PLEASE ANSWER THIS QUESTION USING A DETAILED BIOCHEMICAL PERSPECTIVE Ingestion o

Question

PLEASE ANSWER THIS QUESTION USING A DETAILED BIOCHEMICAL PERSPECTIVE

Ingestion of methanol is a medical emergency. It is often treated by administering ethanol, which prevents the dangerous effects of methanol metabolism. In the body, methanol is oxidized to formaldehyde (methanal), a toxic molecule that damages proteins (and many other biomolecules). Ethanol is oxidized by the same enzyme as methanol, alcohol dehydrogenase, to acetaldehyde, a metabolite that can be further processed and is less harmful to biomolecules. Why is ethanol given to patients that have ingested methanol? Justify your answer with an explanation that uses theory from the course content

Explanation / Answer

Methanol is metabolized to formaldehyde and formic acid by alcohol and aldehyde dehydrogenases respectively. The rate at which formic acid is metabolized is only 1/7th to that of ethanol and has a half life of 20-60 hours. The metabolism of both formaldehyde and formic acid are slow and requires folate. Thus a blood level of > 50 mg/dl methanol causes severe poisoning, 15 ml of methanol consumption leads to blindness, and fatal dose is 75-100 ml.

Symptoms of methanol poisoning: Vomiting, headache, epigastric pain, uneasiness, dyspnoea, bradycardia and hypotension. Delirium may occur and the patient may suddenly pass into coma. Acidosis is prominent and entirely due to production of formic acid. The specific toxicity of formic acid is retinal damage. Blurring of vision, congestion of optic disc followed by blindness which is followed by death due to respiratory failure.

Why ethanol is given for methanol poisoning treatment?

Ethanol 100 mg/dl in blood saturates alcohol dehydrogenase and retards methanol metabolism. This helps by reducing the rate of generation of toxic metabolites. Ethanol (10% in water) is administered through nasogastric tube with loading dose of 0.7 ml / kg followed by 0.15 ml/kg/ hour drip.

1. Methanol-----Alcohol dehydrogenase---> Formaldehyde------Aldehyde dehydrogenase--------Formic acid (Formate)---------Folate dependent-------> CO2 + H20

2. Ethanol ------Alcohol dehydrogenase---> Acetaldehyde----Aldehyde dehydrogenase-----> Acetic acid

As seen from the above two reactions aldehyde dehydrogenase is the principle enzyme in metabolising alcohols. When ethanol is given in metanol treatment, alcohol dehydrogenase is fully saturated with ethanol instead of methanol, thus forming acetaldehyde due to the greater selectivity of alcohol dehydrogenase to the ethanol when compared to methanol and thus avoids the formation of formaldeyde.

Since, the pharmacokinetics of alcohol is unstable and non availability of intravenous formulation is available, maintenance of effective concentration is difficult and needs to be repeatedly measured. The enyzme saturating concentration of ethanol may produce intoxication and may cause hypoglycemia.Treatment for methanol is to be continued for long time as the half life of methanol in the body is long.

(Additional information: Fomepizole an inhibitor of alcohol dehydrogenase which reduces the methanol metabolism also used as drug for treatment of methanol poisoning. Folate therapy with Calcium leucovorin reduce blood formate levels and increases the oxidation of methanol and also used as adjuvant therapy for methanol poisoning.)

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