Discuss the bacteriocidal activity, and toxicity, of gentamicin
The first part of the question on bactericidal activity of gentamicin was better
answered than the second part on its toxicity. Details on the cellular mechanisms of
bactericidal action and toxicity were lacking in most answers.
Most candidates did not appreciate that gentamicin is avidly accumulated and
retained by proximal renal tubular cells in concentrations many times higher than the
plasma concentration. Also these high tubular cell concentrations of gentamicin are
maintained long after the plasma concentrations have fallen to very low levels, thus
enhancing its toxic effects. Gentamicin has multiple toxic effects within the tubular
cell including adverse effects on protein synthesis, translation and folding,
impairment of mitochondrial function and production of reactive oxygen species and
damage to the nucleus.
Syllabus: M2a, 2d
Recommended sources: Pharmacological Basis of Therapeutics, Goodman and
Gillman, Chp 45 and page 1162