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Pharmacology Mentor > Blog > Pharmacology > Neuropharmacology > Pharmacology of Alcohols
NeuropharmacologyPharmacology

Pharmacology of Alcohols

Last updated: 2025/05/11 at 11:25 AM
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Pharmacology of alcohols
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1 · Introduction

“Alcohol” in pharmacology typically refers to ethanol, the psychoactive ingredient of alcoholic beverages, but also includes toxic congeners—methanol, ethylene glycol, isopropanol. All share the –OH functional group yet differ in metabolism and clinical impact. This review contrasts their pharmacokinetics, pharmacodynamics, toxicology and therapeutic considerations.

2 · Ethanol

2.1 Pharmacokinetics

  • Absorption: rapid passive diffusion; 80 % from small intestine, 20 % gastric. Peak blood conc. 30–90 min (faster on empty stomach).
  • Distribution: total body water; Vd ≈ 0.6 L/kg (men) vs. 0.5 L/kg (women).
  • Metabolism: hepatic oxidation ≈ 90 %. Two-step pathway (see Table 1): ADH → acetaldehyde, then ALDH → acetate. Microsomal ethanol-oxidising system (MEOS, CYP2E1) induced with chronic intake, ↑ clearance & drug interactions.
  • Elimination: zero-order (constant rate) at 7–10 g/h in average adult; <1 % excreted unchanged in breath, urine, sweat.
Step Enzyme / Cofactor Product Inhibitors / Variants
1 Alcohol dehydrogenase (ADH1B*2 ↑ Vmax) NAD+ → NADH Acetaldehyde Fomepizole, pyrazoles
2 Aldehyde dehydrogenase-2 (mitochondrial) Acetate → CO2 + H2O Disulfiram, ALDH2*2 polymorphism

Ethyl Alcohol or ethanol Metabolism

2.2 Acute Pharmacodynamics

  • CNS: dose-dependent depression via GABAA potentiation, NMDA inhibition, ↑ endogenous opioids.
  • CV: vasodilation (cutaneous flushing), slight ↑ HR; high doses depress myocardium.
  • Endocrine/metabolic: hypoglycaemia (inhibits gluconeogenesis), diuresis (↓ ADH release), ↑ lactate (NADH excess).
  • Behavioural staging: euphoria (BAC 0.02–0.05 %), incoordination (0.08 %), coma >0.3 %, respiratory depression >0.45 %.

2.3 Chronic Effects

  1. Hepatic: fatty liver → alcoholic hepatitis → cirrhosis.
  2. GI: gastritis, pancreatitis, malabsorption, cancer risk (oropharynx, oesophagus).
  3. Neurological: peripheral neuropathy, Wernicke–Korsakoff (thiamine deficit), cerebellar degeneration.
  4. Cardiovascular: dilated cardiomyopathy, hypertension; modest intake may raise HDL.
  5. Foetal alcohol spectrum disorders from in-utero exposure.

2.4 Tolerance & Dependence

Chronic intake induces pharmacokinetic tolerance (CYP2E1 up-regulation) and functional tolerance (receptor down-regulation). Abrupt cessation → sympathetic overdrive, tremor, hallucinosis, seizures, delirium tremens (treated with benzodiazepines ± thiamine).

2.5 Therapeutic & Preventive Agents

Drug Mechanism Clinical Use
Disulfiram Irreversible ALDH inhibition → ↑ acetaldehyde → aversive reaction Deterrent (supervised)
Naltrexone (oral / depot) μ-opioid antagonist ↓ reward craving First-line relapse prevention
Acamprosate Modulates glutamatergic tone (NMDA) → restores balance Maintains abstinence
Diazepam, chlordiazepoxide GABAA potentiation Withdrawal management

3 Other Toxic Alcohols

3.1 Methanol

  • Sources: windshield-washer fluid, industrial solvents, illicit spirits.
  • Toxic metabolite: formic acid → metabolic acidosis, optic nerve injury (“snowfield” vision), basal ganglia necrosis.
  • Treatment: fomepizole (ADH inhibitor) or IV ethanol, bicarbonate, folinic acid, haemodialysis if pH<7.25, methanol >20 mg/dL or visual symptoms.

3.2 Ethylene Glycol

  • Sources: antifreeze, brake fluid.
  • Metabolism: glycolic → glyoxylic → oxalic acid; precipitates Ca-oxalate crystals → renal failure.
  • Clinical phases: neurologic (0–12 h), cardiopulmonary (12–24 h), renal (24–72 h).
  • Treatment: fomepizole/ethanol, dialysis, thiamine & pyridoxine co-factors to shunt metabolism.

3.3 Isopropanol

  • Sources: rubbing alcohol, hand sanitisers.
  • Metabolite: acetone (non-acidic) → profound CNS depression, ketosis without acidosis.
  • Management: supportive (airway, fluids); ADH blockade not required.

4 Key Drug Interactions with Ethanol

  • Acute ethanol: inhibits hepatic CYPs → ↑ warfarin, phenytoin levels.
  • Chronic ethanol: induces CYP2E1 → ↑ hepatotoxicity of paracetamol, ↑ clearance of some drugs.
  • Synergistic CNS depression with benzodiazepines, opioids, H1 antihistamines.
  • Hypoglycaemic potentiation with insulin or sulfonylureas.

5 Clinical Pearls

  1. Ethanol exhibits zero-order elimination at typical blood levels; small dose increases markedly prolong impairment.
  2. Formic and oxalic acids, not methanol or ethylene glycol themselves, cause end-organ toxicity → block ADH early.
  3. Osmolar gap & anion gap together guide diagnosis of toxic alcohol ingestions.
  4. Thiamine 100 mg IV before glucose prevents Wernicke encephalopathy in alcohol-dependent patients.
  5. Combination pharmacotherapy (e.g., naltrexone + acamprosate) may improve long-term abstinence rates.

References (Vancouver style)

  1. Brunton LL, Hilal-Dandan R, Knollmann BC, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill; 2022.
  2. Trevor AJ, Katzung BG, Kruidering-Hall M. Pharmacology: Examination & Board Review. 13th ed. New York: McGraw-Hill; 2021.
  3. Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G. Rang & Dale’s Pharmacology. 9th ed. London: Elsevier; 2020.
  4. Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med. 2018;378(3):270-80.
  5. Lal R, Pattanayak R. Alcohol use disorders. Indian J Med Res. 2017;146(6):593-602.
  6. Wilde M, Bibi A, Saran JS. Management of alcohol withdrawal and intoxication. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always seek the advice of a healthcare provider with any questions regarding a medical condition.

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TAGGED: Acetaldehyde, Al-Anon, Alateen, Alcohol and cancer, Alcohol and pregnancy, Alcohol and the brain, Alcohol cravings, Alcohol dehydrogenase, Alcohol metabolism, Alcohol rehab, Alcohol withdrawal, Alcoholic Anonymous, Alcoholic cardiomyopathy, Alcoholic liver disease, Alcoholism, Alcohols, Binge drinking, Blood alcohol concentration, Breathalyzer, Ethanol, Fatty liver, Hangover, Isopropanol, Methanol, Treatment for alcoholism

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