Tiotropium provides sustained bronchodilation in COPD with once-daily dosing. The properties underlying this profile are:

• A Nonselective muscarinic antagonism with a short plasma half-life requiring slow release formulation
• B Kinetically selective binding to M3 receptors with very slow dissociation ✓
• C Irreversible covalent blockade of all muscarinic receptor subtypes
• D Selective M2 receptor antagonism enhancing cholinergic bronchodilation

Explanation

Tiotropium is a long-acting muscarinic antagonist whose duration comes from kinetic selectivity: it dissociates very slowly from M3 receptors on airway smooth muscle while separating rapidly from M2 receptors. This gives prolonged functional M3 blockade with once-daily dosing and avoids loss of the presynaptic M2 autoinhibitory brake on acetylcholine release. The binding is reversible, not covalent, and the drug is not a nonselective short-acting agent like ipratropium.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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