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CHAPTER 23 The Alcohols 405

causes of intoxication. Isopropyl alcohol (isopropanol, rubbing may sometimes be detected on examination, but these are usually
alcohol) is another alcohol that is sometimes ingested when late. The development of bradycardia, prolonged coma, seizures,
ethanol is not available. It produces coma and gastrointestinal and resistant acidosis all imply a poor prognosis. The cause of
irritation, nausea, and vomiting, but is not usually associated with death in fatal cases is sudden cessation of respiration. A serum
retinal or renal injury. methanol concentration higher than 20 mg/dL warrants treat-
ment, and a concentration higher than 50 mg/dL is considered
serious enough to require hemodialysis. Serum formate levels are a
METHANOL better indication of clinical pathology but are not widely available.
The first treatment for methanol poisoning, as in all critical poi-
Methanol (methyl alcohol, wood alcohol) is widely used in the soning situations, is support of respiration. There are three specific
industrial production of synthetic organic compounds and as a modalities of treatment for severe methanol poisoning: suppression
constituent of many commercial solvents. In the home, metha- of metabolism by alcohol dehydrogenase to toxic products, hemo-
nol is most frequently found in the form of “canned heat” or in dialysis to enhance removal of methanol and its toxic products, and
windshield-washing products. Poisonings occur from accidental alkalinization to counteract metabolic acidosis.
ingestion of methanol-containing products or when it is misguid- The enzyme chiefly responsible for methanol oxidation in the
edly ingested as an ethanol substitute. liver is alcohol dehydrogenase (Figure 23–3). Fomepizole, an
Methanol can be absorbed through the skin or from the respira- alcohol dehydrogenase inhibitor, is approved for the treatment of
tory or gastrointestinal tract and is then distributed in body water. methanol and ethylene glycol poisoning. It is administered intrave-
The primary mechanism of elimination of methanol in humans is nously in a loading dose of 15 mg/kg followed by 10 mg/kg every
by oxidation to formaldehyde, formic acid, and CO (Figure 23–3). 12 hours for 48 hours and then 15 mg/kg every 12 hours thereafter
2
Animal species show great variability in mean lethal doses of until the serum methanol level falls below 20–30 mg/dL. The
methanol. The special susceptibility of humans to methanol toxic- dosage increase after 48 hours is based on evidence that fomepi-
ity is due to metabolism to formate and formaldehyde, not due zole rapidly induces its own metabolism by the cytochrome P450
to methanol itself. Since the conversion of methanol to its toxic system. Patients undergoing hemodialysis are given fomepizole
metabolites is relatively slow, there is often a delay of 6–30 hours more frequently (6 hours after the loading dose and every 4 hours
before the appearance of severe toxicity. thereafter). Fomepizole appears to be safe during the short time it is
Physical findings in early methanol poisoning are generally administered for treatment of methanol or ethylene glycol poison-
nonspecific, such as inebriation and gastritis, and possibly an ing. The most common adverse effects are burning at the infusion
elevated osmolar gap (see Chapter 58). In severe cases, the odor of site, headache, nausea, and dizziness. Intravenous ethanol is an
formaldehyde may be present on the breath or in the urine. After alternative to fomepizole. It has a higher affinity than methanol
a delay, the most characteristic symptom in methanol poisoning— for alcohol dehydrogenase; thus, saturation of the enzyme with
visual disturbance—occurs along with anion gap metabolic acido- ethanol reduces formate production. Ethanol is used intravenously
sis. The visual disturbance is frequently described as “like being in as treatment for methanol and ethylene glycol poisoning. The dose-
a snowstorm” and can progress to blindness. Changes in the retina dependent characteristics of ethanol metabolism and the variability
of ethanol metabolism require frequent monitoring of blood etha-
nol levels to ensure appropriate alcohol concentration.
In cases of severe poisoning, hemodialysis (discussed in Chap-
Fomepizole
CH OH ter 58) can be used to eliminate both methanol and formate from
3
Methanol –
the blood. Two other measures are commonly taken. Because of
Alcohol profound metabolic acidosis in methanol poisoning, treatment
dehydrogenase
with bicarbonate often is necessary. Since folate-dependent sys-
–
H CO tems are responsible for the oxidation of formic acid to CO 2 in
2
Formaldehyde Ethanol humans (Figure 23–3), folinic and folic acid are often adminis-
Aldehyde tered to patients poisoned with methanol, although this has never
dehydrogenase been fully tested in clinical studies.
HCOO –
Formate ETHYLENE GLYCOL
Folate-dependent
pathway
Polyhydric alcohols such as ethylene glycol (CH OHCH OH) are
2
2
CO 2 + H O used as heat exchangers, in antifreeze formulations, and as industrial
2
solvents. Young children and animals are sometimes attracted by the
FIGURE 23–3 Methanol is converted to the toxic metabolites sweet taste of ethylene glycol and, rarely, it is ingested intentionally
formaldehyde and formate by alcohol dehydrogenase and aldehyde as an ethanol substitute or in attempted suicide. Although ethylene
dehydrogenase. By inhibiting alcohol dehydrogenase, fomepizole glycol itself is relatively harmless and eliminated by the kidney, it is
and ethanol reduce the formation of toxic metabolites. metabolized to toxic aldehydes and oxalate.