AlcoholsAlcohols
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ALCOHOLSALCOHOLS
Methanol (CHMethanol (CH33OH)OH)
Wood alcoholWood alcohol
Ethanol (CHEthanol (CH33CHCH22OH)OH)
Grain alcoholGrain alcohol
Ethylene Glycol Ethylene Glycol (CH2OHCH2OH)(CH2OHCH2OH)
Polyhydric alcoholPolyhydric alcohol
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Ethyl AlcoholEthyl Alcohol
The most commonly abused drug in The most commonly abused drug in the worldthe world
75% of adults drink alcohol regularly75% of adults drink alcohol regularly In the United States, 18% of adults In the United States, 18% of adults
are classified as heavy drinkersare classified as heavy drinkers Approx. 10% are considered Approx. 10% are considered
alcoholicsalcoholics Cost attributed to alcohol abuse Cost attributed to alcohol abuse
exceed 200 billion dollars annuallyexceed 200 billion dollars annually Traffic fatalities, homicides, rapes Traffic fatalities, homicides, rapes
and suicides are all alcohol related and suicides are all alcohol related Moderate alcohol use protect against Moderate alcohol use protect against
cardiovascular diseases in individualscardiovascular diseases in individuals Alcoholism is a complex disorder Alcoholism is a complex disorder
with a genetic and environmental with a genetic and environmental component component
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PharmacokineticsPharmacokinetics Ethanol is a small water soluble molecule Ethanol is a small water soluble molecule
rapidly absorbed from stomach and rapidly absorbed from stomach and small intestine ( 75%) after oral small intestine ( 75%) after oral ingestioningestion
Rate of absorption from the stomach is Rate of absorption from the stomach is reduced by the presence of foodreduced by the presence of food
Peak blood alcohol levels are achieved in Peak blood alcohol levels are achieved in 30 minutes30 minutes
About 60% of inspired ethanol vapor is About 60% of inspired ethanol vapor is absorbed through the lungs and can lead absorbed through the lungs and can lead to intoxicationto intoxication
Percutaneous absorption also occurs (in Percutaneous absorption also occurs (in infants)infants)
Distribution is rapid, with tissue levels Distribution is rapid, with tissue levels approximating blood alcohol approximating blood alcohol concentration (BAC)concentration (BAC)
BAC for a fixed amount of alcohol BAC for a fixed amount of alcohol depends on sex, age and adipocitydepends on sex, age and adipocity
Volume of distribution of ethanol is 0.5-Volume of distribution of ethanol is 0.5-0.7 L/kg which is approximately total 0.7 L/kg which is approximately total body water. body water.
For the same oral dose of alcohol, For the same oral dose of alcohol, women will have a higher peak women will have a higher peak concentration than men because of concentration than men because of lower total body water and lower (50 %) lower total body water and lower (50 %) gastric Alcohol dehydrogenase (ADH)gastric Alcohol dehydrogenase (ADH)
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PharmacokineticsPharmacokinetics >90% of ingested ethanol is >90% of ingested ethanol is
metabolized by oxidation in the livermetabolized by oxidation in the liver <10% is excreted by the lungs and <10% is excreted by the lungs and
kidneyskidneys Ethanol in the alveolar air is in Ethanol in the alveolar air is in
equilibrium with BAC and is measured equilibrium with BAC and is measured in test for drunkenessin test for drunkeness
80 mg% (80 mg EtOH/100 ml of blood) 80 mg% (80 mg EtOH/100 ml of blood) is the BAC for legal intoxication in the is the BAC for legal intoxication in the US.US.
The concentration. of alcohol in expired The concentration. of alcohol in expired air is 0.05% times the concentration of air is 0.05% times the concentration of alcohol in blood alcohol in blood
Metabolic oxidation of ethanol occurs Metabolic oxidation of ethanol occurs by zero order kinetics (rate is by zero order kinetics (rate is independent of concentration and time)independent of concentration and time)
A typical 70 kg adult can metabolize 10 A typical 70 kg adult can metabolize 10 g of ethanol (1 can of beer; 3.5 oz wine) g of ethanol (1 can of beer; 3.5 oz wine) per hourper hour
Amount of alcohol oxidized per unit Amount of alcohol oxidized per unit time is approximately proportional to time is approximately proportional to body or liver weightbody or liver weight
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Alcoholic Alcoholic BeveragesBeverages
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Estimates of Blood Estimates of Blood Alcohol LevelsAlcohol Levels
A typical adult (70 kg/150 lb) can A typical adult (70 kg/150 lb) can metabolize 7-10 g of alcohol/hourmetabolize 7-10 g of alcohol/hour
Blood alcohol levels of a 70 kg male Blood alcohol levels of a 70 kg male will increase by 20 mg% per drinkwill increase by 20 mg% per drink
12 oz beer (3 % EtOH) = 9 g EtOH12 oz beer (3 % EtOH) = 9 g EtOH 3 oz wine (12 % EtOH) = 9 g EtOH3 oz wine (12 % EtOH) = 9 g EtOH 1 oz whisky(40 % EtOH)= 9 g EtOH1 oz whisky(40 % EtOH)= 9 g EtOH A 70 kg adult male will be legally A 70 kg adult male will be legally
intoxicated after 4 drinks in one intoxicated after 4 drinks in one hourhour
Total body water in lean Total body water in lean males=68%males=68%
Total body water in females = 55 %Total body water in females = 55 % BAC =BAC = Amount of EthanolAmount of Ethanol
(Body weight)(% body water(Body weight)(% body water
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Estimates of Estimates of Blood Alcohol Blood Alcohol
levels levels A lean and healthy 90 kg man A lean and healthy 90 kg man drank 4 (1oz) whisky in 1 hourdrank 4 (1oz) whisky in 1 hour
His BAC will be:His BAC will be:(10g EtOH/drink) (4 drinks)(10g EtOH/drink) (4 drinks) = 0.65mg = 0.65mg
(90 kg) (0.68)(90 kg) (0.68) or 65 mg% or 65 mg%
If his lean and healthy 45 kg (100 lb)If his lean and healthy 45 kg (100 lb)
female friend also dank same amountfemale friend also dank same amount
Her BAC will be:Her BAC will be:
(10g EtOH/drink) (4 drinks)(10g EtOH/drink) (4 drinks) = 1.62 mg = 1.62 mg
(45 kg) (0.55)(45 kg) (0.55)
Or 162 mg %Or 162 mg % She is legally drunkShe is legally drunk
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Metabolic Metabolic PathwaysPathways
ALCOHOL DEHYDROGENASEALCOHOL DEHYDROGENASE Major Pathway for ethanol oxidationMajor Pathway for ethanol oxidation Cytosolic enzyme containing zinc Cytosolic enzyme containing zinc
and sulfhydryl groupsand sulfhydryl groups Human alcohol dehydrogenase Human alcohol dehydrogenase
(ADH) also oxidizes methanol and (ADH) also oxidizes methanol and ethylene glycolethylene glycol
Found mainly in liver, but there are Found mainly in liver, but there are gastric and brain ADHgastric and brain ADH
Significant amount of ethanol is Significant amount of ethanol is oxidized in the stomach by gastric oxidized in the stomach by gastric ADHADH
Lower levels of gastric ADH present Lower levels of gastric ADH present in women (50% lower than in men)in women (50% lower than in men)
4-methylpyrazole (fomepizole), an 4-methylpyrazole (fomepizole), an orphan drug, is a potent ADH orphan drug, is a potent ADH inhibitorinhibitor
Polymorphic genotypes occur as Polymorphic genotypes occur as ADH2 1, 2,3ADH2 1, 2,3
There are 3 phases of hepatic There are 3 phases of hepatic oxidation of ethanoloxidation of ethanolwww.freelivedoctor.comwww.freelivedoctor.com
Phases of Liver Ethanol OxidationPhases of Liver Ethanol Oxidation
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Metabolism Of EthanolMetabolism Of Ethanol
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MEOS PATHWAYMEOS PATHWAY
Microsomal enzyme-oxidation system Microsomal enzyme-oxidation system (MEOS) or mixed function oxidase(MEOS) or mixed function oxidase
An alternative oxidative pathway for ethanol An alternative oxidative pathway for ethanol metabolismmetabolism
Metabolizes less than 5 % of alcohol in Metabolizes less than 5 % of alcohol in regular drinkersregular drinkers
Becomes important at BAC >100 mg%Becomes important at BAC >100 mg% Uses NADPUses NADP++ instead of NAD instead of NAD++
Chronic alcoholism induces the MEOS Chronic alcoholism induces the MEOS pathwaypathway
Result is increased clearance of drugs handled Result is increased clearance of drugs handled by hepatic microsomal enzyme system or the by hepatic microsomal enzyme system or the cytochrome P450 enzyme multifamily.cytochrome P450 enzyme multifamily.
Genetic polymorphism occurs in the EtOH-Genetic polymorphism occurs in the EtOH-inducible cytochrome P450inducible cytochrome P450
(CYP2E1) enzyme family. Also varies with (CYP2E1) enzyme family. Also varies with ethnic groups.ethnic groups.
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Summary Of Ethanol Summary Of Ethanol Oxidizing Enzyme SystemsOxidizing Enzyme Systems
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CNS EFFECTS OF ETHANOLCNS EFFECTS OF ETHANOL
Ethanol is a sedative-hypnotic Ethanol is a sedative-hypnotic agentagent
Membrane-active CNS depressant Membrane-active CNS depressant similar to anesthetic agentssimilar to anesthetic agents
Primarily affects the Reticular Primarily affects the Reticular Activating systemActivating system
Mechanism of CNS action involves Mechanism of CNS action involves the potentiation of GABA receptor the potentiation of GABA receptor and inhibition of Glutamate and inhibition of Glutamate receptor neurotransmissionreceptor neurotransmission
Ethanol may induce the release of Ethanol may induce the release of endogenous opiates (basis for endogenous opiates (basis for opiate antagonist Naltrexone opiate antagonist Naltrexone treatment)treatment)
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Ligand-gated ion Ligand-gated ion channels: allosteric channels: allosteric
enhancement enhancement Ion channel pore
GABAbarbiturates
Cl-Cl-
Ethanol
?
Intracellular
Extracellular
benzodiazepines
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Signs & SymptomsSigns & Symptoms
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Cardiovascular Cardiovascular Effects of EthanolEffects of Ethanol
ACUTE EFFECTS:ACUTE EFFECTS: Cutaneous vasodilation with Cutaneous vasodilation with
increased blood flow to the skinincreased blood flow to the skin Increased coronary blood flowIncreased coronary blood flow Depressed myocardial contractilityDepressed myocardial contractility Acetaldehyde induce Acetaldehyde induce
cathecholaminecathecholaminerelease result in tachycardiarelease result in tachycardia
Vasoconstriction in cerebral and Vasoconstriction in cerebral and renalrenalvascular bedsvascular beds
CHRONIC EFFECTSCHRONIC EFFECTS Dilated cardiomyopathyDilated cardiomyopathy Ventricular hypertrophyVentricular hypertrophy Atrial & Ventricular arrhythmiasAtrial & Ventricular arrhythmias Mild Anemia from Folate deficiencyMild Anemia from Folate deficiencywww.freelivedoctor.comwww.freelivedoctor.com
Gastrointestinal Effects Gastrointestinal Effects of Ethanolof Ethanol
Gastrin release and gastric acid Gastrin release and gastric acid secretionsecretion
Inflammation and bleeding by Inflammation and bleeding by ulceration of the stomach linningulceration of the stomach linning
Retards intestinal absorption of Retards intestinal absorption of glucose, amino acid, folic acid, glucose, amino acid, folic acid, thiamine & vitamin Bthiamine & vitamin B12 12
(alcoholics)(alcoholics) Chronic CNS effects (Korsakoff Chronic CNS effects (Korsakoff
Psychosis & Wernicke Psychosis & Wernicke encephalopathy occurs from encephalopathy occurs from thiamine deficiencythiamine deficiency
Liver acidosis, hypoglycemia, Liver acidosis, hypoglycemia, increased fatty acid and lactate increased fatty acid and lactate formation; steatosisformation; steatosis
Alcoholic hepatitis; Liver Alcoholic hepatitis; Liver Cirrhosis;Cirrhosis;Liver failure (Alcoholism) Liver failure (Alcoholism) www.freelivedoctor.comwww.freelivedoctor.com
Cell & Organ damage Cell & Organ damage by Ethanolby Ethanol
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Facies in Fetal Facies in Fetal Alcohol SyndromeAlcohol Syndrome
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Fetal Alcohol SyndromeFetal Alcohol Syndrome
Specific pattern Specific pattern of facial featuresof facial features
Pre- ad/or Pre- ad/or postnatal growth postnatal growth deficiencydeficiency
Evidence of Evidence of central nervous central nervous system system dysfunctiondysfunction
Photo courtesy of Teresa Kellerman
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Ethanol Drug Ethanol Drug InteractionsInteractions
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Acute Ethanol Acute Ethanol IntoxicationIntoxication
Occurs from consumption of large Occurs from consumption of large quantities by naiives individualsquantities by naiives individuals
Degree of intoxication dependsDegree of intoxication depends on on
1.1. Blood ethanol concentration (BAC)Blood ethanol concentration (BAC)2.2. How fast the blood ethanol level risesHow fast the blood ethanol level rises
3.3. How long the BAC is maintainedHow long the BAC is maintained
Other factors are: Drinking patterns, G.I.Other factors are: Drinking patterns, G.I.
Absorptive surface, other medications.Absorptive surface, other medications. Acute Effects: Vasodilation, Acute Effects: Vasodilation,
TachycardiaTachycardia
G.I. Irritation, respiratory depressionG.I. Irritation, respiratory depression Managemaent: Prevention of Managemaent: Prevention of
respiratory depression; aspiration of respiratory depression; aspiration of vomitusvomitus
Treatment of: Hypoglycemia & ketosis Treatment of: Hypoglycemia & ketosis with glucosewith glucose
Treatment of dehydration with Treatment of dehydration with electrolyteselectrolyteswww.freelivedoctor.comwww.freelivedoctor.com
Tolerance & Physical Tolerance & Physical DependenceDependence
Acute Tolerance: Occur in naiive & Acute Tolerance: Occur in naiive & alcoholics after only a few drinksalcoholics after only a few drinks
Chronic tolerance: Occurs after Chronic tolerance: Occurs after high doses of EtOH for long periodshigh doses of EtOH for long periods
Can result in physical dependenceCan result in physical dependence Tolerance and dependence resultsTolerance and dependence results in in
Metabolic increase in EtOH oxidationMetabolic increase in EtOH oxidation
Adaptation of CNS receptorsAdaptation of CNS receptors
Changes in receptor-coupled signal Changes in receptor-coupled signal transduction system. i.e. cAMPtransduction system. i.e. cAMP
Limited tolerance can result in deathLimited tolerance can result in death
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Alcoholism & Alcoholism & TreatmentTreatment
Chronic alcohol use (alcoholism) Chronic alcohol use (alcoholism) results in CNS adaptations called results in CNS adaptations called Tolerance and Physical Tolerance and Physical dependencedependence
Withdrawal symptoms during Withdrawal symptoms during abstinence from alcohol include abstinence from alcohol include delirium tremens, convulsion, delirium tremens, convulsion, seizure, tremulousness and nauseaseizure, tremulousness and nauseaTREATMENT/DETOXIFICATIONTREATMENT/DETOXIFICATION
Substitution of a long acting Substitution of a long acting sedative/hypnotic drug for ethanol, sedative/hypnotic drug for ethanol, i.e. Benzodiazepine or Oxazepami.e. Benzodiazepine or Oxazepam
I.V. infusion of Phenytoin to stopI.V. infusion of Phenytoin to stop SeizuresSeizures Disulfiram (250 mg daily)Disulfiram (250 mg daily) Supplementary dietary thiamine to Supplementary dietary thiamine to
replace body vitamin lossreplace body vitamin losswww.freelivedoctor.comwww.freelivedoctor.com
Therapeutic UsesTherapeutic UsesTOPICALTOPICAL
To cleanse the skin (poison To cleanse the skin (poison ivy)ivy)
To denature protein and To denature protein and toughen skin with 50-70 % toughen skin with 50-70 % EtoH in bed sores.EtoH in bed sores.
To reduce body temperature To reduce body temperature during high feverduring high fever
Antiseptic 70 % EtOH (needle Antiseptic 70 % EtOH (needle puncture, cavity preparation)puncture, cavity preparation)
SYSTEMICSYSTEMIC Mild Sedative, Digestive aidMild Sedative, Digestive aid Trigeminal neuralgia (to Trigeminal neuralgia (to
destroy painful facial nerves)destroy painful facial nerves) Pulmonary Edema (to Pulmonary Edema (to
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MethanolMethanol
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
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Ethylene GlycolEthylene 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 poisoningwww.freelivedoctor.comwww.freelivedoctor.com
Drugs for Treatment of Drugs for Treatment of Alcohol Abuse & Alcohol Abuse &
AlcoholismAlcoholism
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