Cholinolytic Drugs

Dr. Mohammed Ezzi

Introduction • Divided into muscarinic and nicotinic antagonists.Ganglion blockers. NMJ blockers . • Antinicotinic .

. M5 (CNS) • Block PNS discharge. presynaptic) – M2 (myocardium. smooth muscle). sympathetic postganglionic. – M3 (glandular) – M4.Antimuscarinic • Five subtypes of muscarinic receptors: – M1 (CNS.Introduction . • Prototype is atropine.

• Tertiary amines have both peripheral and CNS effects • Quartanery amines have more peripheral effects. scopolamine (hyoscine) are tertiary amines (alkaloid esters of tropic acid).Chemistry • Atropine (hyocyamine). . • Occur as both d(+) and l(-) isomer (X 100 potent).

• Scopolamine is also absorbed through the skin. • 10 .Absorption • Tertiary amines are well absorbed.30% of quaternary amine is absorbed. .

Distribution • Tertiary amines widely distributed (significant CNS levels). • Scopolamine has the most CNS effects. • Quaternary amines are free of CNS effects. .

Metabolism and Excretion • Atropine elimination occurs in two phases: – Rapid (2 hours) – Slow phase (13 hours) • 50% excreted unchanged (hydrolysis. conjugation) • Rapid decline of function except the eye (72 hours). .

• Some are inverse agonist: – Atropine – Trihexyphenidyl – Glycopyrrolate Pirenzepine Ipratropium . • Prevents release of IP3 and cAMP.Mechanism of Action • Reversible but surmountable muscarinic blockade.

– Least sensitive: gastric parietal cells • Block exogenous agonist more than endogenous Ach.Mechanism of Action • Effectiveness varies with tissues: – Most sensitive: salivary. bronchial. . sweat glands.

CNS Effects • Normal doses: – Minimal stimulant effects – Drowsiness (scopolamine) – Amnesia (scopolamine) .

CNS Effects • Toxic doses: – Excitement – Hallucinations Agitation Coma. . • Reduce tremor of Parkinson’s disease • Reversing or preventing vestibular disturbances.

• Weakened contraction of the ciliary muscle (cycloplegia with loss of accommodation) • Reduced lacrimation. .Eye • Unopposed sympathetic pupillary dilator activity (mydriasis).

– Bradycardia (low dose .prejunctional M1 blockade).CVS Effects • Heart: – Tachycardia (high dose . – Reduce the PR interval (AVN blockade) – Intraventricular conduction block (toxic doses) .vagal blockade).

CVS Effects • Vessels: – Coronary artery vasocontriction – Skeletal vasculature vasoconstriction – Cutaneous vasodilation (toxic doses) .

. although the antimuscarinic drugs are not as useful as the β-adrenoceptor stimulants in the treatment of asthma (see Chapter 20 ). Even in normal individuals.• • • • • • • • • • • • • • • • 4. Nevertheless. Respiratory system— Both smooth muscle and secretory glands of the airway receive vagal innervation and contain muscarinic receptors. The effectiveness of nonselective antimuscarinic drugs in treating chronic obstructive pulmonary disease (COPD) is limited because block of autoinhibitory M 2 receptors on postganglionic parasympathetic nerves can oppose the bronchodilation caused by block of M 3 receptors on airway smooth muscle. The effect is more significant in patients with airway disease. Antimuscarinic drugs are frequently used before the administration of inhalant anesthetics to reduce the accumulation of secretions in the trachea and the possibility of laryngospasm. antimuscarinic agents are valuable in some patients with asthma or COPD. administration of atropine can cause some bronchodilation and reduce secretion.