Alcohol toxicity
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ethanol and its acute and chronic toxicity on the human body.
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Alcohol toxicity
- 1. Ethanol toxicity Zaid S. Jumaah Collage of pharmacy University of Baghdad
- 2. INTRODUCTION • Historical background 7000 B.C ! • Today 3.8% deaths 4.6% disabilities
- 3. What is ethanol • Amphipathic • Volatile, colorless and flammable liquid How it synthesize • Fermentation • Synthetic means INTRODUCTION
- 4. PHARMACO-KINETICS/DYNAMICS Absorption • Its absorbed mainly through GIT by passive diffusion • Peak serum conc. 30-60 min after ingestion • Could be absorbed form other routs 20% 80% Presence of food Delay the peak serum conc. Up to 2-6 hrs but not decrease
- 5. metabolism PHARMACO-KINETICS/DYNAMICS Distribution & Elimination • VD = 0.6 L/kg • Rate of elimination 8-35 mg/dl/hr with average 20mg/dl/hr Distribute through out the body Fast Excretion5-7% Breathalyzer
- 6. ALDH PHARMACO-KINETICS/DYNAMICS Metabolism: Ethanol MEOS P450 ADH Peroximal catalase Acetaldehyde NAD+ NADH O2 NADPH H2O2 NADP+ H2O2 H2O Peripheral tissue AcetateH2O + CO2 Disulfiram PyrazoleAminotriazole
- 7. PHARMACO-KINETICS/DYNAMICS Mechanism of action • Compilcated • Modifying of neuronal membranes • Its thought to affect many receptors GABA Glutamate Dopamine
- 8. PHARMACO-KINETICS/DYNAMICS • Blood Alcohol Concentration (BAC) • Alcohol Standard drink (alcohol unit): around 10gm or 10ml (UK) Total amount of alcohol Total body water Regular beer can 0.5 Unit 1.4 Unit Wine glass 4.2 Unit Gin glass
- 10. ACUTE TOXICITY • Human Metabolize one UK unit per hour • When the metabolizing enzymes is saturated TOXICITY OCCURE consumption Metabolism
- 11. ALDH ACUTE TOXICITY Ethanol MEOS P450 ADH Peroximal catalase Acetaldehyde NAD+ NADH O2 NADPH H2O2 NADP+ H2O2 H2O Peripheral tissue AcetateH2O + CO2 Metabolites Flushing , Nausea, headach and general discomfort Lactic acidosis, ketoacidosis and increase TG formation ROS, and muscle weakness
- 12. ACUTE TOXICITY CNS toxicity • It’s BAC dependent • Ranged from mild euphoria to death
- 14. ACUTE TOXICITY Management • Correct any deterioration in Vital signs • Increase ethanol clearance • If the ingestion occurred within 1 hour of presentation Airway IV fluid Nasogastric tube No benefit from charcoal Fructose Hemodialysis
- 15. CHRONIC TOXICITY • Tolerance Low response to alcohol • Withdrawal Metabolic Functional Psychological GABA Glutamate DopamineTremor Insomnia Hallucination 15% death if untreated
- 16. Ethanol Acetaldehydemetabolism Acetate Acetaldehyde dehydrogenase Gultathione depletion ROS & Free radicals Altered membrane proteins Neoantigens formation Impaired cytoskeletal transport Stimulation of HSC Immunological injury Damage to cell membranes Increase fatty acid synthesis Decrease fatty acid oxidation Down regulated in chronic alcohol use Gut Permeability Endotoxaemia Kupfer cell activation TNFα CHRONIC TOXICITY Liver Toxicity Increase NADH/NAD+
- 17. CHRONIC TOXICITY Central Nervous System • Increased homocysteine : withdrawal seizure, Brain atrophy and cognitive problems • Disruption in memory learning and sleep patterns
- 18. CHRONIC TOXICITY Wernicke-Korsakoff syndrome • thiamine deficiency • Korsakoff's Psychosis • Wernicke's encephalopathy
- 19. CHRONIC TOXICITY Cardiovascular toxicity • Acetaldehyde : protein, Ca+ and actin myocin • Lipid peroxidation : ROS and others Alcohol Induced Hypertension
- 20. CHRONIC TOXICITY Gastrointestinal tract • Irritation • Pancreatitis : Acute and chronic Pancreatic pain
- 21. CHRONIC TOXICITY Cancer • Acetaldehyde • defect in aldehyd dehydrogenase • GIT, liver cancer
- 22. CHRONIC TOXICITY Alcohol and pregnancy (Fetal alcohol syndrome) • physical, mental, and/or behavioural problems • Mental retardation
- 23. Hormonal Imbalance Respiratory Gouty arthritis Genitalia Immune CHRONIC TOXICITY Other toxicities Skin
- 24. CHRONIC TOXICITY Management of chronic alcoholism • Psychosocial treatment • Long-term treatment of alcohol-related diseases • Nutritional supplements • Antabuse (Disulfiram)
- 25. CHRONIC TOXICITY Management of withdrawal symptoms • Benzodiazepines • Nitrous oxide • Vitamins
- 26. ETHANOL TOXICITY
- 27. Dose beer truly give you a beer belly ? The answer is NO drinking beer ALONE dose not cause a beer belly