A 45-year-old woman is started on linezolid for MRSA bacteremia. After 3 weeks she develops thrombocytopenia and peripheral neuropathy. Which mechanism explains linezolid's myelosuppression?
- A Inhibition of mitochondrial ribosomal protein synthesis (70S) in bone marrow precursors ✓
- B Competitive antagonism at folate synthesis pathway in erythroid precursors
- C Alkylation of thymidine in megakaryocyte DNA
- D Inhibition of dihydrofolate reductase in platelet precursors
Correct answer: A. Inhibition of mitochondrial ribosomal protein synthesis (70S) in bone marrow precursors
Explanation
Linezolid inhibits bacterial 70S ribosomes by binding the 23S rRNA of the 50S subunit. Mitochondria possess 70S-like (55S) ribosomes that are sufficiently similar to be inhibited by linezolid with prolonged use, impairing mitochondrial protein synthesis in rapidly dividing bone marrow cells and causing reversible myelosuppression including thrombocytopenia, anemia, and leukopenia. This is a time-dependent adverse effect typically seen after >2 weeks of therapy.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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