – Cevimeline

11. CHOLINOMIMETIC ALKALOIDS Pilocarpine :- - As eye drops – Miosis - Ch. simple glaucoma – Drops Vs. Ocusert - To prevent and break adhesions between iris / lens and iris / cornea Muscarine , Arecoline and Nicotine

12. CHOLINESTERASE INHIBITORS Reversible Physostigmine ( Eserine ) :- - Natural ,lipid soluble compound -Rapidly absorbed and crosses BBB – CNS effects -Poisoning with Atropine , Phenothiazines & Tricyclic Antidepressants

13. CHOLINESTERASE INHIBITORS(contd.) Neostigmine – - Synthetic, much less lipid soluble -Does not cross BBB – No central effects - ACh action on NMJ – Myasthenia gravis - If intolerable M effects – Atropine - S teroids – ↓ production of N m antibodies - Thymectomy Also in paralytic ileus & bladder atony .

14. CHOLINESTERASE INHIBITORS (contd.) Pyridostigmine - Less potent , Long duration Edrophonium - Very short duration - To identify between “ Myasthenic ” and “Cholinergic” crisis Rivastigmine Newer agents, AD, Long acting, Donepezil Well tolerated

15. OTHER USES :- a ) Cobra bite –venom b ) D ecurarisation after G.A c) Curare & other poisonings d) E drophonium (PSVT)

16. ChE INHIBITORS – IRREVERSIBLE High efficacy ------ Toxicity (cross BBB) High lipid soluble – Rapid absorption from all routes Poisoning occurrence - Accidental , suicidal, homicidal

17. Muscarinic Effects - Inhalation / ingestion/ vapours (Eye) Miosis , lacrimation - ↑ secretion – Dehydration - Fall in BP – Reflex Tachycardia - ↑ dose –VMC at medulla ( Bradycardia ) - ↑ contraction of smooth muscle - Ataxia , convulsion , coma , death due to Respiratory Failure

18. TREATMENT Change clothes. Wash skin , eyes. Gastric lavage. Fresh air, Patent airway, PPR, Hydration Maintenance of BP- vasopressor agent CONVULSION – Diazepam i.v Atropine Enzyme Reactivator – Oximes DAM, Pralidoxime , Obidoxime