Ethanol: Pharmacology (Alcohol)

MBBS Sem IV theory class

1. Alcohols Dr. Pravin Prasad M.B.B.S., MD Clinical Pharmacology Lecturer, Lumbini Medical College 31 July 2018 (15 Shrawan 2075), Tuesday

2. By the end of the discussion, MBBS Sem IV students will be able to: Describe the effects of alcohol on central nervous system List the effects of alcohol on different organ system Explain the metabolism of ethanol List the uses, toxicity and contraindications of ethanol consumption

3. Alcohols: Introduction Hydroxy derivatives of aliphatic hydrocarbons Types: Alcoholic beverages: Malted liquors (3-6%), Wines (9-22%), Spirits (42.8%) Non-beverage alcohols: Absolute alcohol (99%), Rectified spirit (90%), Proof spirit(49.29%), Methylated spirit

4. Ethanol: Local actions Application area/method Effects Rubbing on skin Rubefacient, counter-irritant Injected around nerve Permanent damage of nerve Delicate skin Irritation, burning sensation Bacteria Not effective against spores Astringent  antiseptic

5. Ethanol: Local actions Application area/method Effects Applied to surface Astringent Subcutaneous injection Intense pain, inflammation, necrosis and fibrosis

6. Ethanol: Systemic actions Central Nervous System: Neuronal depressant Effect on sleep, anaesthesia, analgesia, anticonvulsant action NOT RELIABLE Hangover: Headache, dry mouth, laziness, disturbed mood, impaired performance

7. Ethanol: Systemic actions Blood Alcohol level (mg/dl) Effects seen 30-60 Apparent excitation and euphoria 80-150 Mental clouding, impaired attention, memory, gait Drowsy 150-200 Sloppy, ataxic Blackouts 200-300 Vomiting, Stupor 300-400 Coma >400 Respiratory depression, death

8. Ethanol: Systemic actions CNS effects: Mechanism Acute ingestion: Increase GABA release activity with decreased glutamate activity (NMDA receptors) Chronic ingestion: Increased GABA receptors as well as NMDA receptors Increased dopamine levels: reward function

9. Ethanol: Systemic actions Cardiovascular system: Small doses: Cutaneous vasodilatation (flushing); BP not affected Moderate doses: Tachycardia and mild rise in BP Large doses: Fall in BP

10. Ethanol: Systemic actions Blood: Plasma lipids: 20-30g ethanol/day: Increase HDL, prevents LDL from oxidative damage Mild anaemia Megaloblastic anaemia

11. Ethanol: Systemic actions Body temperature: Low dose: Cutaneous vasodilatation  sensation of warmth (increased heat loss) High dose: Depress temperature regulating centre

12. Ethanol: Systemic actions Gastrointestinal tract: Variable effect on gastric secretion: 10%  stimulates gastric secretion 20%  inhibits gastric secretion; vomiting, mucosal congestion, gastritis Reduced Lower Esophageal Sphincter tone Accentuate gastric reflux Acute Pancreatitis

13. Liver: Liver exposed to oxidative stress  cellular necrosis and fibrosis (cirrhosis of liver) Alcohol  Acetaldehyde: damages hepatocytes, hepatitis Induces microsomal enzymes Ethanol: Systemic actions

14. Ethanol: Systemic actions Kidney Diuresis: Co-ingestion of fluids Inhibition of ADH secretion Endocrine: Acute intoxication: hypoglycaemia and depletion of hepatic glycogen

15. Ethanol: Pharmacokinetics Absorption: intestine Limited first pass metabolism Intact skin of infant: significant absorption Widely distributed in body Vd : 0.7 L/kg Metabolised in liver Follows zero order kinetics Excretion: 0.05%

16. Ethanol: Metabolism Ethanol Acetaldehyde Acetaldehyde Acetic acid Fatty acid synthesis TCA cycle Ketone bodies CYP2E1 (20%) Alcohol dehydrogenase (80%) Aldehyde dehydrogenase Inhibited by acute alcohol intake Induced by chronic alcohol intake Metabolises warfarin, phenytoin Disulfiram

17. Ethanol: Uses Treatment of methanol poisoning Intractable neuralgia As antiseptic Rubefacient and counter-irritants

18. Ethanol: Toxicity Moderate drinking: Nausea, vomiting, flushing, hangover Acute alcohol intoxication: Unresponsive, hypotension, hypoglycaemia, gastritis, respiratory depression, (death) Treatment: ABC, glucose, thiamine

19. Ethanol: Toxicity Chronic alcoholism: Tolerance (PK as well as PD) Psychological dependence Physical dependence Associated with nutritional deficiencies Neurological afflictions: polyneuritis, tremors, brain atrophy, seizures Wernicke’s encephalopathy, Korsakoff’s psychosis All organ system involved

20. Ethanol: Toxicity Withdrawal syndrome: Seen in physical dependent individuals Anxiety, sweating, tachycardia, tremor, confusion, hallucinations Treatment: Psychological support Medical support: benzodiazepines (diazepam), opioid antagonist (naltrexone), NMDA receptor antagonist (acamprosate)

21. Ethanol: Contraindication Peptic ulcer, hyperacidity, Gastro-Esophageal reflux disease Epileptics Severe liver disease patients Unstable personalities Pregnant women Moderate drinking- foetal alcohol syndrome Heavy drinking- miscarriage, stillbirths, LBW babies