A patient on chronic phenytoin therapy requires general anaesthesia. The anaesthetist notices that significantly higher doses of vecuronium are needed for intubation. The MOST likely mechanism is:

• A Phenytoin upregulates hepatic CYP enzymes, accelerating vecuronium metabolism
• B Phenytoin blocks vecuronium binding to plasma proteins, increasing free drug clearance
• C Phenytoin upregulates nicotinic acetylcholine receptors at the neuromuscular junction ✓
• D Phenytoin inhibits acetylcholinesterase at the NMJ, competing with vecuronium

Explanation

Chronic anticonvulsant therapy, particularly with phenytoin and carbamazepine, leads to upregulation (proliferation) of nicotinic acetylcholine receptors at the neuromuscular junction, requiring higher doses of non-depolarising neuromuscular blockers to achieve adequate blockade. CYP induction does contribute to faster hepatic metabolism of steroid-based NMBAs like vecuronium, but receptor upregulation is the primary and more clinically significant mechanism for resistance. Acetylcholinesterase inhibition is the mechanism of reversal agents like neostigmine, not phenytoin.

Reference: Morgan & Mikhail's Clinical Anesthesiology, 6th ed.

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Written and medically reviewed by the StethoPrep medical team.