Pharmacology

January 2015
Marites T. Sibbaluca, Md

Alcohol
OUTLINE
A.
B.
C.

Alcohol
Methanol
Ethylene glycol

ALCOHOL
Basic pharmacology of Ethanol
Pharmacokinetics
Ethanol is a small water-soluble molecule absorbed rapidly from the GIT. After ingestion of alcohol in the fasting state, peak blood
alcohol concentrations are reached within 30 minutes.
The presence of food in the stomach delays absorption by slowing gastric emptying.
For an equivalent oral dose of alcohol, women have a higher peak concentration than men, in part because women have a lower
total body water content and in part because of differences in first-pass metabolism.
In the CNS, the concentration of ethanol rises quickly
Oxidized in the liver
Much of the remainder is excreted through the lungs and in the urine
At levels of ethanol usually achieved in blood, the rate of oxidation follows zero-order kinetics
The typical adult can metabolize 7-10 g (150-220 mmol) of alcohol per hour, the equivalent of approximately one drink (10- oz (300
ml) beer, 3.5 oz (105 ml) wine, or 1 oz (30 ml) distilled 80-proof spirits

ACETALDEHYDE Metabolism

Much of the acetaldehyde formed from alcohol is oxidized in the liver in a reaction catalyzed by mitochondrial NADdependent aldehyde dehydrogenase (ALDH).

Oxidation of acetaldehyde is inhibited by disulfiram, a drug that has been used to deter drinking by alcohol dependent
patients undergoing treatment

When ethanol is consumed in the presence of disulfiram, acetaldehyde accumulates and causes an unpleasant reaction of
facial flushing, nausea, vomiting, dizziness, and headache. Several other drugs (eg, metronidazole, cefotetan, trimethoprim)
inhibit ALDH and can cause a disulfiram-like reaction if combined with ethanol.
Pharmacodynamics of Acute Ethanol Consumption

At high blood concentrations, it induces coma, respiratory depression, and death.

Ethanol affects a large number of membrane proteins that participate in signaling pathways, including neurotransmitter receptors for amines,
amino acids, opioids, and neuropeptides; enzymes such as Na + /K + -ATPase, adenylyl cyclase, phosphoinositide-specific phospholipase C;
a nucleoside transporter; and ion channels.

Enciso, Vanessa Soriano

Medicine - IIA

Page 1 of 4

Ethanol inhibits the ability of glutamate to open the cation channel associated with the N -methyl-D-aspartate (NMDA) subtype of
glutamate receptors.
The NMDA receptor is implicated in many aspects of cognitive function, including learning and memory. Blackoutsperiods of
memory loss that occur with high levels of alcoholmay result from inhibition of NMDA receptor activation.
Heart

Significant depression of myocardial contractility has been observed in individuals who acutely consume moderate
amounts of alcohol, ie, at a blood concentration above 100 mg/dL.

Consequences of Chronic Alcohol Consumption

Direct effects of ethanol and the metabolic consequences of processing a heavy load of a metabolically active
substance.
Increased oxidative stress
Depletion of glutathione
Damage to mitochondria
Growth factor dysregulation
Potentiation of cytokine-induced injury

Chronic consumption of large amounts of alcohol is associated with an increased risk of death. Deaths linked to alcohol
consumption are caused by liver disease, cancer, accidents, and suicide.

Liver and GIT

Liver disease is the most common medical complication of alcohol abuse; an estimated 1530% of chronic heavy
drinkers eventually develop severe liver disease.

Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure.

Nervous System
1. Tolerance and dependence

As with other sedative-hypnotic drugs, there is a limit to tolerance, so that only a relatively small increase in the lethal
dose occurs with increasing alcohol use.

Alcohol withdrawal symptoms

classically consist of hyperexcitability in mild cases and seizures, toxic psychosis, and delirium tremens in
severe ones.
The dose, rate, and duration of alcohol consumption determine the intensity of the withdrawal syndrome.
When consumption has been very high, merely reducing the rate of consumption may lead to signs of
withdrawal.

Psychological dependence on alcohol is characterized by a compulsive desire to experience the rewarding effects of
alcohol and, for current drinkers, a desire to avoid the negative consequences of withdrawal.
2. Neurotoxicity

The most common neurologic abnormality in chronic alcoholism is generalized symmetric peripheral nerve injury, which
begins with distal paresthesias of the hands and feet. Degenerative changes can also result in gait disturbances and
ataxia.
3. Wernicke-korsakoff syndrome

characterized by paralysis of the external eye muscles, ataxia, and a confused state that can progress to coma and
death. It is associated with thiamine deficiency but is rarely seen in the absence of alcoholism.

Cardiovascular System
1) Cardiomyopathy and heart failure
2) Arrhythmia
3) Hypertension
4) Coronary heart disease
METHANOL

Methyl alcohol, wood alcohol

Methanol can be absorbed through the skin or from the respiratory or GIT and is then distributed in body water

The primary mechanism of elimination of methanol n humans is by oxidation to formaldehyde, formic acid and CO2.

Precious Angelique A. Dy

Doctor of Medicine - II

Page 2 of 4

The special susceptibility of humans to methanol toxicity is due to metabolism to formate and formaldehyde, not to methanol itself
or to formaldehyde, the intermediate metabolite.

METHANOL POISONING
The visual disturbance is frequently described as like being in a snowstorm
A complaint of blurred vision with relatively clear sensorium should strongly suggest the diagnosis of methanol poisoning
Toxicity is due to metabolites of methanol, there is often a delay of up to 30 hours before development of visual
disturbances and other signs of severe intoxication
In severe cases, the odor of formaldehyde may be present on the breath or in the urine. Changes in the retina may
sometimes be detected on examination.
The development of bradycardia, prolonged coma, seizures, and resistant acidosis all imply a poor prognosis. The
cause of death in fatal cases is sudden cessation of respiration.

ETHYLENE GLYCOL

Polyhydric alcohols such as ethylene glycol (CH 2 OHCH 2 OH) are used as heat exchangers, in antifreeze
formulations, and as industrial solvents. Young children and animals are sometimes attracted by the sweet taste of
ethylene glycol and, rarely, it is ingested intentionally as an ethanol substitute or in attempted suicide.

Three stages of ethylene glycol overdose occur.

1. Within the first few hours after ingestion, there is transient excitation followed by CNS depression.
2. After a delay of 412 hours, severe metabolic acidosis develops from accumulation of acid metabolites and
lactate.
3. 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.

Precious Angelique A. Dy

Doctor of Medicine - II

Page 3 of 4

Precious Angelique A. Dy

Doctor of Medicine - II

Page 4 of 4