At necropsy, all three dogs had severe renal tubular damage. The three animals in the untreated group became progressively obtunded, moribund, and died. In a study of dogs given a lethal dose of ethylene glycol, three animals each were administered fomepizole, ethanol, or left untreated (control group). The concentration of fomepizole at which alcohol dehydrogenase is inhibited by 50% in vitro is approximately 0.1 µmol/L. A lethal dose of methanol in humans is approximately 1-2 mL/kg.įomepizole has been shown in vitro to block alcohol dehydrogenase enzyme activity in dog, monkey, and human liver. Formic acid is primarily responsible for the metabolic acidosis and visual disturbances (e.g., decreased visual acuity and potential blindness) associated with methanol poisoning. Methanol, the main component of windshield wiper fluid, is slowly metabolized via alcohol dehydrogenase to formaldehyde with subsequent oxidation via formaldehyde dehydrogenase to yield formic acid. The lethal dose of ethylene glycol in humans is approximately 1.4 mL/kg. Glycolate and oxalate are the metabolic by-products primarily responsible for the metabolic acidosis and renal damage seen in ethylene glycol toxicosis. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.Įthylene glycol, the main component of most antifreezes and coolants, is metabolized to glycoaldehyde, which undergoes subsequent sequential oxidations to yield glycolate, glyoxylate, and oxalate. Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde. ![]() Antizol (fomepizole) is a competitive inhibitor of alcohol dehydrogenase.
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