Overview
This lecture covers cholinergic antagonists, focusing on their classification, mechanisms, clinical uses, and major drugs. Side effects and key differences between drug classes are emphasized.
Cholinergic Antagonists Classification
- Cholinergic antagonists are divided into antimuscarinic agents, ganglionic blockers, and neuromuscular blockers.
- Each class targets different cholinergic receptors and produces distinct clinical effects.
Antimuscarinic Agents
- Antimuscarinic drugs block muscarinic receptors, inhibiting muscarinic functions.
- Atropine acts on the eye (causes mydriasis, cycloplegia), GI tract (reduces motility), heart (increases rate), and glands (dry mouth, skin).
- Cyclopentolate and Tropicamide are preferred over Atropine for eye exams due to shorter duration.
- Scopolamine is used for motion sickness and post-operative nausea; it acts mainly on the CNS and lasts up to three days.
- Ipratropium and Tiotropium are inhaled for COPD, causing bronchodilation and decreased mucus; Tiotropium is long-acting, Ipratropium is short-acting.
- Antimuscarinics like Tolterodine, Oxybutynin, etc., treat overactive bladder by targeting M3 receptors.
- Benztropine and Trihexyphenidyl treat Parkinson-like disorders by suppressing central cholinergic activity.
- Common adverse effects remembered as "ABCDS": agitation, blurred vision, constipation/confusion, dry mouth, stasis of urine/sweating.
Ganglionic Blockers
- Nicotine is a ganglionic blocker, acting as a functional antagonist by stimulating then blocking nicotinic receptors in autonomic ganglia.
- Nicotine affects both sympathetic and parasympathetic systems, increasing neurotransmitter release, BP, HR, and GI motility.
- High doses can cause CNS depression, respiratory paralysis, and addiction; limited clinical use except smoking cessation.
Neuromuscular Blockers
- Neuromuscular blockers inhibit cholinergic transmission at the neuromuscular junction, preventing muscle contraction.
- Nondepolarizing agents (e.g., Cisatracurium, Rocuronium) are competitive antagonists; used for surgical muscle relaxation and intubation.
- Onset is rapid; muscles paralyzed in order: face, limbs, then diaphragm; recovery is the reverse.
- Atracurium can cause histamine release and seizures; Cisatracurium is safer in organ failure patients.
- Vecuronium and Rocuronium are liver-metabolized; Pancuronium excreted in urine and can raise HR.
- Depolarizing agent Succinylcholine mimics acetylcholine, causing persistent depolarization and paralysis (used for rapid intubation).
- Succinylcholine can cause adverse effects like prolonged apnea (in pseudocholinesterase deficiency), hyperkalemia, and malignant hyperthermia.
Key Terms & Definitions
- Antimuscarinic agents — Drugs that block muscarinic acetylcholine receptors.
- Ganglionic blockers — Agents that block transmission in autonomic ganglia.
- Neuromuscular blockers — Drugs that block acetylcholine at skeletal muscle junctions.
- Nondepolarizing agents — Competitive antagonists at nicotinic receptors, prevent depolarization.
- Depolarizing agents — Cause persistent activation of nicotinic receptors, leading to paralysis.
- Mydriasis — Pupil dilation.
- Cycloplegia — Inability to focus visually.
Action Items / Next Steps
- Review the adverse effects mnemonic "ABCDS."
- Watch a brief video on action potential for membrane depolarization review (if needed).
- Study clinical uses and contraindications for key drugs mentioned.