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Pharmacology of Muscarinic Receptor Blockade
Acetylcholine is an agonist at both muscarinic and nicotinic receptors The nicotinic actions of acetylcholine remain when muscarinic receptors are blocked
Muscarinic Receptor Blockade Does Not Affect  Ganglionic Transmission Muscarinic receptor blockade prevents generation of  the IPSP and the sEPSP but not the fEPSP X
Muscarinic receptor blockade does not interfere with transmission at autonomic ganglionic sites, the adrenal medulla, or skeletal muscle fibers. Sympathetic adrenergic functions are not affected. X X
In Dual Innervated Organs, Muscarinic Receptor Blockade Allows Sympathetic Dominance X
Atropine
Characteristics of Atropine ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Response to ACh in the Presence of Atropine Atropine competitively inhibits muscarinic reponses to ACh Log dose of acetylcholine Response control atropine
Actions of Atropine at Tissue Sites ,[object Object],[object Object],[object Object],Atropine limits focusing to distant objects Accomodation is blocked by atropine
Changes in Accomodation and Pupillary Diameter after Administration of an Antimuscarinic Agent Reproduced from  Basic and Clinical Pharmacology
Actions of Atropine At Smooth Muscles And Glands ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cardiovascular Actions of Atropine  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Response to Doses of Atropine Reproduced from  Basic and Clinical Pharmacology
M 1 Receptor  Activation  at Parasympathetic Nerve Terminals Exerts A Small Negative Feedback Effect Upon ACh Release in Response to Nerve Impulse Flow postsynaptic fiber cardiac muscle fiber ACh ACh ACh (----) M1 M2
M 1 Receptor  Blockade  Eliminates the Negative Feedback Effect and Increases ACh Release in  Response to Nerve Impulse Flow postsynaptic fiber cardiac muscle fiber Pirenzepine is an M 1  antagonist x ACh ACh ACh ACh M1 M2
Intravenous infusion of acetylcholine in high doses produces actions at numerous sites. Bradycardia and hypotension are among the results. Such actions are accentuated in the presence of inhibitors of AChE (they also block plasma pseudocholinesterase).   i.v. infusion
Prior blockade of muscarinic receptors followed by intravenous infusion of a high dose of ACh converts the bradycardiac and hypotensive responses to tachycardia and hypertension, mediated through the nicotinic receptors.  x x x i.v. infusion
Effect Of Atropine in Relation to Dosage ...
Dose of Atropine DOSE EFFECT 0.5 mg Slight decline in heart rate  Some dryness of mouth Inhibition of sweating
Dose of Atropine DOSE EFFECT 1.0 mg Definited dryness of mouth  Thirst Inreased heart rate, sometimes    preceded by slowing Mild dilatation of pupil
Dose of Atropine DOSE EFFECT 2.0 mg Rapid heart rate   Palpitation Marked dryness of mouth Dilated pupils Some blurring of near vision
Dose of Atropine DOSE EFFECT 5.0 mg All the previous symptoms are    marked   Difficulty in speaking and swallowing Restlessness and fatigue Headache Dry hot skin Difficulty in micturition Reduced intestinal peristalsis
Dose of Atropine DOSE EFFECT 10 mg Previous symtoms are more marked and more Pulse, rapid and weak Iris practically obliterated Vision very blurred Skin flushed, hot, dry, and scarlet Ataxia Restlessness and excitement Hallucinations and delirium Coma
The previous five slides are reproduced from Goodman and Gilman’s  The Pharmacological Basis of Therapeutics
Scopolamine (1) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Scopolamine (2) ,[object Object],[object Object],[object Object]
Therapeutic Uses of Antimuscarinic Agents
Therapeutic Uses of Muscarinic Antagonists (1) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Therapeutic Uses of Muscarinic Antagonists (2) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Therapeutic Uses of Muscarinic Antagonists (3) ,[object Object],[object Object],[object Object],[object Object]
Therapeutic Uses of Muscarinic Antagonists (4) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Therapeutic Uses of Muscarinic Antagonists (5) ,[object Object],[object Object],[object Object],[object Object],[object Object],Atropine is used for the above
Toxicity of Atropine
Contraindications to the Use Of Antimuscarinic Agents ,[object Object]
Flow of Aqueous and Its Escape From the Eye
Contraindications to the Use of Antimuscarinic Agents ,[object Object],[object Object],[object Object],[object Object]
Tertiary Muscarinic Antagonists and Their Uses ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Tertiary Muscarinic Antagonists and Their Uses ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],In general, they are useful for spasms of the g.t. tract, bile duct, ureters,
Tolterodine ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Quaternary Ammonium Antagonists (1) ,[object Object],[object Object],[object Object]
Quaternary Ammonium Antagonists (2) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Quaternary Ammonium Antagonists (3) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Ipratropium ,[object Object],[object Object]
M 1  Muscarinic Receptor Antagonists ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
M 2  Muscarinic Receptor Antagonists ,[object Object],[object Object],[object Object],[object Object],[object Object]
M 3  Muscarinic Receptor Antagonist ,[object Object],[object Object],[object Object]
Drugs of Other Classes With Antimuscarinic Activity (1) ,[object Object],[object Object],[object Object],[object Object],[object Object],.: DEMONSTRATION
Drugs of Other Classes With Antimuscarinic Activity (2) ,[object Object],[object Object],[object Object],[object Object],[object Object],.: DEMONSTRATION
Drugs of Other Classes With Antimuscarinic Activity (3) ,[object Object],[object Object],[object Object],[object Object],[object Object],.: DEMONSTRATION
Drugs of Other Classes With Antimuscarinic Activity (4) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],.: DEMONSTRATION

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Cholinergic antagonists

  • 1. Pharmacology of Muscarinic Receptor Blockade
  • 2. Acetylcholine is an agonist at both muscarinic and nicotinic receptors The nicotinic actions of acetylcholine remain when muscarinic receptors are blocked
  • 3. Muscarinic Receptor Blockade Does Not Affect Ganglionic Transmission Muscarinic receptor blockade prevents generation of the IPSP and the sEPSP but not the fEPSP X
  • 4. Muscarinic receptor blockade does not interfere with transmission at autonomic ganglionic sites, the adrenal medulla, or skeletal muscle fibers. Sympathetic adrenergic functions are not affected. X X
  • 5. In Dual Innervated Organs, Muscarinic Receptor Blockade Allows Sympathetic Dominance X
  • 7.
  • 8. Response to ACh in the Presence of Atropine Atropine competitively inhibits muscarinic reponses to ACh Log dose of acetylcholine Response control atropine
  • 9.
  • 10. Changes in Accomodation and Pupillary Diameter after Administration of an Antimuscarinic Agent Reproduced from Basic and Clinical Pharmacology
  • 11.
  • 12.
  • 13. Response to Doses of Atropine Reproduced from Basic and Clinical Pharmacology
  • 14. M 1 Receptor Activation at Parasympathetic Nerve Terminals Exerts A Small Negative Feedback Effect Upon ACh Release in Response to Nerve Impulse Flow postsynaptic fiber cardiac muscle fiber ACh ACh ACh (----) M1 M2
  • 15. M 1 Receptor Blockade Eliminates the Negative Feedback Effect and Increases ACh Release in Response to Nerve Impulse Flow postsynaptic fiber cardiac muscle fiber Pirenzepine is an M 1 antagonist x ACh ACh ACh ACh M1 M2
  • 16. Intravenous infusion of acetylcholine in high doses produces actions at numerous sites. Bradycardia and hypotension are among the results. Such actions are accentuated in the presence of inhibitors of AChE (they also block plasma pseudocholinesterase). i.v. infusion
  • 17. Prior blockade of muscarinic receptors followed by intravenous infusion of a high dose of ACh converts the bradycardiac and hypotensive responses to tachycardia and hypertension, mediated through the nicotinic receptors. x x x i.v. infusion
  • 18. Effect Of Atropine in Relation to Dosage ...
  • 19. Dose of Atropine DOSE EFFECT 0.5 mg Slight decline in heart rate Some dryness of mouth Inhibition of sweating
  • 20. Dose of Atropine DOSE EFFECT 1.0 mg Definited dryness of mouth Thirst Inreased heart rate, sometimes preceded by slowing Mild dilatation of pupil
  • 21. Dose of Atropine DOSE EFFECT 2.0 mg Rapid heart rate Palpitation Marked dryness of mouth Dilated pupils Some blurring of near vision
  • 22. Dose of Atropine DOSE EFFECT 5.0 mg All the previous symptoms are marked Difficulty in speaking and swallowing Restlessness and fatigue Headache Dry hot skin Difficulty in micturition Reduced intestinal peristalsis
  • 23. Dose of Atropine DOSE EFFECT 10 mg Previous symtoms are more marked and more Pulse, rapid and weak Iris practically obliterated Vision very blurred Skin flushed, hot, dry, and scarlet Ataxia Restlessness and excitement Hallucinations and delirium Coma
  • 24. The previous five slides are reproduced from Goodman and Gilman’s The Pharmacological Basis of Therapeutics
  • 25.
  • 26.
  • 27. Therapeutic Uses of Antimuscarinic Agents
  • 28.
  • 29.
  • 30.
  • 31.
  • 32.
  • 34.
  • 35. Flow of Aqueous and Its Escape From the Eye
  • 36.
  • 37.
  • 38.
  • 39.
  • 40.
  • 41.
  • 42.
  • 43.
  • 44.
  • 45.
  • 46.
  • 47.
  • 48.
  • 49.
  • 50.