Poisoning, methanol

The emeigency room treatment for methanol poisoning is to inject ethanol intravenously to tie up the alcohol dehydrogenase enzyme so that methanol will not be converted to formic acid and fonnate. which causes blindness. The goal of this open-ended problem is to build on the physiological-based model for ethanol metabolism to predict the ethanol injection rate for methanol poisoning. 

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Methanol poisoning can also occur by inhalation of the vapors or by prolonged exposure to the skin. 

Biological oxidation of methanol and ethanol in the body produces the corresponding aldehyde followed by the acid. At times the alcoholics, by mistake, drink ethanol, mixed with methanol also called denatured alcohol. In the body, methanol is oxidised first to methanal and then to methanoic acid, which may cause blindness and death. A methanol poisoned patient is treated by giving intravenous infusions of diluted ethanol. The enz5mie responsible for oxidation of aldehyde (HCHO) to acid is swamped allowing time for kidneys to excrete methanol. 

Ekins BR et al Standardized treatment of severe methanol poisoning with ethanol and hemodialysis. WestJ Med 142 337-340, 1985... 

Contraindications Intestinal obstruction, GI tract not anatomically intact patients at risk of hemorrhage or GI perforation, if use would increase risk and severity of aspiration not effective for cyanide, mineral acids, caustic alkalis, organic solvents, iron, ethanol, methanol poisoning, lithium do not use charcoal with sorbitol in patients with fructose intolerance, hypersensitivity to charcoal or any component of the formulation... 

The most characteristic symptom in methanol poisoning is a visual disturbance, frequently described as "like being in a snowstorm." A complaint of blurred vision with a relatively clear sensorium should strongly suggest the diagnosis of methanol poisoning. Since much of the toxicity is due to metabolites of methanol, there is often a delay of up to 30 hours before development of visual disturbances and other signs of severe intoxication. 

Physical findings in methanol poisoning are generally nonspecific. In severe cases, the odor of formaldehyde may be present on the breath or in the urine. Changes in the retina may sometimes be detected on examination, but these are usually late. The development of bradycardia, prolonged coma, seizures, and resistant acidosis all imply a poor prognosis. The cause of death in fatal cases is sudden cessation of respiration. 

It is critical that the blood methanol level be determined as soon as possible if the diagnosis is suspected. Methanol concentrations higher than 50 mg/dL are thought to be an absolute indication for hemodialysis and treatment with fomepizole or ethanol, although formate blood levels are a better indication of clinical pathology. Additional laboratory evidence includes metabolic acidosis with an elevated anion gap and osmolar gap (see Chapter 59). A decrease in serum bicarbonate is a uniform feature of severe methanol poisoning. 

The first treatment for methanol poisoning, as in all critical poisoning situations, is support of respiration. There are three specific modalities of treatment for severe methanol poisoning suppression of metabolism by alcohol dehydrogenase to toxic products, hemodialysis to enhance removal of methanol and its toxic products, and alkalinization to counteract metabolic acidosis. 

As with methanol poisoning, early fomepizole or ethanol infusion and hemodialysis are standard treatments for ethylene glycol poisoning. Fomepizole, an inhibitor of alcohol dehydrogenase, has FDA approval for treatment of ethylene glycol poisoning in adults based on its ability to decrease concentrations of toxic metabolites in blood and urine and to prevent... 

Methanol Poisonings result in toxic levels of formate, which causes characteristic visual disturbance plus coma, seizures, acidosis, and death due to respiratory failure ... 

Methyl alcohol is poisonous and is commonly used to denature ethyl alcohol. Methanol poisoning results from ingestion, inhalation of methanol vapors, or absorption through the skin. Methanol is transformed in the body to formaldehyde (H2CO) by the enzyme alcohol dehydrogenase. The formaldehyde is then metabolized to formic acid (HCOOH)... 

We have already discussed a therapeutic application of inhibition in the example of ethanol being used as an antidote to ethylene glycol or methanol poisoning. There are many other such cases which could also be cited. Antabuse , disulfiram, prevents the metabolism of ethanol. As a result a person under treatment with Antabuse will become violently ill if s/he consumes ethanol. Barbiturates are rapidly metabolized especially if a person has been on a prescription for some time. Administering the antibacterial chloramphenicol will inhibit the breakdown of barbiturates and in so doing prolong their sedative action. 

Competitive inhibition. Any two compounds, which are metabolized by the same enzyme, may competitively inhibit the metabolism of the other. The extent of this will depend on the affinity each compound has for the enzyme. One example where this is important toxicologically is in the treatment of ethylene glycol and methanol poisoning. Both of these... 

The result of formate accumulation is metabolic acidosis. However, at later stages, the acidosis may also involve the accumulation of other anions such as lactate. This may be a result of inhibition of cytochrome oxidase and hence of mitochondrial respiration, tissue hypoxia due to reduced circulation of blood, or an increase in the NADH/NAD ratio. The acidosis that results from methanol poisoning will result in more formic acid being in the nonionized state and hence more readily able to enter the CNS. This will cause central depression and hypotension and increased lactate production. This situation is known as the "circulus hypoxicus."... 

Ingestion of methanol, particularly during the prohibition era, resulted in significant illness and mortality. Where epidemics of methanol poisoning have been reported, one-third of the exposed population recovered with no ill effects, one-third have severe visual loss or blindness, and one-third have died. Methanol itself is not responsible for the toxic effects but is rapidly metabolized in humans by alcohol dehydrogenase to formaldehyde, which is subsequently metabolized by aldehyde dehydrogenase to form... 

On the other hand, drugs may inhibit the metabolism of other drugs. For example, allopurinol (a xanthine oxidase inhibitor that inhibits the synthesis of uric acid) increases the effectiveness of anticoagulants by inhibiting their metabolism. Chloramphenicol (a potent inhibitor of microsomal protein synthesis) and cimetidine (an H2-receptor blocker used in acid-pepsin disease) have similar properties. In addition, drugs may compete with each other in metabolic reactions. In methyl alcohol (methanol) poisoning, ethyl alcohol may be given intravenously to avert methanol-induced blindness and minimize the severe acidosis. Ethyl alcohol competes with methyl alcohol for... 

Two other measures are commonly taken. Because of profound metabolic acidosis in methanol poisoning, treatment with bicarbonate often is necessary. Since folate-dependent systems are... 

Hemodialysis is more efficient than peritoneal dialysis and has been well studied. It assists in correction of fluid and electrolyte imbalance and may also enhance removal of toxic metabolites (eg, formate in methanol poisoning, oxalate and glycolate in ethylene glycol poisoning). The efficiency of both peritoneal dialysis and hemodialysis is a function of the molecular weight, water solubility, protein binding, endogenous clearance, and distribution in the body of the specific toxin. 

Ethyl alcohol has a density of 0.79 g/mL. What volume of ethyl alcohol is needed to treat methanol poisoning, if the physician orders 200 g of ethanol ... 

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