Antidotes

The main aim of treatment for methanol poisoning is to block the formation of the toxic metabolites. Alcohol dehydrogenase has a higher affinity for ethanol than methanol. Therefore ethanol therapy and haemodialysis, to enhance the elimination of unmetabolised methanol and formic acid, have long been the standard treatment for methanol toxicity. Recently fomepizole, has been found to be useful as an alternative antidote to ethanol in methanol poisoning (Brent et al., 2001).

Ethanol

The prompt use of ethanol in methanol poisoning is associated with a good outcome. Early and aggressive treatment can completely prevent the toxic effects of methanol (Bergeron et al., 1982). The endpoint for ethanol therapy is controversial but it should be continued until methanol is no longer detectable. Mahieu et al. (1989) observed that when ethanol was stopped too soon after methanol concentrations had become undetectable, a rebound of formic acid up to 100 mg/l sometimes followed. In view of the possible ocular risk of local production of formic acid, it is worthwhile maintaining an adequate blood ethanol concentration for at least 48 hours after the disappearance of methanol from the blood. However, in a study of 11 methanol poisoned patients, no rebound effect in whole blood concentrations of methanol were seen after termination of dialysis (Jacobsen et al., 1982).

Fomepizole

Fomepizole (4-methylpyrazole) is an inhibitor of alcohol dehydrogenase that appears to have few of the side effects of ethanol. It is currently only licensed in the UK for the treatment of ethylene glycol poisoning. However, Brent et al. (2001) treated 11 methanol poisoned patients with fomepizole. The median duration of therapy was 30 hours (range 0.5-60), and the patients received a median of 4 doses. After the institution of fomepizole therapy, plasma formic acid concentrations fell in all patients, with simultaneous resolution of metabolic acidosis. This also resulted in improvement in mental status and visual symptoms. Methanol elimination in patients who did not receive haemodialysis followed first order kinetics, with a half-life of 54 hours. Adverse events in 6 patients were classified by the treating physicians as possibly related to fomepizole. These were phlebitis, dyspepsia, anxiety, agitation, a local reaction at the site of injection, transient tachycardia, transient rash, and a 'strange' feeling. Two patients died as a result of methanol poisoning, both were comatose and acidotic on admission, and had the highest plasma formic acid concentrations. Fomepizole is a safe and effective antidote for use in the treatment of methanol poisoning (Brent et al., 2001).

Fomepizole may be useful for treatment of the ocular effects of methanol intoxication. Sivilotti et al. (1998) report a case of complete visual recovery following treatment with fomepizole.

Folic acid and folinic acid

Administration of folates may be useful in methanol poisoning. They stimulate the folate-mediated oxidation of formic acid to carbon dioxide, thereby decreasing its accumulation (McMartin et al., 1977; Noker et al., 1980). The folates, both when administered before and after methanol, decrease the blood concentrations of formic acid to non toxic concentrations. In most human cases where folates have been administered their effectiveness has been difficult to determine, as ethanol and haemodialysis have also been administered. However studies in monkeys suggest that folates would be useful in humans also (Jacobsen and McMartin, 1997). Pretreatment of monkeys with folic acid for 48 hours, or folinic acid given after methanol administration, decreased formic acid concentrations and reduced the accompanying metabolic acidosis, without affecting the rate of methanol elimination. Folinic acid was still effective in hastening the elimination of formic acid when given 10 hours following methanol administration (Noker et al., 1980).

Thiamine (Vitamin B1)

Thiamine and steroids (prednisone) have been successfully used in the treatment of ocular toxicity following methanol intoxication. As thiamine is used in the treatment of ethanol induced Wernike-Korsakoff syndrome and is effective in the treatment of nutritional ambylopia and infantile necrotising encephalomyopathy, Rotenstreich et al. (1997) felt that there was a role for its use in the treatment of methanol induced bilateral visual loss. The combination of steroids and thiamine proved highly effective in this case, but it is not clear whether using only one drug might have been sufficient. The authors recommend the use of this combination of agents in the treatment of methanol induced ocular toxicity, as the risk of permanent ocular damage is high (Rotenstreich et al., 1997).

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

Get My Free Ebook


Post a comment