Ethylene glycol poisoning, ethanol

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... 

Ethylene glycol, an industrial solvent and an antifreeze compound, is involved in accidental and intentional poisonings. This compound is initially oxidized by alcohol dehydrogenase and then further biotransformed to oxalic acid and other products. Oxalate crystals are found in various tissues of the body and are excreted by the kidney. Deposition of oxalate crystals in the kidney causes renal toxicity. Ethylene glycol is also a CNS depressant. In cases of ethylene glycol poisoning, ethanol is administered to reduce the first step in the biotransformation of ethylene glycol and, thereby, prevent the formation of oxalate and other products. 

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... 

Drugs for the Treatment of Acute Methanol or Ethylene Glycol Poisoning Ethanol (generic)... 

The treatment for methanol or ethylene glycol poisoning is the same. The patient is given intravenous infusions of diluted ethanol. The ADH enzyme is swamped by all the ethanol, allowing time for the kidneys to excrete most of the methanol (or ethylene glycol) before it can be oxidized to formic acid (or oxalic acid). This is an example of competitive inhibition of an enzyme. The enzyme catalyzes oxidation of both ethanol and methanol, but a large quantity of ethanol ties up the enzyme, allowing time for excretion of most of the methanol before it is oxidized. 

Ammar KA, Heckerling PS. Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion importance of the osmolal gap. Am J Kidney Dis 1996 27 130. 

Peterson CD, Collins AJ, Himes JM, Bullock ML, Keane WF. Ethylene glycol poisoning Pharmacokinetics during therapy with ethanol and hemodialysis. N Engl J Med 1981 304 21-3. 

Methyl pyrazole has been developed as a long-acting and less toxic alternative to ethanol in the treatment of ethylene glycol poisoning. Shown is a Lineweaver-Burk plot of the inhibition of alcohol dehydrogenase by various concentrations of 4-methyl pyrazole. What type of inhibidon appears to be exhibited by this molecule ... 

Ethanol Methanol or ethylene glycol Fomepizole (ADH inhibitor) was recently approved for ethylene glycol poisoning... 

Treatment of ethylene glycol poisoning. The metabolic pathway shown across the top of the figure illustrates the conversion of ethylene glycol to oxalic acid. This can be inhibited by the action of the competitive inhibitor, ethanol, shown in purple. 

Figure 23-2. The oxidation of alcohols by alcohol dehydrogenase results in the formation of metabolites that cause serious toxicities. Ethanol, a preferred substrate for ADH, is used in methanol or ethylene glycol poisoning to slow the rate of formafion of fhe toxic metabolites of these alcohols. Acetaldehyde formed from ethanol is oxidized rapidly by aldehyde dehydrogenase except in the presence of disuifiram.

B. Other useful laboratory studies include electrolytes, lactate, ethanol, glucose, BUN, creatinine, calcium, hepatic transaminases, urinalysis (for crystals and Wood s lamp examination), measured osmolality, arterial blood gases, and ECG monitoring. Serum beta-hydroxybutyrate levels may help distinguish ethylene glycol poisoning from alcoholic ketoacidosis, which may also cause increased anion and osmolar gaps. (Patients with alcoholic ke-... 

Physicians treat methanol or ethylene glycol poisoning with intravenous injections of ethanol before substantial oxidation has occurred. LADH binds more tightly to ethanol than to methanol or ethylene glycol, and the rate of oxidation of ethanol is about six times faster than that of ethylene glycol. The ethanol concentration can be kept higher because it is directly injected. As a result, neither methanol nor ethylene glycol is competitively oxidized to toxic products, and the kidneys can slowly excrete them. 

Cyanide poisoning (e.g., nitroprusside), methanol, ethanol, and ethylene glycol... 

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. 

Other alcohols related to ethanol have wide applications as industrial solvents and occasionally cause severe poisoning. Of these, methanol and ethylene glycol are two of the most common causes of intoxication. 

Table 58-2 lists the concentration and expected contribution to the serum osmolality in ethanol, methanol, ethylene glycol, and isopropanol poisonings. 

---