Acetylcholinesterase inhibitors prolong the action of acetylcholine by preventing its breakdown. Which of the following is the PRIMARY mechanism by which these drugs achieve this effect?

Explanation

## Mechanism of Acetylcholinesterase Inhibitors **Key Point:** Acetylcholinesterase inhibitors work by reversibly or irreversibly binding to the active site of acetylcholinesterase (AChE), preventing the hydrolysis of acetylcholine into choline and acetic acid. ### Mechanism of Action Flowchart ```mermaid flowchart TD A[Acetylcholine released at synapse]:::outcome --> B[Binds to AChE active site]:::action B --> C{AChE inhibitor present?}:::decision C -->|No| D[AChE hydrolyzes ACh to choline + acetate]:::action D --> E[Rapid termination of signal]:::outcome C -->|Yes| F[Inhibitor occupies active site]:::action F --> G[ACh accumulates in synaptic cleft]:::outcome G --> H[Prolonged receptor activation]:::outcome ``` **High-Yield:** The mechanism is **enzyme inhibition**, not receptor activation or neurotransmitter synthesis. AChE inhibitors are indirect-acting cholinomimetics — they do not directly activate receptors but increase endogenous acetylcholine concentration. ### Types of AChE Inhibition | Type | Example | Reversibility | Clinical Use | | --- | --- | --- | --- | | Competitive reversible | Physostigmine, neostigmine, donepezil | Reversible | Myasthenia gravis, Alzheimer's disease | | Non-competitive irreversible | Organophosphates, echothiophate | Irreversible (covalent) | Pesticides, rarely glaucoma | **Mnemonic:** **ACHE = Acetylcholinesterase = Enzyme inhibition** — the drug blocks the enzyme, not the receptor. **Clinical Pearl:** Because AChE inhibitors work by accumulating endogenous acetylcholine, they produce effects at BOTH muscarinic and nicotinic receptors, unlike selective agonists. [cite:KD Tripathi 8e Ch 6]