Linezolid acts at the 23S rRNA of the 50S ribosomal subunit. Its most clinically significant adverse effect with prolonged use (>2 weeks) relates to which mechanism?
- A Inhibition of mitochondrial protein synthesis because mitochondrial ribosomes (70S) are susceptible, causing sideroblastic anaemia and lactic acidosis ✓
- B Competitive inhibition of monoamine oxidase (MAO) causing serotonin syndrome when co-administered with SSRIs
- C Depletion of folic acid due to structural similarity to dihydrofolate reductase substrates
- D Accumulation of toxic metabolites in peripheral nerves causing dose-dependent optic and peripheral neuropathy via axonal energy failure
Explanation
Mitochondria evolved from prokaryotes and retain 70S ribosomes. Linezolid's 23S rRNA inhibition is not entirely selective for bacterial ribosomes; with prolonged use, it inhibits mitochondrial protein synthesis, disrupting oxidative phosphorylation (OXPHOS) complexes. This produces: bone marrow suppression (cytopenias, including sideroblastic anaemia from impaired mitochondrial heme synthesis), lactic acidosis, peripheral neuropathy, and optic neuropathy. Serotonin syndrome is also a real risk (linezolid is a weak, reversible MAO inhibitor) but is not the mechanism of bone marrow toxicity.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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