Pharm Of Alcohol DSA

Question 1

What drugs are used for treatment of acute alcohol withdrawal syndrome?

Answer 1

Diazepam (valium)
Lorazepam (ativan)
Oxazepam
Thiamine (vitamin B1)

Question 2

What drugs are for prevention of alcohol abuse?

Answer 2

Acamprosate
Disulfiram (antabuse)
Naltrexone

Question 3

What drugs are for treatment of acute methanol or ethylene glycol poisoning?

Answer 3

Ethanol

Fomepizole

Question 4

Define alcohol abuse

Answer 4

Alcohol use disorder characterized by compulsive use of ethanol in dangerous situations (driving, combined with other CNS depressants) or despite adverse consequences directly related to drinking

Question 5

Define alcohol dependence

Answer 5

All characteristics of alcohol abuse plus physical dependence on alcohol, such as tolerance to alcohol and signs/symptoms upon withdrawal

Question 6

Define alcohol withdrawal syndrome

Answer 6

Characteristic syndrome of insomnia, tremor, agitation, seizures, and autonomic instability engendered by deprivation in individual who is physically dependent on ethanol

Question 7

Define Delirium Tremens (DTs)

Answer 7

Severe form of alcohol withdrawal whose main symptoms are sweating, tremor, confusion, and hallucinations

Question 8

Define fetal alcohol syndrome

Answer 8

Craniofacial dysmorphia, heart defects, and mental retardation caused by teratogenic effects of ethanol consumption during pregnancy

Question 9

Wernicke-Korsakoff syndrome

Answer 9

Ataxia, confusion, paralysis of extraocular muscles that is associated with chronic alcoholism and thiamine deficiency

Question 10

Describe the chemistry of ethanol

Answer 10

Alcohols are amphipathic compounds and have both hydrophilic (polar, water-soluble) and hydrophobic (nonpolar, water-insoluble) portions in their structures
Amphipathic quality greatly enhances their ability to cross membranes and increases their extent of absorption and distribution

Question 11

Describe the absorption of ethanol

Answer 11

Peak blood levels of alcohol are reached within 30 minutes when stomach is empty
Absorption occurs more rapidly from small intestine than from stomach
Presence of food delays absorption by slowing gastric emptying
Ethanol undergoes extensive first-pass metabolism by gastric and liver alcohol dehydrogenase (ADH)

Question 12

Describe distribution of ethanol

Answer 12

Widely distributed with volume of distribution equaling approximate total body water (0.5-0.7 L/kg)
For an equivalent oral dose of alcohol, women have higher peak concentration than men. Women have lower total body water content and differences in first-pass metabolism
Alcohol crosses blood-brain barrier and its distribution is proportional to total blood flow (conc rises quickly due to blood flow to CNS)

Question 13

Describe metabolism of ethanol

Answer 13

Zero-order kinetics (independent of time and concentration)
Typical 70 kg adult can metabolize 7-10 g of alcohol per hour (1 drink)
Small amounts are excreted in urine, sweat, and breath. Metabolism to acetate accounts for 90-98% of ingested ethanol, mostly owing to hepatic metabolism by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)

Question 14

Fomepizole inhibits __, while disulfiram inhibits __

Answer 14

ADH

ALDH

Question 15

Describe the alcohol dehydrogenase pathway

Answer 15

Primary pathway for alcohol metabolism
ADH is a cytosolic enzyme that catalyzes conversion of ethanol to acetaldehyde and is located predominantly in liver (others include stomach and brain)
Gastric metabolism is lower in women than in men, which may contribute to greater susceptibility of women to alcohol
NAD+ is required to convert ethanol to acetaldehyde. This produces NADH, of which excess production may contribute to metabolic disorders that accompany chronic alcoholism and to lactic acidosis and hypoglycemia that frequently accompany acute alcohol poisoning
Aspirin inhibits gastric ADH and can increase ethanol bioavailability
*Fomepizole inhibits ADH and is used in treatment of acute methanol or ethylene glycol poisoning

Question 16

Describe acetaldehyde metabolism

Answer 16

Mitochondrial NAD+-dependent ALDH catalyzes reaction of acetaldehyde to acetic acid, which is further metabolized to carbon dioxide and water
NAD+ is required to convert acetaldehyde to acetic acid (produces NADH)
NAD+ requirements for alcohol metabolism (2 mol NAD+ for 1 mol ethanol conversion to acetic acid; 46 g ethanol requires 1.3 kg NAD+ > than liver supply)
ALDH is inhibited by disulfiram (used to treat alcohol abuse and dependence)

Question 17

Describe genetic polymorphism of ALDH

Answer 17

Some individuals of primarily Asian descent have low activity level of mitochondrial ALDH
When they drink alcohol, they develop high acetaldehyde concentrations and may experience facial flushing, light headedness, palpitations, nausea, and general hangover symptoms
Appears to protect against alcohol dependence and abuse
Those with this and who are chronic heavy drinkers and/or alcohol dependent have increased risk of severe liver diseases due to toxic effects of acetaldehyde

Question 18

Describe microsomal ethanol oxidizing system (MEOS)

Answer 18

Mixed function oxidases (cytochrome P450s) use NADPH as a cofactors in metabolism of ethanol to acetaldehyde
At higher concentrations of ethanol (when NAD+ is depleted and alcohol dehydrogenase is saturated), there is increased contribution from P450s, particularly 2E1, 1A2 and 3A4
Chronic alcohol consumption induces MEOs activity (2E1) and can result in enhanced activation of toxins, free radicals, and hydrogen peroxide

Question 19

Describe alcohol-drug interactions

Answer 19

Chronic ethanol consumption increases levels of CYP450s (particularly 2E1)
Example: acetaminophen-induced hepatoxicity
Acute ethanol may inhibit drug metabolism due to decrease in enzyme activity or liver blood flow (phenothiazines, tricyclic antidepressants, and sedative-hypnotic agent metabolism may be impaired)
Addictive CNS depression with other CNS depressants (sedative-hypnotics)

Question 20

Describe management of acute alcohol intoxication

Answer 20

Goals include prevention of severe respiratory depression and aspiration of vomitus
Glucose can treat metabolic alterations such as hypoglycemia and ketosis
Thiamine is provided to protect against Wernicke-Korsakoff syndrome
Potassium may be required in event of severe vomiting (if renal function is normal) along with electrolyte solutions

Question 21

Describe management of alcohol withdrawal syndrome

Answer 21

Moderate forms of alcohol withdrawal syndrome, characterized by tremor, anxiety, and insomnia, occur 6-8 hours after alcohol consumption is stopped and usually abate in 1-2 days
Major pharm objective is to prevent seizures, delirium, and arrhythmias and include electrolyte rebalancing and thiamine therapy

Question 22

Describe drug therapy for detoxification of severe withdrawal cases

Answer 22

Long-acting benzodiazepines (chlordiazepoxide, clorazepate, diazepam)
Benefits: less frequent dosing and built-in tapering effect
Disadvantages: pharmacologically active metabolites may accumulate, esp in pts with compromised liver function

Short-acting benzodiazepines (lorazepam, oxazepam)
Rapidly converted to inactive metabolites and are useful in pts with liver disease

Tapering of sedative-hypnotic medications can occur over several weeks with complete alcohol detoxification requiring several months of abstinence for restoration of normal CNS function

Question 23

Describe naltrexone

Answer 23

Approved for treatment of alcohol and opiate dependence
MOA: mu opioid receptor antagonist (long-acting)
Reduces craving for alcohol and rate of relapse to either drinking or alcohol dependence for short term (12 weeks)
Extensive first-pass metabolism. Contraindicated in pts with acute hepatitis or liver failure
Causes dose-related hepatocellular injury. Avoid combination of naltrexone and disulfiram (also hepatotoxic)
Individuals physically dependent on alcohol and opioids must be opioid-free before initiating therapy because naltrexone precipitates acute withdrawal syndrome

Question 24

Describe acamprosate

Answer 24

MOA: weak NMD-receptor antagonist and GABAa receptor agonist (also affects serotnergic, noradrenergic, and dopaminergic systems)
Reduces short-term and long-term relapse rates (>6 months)
Eliminated in urine as uncharged drug. Use caution in pts with kidney disease
Can be used in combination with naltrexone or disulfiram

Question 25

Describe disulfiram

Answer 25

MOA: irreversibly inhibits aldehyde dehydrogenase and causes extremes discomfort in pts who drink alcoholic beverages (flushing, throbbing headache, nausea, vomiting, sweating, hypotension, confusion due to accumulation of aldehyde)
Slowly absorbed from GI tract with onset of action from 3-12 hrs. Effects may persist up to 14 days from previous dose
Hepatotoxic and inhibits metabolism of other therapeutic agents (phenytoin, oral anticoagulants, isoniazid, caffeine, barbiturates)
Should not be administered with any meds that contain alcohol (cough syrups, cold preparations, mouthwashes)
Not a cure for alcohol dependent and must be used in pts who are highly motivated and have supportive therapy
Never administer to pt in state of alcohol intoxication or without pt’s knowledge
Not commonly used due to low compliance

Question 26

Describe methanol poisoning and treatment

Answer 26

Poisonings can occur from accidental ingestion of methanol-containing products or when it is used by alcoholics as ethanol substitute
Most common characteristic symptom is blurred vision (being in snowstorm)

Treatment:
Respiratory support
Suppression of metabolism of ADH (ethanol and fomepizole)
Hemodialysis to enhance methanol removal
Alkalinization to counteract metabolic acidosis (bicarbonate)
Ethanol has higher affinity than methanol for ADH and is often used IV as treatment
Fomepizole inhibits ADH and is approved for treatment of methanol poisoning

Question 27

Describe ethylene glycol poisoning and treatment

Answer 27

Accidental overdose in pets and children due to sweet taste of ethylene glycol in antifreeze (also in heat exchangers and industrial solvents)
Metabolized to toxic aldehydes and oxalate

Treatment:
hemodialysis
Ethanol infusion
Fomepizole