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

6. Atropine

8. Response to ACh in the Presence of Atropine Atropine competitively inhibits muscarinic reponses to ACh Log dose of acetylcholine Response control atropine

10. Changes in Accomodation and Pupillary Diameter after Administration of an Antimuscarinic Agent Reproduced from Basic and Clinical Pharmacology

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

27. Therapeutic Uses of Antimuscarinic Agents

33. Toxicity of Atropine

35. Flow of Aqueous and Its Escape From the Eye