Ethyl & methyl alcohols
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Ethyl & methyl alcohols

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Ethyl & methyl alcohols Ethyl & methyl alcohols Document Transcript

  • Alcohols www.freelivedoctor.com
  • ALCOHOLS
    • Methanol (CH 3 OH)
    • Wood alcohol
    • Ethanol (CH 3 CH 2 OH)
    • Grain alcohol
    • Ethylene Glycol (CH2OHCH2OH)
    • Polyhydric alcohol
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  • Ethyl Alcohol
    • The most commonly abused drug in the world
    • 75% of adults drink alcohol regularly
    • In the United States, 18% of adults are classified as heavy drinkers
    • Approx. 10% are considered alcoholics
    • Cost attributed to alcohol abuse exceed 200 billion dollars annually
    • Traffic fatalities, homicides, rapes and suicides are all alcohol related
    • Moderate alcohol use protect against cardiovascular diseases in individuals
    • Alcoholism is a complex disorder with a genetic and environmental component
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  • Pharmacokinetics
    • Ethanol is a small water soluble molecule rapidly absorbed from stomach and small intestine ( 75%) after oral ingestion
    • Rate of absorption from the stomach is reduced by the presence of food
    • Peak blood alcohol levels are achieved in 30 minutes
    • About 60% of inspired ethanol vapor is absorbed through the lungs and can lead to intoxication
    • Percutaneous absorption also occurs (in infants)
    • Distribution is rapid, with tissue levels approximating blood alcohol concentration (BAC)
    • BAC for a fixed amount of alcohol depends on sex, age and adipocity
    • Volume of distribution of ethanol is 0.5-0.7 L/kg which is approximately total body water.
    • For the same oral dose of alcohol, women will have a higher peak concentration than men because of lower total body water and lower (50 %) gastric Alcohol dehydrogenase (ADH)
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  • Pharmacokinetics
    • >90% of ingested ethanol is metabolized by oxidation in the liver
    • <10% is excreted by the lungs and kidneys
    • Ethanol in the alveolar air is in equilibrium with BAC and is measured in test for drunkeness
    • 80 mg% (80 mg EtOH/100 ml of blood) is the BAC for legal intoxication in the US.
    • The concentration. of alcohol in expired air is 0.05% times the concentration of alcohol in blood
    • Metabolic oxidation of ethanol occurs by zero order kinetics (rate is independent of concentration and time)
    • A typical 70 kg adult can metabolize 10 g of ethanol (1 can of beer; 3.5 oz wine) per hour
    • Amount of alcohol oxidized per unit time is approximately proportional to body or liver weight
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  • Alcoholic Beverages www.freelivedoctor.com
  • Estimates of Blood Alcohol Levels
    • A typical adult (70 kg/150 lb) can metabolize 7-10 g of alcohol/hour
    • Blood alcohol levels of a 70 kg male will increase by 20 mg% per drink
    • 12 oz beer (3 % EtOH) = 9 g EtOH
    • 3 oz wine (12 % EtOH) = 9 g EtOH
    • 1 oz whisky(40 % EtOH)= 9 g EtOH
    • A 70 kg adult male will be legally intoxicated after 4 drinks in one hour
    • Total body water in lean males=68%
    • Total body water in females = 55 %
    • BAC = Amount of Ethanol
    • (Body weight)(% body water
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  • Estimates of Blood Alcohol levels
    • A lean and healthy 90 kg man drank 4 (1oz) whisky in 1 hour
    • His BAC will be:
    • (10g EtOH/drink) (4 drinks) = 0.65mg
    • (90 kg) (0.68) or 65 mg%
    • If his lean and healthy 45 kg (100 lb)
    • female friend also dank same amount
    • Her BAC will be:
    • (10g EtOH/drink) (4 drinks) = 1.62 mg
    • (45 kg) (0.55)
    • Or 162 mg %
    • She is legally drunk
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  • Metabolic Pathways
    • ALCOHOL DEHYDROGENASE
    • Major Pathway for ethanol oxidation
    • Cytosolic enzyme containing zinc and sulfhydryl groups
    • Human alcohol dehydrogenase (ADH) also oxidizes methanol and ethylene glycol
    • Found mainly in liver, but there are gastric and brain ADH
    • Significant amount of ethanol is oxidized in the stomach by gastric ADH
    • Lower levels of gastric ADH present in women (50% lower than in men)
    • 4-methylpyrazole (fomepizole), an orphan drug, is a potent ADH inhibitor
    • Polymorphic genotypes occur as ADH2 1, 2,3
    • There are 3 phases of hepatic oxidation of ethanol
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  • Phases of Liver Ethanol Oxidation www.freelivedoctor.com
  • Metabolism Of Ethanol www.freelivedoctor.com
  • MEOS PATHWAY
    • Microsomal enzyme-oxidation system (MEOS) or mixed function oxidase
    • An alternative oxidative pathway for ethanol metabolism
    • Metabolizes less than 5 % of alcohol in regular drinkers
    • Becomes important at BAC >100 mg%
    • Uses NADP + instead of NAD +
    • Chronic alcoholism induces the MEOS pathway
    • Result is increased clearance of drugs handled by hepatic microsomal enzyme system or the cytochrome P450 enzyme multifamily.
    • Genetic polymorphism occurs in the EtOH-inducible cytochrome P450
    • (CYP2E1) enzyme family. Also varies with ethnic groups.
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  • Summary Of Ethanol Oxidizing Enzyme Systems www.freelivedoctor.com
  • CNS EFFECTS OF ETHANOL
    • Ethanol is a sedative-hypnotic agent
    • Membrane-active CNS depressant similar to anesthetic agents
    • Primarily affects the Reticular Activating system
    • Mechanism of CNS action involves the potentiation of GABA receptor and inhibition of Glutamate receptor neurotransmission
    • Ethanol may induce the release of endogenous opiates (basis for opiate antagonist Naltrexone treatment)
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  • Ligand-gated ion channels: allosteric enhancement Ion channel pore GABA barbiturates Cl - Cl - Ethanol ? Intracellular Extracellular benzodiazepines www.freelivedoctor.com
  • Signs & Symptoms www.freelivedoctor.com
  • Cardiovascular Effects of Ethanol
    • ACUTE EFFECTS:
    • Cutaneous vasodilation with increased blood flow to the skin
    • Increased coronary blood flow
    • Depressed myocardial contractility
    • Acetaldehyde induce cathecholamine
    • release result in tachycardia
    • Vasoconstriction in cerebral and renal
    • vascular beds
    • CHRONIC EFFECTS
    • Dilated cardiomyopathy
    • Ventricular hypertrophy
    • Atrial & Ventricular arrhythmias
    • Mild Anemia from Folate deficiency
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  • Gastrointestinal Effects of Ethanol
    • Gastrin release and gastric acid secretion
    • Inflammation and bleeding by ulceration of the stomach linning
    • Retards intestinal absorption of glucose, amino acid, folic acid, thiamine & vitamin B 12 (alcoholics)
    • Chronic CNS effects (Korsakoff Psychosis & Wernicke encephalopathy occurs from thiamine deficiency
    • Liver acidosis, hypoglycemia, increased fatty acid and lactate formation; steatosis
    • Alcoholic hepatitis; Liver Cirrhosis;
    • Liver failure (Alcoholism)
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  • Cell & Organ damage by Ethanol www.freelivedoctor.com
  • Streissguth, 1994 Facies in Fetal Alcohol Syndrome www.freelivedoctor.com
  • Fetal Alcohol Syndrome
    • Specific pattern of facial features
    • Pre- ad/or postnatal growth deficiency
    • Evidence of central nervous system dysfunction
    Photo courtesy of Teresa Kellerman www.freelivedoctor.com
  • Ethanol Drug Interactions www.freelivedoctor.com
  • Acute Ethanol Intoxication
    • Occurs from consumption of large quantities by naiives individuals
    • Degree of intoxication depends on
    • Blood ethanol concentration (BAC)
    • How fast the blood ethanol level rises
    • How long the BAC is maintained
    • Other factors are: Drinking patterns, G.I.
    • Absorptive surface, other medications.
    • Acute Effects: Vasodilation, Tachycardia
    • G.I. Irritation, respiratory depression
    • Managemaent: Prevention of respiratory depression; aspiration of vomitus
    • Treatment of: Hypoglycemia & ketosis with glucose
    • Treatment of dehydration with electrolytes
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  • Tolerance & Physical Dependence
    • Acute Tolerance: Occur in naiive & alcoholics after only a few drinks
    • Chronic tolerance: Occurs after high doses of EtOH for long periods
    • Can result in physical dependence
    • Tolerance and dependence results in
    • Metabolic increase in EtOH oxidation
    • Adaptation of CNS receptors
    • Changes in receptor-coupled signal transduction system. i.e. cAMP
    • Limited tolerance can result in death
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  • Alcoholism & Treatment
    • Chronic alcohol use (alcoholism) results in CNS adaptations called Tolerance and Physical dependence
    • Withdrawal symptoms during abstinence from alcohol include delirium tremens, convulsion, seizure, tremulousness and nausea
    • TREATMENT/DETOXIFICATION
    • Substitution of a long acting sedative/hypnotic drug for ethanol, i.e. Benzodiazepine or Oxazepam
    • I.V. infusion of Phenytoin to stop
    • Seizures
    • Disulfiram (250 mg daily)
    • Supplementary dietary thiamine to replace body vitamin loss
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  • Therapeutic Uses
    • TOPICAL
    • To cleanse the skin (poison ivy)
    • To denature protein and toughen skin with 50-70 % EtoH in bed sores.
    • To reduce body temperature during high fever
    • Antiseptic 70 % EtOH (needle puncture, cavity preparation)
    • SYSTEMIC
    • Mild Sedative, Digestive aid
    • Trigeminal neuralgia (to destroy painful facial nerves)
    • Pulmonary Edema (to collapse airway foam)
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  • Methanol Industrial Solvent, Gasoline additive, home heating Oxidized by the ADH enzyme system Death from 2-8 oz methanol ingestion Ethanol or 4-MP dosage may rescue poisoning www.freelivedoctor.com
  • Ethylene Glycol Heat exchanger in antifreeze formulations Industrial solvent more poisonous to humans than to animals Metabolized by the ADH enzyme system Acute renal failure from oxalate crystal deposition Treatment with ethanol or 4-MP may treat acute poisoning www.freelivedoctor.com
  • Drugs for Treatment of Alcohol Abuse & Alcoholism www.freelivedoctor.com