Details About Overdose or Poisoning Generic Salt ::  Ethanol

Ethanol

    

Drug Pharmacology ::

I. Pharmacology. Ethanol(ethyl alcohol) acts as a competitive substrate for the enzyme alcoholdehydrogenase, preventing the metabolic formation of toxic metabolitesfrom methanol or ethylene glycol. Blood ethanol concentrations of 100mg/dL, or at least a 1:4 molar ratio of ethanol to toxicalcohol/glycol, effectively saturate alcohol dehydrogenase and preventfurther methanol and ethylene glycol metabolism (see also Fomepizole,Fomepizole (4-Methylpyrazole, 4-MP)). Ethanol is well absorbed from theGI tract when given orally, but the onset is more rapid and predictablewhen it is given intravenously. The elimination of ethanol is zeroorder; the average rate of decline is 15 mg/dL/h. However, this ishighly variable and will be influenced by prior chronic use of alcohol,recruitment of alternate metabolic pathways, and concomitanthemodialysis (eg, to remove methanol or ethylene glycol).

Drug Indications ::

Indications. Suspected methanol (methyl alcohol, see Methanol) or ethylene glycol (see Ethylene Glycol and Other Glycols) poisoning with:

   

A suggestive history of ingestion of a toxic dose but no available blood concentration measurements;

Metabolic acidosis and an unexplained elevated osmolar gap (see Serum osmolality and osmolar gap); or

A serum methanol or ethylene glycol concentration 20 mg/dL.

Note:Since the introduction of fomepizole (4-methylpyrazole, see Fomepizole(4-Methylpyrazole, 4-MP)), a potent inhibitor of alcohol dehydrogenase,most patients with ethylene glycol or methanol poisoning probably willbe treated with this drug instead of ethanol, particularly in casesinvolving small children, patients taking disulfiram, patients withpancreatitis, and hospitals lacking laboratory support to perform rapidethanol levels (for monitoring treatment). Ethanol is more difficult todose, requires more monitoring, and has a greater risk of adverseeffects. Studies suggest that despite the higher acquisition costs forfomepizole, it may be more cost-effective than ethanol.

E. Othersubstances that are metabolized by alcohol dehydrogenase to toxicmetabolites include propylene glycol, diethylene glycol, triethyleneglycol, glycol ethers (eg, ethylene glycol ethyl ether, ethylene glycolbutyl ether), and 1,4-butanediol. The criteria for ethanol therapy andevidence for improved outcomes are lacking for these substances.

Drug Contra-Indications ::

III. Contraindications. Use of interacting drugs, which may cause disulfiram-type reaction (see V.B, below).

Drug Adverse Effects ::

IV. Adverse effects

   

Nausea, vomiting, and gastritis may occur with oral administration. Ethanol may also exacerbate pancreatitis.

Inebriation, sedation, and hypoglycemia (particularly in children and malnourished adults) may occur.

Intravenoususe sometimes is associated with local phlebitis (especially withethanol solutions 10%). Hyponatremia may result from large doses ofsodium-free intravenous solutions.

Acuteflushing, palpitations, and postural hypotension may occur in patientswith atypical aldehyde dehydrogenase enzyme (up to 50–80% of Japanese,Chinese, and Korean individuals).

E. Use in pregnancy. FDAcategory C (indeterminate). Ethanol crosses the placenta. Chronicoveruse in pregnancy is associated with birth defects (fetal alcoholsyndrome). The drug reduces uterine contractions and may slow or stoplabor. However, these effects do not preclude its acute, short-term usefor a seriously symptomatic patient (see Table III–1).

Drug Lab Interactions ::

Drug or laboratory interactions

   

Ethanol potentiates the effect of CNS–depressant drugs and hypoglycemic agents.

Disulfiram reaction(see Disulfiram), including flushing, palpitations, and posturalhypotension, may occur in patients taking disulfiram as well as avariety of other medications (eg, metronidazole, furazolidone,procarbazine, chlorpropamide, some cephalosporins, and Coprinus mushrooms). In such cases, fomepizole is the recommended alternative to ethanol treatment.

Drugsor chemicals metabolized by alcohol dehydrogenase (eg, chloral hydrate,isopropyl alcohol) also have impaired elimination. Fomepizole andethanol mutually inhibit each other’s metabolism.

Drug Dose Management ::

Dosage and method of administration. Obtainserum ethanol levels after the loading dose and frequently duringmaintenance therapy to ensure a concentration of 100–150 mg/dL (eg,every 1–2 hours until goal achieved, eg, level = 100 mg/dL, or afterchange in infusion rate and then every 2–4 hours during the maintenancedosing).

   

Ethanolmay be given orally or intravenously. The desired serum concentrationis 100 mg/dL (20 mmol/L); this can be achieved by giving approximately750 mg/kg (Table III–8) as a loading dose, followed by a maintenanceinfusion of approximately 100–150 mg/kg/h (give a larger dose tochronic alcoholics). A 10% ethanol solution is preferred for IV (tominimize fluids, but it may require central venous access in children),and a solution of less than 30% (usually 20% given for palatability andabsorption) is preferred for oral administration.

Increasethe infusion rate to 175–250 mg/kg/h (larger dose for chronicalcoholics) during hemodialysis to offset the increased rate of ethanolelimination. Alternatively, ethanol may be added to the dialysate.

Drug Chemical Formulations ::

Formulations

   

Oral. Pharmaceutical-grade ethanol (96% USP). Note:Commercial liquor may be used orally if pharmaceutical-grade ethanol isnot available; administer 160 mL/kg divided by the “proof” of theliquor (eg, if using 80 proof liquor, give 2.0 mL/kg). Mix with juiceand dilute to a concentration of 20%.

Parenteral. Ethanol 5% in 5% dextrose solution; 10% in 5% dextrose solution in 1000 mL.

The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is three bottles (10% ethanol, 1 L each).

Table III–8. Ethanol Dosing (Adults and Children)


 Intravenousc
 OralDose 5% 10% 50% Loadinga
 15 mL/kg7.5 mL/kg2 mL/kgMaintenanceb
 2–4 mL/kg/h1–2 mL/kg/h0.2–0.4 mL/kg/hMaintenance during hemodialysisb
 4–7 mL/kg/h2–3.5 mL/kg/h0.4–0.7 mL/kg/h

aIfthe patient’s serum ethanol level is greater than 0, reduce the loadingdose in a proportional manner. Multiply the calculated loading dose bythe following factor:

bDosesmay vary on the individual. Chronic alcoholics have a higher rate ofethanol elimination, and maintenance doses should be adjusted tomaintain an ethanol level of approximately 100 mg/dL.

cInfuse intravenous loading dose over 20–30 minutes or longer.

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