Alcohol
ALCOHOL
Alcohols are hydroxy derivatives of aliphatic hydrocarbons.
Alcohol is one of the commonly abused substances. It is a neuronal depressant. At lower plasma
concentrations excitation and euphoria are experienced. With increasing concentration mental clouding,
disorganization of thought, impairment of attention, memory, alteration of gait and perception,
drowsiness occurs. At higher concentrations medullary centers are paralysed. General CNS depression
lead to coma and respiratory depression.
These effects of ethanol are thought to be due to different mechanisms,
Enhancing the effect of GABA
Inducing release of endogenous opioid peptides
Alteration of serotonin and dopamine levels
Pharmacokinetics:
Alcohol is absorbed from stomach and duodenum; food slows and decreases absorption. Gastric
emptying determines rate of absorption. It is widely distributed (0.7 L/Kg), Crosses blood brain barrier
efficiently and also crosses placenta freely.
Alcohol is oxidized in liver mainly by the enzyme alcohol dehydrogenase and a small amount is oxidized
by hepatic microsomal enzymes (mainly CYP2E1).
Acetaldehyde AcetateMetabolism
CO2of+Alcohol
H2O follows zero order kinetics.
Excretion of Alcohol occurs through kidney and lungs.
Ethyl alcohol
Alcohol Aldehyde
dehydrogenase dehydrogenase
Interactions:
Exhibits synergism with Anxiolytics, Antidepressants, Antihistaminics, Hypnotics, Opioids
produce marked CNS depression with motor impairment (increased chance of accidents).
Disulfiram-like reactions with sulfonylurea, cefoperazone metronidazole.
Acute alcohol ingestion inhibits enzymes
Chronic intake induces CYP enzymes (especially CYP2E1). Metabolism of Paracetamol,
Tolbutamide, Phenytoin is affected by acute and chronic alcohol intake.
Enhanced hypoglycaemic action of insulin and sulfonylureas.
Aspirin and other NSAIDs cause more gastric bleeding when taken with alcohol.
Food value of Alcohol:
It is an energy yielding substrate. It produces 7 Cal/g.
Contraindications:
Peptic ulcer and GERD
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Alcohol
Epilepsy
Liver diseases
Pregnancy - produce foetal alcohol syndrome resulting in intrauterine and postnatal growth
retardation, low IQ, microcephaly, cranio-facial and other abnormalities, and immunological
impairment leading to increased susceptibility to infections. Heavy drinking during pregnancy
increases the incidence of miscarriage, stillbirths and low birth-weight babies.
Management of acute alcohol intoxication:
Gastric lavage (if the patient is brought soon)
Maintain patent airway, prevent aspiration of vomitus.
Tracheal intubation and positive pressure respiration if needed
Maintain fluid electrolyte balance
Glucose infusion- for correcting hypoglycemia
Thiamine should be added.
Hemodialysis
Management of withdrawal syndrome:
Benzodiazepines: Chlordiazepoxide, Diazepam
Naltrexone: Long-acting opioid antagonist, decreases alcohol craving.
Acamprosate: Weak NMDA receptor antagonist. Reduces relapse of drinking behaviour.
Aversion therapy: Disulfiram:
Irreversible inhibitor of enzyme aldehyde dehydrogenase.
Accumulation of acetaldehyde in blood causes flushing, tachycardia, hyperventilation and nausea.
The subjects resolve not to drink is reinforced by distressing symptoms if he drinks.
Disulfiram aversion therapy is suitable in those subjects who seriously desire to stop the habit of
drinking.
Should not be used in subjects who are physically dependent.
Side effects: Rashes, metallic taste, nervousness, malaise and abdominal upset.
It also inhibits: Alcohol dehydrogenase, Dopamine β hydroxylase and other CYP450 enzymes
(prolongs t of many drugs)
Uses of Ethanol:Rubefacient and Counterirritant when rubbed on skin.
Rubbed on skin to prevent bed sores
Astringent- Antiperspirants, Aftershave lotions.
Antiseptic - Precipitates bacterial proteins (action is good at 70% to 90% concentration)
Alcoholic sponges- reduce body temperature in fever
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Intractable neuralgias and severe cancer pain
Appetite stimulant and carminative
Reflex stimulation in fainting/ Hysteria
Methanol poisoning
Methyl Alcohol (Methanol, Wood Alcohol):
Methyl alcohol is added to industrial rectified spirit to make it unfit for drinking.
It is metabolized to formaldehyde and to formic acid by alcohol and aldehyde dehydrogenases
respectively.
Toxic effects are due to formic acid. The specific toxicity is retinal damage.
Blurring of vision, blindness and death due to respiratory depression can occur.
Treatment:
Keep patient in a quiet dark room, protect eyes from light.
Gastric lavage with sodium bicarbonate
i.v. sodium bicarbonate infusion for acidosis
If hypokalemia occurs – KCl infusion
Ethanol (administered through nasogastric tube)
Hemodialysis
Fomepizole (4- methyl pyrazole) – Inhibits alcohol dehydrogenase- drug of choice in methanol
poisoning.
Folate therapy: Injection of calcium leucovorin reduce blood formate level by enhancing its
oxidation.
Problems associated with chronic alcoholism:
Physical dependence
Nutritional deficiencies
Impaired mental and physical performance
Neurological effects like - polyneuritis, pellagra, tremors, seizures, loss of brain mass, Wernicke’s
encephalopathy, Korsakoff’s psychosis.
Megaloblastic anaemia- due to interference with folate metabolism.
Alcoholic cirrhosis of liver
Hypertension, cardiomyopathy, CHF, arrhythmias, stroke
Acute pancreatitis
Impotence, gynaecomastia, infertility
Skeletal myopathy
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