MIDWESTERN UNIVERSITY Dr. Pamela E.

Potter
PHARMACOLOGY 1620/1612, 2023 Alcohol Use and Abuse

Alcohol, Treatment of Alcohol Withdrawal,

and Alcoholism

Katzung, Chapter 23

Ethanol

Disulfiram (Antabuse®)

Diazepam (Valium®)
Chlordiazepoxide (Librium®)
Lorazepam (Ativan®)

Phenytoin (Dilantin®)

Naltrexone (ReVia®; Vivitrol®)

Nalmefene (ReVex®)
Acamprosate (Campral®)
Disulfiram (Antabuse®)
Topiramate (Topamax)
Ondansetron (Zofran®)
Gabapentin (Neurontin®)

Fomepizole (Antizol®)

A 52-year-old man with a history of alcohol dependency was admitted to the emergency room with life-
threatening anion gap metabolic acidosis. He admitted to drinking large quantities of alcohol during the
previous day.

• Investigations. Physical examination, blood and urine analyses, including calculation of his anion
gap and plasma osmolal gap, and measurement of serum alcohol levels.
• Diagnosis. Severe but rapidly reversible lactic acidosis and associated alcohol-induced ketoacidosis.
• Management. Intravenous thiamine, intravenous fluids and bicarbonate.

Nature Reviews Nephrology 6, 555-55

Animal behavioral paradigm used to explore the positive and negative

reinforcing action of alcohol.

(A) Oral alcohol self-administration paradigm, in which the animal is trained to

press a lever to obtain alcohol instead of water. Rats will readily self-
administer enough alcohol in daily 30-minute sessions to become mildly
intoxicated.

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Learning Objectives:
1. Compare and contrast the mechanism and effects of alcohol with those of other CNS depressants
2. Describe the synergistic effects of combining CNS depressants
3. Outline and discuss the major enzymes involved in alcohol metabolism
4. Discuss the effect of zero-order kinetics on alcohol blood levels
5. Discuss the mechanism by which alcohol consumption causes acetaminophen toxicity
6. Describe the effects of alcohol on various organ systems
7. Describe the physical and metabolic consequences of excessive alcohol intake
8. Identify the signs and effects of chronic alcohol use
9. Discuss current theories regarding alcoholism, and describe current treatment options
10. Discuss the use of benzodiazepines in prevention of alcohol withdrawal for acute treatment
11.Distinguish between acute treatment of alcohol withdrawal, and long-term treatment of alcoholism
12. Describe the mechanism of action of naltrexone, as well as side effects that preclude its use in
treatment of alcoholism
13. Describe the mechanism of action of acamprosate and discuss its use in treatment of alcoholism
14. Describe the mechanism of action of disulfiram (Antabuse®) and why it is rarely used
15. Discuss the use of topiramate, ondansetron, and gabapentin for adjunct treatment of alcoholism
16. Discuss the role of non-pharmacological treatments and treatment of depression in preventing
relapse in alcoholism
17. Discuss the treatment of methanol and ethylene glycol poisoning.

Alcohol (Ethanol)
 Alcohol is the most widely used psychoactive
drug in the US.
 In small amounts, it may have positive health
benefits – decreased risk of heart attack, etc.
 It also decreases anxiety and fosters a sense of
well-being and sociability.
 About 75% of the adult population of the US
drinks alcohol. The majority do not experience
any problem with alcohol.
 However, in about 10% of the population,
alcohol causes significant medical and social
problems.
 It is estimated that at least 14 million Americans
meet criteria for alcoholism or alcohol abuse. Only about 10% of the people who need help for
alcoholism get it.
 People who cannot limit their alcohol consumption are said to suffer from alcohol abuse. Those
who continue to drink alcohol in spite of adverse physical and social consequences related directly
to alcohol consumption are considered alcoholics.
 Alcohol abuse and alcoholism costs our economy $235 billion per year and causes more than
25,000 deaths (excludes accidents and homicides). About 30% of patients admitted to hospital
have a problem with alcohol.
 In addition, each year thousands of children are born with defects due to use of alcohol by their
mothers during pregnancy.
 Alcoholics Anonymous has been shown to be effective in the treatment of alcoholism; its world-
wide membership is now more than 2 million.

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Mechanism of Action

Alcohol is a CNS depressant

 Alcohol depresses synaptic transmission in the CNS by interacting with the GABAA receptor
complex (like barbiturates and benzodiazepines), to increase Cl- influx and augment GABA
transmission. Long-term chronic use down-regulates GABA receptors through decreased
synthesis of receptors.
 Alcohol also inhibits the effect of the excitatory amino acid glutamate on the NMDA receptor. It
inhibits glutamate activated Ca++ channels. The NMDA receptor is involved in learning and
memory, as well as generation of seizure activity. Long-term chronic alcohol use causes up-
regulation of NMDA receptors through increased synthesis of receptors.
 Alcohol may also act to facilitate glycine receptor gated Cl- channels and 5-HT3 gated K+ influx

 Alcohol appears to be a stimulant because it inhibits inhibitory pathways at low doses, causing
disinhibition. Memory, concentration, and rational thought are affected fairly early. Confidence
increases, people become vivacious and expansive, and uncontrolled mood swings and outbursts
may occur.
 As the dose increases further, it begins to inhibit excitatory pathways as well, and the more general
CNS depressant and sedative properties become apparent.

 Even at low doses, there is impairment of intellectual and motor function, which interferes with
driving and other complex tasks.
 Anterograde amnesia may occur (blockade of NMDA receptors). There may be no memory of
what happened while intoxicated, although the person appeared awake and functioning during that
time (blackouts).
 The dose-response curve for alcohol is very steep since alcohol is eliminated by zero order
kinetics. There is only a 5-fold difference between the concentration that produces intoxication
and that which is fatal.
 Many people use alcohol to help them sleep. However, alcohol reduces the time spent in REM
sleep and decreases the overall quality of sleep. Chronic alcoholics have very poor and
fragmented sleep.
 Combination of alcohol with other CNS depressants, especially benzodiazepines or
barbiturates, may be fatal due to a synergistic effect (supra-additive CNS depression).

Pharmacokinetics

 Alcohol is absorbed from the stomach and small intestine. Since absorption is greatest from the
small intestine, it will be faster on an empty stomach, and is slowed by food. Peak blood levels
can occur within 30-90 minutes after the last drink.
 There is alcohol dehydrogenase, the enzyme that metabolizes alcohol, in the gastrointestinal tract.
The levels of this enzyme are much higher in men than in women. Gastric metabolism of alcohol
is much lower in women than in men.

 Alcohol is evenly distributed in the body water. It crosses the blood-brain barrier easily.
 It also crosses the placenta rapidly and easily. Fetal alcohol levels reach the same levels as in the
mother.
 Blood alcohol levels are a function of the amount of alcohol ingested and the amount of body water
in which it distributes. Sex, age, and obesity all affect the amount of body water.

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Alcohol Metabolism

 Alcohol is metabolized in the GI tract and liver

by alcohol dehydrogenase (ADH) to
acetaldehyde.
 Acetaldehyde is then oxidized by aldehyde
dehydrogenase to acetate.
 Oxidation requires NAD+, of which there is a
limited supply. Because the amount of NAD+ is
used up at fairly low concentrations of alcohol,
metabolism follows ZERO order kinetics, i.e.
the rate of metabolism is independent of
concentration.
 A typical adult metabolizes 8-10 g of alcohol per
hour, assuming there is no liver damage. This is
one hour for one oz of 80 proof whiskey, 4 oz of
wine, or 12 oz of beer.

 Chronic alcohol consumption induces CYP

2E1, thus increasing EtOH metabolism.
Increased metabolism accounts to some extent
for the greater tolerance of chronic drinkers (see Fig Blood Ethanol Concentration,

23-1).
 In chronic drinkers, elevated NADP+ decreases the
availability of NADPH for regeneration of reduced
glutathione, increasing oxidative stress. This probably
contributes to the liver damage common in chronic
alcoholics.
mg/dl

 Alcohol metabolism uses up NAD+ and generates

excess NADH. This inhibits the TCA cycle, and
acetyl-CoA accumulates. As the TCA cycle is inhibited,
acetyl-CoA enters the pathway for
ketone synthesis, leading to
ketoacidosis.
 The high NADH/NAD+ ratio inhibits
oxidation of fatty acids, which are
resterified into triacylglycerols, then to
VLDL, causing hyperlipidemia. Alcohol
consumption leads to fat deposition in
the liver, which with chronic
consumption causes fatty liver.
 The high NADH/NAD+ ratio also shifts
the balance in the lactate dehydrogenase
reaction toward lactate, resulting in
lactic acidosis.
 Increased lactate may decrease
excretion of uric acid, worsening the
symptoms of gout.

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 Acetaldehyde can accumulate in some people, especially those of Asian descent, who have an
aldehyde dehydrogenase deficiency, leading to facial flushing, headache andMarks’
nausea when alcohol
Essentials of Medical Biochemistry 23.13
is consumed. Disulfiram (Antabuse®) acts by inhibiting aldehyde dehydrogenase, producing very
unpleasant and possibly dangerous effects with alcohol.
 Therapeutic amounts of acetaminophen (Tylenol®) can cause hepatotoxicity in alcoholics, because
CYP2E1 is induced, increasing conversion of acetaminophen to a toxic metabolite. The effect is at
its peak during alcohol withdrawal, when someone with a hangover is most likely to reach for a
painkiller.
 Many drugs are metabolized by the cytochrome P-450 system. Therefore, chronic alcohol
consumption may increase the metabolism of drugs metabolized by this system, for example
phenytoin and oral hypoglycemic agents.
 Conversely, acute alcohol consumption may compete for metabolic enzymes. This is particularly
important for phenothiazines, benzodiazepines, barbiturates and tricyclic antidepressants.

Effects of Alcohol

Central Nervous System:

At low concentrations, disinhibition, decreased anxiety, mild euphoria, and sedation occur. With
increased dose, motor function and judgement are impaired, speech slurs, and ataxia may occur.
This is called
intoxication.

In chronic drinkers,
much higher levels
are required to
produce the same
effect as in
occasional drinkers,
as not only
increased
metabolism, but
pharmacodynamic
tolerance, develops.

Pharmacodynamic tolerance is probably due to down-regulation of GABA receptors, and perhaps

up-regulation of NMDA receptors.

Smooth Muscle: Ethanol is a vasodilator, and large amounts can cause hypothermia due to
vasodilation (drinking alcohol in the winter will not make you warmer). Ethanol also relaxes the
uterus, and has been used intravenously to prevent premature labor.

Kidney: Alcohol decreases antidiuretic hormone (ADH) in the kidney, and has a diuretic effect.

Alcohol Toxicity
 As the concentration of alcohol increases from 200 to 500 mg/dL, effects include emesis, stupor,
coma, respiratory depression, and possible death. Alcohol toxicity and death from overdose is
becoming more common on college campuses, in teenagers who engage in binge drinking.
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 Treatment of severe intoxication includes management of respiratory depression, and preventing

aspiration of vomitus.
 Thiamine is also given in an effort to decrease further neurological damage.
 Alcohol toxicity may also cause metabolic and electrolyte disturbances. If necessary, treat
dehydration with fluids, hypoglycemia with glucose, and balance electrolytes.
 If seizures occur, treat with phenytoin.
 Hypothermia may result, as alcohol causes cutaneous vasodilation, producing flushing of the
skin and a feeling of warmth. In severe intoxication, blood pressure and cardiac output can be
decreased.

Effects of Chronic Alcohol Consumption

Malnutrition:
 Alcohol has a significant number of calories.
 In chronic alcoholics, much of the food intake may come from alcohol, displacing nutrition from
other sources. Malnutrition is common, as are deficiencies in folate and thiamine.

Gastritis and pancreatitis:

 Alcohol causes direct damage to pancreatic cells, which frequently results in pancreatitis.
Alcohol stimulates acid production, and causes severe erosive gastritis, malabsorption. There is a
malabsorption of water-soluble vitamins. All of these add to malnutrition.
 Alcohol disrupts the gastric mucosa and may lead to gastritis and esophageal reflux. Lesions of
the esophagus and duodenum are frequently seen.

Hepatotoxicity:

 Liver disease is the most common medical complication of alcohol abuse: 15-30% of heavy
drinkers eventually develop liver disease.
 Malnutrition is thought to contribute to hepatotoxicity, but is not necessary.
 Metabolism of alcohol lowers concentrations of glutathione, which normally scavenges free
radicals that can destroy the liver. This results in oxidative stress and tissue damage.
 Acetaldehyde increases lipid peroxidation, damaging mitochondrial and cell membranes.
Hepatocytes fill with protein, fat and water.
 Fatty liver develops within days after prolonged heavy drinking, due to metabolic effects
described above.
 This is followed by fibrosis, a result of necrosis and inflammation of the liver.
 Collagen gets deposited, and leads to cirrhosis.
 Alcoholic hepatitis may occur; incidence of viral hepatitis B and/or C also increases due to risky
behavior. Co-existence of hepatitis B or C will increase the amount of liver damage. Liver cancer
is most likely to occur in patients with cirrhosis and hepatitis C about 10 years after alcohol
consumption is stopped.
 Liver damage is more frequent and progresses faster in women than in men.
 The risk of disease is related both to the amount consumed and the duration of abuse.

Cardiovascular Effects:

 While small amounts of alcohol (1-3 drinks a day) may reduce the incidence of coronary heart
disease, by increasing HDL levels, chronic heavy drinking may cause heart damage.
 Binges may cause severe increases in blood pressure and may also result in arrhythmias.

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 Significant depression of myocardial contractility may occur at blood concentrations above 100
mg/dL (0.1%).
 Cardiomyopathy may develop due to direct toxic effects of acetaldehyde on the heart. This is
seen much more commonly in women, and 40-50% of people who develop this will die within a
few years unless they stop drinking.
 Heavy alcohol consumption contributes to hypertension. The mechanism of this effect is
unknown. Blood pressure generally will return to more normal levels if drinking ceases.
 There is an increased risk of stroke in people who drink more than 4-6 drinks per day, or following
binge drinking.

Teratogenicity:

 Use of alcohol by pregnant women is a leading cause of mental retardation and congenital
malformation.
 Drinking in the first trimester (before a woman may realize she is pregnant) may have the greatest
effect, but the fetus can be affected at any time during gestation.
 Fetal alcohol syndrome is characterized by microcephaly, mental retardation, poor coordination,
flattened face, joint abnormalities, heart defects, and impaired immune system. This may occur in
one-third of babies of active alcoholic mothers.
 Even moderate consumption, especially binge drinking, may cause fetal alcohol syndrome.
Recent evidence suggests that even low levels of drinking, which may not cause severe effects,
may alter CNS development to some degree, causing some mild long-term impairment.

It is recommended that women abstain completely from alcohol during pregnancy.

Other effects of chronic alcohol consumption:

 Alcohol use increases the carcinogenicity of tobacco products.

 Alcohol abuse increases the likelihood of oral cancers, as well as of other alimentary and
respiratory cancers, and perhaps breast cancer.
 Mild anemia often results from folic acid deficiency, and also from iron deficiency and GI
bleeding.
 Testicular atrophy, impotence, and gynecomastia may occur in men because of imbalances in
steroid hormone metabolism, leading to decreased sexual function.
 Chronic alcoholics are especially prone to respiratory infections, possibly due to impairment of
immune function.
 Korsakoff’s psychosis (chronic disabling memory loss) and Wernicke encephalopathy
(paralysis of eye muscles, ataxia, confusion) may occur with chronic alcoholism. These problems
appear to be exacerbated by nutritional deficiencies, especially of thiamine.
 Peripheral neuropathy is quite common, along with ataxia and optic nerve damage.
 Skeletal muscle atrophy is common in heavy drinkers, due to direct toxic effects of alcohol on
skeletal muscle.
 Hypothermia may occur due to cutaneous vasodilation, many homeless alcoholics die during the
winter. People with ischemic limbs secondary to peripheral neuropathy are especially prone to
cold damage.

Tolerance and dependence

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 Tolerance develops both to the effects of alcohol (pharmacodynamic), and because of increased
metabolism (pharmacokinetic).
 GABA receptors are down-regulated; NMDA receptors are up-regulated.
 There is a severe withdrawal syndrome, as a result of pharmacodynamic tolerance. There is
cross-tolerance to the effects of barbiturates, benzodiazepines, and general anesthetics, which act
on GABAA receptors, but the lethal dose of alcohol is not changed.
Tolerance in chronic and naïve drinkers

Alcoholism
Alcohol abuse: a condition whereby the social life of an individual is impaired for at least 1 month as
a result of alcohol (DSM-IV). Of the 112 million Americans who drink, about 14 million are thought
to have serious alcohol problems.

Alcoholism: the occurrence of tolerance and dependence as a result of prolonged alcohol abuse (DSM-
IV). There are about 7 million Americans considered active alcoholics.

Alcoholism involves continuous or periodic lack of control over drinking, preoccupation with alcohol,
use of alcohol despite adverse consequences, and distortions in thinking, especially denial.

Alcoholism is at least to some extent genetic. The incidence is four times higher in the offspring of
alcoholics, and twice as high in identical twins compared to fraternal twins (even when children are
adopted at birth and raised separately).

Recently, a genetic mutation has been identified for the metabotropic glutamate receptor 2 (Grm2),
known as a stop codon, in alcohol-preferring rats but not in non-preferring rats. Blocking Grm2
increased alcohol consumption in normal rats and mice.

Use of alcohol in people with a predisposition to alcoholism causes a marked increase in release of β-
endorphins in the dopamine reward pathway that goes from the ventral tegmental area to the
nucleus accumbens and prefrontal cortex. The effect is minimal in people who are not predisposed to
be alcoholic. This pathway is involved in essential functions such as eating, sleeping and sex.

In many people with a predisposition to alcoholism, β-endorphin levels are low, so that this pathway is
underactive. In addition, opioid receptor density may also be reduced. Use of alcohol may stimulate

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the reward pathway to cause the alcoholic to feel “normal” or cause an exaggerated response compared
those with normal brain chemistry.

Stimulation of these pathways with alcohol may shift the sensitivity of the receptors toward alcohol,
and the response to the normal transmitters may become reduced or desensitized. Thus more and more
alcohol is required to produce the response, which creates a vicious cycle that underlies addiction.

Alcoholism is considered to be a disease. People who are prone to become alcoholics often react
differently to alcohol than those who are not. People who display tolerance to alcohol by age 22, or
who begin drinking before age 15, are more likely to become alcoholics.

Signs of alcoholism may include malnutrition, physical degeneration, tremor, recurrent infections,
decreased stamina, increased liver enzymes, gastritis, pancreatitis and hypertension.
Patients may realize that they will die if they continue drinking, but feel they can’t live without it.
Depression often occurs or worsens in alcoholics.

Other substances are sometimes used if alcohol is unavailable, including rubbing alcohol, Sterno, and
ethanol-containing gasoline.

Alcohol Withdrawal
 Symptoms usually begin within 6-24 hours, and may last about 5 days.
 Mild withdrawal includes anxiety, irritability, insomnia, nightmares, nausea, tachycardia and
palpitations, which may last 1-2 days.
 Severe withdrawal may involve anxiety, fear, hallucinations, delirium and tremors (the DT’s),
tonic-clonic seizures, arrhythmias, increased blood pressure.

Alcohol withdrawal can be very serious, even life-threatening!

Treatment of Alcohol Withdrawal- ACUTE TREATMENT

 Objective is to prevent seizures, DTs and arrhythmias.
 Electrolyte imbalances must be addressed, hydration is necessary, and thiamine should be given.
 Long-acting benzodiazepines such as chlordiazepoxide (Librium®), diazepam (Valium®), or are
used to taper the withdrawal. A shorter acting benzodiazepine such as oxazepam (Serax®) is used
if there is liver damage. The dose is slowly reduced, and ultimately the drug discontinued after
several days.
 Anticonvulsants are sometimes used to prevent seizures.
 Antipsychotics such as haloperidol (Haldol®) are sometimes used to treat hallucinations or
aggression in an emergency room setting.
 This is an acute treatment, lasting three to four days.
 Once the patient has been detoxified and stabilized, chronic treatment measures should be
instituted.

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Treatment of Alcoholism- CHRONIC TREATMENT- after withdrawal complete

Alcoholism is considered by most people in the field to be a chronic, treatable disease. Although
relapse is common, and treatment may take several attempts, combinations of pharmacological and
psychosocial treatments produce relatively high success rates, especially if treatment is continued for
the long term. Pharmacological treatment alone is unlikely to be successful, but it may be a useful
adjunct to long-term support systems.

Naltrexone (ReVia®; Vivitrol®)

 Naltrexone is an opioid receptor antagonist. Alcohol stimulates release of β-endorphins which act
on opioid receptors to facilitate the dopaminergic reward pathway in the brain.
 Naltrexone can be administered orally (ReVia) or once a month by depot injection (Vivitrol)
 Naltrexone blocks the ability of alcohol to stimulate this reward pathway.
 Naltrexone reduces craving for alcohol, reducing the urge to drink.
 Decreases the rate of relapse by 50%, when combined with psychosocial treatments.
 Typically given for several months following detoxification.
 A major side effect is nausea which is more common in women.
 Large doses may cause liver damage, so should not be given to alcoholics with active liver
disease, hepatitis or liver failure.
 Other opioids will not be effective to treat pain in patients taking naltrexone.
 Nalmefene (Revex) is a similar opioid antagonist with a longer duration of action and appears less
likely to cause liver damage.

Acamprosate (Campral EC)

 Structural analogue of GABA. Chronic alcohol use up-regulates NMDA receptors to compensate
for the chronic sedative effects of GABA stimulation. When alcohol is withdrawn, anxiety, hyper-
excitability and sleeplessness occur due to this imbalance.
 Acamprosate seems to restore the normal balance of GABA and glutamate transmission.
 Increases the rate of abstinence and decreases likelihood of relapse. Decreases the amount of
voluntary alcohol intake in those who are not abstinent.
 Coupled with psychosocial treatment, may be very effective.
 No anxiolytic, antidepressant or psychotropic effects; no abuse potential.
 Excreted by the kidneys. No liver toxicity.

Disulfiram (Antabuse®)
 Blocks aldehyde dehydrogenase; while it has no effect if taken alone, with cause build up of
acetaldehyde if person consumes alcohol.
 Acetaldehyde produces flushing, intense throbbing headache, nausea and confusion. Effects
can be severe, progressing to vomiting, sweating, chest pain, hypotension, syncompe, weakness,
vertigo, blurred vision, and possibly shock.
 Disulfiram has a long duration of action, it is important not to drink for 3-4 days after a dose of
disulfiram.
 Anything containing alcohol, such as mouthwash, after-shave and rubbing alcohol, cough syrup,
vinegars, and sauces, must be avoided.
 Other drugs, such as metronidazole, some cephalosporins and oral hypoglycemic agents, have
disulfiram-like effects and should not be combined with alcohol.
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 Disulfiram inhibits p-450 and can interfere with metabolism of phenytoin, chlordiazepoxide,
barbiturates and warfarin.
 Disulfiram alone may cause hives and itching, tremor, headache, dizziness, a metallic taste, GI
disturbances, peripheral neuropathies and ketosis.
 Dangerous and not recommended.

Topiramate (Topamax)

 Anticonvulsant drug
 Appears to decrease craving and increase abstinence in recovering alcoholics
 The mechanism is not understood, but is distinct from that of naltrexone or acamprosate.

Other drugs
 Gabapentin, an anticonvulsant also used for neuropathic pain, has shown effectiveness in
clinical trials- people taking the drug were 4 times as likely to stop drinking. They also report
better sleep and overall feel better with the drug.
 Ondansetron (Zofran), an antiemetic drug has some effectiveness at decreasing consumption
and preventing relapse in early-onset alcoholics, but does not work in other types of alcoholics.

Antidepressants
 Many alcoholics suffer from depression, and may use alcohol to self-medicate.
 A study reported in JAMA found that recovering alcoholics who were treated with
antidepressants were less likely to relapse.
 Many recovering alcoholics are reluctant to use antidepressants. Antidepressants are not mood
altering, nor are they addictive.

Non-pharmacological treatments
 Inpatient detoxification followed by an intensive outpatient program is very effective.

 Most programs recommend Alcoholics Anonymous as an effective long-term treatment for

alcoholism. Very few people achieve long-term sobriety without some sort of support group such
as AA.
 There are other support groups (e.g. Rational Recovery) that emphasize moderate drinking, but
few alcoholics seem able to drink moderately over the long term.
 Combination of detoxification, inpatient treatment center and post-treatment support (e.g.
intensive outpatient programs and Alcoholics Anonymous) produces significant recovery.
 Although only about 5% of people who initially come to Alcoholics Anonymous stay, an internal
AA report estimated that as length of sobriety increased, chances of remaining sober for at least
another year increased, from 41% with less than a year of sobriety to 91% with five years or more.

For more information on alcoholism and treatment, visit http://www.niaaa.nih.gov

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Treatment of Methanol and Ethylene Glycol Poisoning

 Methanol and ethylene glycol are sometimes ingested accidentally, by children, or by chronic
alcoholics.
 Methanol is converted by alcohol dehydrogenase to formaldehyde, and then to formate, which
is toxic.
 Characteristic symptoms of methanol poisoning are visual disturbances “like being in a
snowstorm”.
 In severe cases, formaldehyde may be smelled on the breath.
 Bradycardia, coma, seizures and acidosis may occur, followed by cessation of respiration.

 Ethylene glycol (antifreeze) is metabolized by alcohol dehydrogenase to very toxic aldehydes

and oxalate.
 Ingestion causes transient CNS excitation followed by depression, then a severe metabolic
acidosis.
 General treatment for methanol poisoning involves support of respiration, gastric lavage,
alkalization to combat the acidosis, and dialysis to remove the methanol and formate.

 Fomepizole (Antizol) is an alcohol dehydrogenase inhibitor that decreases the conversion of

ethylene glycol and methanol to aldehydes. There are few side effects.
 Specific treatment involves giving ethanol or fomepizole to compete with alcohol
dehydrogenase, and decrease the formation of formaldehyde.
 Similarly, treatment of ethylene glycol poisoning includes supportive measures, dialysis and
administration of ethanol or fomepizole.

It is recommended that physicians screen for alcohol abuse if they suspect it in a patient. There are
various screening questionnaires, but all are similar to this one, from Alcoholics Anonymous

Questions From the AA Pamphlet “Is AA For You?”

1. Do you wish people would mind their own business about your drinking - stop telling you what to do?
2. Have you ever decided to stop drinking for a week or so, but only lasted for a couple of days?
3. Have you ever switched from one kind of drink to another in the hope that this would keep you from getting
drunk?
4. Have you had a drink in the morning during the past year? Do you need a drink to get started, or to stop
shaking?
5. Do you envy people who can drink without getting into trouble?
6. Have you had problems connected with drinking during the past year?
7. Has your drinking caused trouble at home?
8. Do you ever try to get ‘extra’ drinks at a party because you do not get enough?
9. Do you tell yourself you can stop drinking any time you want to, even though you keep getting drunk when you
don’t mean to?
10. Have you missed days off work because of drinking?
11. Do you have ‘blackouts’? A blackout is when there are drinking hours or days we cannot remember.
12. Have you ever felt that your life would be better if you did not drink?

What’s your score? Did you answer YES four times or more? If so, you are probably in trouble with alcohol.
Alcoholics Anonymous is in your local telephone directory or on the Internet: www.aaphoenix.org; www.aa.org

Lecture 5 Page 12 of 12