A 70-year-old man with creatinine clearance of 25 mL/min receives imipenem-cilastatin without dose adjustment for a ventilator-associated pneumonia. Three days later he develops generalized tonic-clonic seizures. The mechanism underlying imipenem-induced seizures is:

• A Antagonism of GABA at central inhibitory receptors ✓
• B Blockade of voltage-gated sodium channels in cortical neurons
• C Inhibition of glutamate reuptake by astrocytes
• D Direct activation of NMDA receptors in the hippocampus

Explanation

Imipenem lowers the seizure threshold by antagonizing GABA-A mediated inhibition in the CNS, an effect shared to a lesser degree by other carbapenems and penicillins in very high doses. Risk rises sharply when renal impairment allows accumulation, so dose reduction or a switch to meropenem, which has less GABAergic activity, is advised.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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