ethyl & methyl alcohols

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Page 1: Ethyl & methyl alcohols

AlcoholsAlcohols

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Page 2: Ethyl & methyl alcohols

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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Page 3: Ethyl & methyl alcohols

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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Page 4: Ethyl & methyl alcohols

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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Page 5: Ethyl & methyl alcohols

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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Page 6: Ethyl & methyl alcohols

Alcoholic Alcoholic BeveragesBeverages

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Page 7: Ethyl & methyl alcohols

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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Page 8: Ethyl & methyl alcohols

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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Page 9: Ethyl & methyl alcohols

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

Page 10: Ethyl & methyl alcohols

Phases of Liver Ethanol OxidationPhases of Liver Ethanol Oxidation

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Page 11: Ethyl & methyl alcohols

Metabolism Of EthanolMetabolism Of Ethanol

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Page 12: Ethyl & methyl alcohols

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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Page 13: Ethyl & methyl alcohols

Summary Of Ethanol Summary Of Ethanol Oxidizing Enzyme SystemsOxidizing Enzyme Systems

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Page 14: Ethyl & methyl alcohols

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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Page 15: Ethyl & methyl alcohols

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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Page 16: Ethyl & methyl alcohols

Signs & SymptomsSigns & Symptoms

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Page 17: Ethyl & methyl alcohols

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

Page 18: Ethyl & methyl alcohols

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

Page 19: Ethyl & methyl alcohols

Cell & Organ damage Cell & Organ damage by Ethanolby Ethanol

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Page 20: Ethyl & methyl alcohols

Facies in Fetal Facies in Fetal Alcohol SyndromeAlcohol Syndrome

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Page 21: Ethyl & methyl alcohols

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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Page 22: Ethyl & methyl alcohols

Ethanol Drug Ethanol Drug InteractionsInteractions

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Page 23: Ethyl & methyl alcohols

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

Page 24: Ethyl & methyl alcohols

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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Page 25: Ethyl & methyl alcohols

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

Page 26: Ethyl & methyl alcohols

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

collapse airway foam)collapse airway foam)www.freelivedoctor.comwww.freelivedoctor.com

Page 27: Ethyl & methyl alcohols

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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Page 28: Ethyl & methyl alcohols

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

Page 29: Ethyl & methyl alcohols

Drugs for Treatment of Drugs for Treatment of Alcohol Abuse & Alcohol Abuse &

AlcoholismAlcoholism

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