Cholinesterase Inhibitors Overview

Cholinesterase Inhibitors Overview

• Function of acetylcholinesterase: Breakdown of acetylcholine at synapses.
• Cholinesterase inhibitors prevent degradation of acetylcholine, acting as indirect-acting agonists by increasing acetylcholine availability.

Key Features of Cholinesterase Inhibitors

• Not selective: Affect all cholinergic receptors (muscarinic and nicotinic).
• Varied duration: Some are reversible while others are irreversible. Irreversible inhibitors bond strongly to enzymes, preventing their activity.

Prototype Drug

• Neostigmine (Prostigmin) is the prototype reversible cholinesterase inhibitor.

Mechanism of Action

• Inhibits acetylcholinesterase, leading to decreased acetylcholine breakdown and increased neurotransmitter availability.

Pharmacologic Effects

• Intensifies ACh transmission at synapses where ACh is the transmitter.
• Effects primarily observed at synaptic junctions and neuromuscular junction, with minimal impact on ganglionic nicotinic receptors or CNS receptors unless high doses are used.
• Muscarinic responses mimic those of direct-acting agonists, leading to effects like increased glandular secretions and GI motility, bradycardia, urinary urgency, and bronchial constriction.
• Neuromuscular effects are dose-dependent; therapeutic doses increase muscle contraction while toxic doses can reduce it due to continuous depolarization.
• Central nervous system effects vary with concentration; therapeutic levels may stimulate while toxic levels may depress CNS activity.

Therapeutic Uses of Neostigmine

• Treatment of Myasthenia Gravis: Increases acetylcholine at nicotinic-M receptors, improving muscle strength and reducing fatigue.
• Reversal of nondepolarizing neuromuscular blockers (e.g., vecuronium) during surgical procedures by increasing synaptic acetylcholine concentration.

Adverse Effects

• Excessive muscarinic stimulation can lead to symptoms like salivation, increased gastric secretions, GI motility, urinary urgency, bradycardia, sweating, pupil constriction (miosis), and accommodation spasm.
• Toxic doses can cause neuromuscular blockade, reducing muscle contraction due to acetylcholine accumulation.

Precautions, Warnings, and Contraindications

• Follow similar guidelines as for direct-acting muscarinic agonists; consult clinical references for specifics.