SN5 SHORT NOTE 5M ★ High-yield

Describe the acute and chronic effects of ethanol, alcohol withdrawal and methanol poisoning.

Pharmacology · 2nd Professional — Para-Clinical

Pharmacology of Ethanol

Rapidly absorbed from the stomach and small intestine; food delays it
Metabolised chiefly in the liver — alcohol dehydrogenase → acetaldehyde → (aldehyde dehydrogenase) → acetate; a smaller amount by the microsomal ethanol oxidising system (CYP2E1), which is induced by chronic use
Zero-order kinetics at almost all concentrations — about 10 to 15 mL per hour whatever the amount consumed. Nothing accelerates it; only time works
Acute intake inhibits drug metabolism (competition); chronic intake induces it — which is why a chronic alcoholic needs more of some drugs yet is more vulnerable to paracetamol

Acute and Chronic Effects

System	Acute	Chronic
CNS	Progressive depression, not stimulation — the apparent excitement is loss of inhibitory control; then ataxia, slurred speech, stupor, coma and respiratory depression	Dependence, wernicke encephalopathy and korsakoff psychosis (thiamine deficiency), peripheral neuropathy, cerebellar degeneration, dementia
Cardiovascular	Cutaneous vasodilatation with flushing and heat loss — dangerous in cold exposure, since the person feels warm while losing heat	Cardiomyopathy, hypertension, arrhythmia ("holiday heart")
Liver	Fatty change	Alcoholic hepatitis, cirrhosis, hepatocellular carcinoma
Gastrointestinal	Gastritis, vomiting	Pancreatitis, malabsorption, oesophageal varices
Metabolic	Hypoglycaemia (gluconeogenesis inhibited) — especially in children and the malnourished; lactic acidosis; ketoacidosis	Hyperuricaemia and gout; hyperlipidaemia
Other	Diuresis (ADH inhibited)	Fetal alcohol syndrome; cancers of mouth, oesophagus, liver and breast; thrombocytopenia and macrocytosis

Alcohol Withdrawal and its Treatment

Chronic alcohol enhances GABA and inhibits NMDA transmission → Adaptive down-regulation of GABA receptors and up-regulation of NMDA receptors → Alcohol is stopped → Unopposed glutamate excitation with deficient GABA inhibition → 6–12 h — tremor, sweating, anxiety, nausea, tachycardia → 12–48 h — withdrawal seizures; alcoholic hallucinosis → 48–72 h — delirium tremens: confusion, vivid hallucinations, marked autonomic overactivity, fever; mortality up to 5% untreated

Treatment — long-acting benzodiazepine (chlordiazepoxide or diazepam) in a tapering or symptom-triggered regimen; parenteral thiamine before any glucose; correction of fluids, magnesium and potassium; a quiet, well-lit environment
Giving glucose before thiamine can precipitate wernicke encephalopathy, because glucose metabolism consumes the remaining thiamine — one of the most important practical rules in emergency medicine

CLINICAL PEARL

Methanol is not itself very toxic; its metabolites are. Alcohol dehydrogenase converts it to formaldehyde and then formic acid, which causes the severe metabolic acidosis and the optic nerve damage and blindness. That is why the antidote is to occupy the enzyme — with ethanol, which competes for it, or fomepizole, which inhibits it — buying time for the methanol to be excreted unchanged.

Methanol and Ethylene Glycol Poisoning

Methanol — from illicit or adulterated liquor, a recurrent cause of mass poisoning in India. Features appear after a latent period of 12 to 24 hours: headache, vomiting, abdominal pain, visual blurring and blindness ("snowstorm" vision), severe high anion gap metabolic acidosis, coma
Ethylene glycol (antifreeze) — metabolised to oxalate, causing acidosis, calcium oxalate crystalluria and renal failure
Treatment of both — ethanol or fomepizole to block alcohol dehydrogenase; sodium bicarbonate for acidosis; haemodialysis to remove the parent alcohol and its metabolites; folinic acid in methanol and thiamine and pyridoxine in ethylene glycol poisoning to divert metabolism

Drugs Used in Alcohol Dependence

Disulfiram — inhibits aldehyde dehydrogenase, so acetaldehyde accumulates if alcohol is taken, causing flushing, throbbing headache, vomiting, hypotension and a sense of impending doom. A deterrent only, requiring genuine motivation and full explanation; dangerous in cardiac disease
Acamprosate — modulates glutamate transmission and reduces craving
Naltrexone — an opioid antagonist that reduces the reward of drinking
Thiamine and vitamin supplementation for all
Psychological and social support is the foundation; drugs help only alongside it

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