Metabolites ethylene glycol

Ethylene glycol furosetnide and its metabolites no information 10% citnc acid in ethylene glycol —water (1 + 1), plasma investigations [266]... 

ADH also has clinical significance in the metabolism of methanol and ethylene glycol, two drugs with toxic metabolites. Methanol is oxidized by ADH to formaldehyde, which damages the retina and can cause blindness. Ethylene glycol is metabohzed by ADH to oxalic acid, which has renal tox-... 

Ethylene glycol (and toxic metabolites) Central nervous system... 

Ethylene glycol is rapidly metabolised to glyco-laldehyde, then glycolic acid, glyoxylic acid and finally to oxalic acid. The metabolites are toxic to kidneys, brain and heart. 

Management of methanol and ethylene glycol poisoning is similar. Symptomatic support of respiration and circulation is augmented by correction of metabolic acidosis with intravenous bicarbonate infusion, and control of seizures with diazepam. Ethanol inhibits the metabolism of methanol and ethylene glycol to the toxic metabolites, and can give time for further treatment. The goal is to maintain blood ethanol concentrations between 100 and 150 mg per decilitre, sufficient to saturate alcohol... 

For patients who have ingested more than 30 ml of (pure) methanol or ethylene glycol, dialysis is recommended, and haemodialysis is more effective than peritoneal dialysis. Dialysis both removes the alcohols and their metabolites, and corrects the renal and metabolic disturbances and so is the preferred treatment in severe poisoning. The maintenance dose of ethanol required may be tripled during haemodialysis as ethanol is also removed. Early treatment is indicated if ethylene glycol concentrations are above 20 mg/100 ml (200 mg/1), if the arterial pH is below 7.3, if serum bicarbonate concentrations are less than 20 mM/1, and when there are oxalate crystals in the urine. 

Ethylene glycol Ethanol Blocks metabolism to toxic metabolite... 

Mechanism of Action An alcohol dehydrogenase inhibitor that inhibits the enzyme that catalyzes the metabolism of ethanol, ethylene glycol, and methanol to their toxic metabolites. Therapeutic Effect Inhibits conversion of ethylene glycol and methanol into toxic metabolites. 

Inpatients with high ethyleneglycol levels (>50 mg/dl), significant metabolic acidosis or renal failure, consider hemodialysis to remove ethylene glycol and its toxic metabolites... 

Substances whose poisonous metabolites are eliminated slowly Ethylene glycol, methanol, primidone, isopropyl alcohol, carbon tetrachloride, levothyroxine. 

Three stages of ethylene glycol overdose occur. Within the first few hours after ingestion, there is transient excitation followed by CNS depression. After a delay of 4-12 hours, severe metabolic acidosis develops from accumulation of acid metabolites and lactate. Finally, delayed renal insufficiency follows deposition of oxalate in renal tubules. The key to the diagnosis of ethylene glycol poisoning is recognition of anion gap acidosis, osmolar gap, and oxalate crystals in the urine in a patient without visual symptoms. 

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... 

Ethanol Multiple effects on neurotransmitter receptors, ion channels, and signaling pathways Antidote in methanol and ethylene glycol poisoning Zero-order metabolism duration depends on dose Toxicity Acutely, CNS depression and respiratory failure chronically, damage to many systems, including liver, pancreas, GI tract, and central and peripheral nervous systems Interactions Induces CYP2E1 Increased conversion of acetaminophen to toxic metabolite... 

Fomepizole Inhibits alcohol dehydrogenase, prevents conversion of methanol and ethylene glycol to toxic metabolites Methanol and ethylene glycol poisoning Orphan drug. Toxicity Headache, nausea, dizziness, rare allergic reactions... 

Organic acid metabolites Methanol, ethylene glycol, diethylene glycol... 

COOH Figure 5.7 Metabolism of ethylene glycol showing the production of, . the toxic metabolite. 

The mechanism of toxicity of ethylene glycol involves metabolism, but unlike previous examples, this does not involve metabolic activation to a reactive metabolite. Thus, ethylene glycol is metabolized by several oxidation steps eventually to yield oxalic acid (Fig. 7.84). The first step is catalyzed by the enzyme alcohol dehydrogenase, and herein lies the key to treatment of poisoning. The result of each of the metabolic steps is the production of NADH. The imbalance in the level of this in the body is adjusted by oxidation to NAD coupled to the production of lactate. There is thus an increase in the level of lactate, and lactic acidosis may result. Also, the intermediate metabolites of ethylene glycol have metabolic effects such as the inhibition of oxidative phosphorylation, glucose metabolism, Krebs cycle, protein synthesis, RNA synthesis, and DNA replication. 

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. 

Toxicity. Ethylene glycol itself is probably non-toxic and the serious toxic effects are due to the metabolites. In adults the... 

Disposition in the Body. Less than 5% of ingested oxalic acid is absorbed in healthy adults. About 8 to 40 mg of oxalic acid is normally excreted in the urine daily this is derived mainly from the metabolism of dietary ascorbic acid and glycine with small amounts from dietary oxalic acid and other minor metabolic sources. Calcium oxalate is a major constituent of kidney stones and is frequently found as crystals in freshly-voided urine. In normal subjects concentrations of oxalic acid in blood range from about 1 to 3 pg/ml. Small amounts of oxalate are produced as a metabolite of ethylene glycol. 

Ethylene glycol is sometimes used in suicide attempts. It is not itself toxic, but is converted to toxic metabolites. Conversion to glycoaldehyde by alcohol dehydrogenase is the rate-limiting step, and further metabohsm jdelds gly-colate, glyoxylate, and oxalate. 

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