Specific toxicologic aspects of the quinolones.

ABSTRACT

Possible targets of quinolone toxicity include the juvenile joint, the kidney, the central nervous system (CNS), the eye, and the cardiovascular system. In immature animals all quinolones studied cause arthropathies of the major diarthrodial joints. Arthropathies have also developed in adult dogs after 12 months of pefloxacin treatment. At high doses the quinolones exert effects on renal function that are related to a foreign-body reaction caused by crystals; nephropathologic changes seem not to occur without crystalluria. In humans quinolones can have various CNS effects. The subcellular "substrate" for these effects is unknown. Further understanding of severe CNS reactions (confusion, hallucination, anxiety, agitation, nightmares, convulsive seizures, and depression) is needed. Pefloxacin causes cataracts in dogs after treatment for 8-12 months. Low-dose quinolones (administered as an intravenous bolus) cause pronounced but transient systolic hypotension in dogs and cats; cardiovascular effects may be mediated by histamine release. Quinolones inhibit the bacterial enzyme DNA gyrase. To exclude the possibility of damage to mammalian DNA, mutagenicity studies have been performed. Since all but two tests (which may give false-positive results) have been negative, quinolones appear to be nonmutagenic. Photosensitivity has occurred in humans given quinolones. Drug interactions can be clinically important.