Alcohol

Question 1

lorazepam

Answer 1

Class: Benzodiazepine (BZD), GABA modulator, anti-anxiety agent.
• Action: 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.
• Kinetics: Absorbed rapidly (90%) and metabolized by the liver. Excreted in urine.
Peak onset 1-2 hrs; half-life 10-20 hrs
• Advantages: 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
• Disadvantages: Short-acting means more frequent doses: every hour initially;
possibility of BZD-withdrawal seizure
• Dose in AWS: Symptom-triggered: dosing based on clinical withdrawal scale
(CIWA). Fixed dosing: 1-4mg every 1-4 hrs depending on severity of withdrawal

Question 2

chlordiazepoxide

Answer 2

Class: Benzodiazepine, GABA modulator, anti-anxiety agent.
• Action: 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.
• Kinetics: 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
• Advantages: Original BZD: side effects and interactions well-known after decades
of use. “Auto-taper”. Most physicians familiar with drug.
• Disadvantages: 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. Cognitive effects can persist
for days, even weeks. Numerous drug interactions.
• Dose in AWS: Symptom-triggered: dosing 25-100 mg q 2-4 hrs based on clinical
withdrawal scale (CIWA). Fixed dosing: 25-100 mg every 4-8 hrs depending on
severity of withdrawal anticipated

Question 3

Gabapentin

Answer 3

• Class: GABA analogue; anticonvulsant.
• Action: Exact mechanism of action unknown; interacts with voltage-gated calcium
channels
• Kinetics: Absorbed rapidly, 27-60% bioavailability, peak 2hrs, increased rate and
extent with food
• Advantages: Non-addictive, less sedating and cognitively impairing, less concern
about abuse, less immediate relapse to alcohol, effective in treatment of
protracted withdrawal symptoms (next slide)
• Disadvantages: “Off-label” (no FDA approval for this indication). Not reliable
preventing complications (DT’s, seizures) of severe withdrawal in high-risk
patients; use in treatment of outpatient-level patients only
• Dose in AWS (outpatient only): 300-600 mg po tid-qid

Question 4

thiamine

Answer 4

Class: Vitamin.
• Action: 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
• Kinetics: Absorbed from the GI tract. Metabolized by the liver. Elimination is renal,
the majority being metabolites.
• Adverse Drug Reaction (ADR): Thiamine is not associated with toxicity.
Hypersensitivity reactions after injection may accour. Some tenderness or muscle
soreness may result after IM injection.
• Interactions: Thiamine may enhance the activity of neuromuscular blocking
agents; clinical significance is unknown.
• Dose: Prophylaxis: After the initial IV dose of 100 mg, continue daily doses of
thiamine (100 mg) as IV, IM, or oral doses depending on patient status, x 30d.
• Treatment of Wernicke/korsakoff: 500mg IV TID x 3 days, then 200mg IV qd

Question 5

Naltrexone

Answer 5

• Action: potent opioid antagonist
• Advantages:
– Once daily dosing (or monthly IM)
– FDA-approved: greatest body of evidence
– No longer carries hepatic black-box warning
• Disadvantages:
– Opioid blockade
• Difficulty with acute injury or emergency surgery
• Especially challenging with IM form
– May worsen depression/suicidality

Question 6

Acamprosate

Answer 6

• Action: NMDA/GABA modulator
• Advantages:
– Favorable side effect and safety profile
• No drug-drug interactions
– FDA-approved
• Disadvantages:
– Least powerful effect
– TID dosing

Question 7

Disulfiram

Answer 7

Action: ALDH inhibitor
Advantages:
– Strong deterrent effect promotes abstinence
– FDA-approved
• Disadvantages:
– Works best with witnessed dosing
• Couples
• Criminal justice system
– ETOH/disulfiram rxn: severe: avoid in elderly, CAD
– Side effect profile; safety and monitoring