A 12-day-old term neonate treated with chloramphenicol for a resistant bacterial infection develops vomiting, refusal to feed, hypothermia, and an ashen grey colour with cardiovascular collapse. The pathogenesis of this syndrome is best explained by:

• A Direct mitochondrial toxicity of the p-nitroso metabolite
• B Immature glomerular filtration causing prolonged half-life of the parent drug
• C Displacement of bilirubin from albumin leading to kernicterus
• D Immature hepatic UDP-glucuronosyltransferase activity causing drug accumulation ✓

Explanation

Grey baby syndrome results from accumulation of unmetabolized chloramphenicol because hepatic conjugation by UDP-glucuronosyltransferase is immature in neonates. Reduced renal clearance of the unconjugated drug contributes but is secondary. Displacement of bilirubin is a separate property of many sulphonamides, not the cause here. Bone marrow mitochondrial injury explains the adult idiosyncratic aplastic anaemia, a distinct entity.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.