FLUOROQUINOLONES

Sources: The fluoroquinolones are relatively new to veterinary medicine. Members of this group include enrofloxacin (Baytril, difloxacin, ciprofloxacin, and orbifloxacin (Orbax).

 Toxicokinetics:The fluoroquinolones exhibit rapid gastrointestinal absorption and a large volume of distribution. These antibiotics are excreted by the kidneys.

 Mechanism of Action:. The antimicrobial activity of the fluoroquinolones is due to their ability to inhibit the type II topoisomerase of the bacteria. This prevents the coiling and therefore the replication and synthesis of DNA.

The mechanism of action for fluoroquinolone-mediated arthropathy may be related to the ability to chelate magnesium. The chelation of magnesium from these critical sites in the articular cartilage may account for the lesions. The mechnism of action that may account for seizures is related to the ability of these antibiotics to act as GABA antagonists and bind to the N-methyl-D-aspartate receptor.

Clinical Signs: As a class of antimicrobials, the most common adverse effects are to the gastrointestinal tract (nausea, vomiting, and diarrhea) and CNS (seizures). These toxic syndromes tend to be mild and reversible. The unique aspect of the fluoroquinolones is the clinical picture of a younger animal with lameness and pain of a weight-bearing joint.

Clinical Pathology.: Serum hepatic enzymes may be mildly elevated in response to fluoroquinolone therapy.

 Lesions. :

Gross lesions of fluoroquinolone-induced arthropathy include erosions or vesicle formation of the articular cartilage.

 Histopathologic examination of affected tissues indicates necrosis of chondrocytes followed by disruption of extracellular matrix and formation of fissures.

 Treatment.: The antibiotic should be discontinued at the first sign of toxicosis. Supportive therapy includes fluids to maintain urine production and flow to increase elimination of the fluoroquinolone.

Prognosis:  The gastrointestinal, hepatic, and CNS toxic effects of the fluoroquinolones are generally reversible after discontinuation of therapy. Arthropathy induced by the fluoroquinolones in younger animals carries a more guarded prognosis.