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Pharm Block 2 > Pharmacology of Alcohol > Flashcards

Pharmacology of Alcohol Flashcards

1
Q

What is the yearly prevalence of any alcohol disorder in the U.S.?

A

8.5%

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2
Q

What is the yearly percentage of alcohol abuse in the U.S.?

A

4.7%

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3
Q

What is the yearly percentage of alcohol dependence in the U.S.?

A

3.8%

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4
Q

What is the gender prevalence of alcohol disorder?

A

men>>female *especially under 30 for both sexes

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5
Q

What are alcohol’s effects on GABA?

A

Alcohol increases GABA: -Binds to GABA-A receptor, increasing GABA effect -Major action: inhibitory -Effects: relaxation, loss of coordination, motor slowing, sedation/CNS depressant, slurred speech

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6
Q

What are alcohol’s effects on NMDA/glutamate?

A

Alcohol decreases NMDA/glutamate: - NMDA antagonist: inhibits release of glutamate, the excitatory neurotransmitter - Presynaptic actions on metabotropic glutamate receptors (mGluR) and presynaptic voltage-sensitive calcium channels - Inhibits post-synaptic ionotropic glutamate receptors (iGluR) eg NMDA: - Reduction of actions of glutamate at postsynaptic NMDA, AMPA receptors - Net effects: Sedation; impaired memory, cognition

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7
Q

What are alcohol’s effects on opioid receptors?

A

-Indirect stimulation of beta endorphins -Pleasurable, euphoric effects via m receptors: reinforcenent

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8
Q

What are alcohol’s effects on dopamine?

A

-Indirect stimulation of dopamine neurons in the VTA -Dopamine release: pleasure/reward, motivation and goal pursuit

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9
Q

What delays the absorption of alcohol?

A

Food delays absorption by slowing gastric emptying.

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10
Q

Describe the gender differences in alcohol absorption.

A

Women have a smaller amount of body water and lower activity of the alcohol metabolizing enzyme ADH in the stomach (first-pass metabolism) - Safe drinking recommendations about 50% compared to men

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11
Q

Which membranes does alcohol diffuse through?

A

Alcohol diffuses across all body membranes (inc. breast milk and placenta) except skin and bladder

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12
Q

How does alcohol distribute after it has been absorbed?

A

After absorption it distributes in total body water

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13
Q

Describe the rate of alcohol concentration increase in the CNS.

A

Concentration of ethanol in CNS rises quickly

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14
Q

How is alcohol excreted?

A

Sweat Urine Breath (breath alcohol test → DUI test)

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15
Q

How is alcohol metabolized?

A

-90 % ethanol removed by oxidation. - Most of this ethanol oxidation occurs in the liver via degradative enzymes

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16
Q

What does an increase in NADH/NAD+ lead to?

A
  • Increased production of lactic acid from pyruvate and may result in hyperuricemia and gout. - Increased production of ketone bodies to produce ketosis. - Increased triglyceride synthesis results in a fatty liver. - Decreased gluconeogenesis and liver glycogen cause hypoglycemia.
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17
Q

Where is Alcohol Dehydrogenase found?

A

Alcohol dehydrogenase is a cytosolic liver enzyme

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18
Q

What is the consequence of the microsomal ethanol oxidizing system?

A

NADPH (cytochrome P450) –> Acetaldehyde

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19
Q

Describe acetaldehyde metabolism.

A
  • Metabolism occurs in the liver - 2nd liver enzyme-Aldehyde Dehydrogenase—-> Acetate - Acetate oxidized by body organs —-> CO2 + H2O —-> Acetyl-CoA
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20
Q

What is an inhibitor of acetaldehyde dehydrogenase?

A

Disulfiram (Antabuse) inhibits acetaldehyde dehydrogenase and causes acetaldehyde to accumulate - Causes extreme discomfort in patients who drink alcoholic beverages - The effect may last 30 min in mild cases or several hours in severe ones

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21
Q

Describe alcohol metabolism in the GI tract.

A
  • ADH in the Stomach and small intestine - Gender Differences Exist: - Men have increased levels of GI ADH compared to women - Early metabolism translates to lower BAC levels
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22
Q

Describe alcohol metabolism in the liver.

A

-Plasma disappearance curve follows zero order kinetics once enzymes are saturated: - Constant amount of ethanol is eliminated during each unit of time. It is caused by the saturation (or overload) of ADH - The only known procedure for hastening rate of elimination is hemodialysis

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23
Q

Describe the pharmacokinetics of alcohol.

A
  • Disappearance rates of 15mg% per hour (.015) are probably average for moderate drinkers - The rate of metabolism of alcohol increases with dependence—some alcoholics can metabolize 20–25mg/dL/hr
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24
Q

Describe the symptoms of alcohol intoxication.

A
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25
Q

What are the adverse nervous system effects of alcohol?

A

–Cognitive: repeated detox assoc with impaired executive function and social abilities
•Increased risk of relapse and social isolation
–Generalized symmetric peripheral nerve injury (most common neurologic abnormality)

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26
Q

What is Wernicke-Korsakoff syndrome?

A

Wernicke-Korsakoff syndrome is a thiamine deficiency:

  • Wernicke’s encephalopathy:
    • Ophthalmoplegia (paralysis of the EOM), nystagmus, Ataxia, confusion

-Korsakoff’s psychosis:
–Anterograde and retrograde amnesia
–Confabulation
–Lack of Insight
–Apathy

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27
Q

What is the treatment for Wernicke-Korsakoff syndrome?

A

•Tx: Thiamine 200mg-500mg IV TID initially, followed by PO

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28
Q

What is the effect of chronic alcohol consumption on the liver?

A

–Liver disease is the most common medical complication: 15-30% of heavy drinkers
•Alcoholic fatty liver (reversible condition) à
•Alcoholic hepatitis à
•Cirrhosis (accelerated with hep C) à
•Liver failure (Tx à liver transplantation)
–Women seem more susceptible than men

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29
Q

What GI symptoms are associated with chronic alcohol consumption?

A
  • Increased susceptibility to gastritis
  • Pancreatitis (most common cause in Western world)
  • Anemia and protein malnutrition (blood and plasma loss during drinking).
  • Malabsorption of water-soluble vitamins.
30
Q

What cardiac symptoms are associated with chronic alcohol consumption?

A
  • Cardiomyopathy and heart failure
  • Arrhythmias
  • Hypertension (more than 3 drinks per day)
  • Coronary heart disease (one drink per day helps to prevent CHD)
  • Anemia: macrocytic (folic acid deficiency)
31
Q

What cancers are chronic alcohol consumers at increased risk for?

A

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Increased risk of cancer

  • Mouth, pharynx, larynx, esophagus and liver

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32
Q

Describe alcohol tolerance biochemically(ie effect on neurotransmitters).

A

–Induction of hepatic enzymes with increased metabolism
–Neuroadaption by GABA, Glutamate, and Dopamine pathways mentioned above
•Compensatory decreased GABA, ­ **increased **glutamate, **decreased **dopamine
•Receptor density: **decreased **GABA-A, ­ **increased **NMDA, **decreased **dopamine

33
Q

Describe what happen with acute cessation of alcohol (in terms of effects on NT).

A

Increased glutaminergic activity: “glutamate storm”: neuroexcitation including seizures, delirium
–Locus Ceruleus: chronic ETOH: increase ­DA → ­** increase **NE→ increase BP, P
• **Decreased intrinsic GABA activity: neuromuscular excitation: tremor, seizures
•Decreased **dopamine activity: anhedonia, lack of motivation, dysphoria

34
Q

What are the primary treatment goals in alcohol withdrawal syndrome?

A

•Prevent seizures, delirium, Wernicke-Korsakoff syndrome

35
Q

How is alcohol withdrawal treated?

A

–Glucose (dextrose, 25–50 g IV)
–Thiamine (100 mg IV)
–Multivitamins (1 ampule; gives yellow color)
–Folate 1mg (if not in multivitamin amp)
–Potassium 40 meq/L if needed
–Correct other electrolyte/metabolic abnormalities

36
Q

What benzodiazepines are given in alcohol withdrawal syndrome?

A
  • Lorazepam or oxazepam (shorter duration of action)
  • Chlordiazepoxide or diazepam (longer duration of action)
37
Q

What is thiamine used for?

A

Thiamine is a vitamin used by the body to break down sugars in the diet.

  • It helps correct nerve problems due to the lack of thiamine in Wernicke-Korsakoff syndrome
38
Q

Describe the kinetics of thiamine.

A

Absorbed from the GI tract.

Metabolized by the liver.

Elimination is renal, the majority being metabolites.

39
Q

Describe the adverse drug reactions to thiamine.

A

Hypersensitivity reactions after injection may accour.

Some tenderness or muscle soreness may result after IM injection

40
Q

What reactions should be considered with patients on thiamine?

A

Thiamine may enhance the activity of neuromuscular blocking agents; clinical significance is unknown.

41
Q

What class of drug is Lorazepam/Ativan?

A

Benzodiazepine (BZD), GABA modulator, anti-anxiety agent.

42
Q

How does lorazepam act?

A

Binds to central benzodiazepine receptors which interact allosterically with GABA receptors.

  • This potentiates the effects of the inhibitory neurotransmitter GABA.
  • Used to treat withdrawal syndrome.
43
Q

Describe the kinetics of lorazepam.

A 
Absorbed rapidly (90%) and metabolized by the liver.
Excreted in urine.

Peak onset 1-2 hrs; half-life 10-20 hrs

44
Q

What are the advantages of lorazepam?

A
  • Short duration of action, lack of active metabolites make it attractive for elderly and those with liver disease
    • Available PO, IM, IV with similar dosing
45
Q

What are the disadvantages of lorazepam?

A

Short-acting means more frequent doses:

  • Every hour initially; possibility of BZD-withdrawal seizure
46
Q

To what class of drug does chlordiazepoxide/librium belong?

A

Benzodiazepine, GABA modulator, anti-anxiety agent

47
Q

How does chlordiazepoxide act?

A

Binds to central benzodiazepine receptors which interact allosterically with GABA receptors.

  • Potentiates the effects of the inhibitory neurotransmitter GABA.
  • Used to treat withdrawal syndrome.
48
Q

Describe the kinetics of chlordiazepoxide.

A

High bioavailability (>90%)

Extensive hepatic metabolism to desmethyldiazepam (active).

Peak onset 1.5-4 hrs

Half-life 5-30 hrs but active metabolites 36-200 hrs

49
Q

What are the advantages of chlordiazepoxide?

A

Original BZD: side effects and interactions well-known after decades of use. “Auto-taper”.

Most physicians familiar with drug.

50
Q

What are the disadvantages of chordiazepoxide?

A

Build-up of active metabolites make it less appropriate for the elderly:

  • Cognitively and neuromuscularly impairing.

Extensive hepatic metabolism make it less suitable for patients with liver disease. C

ognitive effects can persist for days, even weeks. Numerous drug interactions.

51
Q

What adrugs are used to treat aclohol dependence?

A
  • Naltrexone (p.o.-ReVia; I.M.- Vivitrol)
  • Acamprosate (Campral®)
  • Disulfiram (Antabuse®)
52
Q

What are the major effects of “anti-craving” drugs?

A

•Relapse prevention
–Increases time to first drink
–Increases time to heavy drinking
–Decreases # drinks on drinking days

53
Q

To what drug class does naltrexone belong?

A

Opiod antagonist.

54
Q

How does naltrexone act?

A

Potent and long-lasting opioid antagonist with highest affinity for the µ-opioid receptor.

55
Q

Describe the kinetics of naltrexone.

A

Metabolized by the liver. Renal excretion.

56
Q

Describe the adverse drug reactions of naltrexone.

A
  • Nausea is the most common side effect.
    • Other less common side effects include headache, constipation, dizziness, nervousness, insomnia, drowsiness and anxiety.
  • Should be used in hepatic disease with caution since it may produce hepatotoxicity.
57
Q

What are the major interactions of naltrexone?

A

Inhibits effects of opiates.

58
Q

What are the advantages of naltrexone?

A

Dosing simplicity; FDA-approved; monthly injection improves compliance.

59
Q

What are the disadvantages of naltrexone?

A
  • Can’t use with patients on opiates
  • Non-compliance
  • Possible interference with endogenous opioid system?
60
Q

To what drug class does acamprosate belong?

A

Analogue of GABA

61
Q

How does acamprosate act?

A
  • NMDA antagonist + GABAA R activator.
    • It acts on serotonergic, noradrenergic and dopaminergic receptors.
    • May restore neuronal excitation and inhibition balance

* brain thinks it already has GABA so less inclined to drink

62
Q

Describe the kinetics of acamprosate.

A

It is not metabolized.

Renal excretion

63
Q

Describe the adverse drug effects of acamprosate.

A

Caution in depressed patients

Should not be used in patients with renal impairment

64
Q

What are the advantages of acamprosate?

A
  • Well-tolerated with few ADR
  • No significant drug interactions
  • May be shown to be effective in combination with Naltrexone or Disulfiram
65
Q

What are the disadvantages of acamprosate?

A

Studies in US have not consistently shown positive effect

66
Q

To what drug class does Disulfiram belong?

A

Alcohol Dependence: deterrent.

67
Q

What is the action of disulfiram?

A

Inhibits the metabolism of alcohol by irreversibly binding to Aldehyde Dehydrogenase

=>buildup of Acetaldehyde, with development of “instant hangover”: facial flushing, headache, dizziness, nausea, vomiting, rapid heart rate, hypotension, and mental confusion

68
Q

Describe the kinetics of disulfiram.

A

High oral bioavailability

Onset: disulfiram-alcohol reaction 5-30 minutes

Half-life: 7 hrs

Duration of effect: up to two weeks: time to resynthesize ALDH

69
Q

What are the adverse drug reactions of disulfiram?

A

Rare fulminant hepatitis: use with caution in liver disease.
Peripheral neuropathy including optic

Neuropsychiatric changes; caution >60

Known or suspected Coronary Artery Disease or Cerebrovascular Disease

70
Q

What are the advantages of disulfiram?

A

Helpful in Couples Behavioral Counseling for Alcohol Dependence

Abstinence rates of 50% or more in controlled setting/observed administration

71
Q

What are the disadvantages of disulfiram?

A

At one year, no more effective than placebo as sole treatment, self-administered

Pharm Block 2 (15 decks)

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