The veterinary literature contains reports of accidental 6 and experimentally induced 15,16 isoniazid toxicosis in dogs. Patients with this classic triad of signs of isoniazid toxicosis can die without prompt diagnosis and proper treatment. 6,14,15 High toxic doses of isoniazid are associated with what is known as the classic triad, which includes seizures that are refractory to conventional treatments, lactic acidosis, and coma. In both dogs and humans, clinical signs of isoniazid toxicosis are generally observed within 30 to 60 minutes after ingestion and are characterized by recurrent grand mal seizures subsequent to a decrease in GABA (an inhibitory neurotransmitter) concentration and an increase in glutamic acid concentration in the CNS. 13 In humans patients, approximately 50% to 70% of isoniazid is excreted unchanged or as metabolites in urine within 24 hours after administration. 13 Thus, in dogs, the elimination half-life of isoniazid is 2 to 5 hours, and the lack of NAT2 increases the risk of isoniazid-induced neurologic and hepatic toxicosis. 10–12 Dogs are considered slow acetylators because of their inherent lack of NAT2. 10,11 In humans, the elimination half-life of isoniazid is dependent on a patient's ability to acetylate the elimination half-life is 1 to 2 hours in fast acetylators and 2 to 5 hours in slow acetylators. Isoniazid has poor protein binding (approx 10%) in plasma, has a small volume of distribution, and readily penetrates into the CNS and CSF. It undergoes substantial first-pass metabolism, and peak plasma concentrations are achieved within 1 to 2 hours after administration. In human patients, isoniazid is rapidly and almost completely absorbed in the gastrointestinal tract following oral administration. Isoniazid inhibits cell wall synthesis of Mycobacterium tuberculosis by inhibiting lipid and DNA synthesis. Human patients and dogs that accidentally ingest or are overdosed with isoniazid can develop acute life-threatening toxicosis. 1–4 Although tuberculosis is rare in developed countries (only 9,421 cases of tuberculosis were reported in the United States in 2014 5), the use of isoniazid with its low margin of safety puts companion animals at risk of accidental ingestion. Isoniazid (isonicotinic acid hydrazide) is a common, first-line antimycobacterial agent used to treat tuberculosis in humans and other animals. ![]() Dogs that received pyridoxine IV were 29 times as likely to survive as dogs that did not receive pyridoxine IV.ĬONCLUSIONS AND CLINICAL RELEVANCE Results indicated rapid diagnosis of isoniazid toxicosis and prompt treatment of affected dogs with pyridoxine and other supportive care were imperative for achieving a successful outcome. Probability of survival was positively associated with body weight and IV administration of pyridoxine and negatively associated with dose of isoniazid ingested and presence of seizures. Of the 87 dogs for which the outcome was available, 61 survived, 18 died, and 8 were euthanized. ![]() RESULTS Clinical signs of isoniazid toxicosis were observed in 134 of 137 (98%) dogs and included seizures (n = 104), CNS signs without seizures (94), and gastrointestinal (41), cardiovascular (19), urogenital (4), and respiratory (1) abnormalities. ![]() ![]() Follow-up communication with pet owners or primary care veterinarians was performed when necessary to obtain missing information. For each dog identified, information extracted from the medical record included signalment, estimated dose of isoniazid ingested, clinical signs, treatment, and outcome. PROCEDURES The electronic database of the American Society for the Prevention of Cruelty to Animals Animal Poison Control Center was reviewed from January 2004 through December 2014 to identify dogs with isoniazid toxicosis. OBJECTIVE To establish the minimum toxic dose of isoniazid in dogs, characterize the clinical signs and outcomes for dogs following isoniazid ingestion, and determine whether IV administration of pyridoxine to dogs with isoniazid toxicosis is protective against death.ĪNIMALS 137 dogs with isoniazid toxicosis.
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