A 55-year-old woman with a creatinine clearance of 20 mL/min receives full-dose IV imipenem-cilastatin for ventilator-associated pneumonia. On day three she develops generalized tonic-clonic seizures. Compared with meropenem, imipenem carries this risk chiefly because it:

• A Causes hyponatremia through drug-induced SIADH
• B Is a stronger inducer of cytochrome P450 enzymes generating neurotoxic metabolites
• C Penetrates the blood-brain barrier far more extensively than other carbapenems
• D Has greater affinity for and antagonism at central GABA-A receptors ✓

Explanation

All carbapenems can cause seizures, but imipenem is the most epileptogenic because its basic side chain binds competitively to GABA-D receptors in the brain and antagonizes GABA-mediated inhibition, an effect amplified by high plasma levels in renal failure when doses are not reduced. Meropenem has a side chain that confers much weaker GABA affinity and is preferred in meningitis and seizure-prone patients. BBB penetration alone does not explain the difference, and neither enzyme induction nor SIADH is involved.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.