A 68-year-old man receives IV gentamicin for enterococcal endocarditis. Two weeks later he reports difficulty hearing high-frequency sounds and unsteadiness on walking. Serum creatinine has risen from 0.9 to 2.1 mg/dL. Which property of aminoglycosides best accounts for this combined injury?

• A Immune complex deposition in the glomerulus and cochlear vasculature
• B Formation of reactive metabolites that bind cochlear hair cell proteins
• C Direct vasoconstriction of the vasa recta reducing medullary perfusion
• D Accumulation of the drug in proximal tubular cells and inner ear perilymph after uptake via megalin receptors ✓

Explanation

Aminoglycosides are taken up by proximal tubular epithelial cells via the megalin/cubilin receptor and are retained there, causing tubular necrosis with a rise in creatinine after several days of therapy. The same drug accumulates in endolymph and perilymph, destroying outer hair cells and vestibular organs, producing irreversible high-frequency hearing loss and vestibular dysfunction. Reactive metabolites, medullary vasoconstriction, and immune complexes are not mechanisms of aminoglycoside toxicity.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.