Diazepam as a Treatment for Metronidazole Toxicosis in Dogs: A Retrospective Study of 21 Cases

Abstract

The currently recommended treatment for metronidazole toxicosis is drug discontinuation and supportive therapy. Reported recovery times are 1-2 weeks. The records of 21 dogs with metronidazole toxicosis were retrospectively analyzed to determine whether diazepam improved recovery. The dosage and duration of metronidazole therapy and the response and recovery times of 13 dogs treated with diazepam were compared to those of 8 dogs receiving only supportive care. Response time was defined as the time to resolution of the debilitating clinical signs. Recovery time was the time to resolution of all residual clinical signs. The average dosage and duration of metronidazole administration for the diazepam-treated and untreated groups were 60.3 mg/kg/d for 44.9 days and 65.1 mg/kg/d for 37.25 days. The protocol for diazepam administration consisted of an initial i.v. bolus and then diazepam PO q8h for 3 days. The average dosage of both the i.v. and PO diazepam was 0.43 mg/kg. The average response time for the diazepam-treated dogs was 13.4 hours compared to 4.25 days for the untreated group. Recovery time also was markedly shorter for the diazepam-treated dogs (38.8 hours) compared to the untreated group (11 days). Results of this study showed that dogs with metronidazole toxicosis recover faster when treated with diazepam. Although the mechanism of metronidazole toxicosis or how diazepam exerts its favorable effect is not known, it is likely related to modulation of the gamma-aminobutyric acid (GABA) receptor within the cerebellar and vestibular systems.

Establishment of a cell line for assessing drugs as canine P‐glycoprotein substrates: proof of principle

“…This is consistent with the fact that the authors are aware of several dogs homozygous for the ABCB1-1D mutation that have been treated with metronidazole and have suffered no apparent adverse reaction. Further supportive evidence that metronidazole is not a substrate for canine P-gp is the fact that among 21 dogs in a retrospective study of metronidazole toxicity, in which dogs that developed metronidazole toxicity received doses of 33-83 mg/kg/day orally for 7 -1099 days, breeds that are known to harbor the ABCB1-1D mutation were not overrepresented (Evans et al, 2003). Thus, although metronidazole can cause neurological toxicosis, there is not an increased risk in dogs with the ABCB1-1D mutation.…”

Metronidazole-induced encephalopathy in a patient with infectious colitis: a case report

“…It has been suggested that metabolites of metronidazole may bind to RNA instead of DNA, possibly inhibiting RNA protein synthesis, which could potentially lead to axonal degeneration [6]. Another proposed mechanism involves the modulation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) receptor within the cerebellar and vestibular systems [7]. …”

Gastrointestinal hyperammonaemia in a 35‐day‐old Warmblood‐cross filly

“…Although a relatively high protein feed (16%) was introduced prior to the neurological signs, excessive ingestion was not noted, and there was no history consistent with exposure to urea or lead containing products. Additionally, metronidazole treatment was withdrawn in case of possible adverse reaction, although metronidazole toxicosis is rarely reported in horses (Sweeney et al 1991); and whilst it has been associated with neurological signs in dogs (Evans et al 2003), it is mostly associated with diarrhoea and gastrointestinal consequences in the horse (Sweeney et al 1991).…”