A patient on pyridostigmine for myasthenia gravis develops a cholinergic crisis after a concurrent prescription of an aminoglycoside. The mechanism by which aminoglycosides worsen neuromuscular blockade is:

• A Inhibition of acetylcholinesterase at the neuromuscular junction
• B Competitive antagonism at nicotinic ACh receptors
• C Reduced presynaptic ACh release by blocking voltage-gated calcium channels and displacing calcium ✓
• D Direct channel-blocking action at the post-synaptic nicotinic receptor

Explanation

Aminoglycosides inhibit presynaptic voltage-gated calcium channels, thereby reducing calcium-dependent exocytosis of acetylcholine vesicles. They also displace calcium from the membrane, further impairing ACh release. This effect synergises with pyridostigmine's action, and in predisposed patients (low ACh receptor reserve) can unmask a crisis. Options A and B are incorrect mechanisms for aminoglycosides; option D refers to channel blockers like succinylcholine.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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