Alcohol

Question 1

Alcohol Metabolism

Answer 1

 Metabolism follows ZERO order kinetics
 Rate is independent of concentration
 Metabolized by alcohol dehydrogenase (ADH) to
acetaldehyde
 Acetaldehyde is oxidized by aldehyde
dehydrogenase (ALDH) to acetate
 Oxidation requires a cofactor, NAD+
 NAD+ is saturated at low concentrations
 Less available NAD+ for other enzymes
 Lactate and acetyl-CoA accumulate
 Fatty acid synthesis and lactic acidosis

Question 2

Alcohol Tolerance

Answer 2

 Pharmacokinetic  
 • Ethanol induces CYP2E1
 • Chronic users tend to have increased ethanol 
    metabolism
 Pharmacodynamic
 • Down-regulation of GABA receptors
 • Up-regulation of NMDA receptors
 •Withdrawal
 Cross tolerance to Benzodiazepines and barbiturates

Question 3

Alcohol - MoA

Answer 3

 Alcohol is a CNS depressant
 Binds to GABAa receptor to increase Cl- influx and
enhance inhibitory GABA transmission
 Increases DA in mesolimbic pathway
 Long-term chronic use will down-regulate GABA
receptors
 Alcohol also inhibits the effect of glutamate on the
NMDA receptor
 Long-term use causes up-regulation of NMDA receptors

Question 4

Effects of Alcohol on the CNS

Answer 4

 Low concentrations: disinhibition, decreased anxiety,
mild euphoria, confidence increases, memory,
concentration is affected, mood swings
 Increased dose: motor function and judgment are
impaired, speech slurs, and ataxia may occur
 CNS depressant and sedative properties become
apparent
 Anterograde amnesia (blackouts) - blockade of NMDA
receptors

Question 5

Effects of Alcohol on Smooth Muscle

Answer 5

 Ethanol is a vasodilator (due to acetaldehyde
metabolite)
 Can lead to hypothermia
 Relaxes the uterus, and has been used to prevent
premature labor

Question 6

Effects of Alcohol on the Heart

Answer 6

Depression of myocardial contractility

Question 7

Effects of Alcohol on the Kidney

Answer 7

Decreases antidiuretic hormone thus producing a diuretic effect

Question 8

Effects of Chronic Abuse - Malnutrition

Answer 8

• Deficiencies in folate and thiamine
• Skeletal muscle atrophy
• Hypothermia

Question 9

Effects of Chronic Abuse - Malnutrition

Answer 9

deficiencies in folate and thiamine

Question 10

Effects of Chronic Abuse - CNS

Answer 10

• Wernicke-Korsakoff syndrome - paralysis of eye
muscles, ataxia, confusion, coma and death; due to
thiamine deficiency
• Korsakoff’s psychosis - chronic disabling memory loss
• Peripheral neuropathy

Question 11

Effects of Chronic Abuse - Cardiovascular

Answer 11

• Cardiomyopathy - due to direct toxic effects of
acetaldehyde
• Arrhythmias - binges can lead to atrial and ventricular
• Hypertension - may cause severe increases in blood
pressure
• Increased risk of stroke; coronary heart disease
• Mild anemia

Question 12

Effects of Chronic Abuse - Carcinogenicity

Answer 12

increases the carcinogenicity of tobacco

Question 13

Effects of Chronic Abuse - Sexual dysfunction

Answer 13

Testicular atrophy, impotence, and gynecomastia

Question 14

Effects of Chronic Abuse - Immune System

Answer 14

Respiratory infections

Question 15

Effects of Chronic Abuse - Teratogenicity

Answer 15

• Fetal alcohol syndrome is characterized by
microcephaly, mental retardation, poor coordination,
flattened face, joint abnormalities, heart defects, and
impaired immune system.

Question 16

Alcohol/Drug Interactions

Answer 16

 Acetaminophen - possible liver damage
 Phenytoin, oral hypoglycemics
• Chronic alcohol use may increase metabolism
 Benzodiazepines, barbiturates, phenothiazines,
tricyclic antidepressants (TCAs)
• Acute use may inhibit breakdown
• Increase CNS depression – superadditive effects

Question 17

Naltrexone (ReVia®)

Answer 17

 Opioid receptor antagonist
 Blocks the ability of alcohol to stimulate the reward
pathway
 Reduces craving; Decreases the rate of relapse by
50%
 Large doses may cause liver damage; do not use in
patients with liver failure

Question 18

Acamprosate (Campral EC®)

Answer 18

 Structural analogue of GABA
 Balance between GABA and glutamate is disturbed
 Restores the normal balance of GABA and glutamate  Decreases craving and likelihood of relapse
 Excreted by the kidneys. No liver toxicity

Question 19

Disulfiram (Antabuse®)

Answer 19

 Inhibits aldehyde dehydrogenase
 Acetyldehyde builds up - causes flushing, headache,
nausea, confusion
 Long duration of action
 Effects can be severe; vomiting, sweating, chest pain,
hypotension, vertigo, blurred vision and shock.
 Dangerous and not recommended

Question 20

Topiramate (Topamax)

Answer 20

 Anticonvulsant drug
 Decreases craving and increase abstinence in
recovering alcoholics
 The mechanism is not understood

Question 21

Alcohol Withdrawal

Answer 21

 Mild withdrawal - anxiety, irritability,
insomnia, nausea, tachycardia
 Severe withdrawal - hallucinations,
delirium and tremors (DT’s), seizures,
arrhythmias, hypotension.

Question 22

Alcohol Withdrawal Treatment

Answer 22

Restore electrolyte imbalances - hydration

• Diazepam (Valium®); Chlordiazepoxide(Librium®) - Used
to prevent seizures and DTs, tapers symptoms

• Lorazepam (Ativan®) - Used to treat seizures

•Phenytoin (Dilantin®) - Secondary drug used to treat
seizures