What are the biochemical findings in methanol toxicity? Outline the specific management along with its physiological rationale. (50% marks)
High anion gap metabolic acidosis, osmolar gap, elevated plasma methanol level.
Antidote therapy, often using ethanol or fomepizole, is directed towards delaying methanol metabolism until the methanol is eliminated from the patient’s system either naturally or via dialysis. Like methanol, ethanol is metabolized by ADH, but the enzyme’s affinity for ethanol is 10-20 times higher than it is for methanol. Fomepizole is also metabolized by ADH; however, its use is limited because of high cost and lack of availability
Dialysis: The toxic products of methanol and ethanol are formic acid and oxalic acid respectively. They are small molecules, are not protein bound and have low volume of distribution so are easily dialysable.
Folic acid – can accelerate the metabolism of formate via tetrahydrofolate.
The characteristic features of toxic alcohol toxicity in general are:
As for specific management:
Morrow, Gregory P., et al. "In vivo kinetics of formate metabolism in folate-deficient and folate-replete rats." Journal of Biological Chemistry 290.4 (2015): 2244-2250.
Kraut, Jeffrey A., and Ira Kurtz. "Toxic alcohol ingestions: clinical features, diagnosis, and management." Clinical Journal of the American Society of Nephrology 3.1 (2008): 208-225.
Henderson, William R., and Jeffrey Brubacher. "Methanol and ethylene glycol poisoning: a case study and review of current literature." Cjem 4.1 (2002): 34-40.
Hovda, Knut Erik, Petter Urdal, and Dag Jacobsen. "Increased serum formate in the diagnosis of methanol poisoning." Journal of analytical toxicology 29.6 (2005): 586-588.