Alcohol Flashcards

1
Q

Alcohol is not very potent:

  • Standard Dose:
  • Consumption:
A
  1. Standard “dose” is about 14 g:
    • 12 ounce beer
    • 5 ounce wine
    • 1.5 ounce 80 proof liquor
  2. Consumption:
    • Blood alcohol concentration of 30 mg/deciliter
      • 30 mg%
      • 0.03% w/v
    • Equal to 7 mM
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2
Q

Pharmacokinetics:

Absoprtion

A
  • Small, water soluble molecule which is absorbed rapidly from GI tract after oral administration
    • Primarily absorbed from small intestine
  • Rate of absorption influenced by:
    • ethanol concentration, rate of consumption and composition of gastric contents
    • Absorption is decreased if gastric emptying is delayed
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3
Q

Pharmacokinetics:

Distribution

A
  • Distributed to total body water (Vd = volume of total body water)
  • Distribution depends on degree of tissue vascularization
    • amount of blood flow
  • Freely membrane permeable
    • ​Including INTO the alveolae from the lung
      capillaries
    • This is the basis for the breathalizer test of expired air

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4
Q

Metabolism/ Biotransformation:

General issues

A
  • Significant first pass effect in liver
    • 90-98% of ethanol ingested is metabolized to acetaldehyde
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5
Q

Alcohol Dehydrogenase Pathway (ADH):

A
  1. Primary pathway for ethanol oxidation to acetaldehyde
    • rate limiting
  2. Primarily in the liver, but also present in other tissues
  3. Kinetics of ethanol elimination by this pathway are zero-order
    • 10 g/hr in 70 g person at the concentrations of ethanol consumed
    • since one drink is about 14g ⇒ 1.5 hours to metabolize the drink
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6
Q

Microsomal Ethanol Oxidizing System (Mixed Function
Oxidase System) (MFOS):

A
  • High Km - little contribution at concentrations below 100 mg/dl
    • low affinity
  • Induced in alcoholics
    • CYP2E1 - influences metabolism of other drugs
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7
Q

Acetaldehyde Metabolism:

A
  1. Mitochondrial aldehyde dehydrogenase (ALDH)
  2. Oxidizes acetaldehyde to acetate
  3. Genetic polymorphisms
  4. Inhibition by disulfiram
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8
Q

Ethanol Metabolism: Consequences

A

Two major metabolic consequences

  1. Increased NADH results in inhibition of TCA cycle
    • Reduced gluconeogenesis
    • Decreased oxidation of fats
  2. Increased acetaldehyde
    • Generation of protein adducts
    • Decreased glutathione
    • Inhibits microtubules
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9
Q

Mechanism of Action in the CNS:

A
  1. Affects function of several ion channels
  2. In particular, activates GABA receptor-ligand gated Cl-channel
  3. Disturbs balance between excitatory and inhibitory neurotransmission
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10
Q

Acute Effects of Ethanol in CNS:

A

Ethanol is a dose-dependent, CNS depressant:

  • BAC: 50-100 (mg/dl) ⇒ Sedation, subjective “high,” increased reaction times
  • BAC: 100-200 (mg/dl) ⇒ Impaired motor function, slurred speech, ataxia
  • BAC: 200-300 (mg/dl) ⇒ Emesis, stupor
  • BAC: 300-400 (mg/dl) ⇒ Coma
  • BAC: > 500 (mg/dl) ⇒ Respiratory depression, death
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11
Q

Consequences of Chronic Alcohol Consumption
Liver and GI tract

A
  1. Liver
    • Steatosis - fatty liver
    • Hepatitis C - often co-morbid
    • Alcoholic cirrhosis - due to necrosis and chronic inflammation
  2. GI Tract
    • Chronic gastritis
    • Pancreatitis
    • Diarrhea
    • Malabsorption of Vitamins
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12
Q

Consequences of Chronic Alcohol Consumption:

Nervous System

A
  1. Tolerance
    • Adaptive neuronal changes
    • Metabolic tolerance
  2. Dependence
    • Psychological dependence - craving
    • Physical dependence - withdrawal is dangerous, can get seizures
  3. Neurotoxicity
    • Neuralgias and peripheral nerve injury
    • Cerebral/Cerebellar Atrophy
    • Wernicke’s Encephalopathy
    • Korsakoff’s Psychosis
    • Psychiatric Disorders
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13
Q

Teratogenic Effects / Fetal Alcohol Syndrome:

A
  1. Associated with chronic maternal alcohol abuse
  2. Characterized by:
    • retarded body growth
    • microcephaly
    • poor coordination
    • facial abnormalities
    • minor joint abnormalities
  3. Mechanism of Teratogenic Effect
    • ​​direct inhibitory effect of ethanol or acetaldehyde on embryonic cellular proliferation
  4. Severitydose-dependent
    • minimum dose not known
    • advise abstinence
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14
Q

Alcohol-Drug Interactions:

A
  1. Effects of ethanol augmented by other CNS depressants
    • ​​Barbiturates; benzodiazepines; opiates; neuroleptics
  2. Ethanol can also interfere with drug metabolism
    • Acute, high doses inhibit CYP2E1 mediated metabolism
    • Chronic ethanol induces CYP2E1 enzymes therefore accelerates metabolism of some drugs
  3. Acetaminophen liver toxicity worse in alcoholic or during acute ethanol intoxication
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15
Q

Management of Acute Intoxication:

A
  1. Goal ⇒ prevention of severe respiratory depression and aspiration of vomitus
  2. Lethal concentration - generally above 400 mg/dl
  3. Metabolic alterations may require treatment of hypoglycemia, ketosis and electrolyte imbalance
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16
Q

Define alcohol withdrawal:

A
  • Syndrome - agitation, anxiety, insomnia, seizures, mood swings
  • Severity - proportional to degree and duration of alcohol abuse
17
Q

What are the objectives of drug therapy for alcohol withdrawal?

A

prevention of seizures, delirium and arrhythmias

  • Benzodiazepines – Diazepam (Diastat® / Dizac™ / Valium®), Chlordiazepoxide (Librium®)
    • Gradual reduction of dose “tapering off”
18
Q

Pharmacotherapy of Alcoholism:

A
  1. Naltrexone (Depade® / Re Via® / Vivitrol™)
    • Therapeutic Use - reduces “urge to drink”; increases control
    • Mechanism of Action - opioid receptor antagonist
    • Best together with psychosocial therapy
  2. Acamprosate (Campral®)
    • Decreases drinking frequency and reduces relapse
    • Mechanism of action - GABA mimetic
    • Well tolerated - primary side effect is diarrhea
  3. Disulfiram (Antabuse®)
    • Therapeutic Use - Aversion Therapy
    • Mechanism of Action - inhibition of aldehyde dehydrogenase
    • Pharmacologic Effects - acetaldehyde syndrome
    • Not very effective