Comprehensive Overview of Alcohol Metabolism and Its Clinical Implications

Comprehensive Overview of Alcohol Metabolism and Its Clinical Implications

• 1.
  Metabolism of alcohol PROFDR VIYATPRA JNA ACHARYA, MD, PHD MEDICAL BIOCHEMISTRY
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  Brief history Vedic scriptures-Somarasa, Sura, Madhu, Sidhu (sugarcane-based fermented drink) Varuni- out of Samudra Manthan- the goddess of wine or divine liquor Ayurveda- Charaka Samhita and Sushruta Samhita describe medicinal fermented preparations (Asava- (आसव) and Arishta-(अरिष्ट) ). Description in Puranas and Jataka tales Regulated intake Modern History- 10,000–7000 BCE- accidentally discovered 16th–18th centuries, alcohol production became more organized with commercial brewing and distilling Louis Pasteur (1857)- demonstrated that fermentation is a biological process caused by living microorganisms, particularly yeast.
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  Colonial India andAlcoholism The colonial administration: Introduced organized distilleries and breweries Imposed excise taxes on alcohol Encouraged alcohol sales as a major revenue source
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  Prevalence of alcoholism Percapita consumption of pure alcohol increasing from 1.6 L (2003-05) to 4.54 L by 2022. Dry states are also on high Higher consumption is recorded in states like Chhattisgarh, Tripura, Punjab, Arunachal Pradesh, and Goa. Roughly 18.8% of men consume alcohol compared to 1.3% of women (NFHS-5, 2019-21).
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  Why a doctorshould know about alcohol metabolism?? 20–30% of hospital admissions may be directly or indirectly related to alcohol use Major alcohol-related diseases include: Alcoholic Liver Disease Liver Cirrhosis Pancreatitis Alcohol Use Disorder Injuries and accidents. Mental health disorders Socio-cultural issues Deaths attributed to alcohol- ~5.4% of all deaths Cirrhosis deaths due to alcohol- ~63% increasing incidence of alcoholic fatty liver, alcoholic hepatitis, and cirrhosis.
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  Ray of hope!!! Ban on New Shops & Alcohol-Free Zones  De-addiction Cess  Restriction in Rural Areas  Raising Excise Duty  Ban on Liquor Near Sacred Sites  Tetra Pack Introduction  Reduced Purchase Limits
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  Metabolism of alcohol Alcohol absorption starts from stomach Majority absorption in intestine 7 Kcal/gm- empty calorie Major part is metabolized in liver; ~1% excreted through lungs and urine  ADH and ALDH – key enzymes 
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  Alcohol dehydrogenase Cytoplasmic enzyme;6 isoenzymes Less expressed in females than males- toxicity more With ethnicity also it may change Mutation may increase activity of this enzyme--- acetaldehyde build up- toxicity Dimer, contains Zn NADH dependent
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  Aldehyde dehydrogenase (ALDH) Homodimeror homotetramer Mitochondrial enzyme NAD+ dependent enzyme Acetaldehyde to acetic acid- acetate is converted to acetyl CoA Activity of ADH is more than ALDH- acetaldehyde accumulates more Indians- ALDH activity is less; alcohol toxicity
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  Alcohol flush/ Orientalflushing syndrome oALDH deficiency- Acetaldehyde accumulation oFacial flushing, hangover, palpitations, nausea oDisulfiram- drug used to cure alcoholism, creates similar symptoms by irreversibly inhibiting ALDH o Variants of ADH genes- slow metabolism- leads to alcoholism
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  Cyt P 450dependent MEOS (Microsomal ethanol oxidizing system) Cytochrome P 450 dependent detoxification- SER Inducible- CYP2E1 is induced Liver microsomes- oxidation Mixed function oxidase NADPH dependent Ethanol →Acetaldehyde Clinical significance: Metabolic tolerance of alcohol as alcohol is metabolized by this pathway faster leading to chronic alcoholism. Acetaldehyde and ROS formation- Alcoholic liver disease, oxidative stress, hepatic inflammation and fibrosis CH3CH2OH + NADPH +H+ +2O2 → CH3CHO + 2 H2O2 + NADP+
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  Biochemical alteration inalcoholism Excess NADH, increasing the NADH/NAD ratio in hepatocytes ⁺ Inhibition of gluconeogenesis → Hypoglycemia Conversion of pyruvate to lactate → Lactic Acidosis Increased FA synthesis from acetyl CoA → Fatty Liver Disease Reduced fatty-acid oxidation. ROS- Mitochondrial damage and apoptosis Lactic acidosis leads to ↓excretion of uric acid– hyperuricemia; gout Alcohol causes CNS depression by inhibiting excitatory receptors and stimulating inhibitory neurotransmitter GABA
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  Alcohol toxicity Acute- euphoria(50-150mg/dl); decreased neuromuscular coordination, speech slurred (150-300 mg/dl) >300mg/dl- stupor, death Management- rest, hydration, stop alcohol Severe cases- IV fluids, supportive care and observation Chronic alcoholism- Metabolic diseases- DM, CVD, HTN, Obesity, Fatty liver, Cirrhosis, Wernicke’s encephalopathy, stroke, cancers, Fetal alcohol syndrome, mental health derangements
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  Diagnosis GGT, AST, AST/ALTratio Late stage- deranged LFT, decreased albumin Alcohol abuse- Decreased ALDH activity in RBCs Chronic alcohol abuse- Desialylated transferrin level Drunken driving- Breath Alcohol Test (Breathalyzer), blood alcohol test, urine alcohol test (less reliable) Legal BAC limit: 30 mg/100 mL blood
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  Methanol (MeOH) Adulteration Only 10mlpure methanol can lead to blindness Same enzymes ADH and ALDH act upon it MeOH- Formaldehyde- Formic acid Formate is toxic Loss of vision, vomiting, abdominal pain, death Antidote- ethanol (competitive inhibition), Fomepizole (drug of choice)
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  Assignment 1. Metabolism ofalcohol 2. Acute and chronic effects of ethanol poisoning 3. Give reasons- In methanol poisoning ethanol is administered 4. Clinical case- Methanol poisoning,
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