Anxiolytics

Question 1

Alprazolam

-Benzodiazepine

Answer 1

Mechanism:

Bind to allosteric site on the GABA-A receptor to enhance action of GABA by increasing frequency of Cl- channel openings upon stimulation

use: - Anxiolytic
- Sedative – induction & maintenance of anesthesia
- Tx of acute EtOH withdrawal (anticonvulsant)

Toxicity:

• Sedation
• Lightheadedness
• ↑ total sleep time & ↓ latency (but ↓ REM)
• Psychomotor - ataxia & lethargy
• Muscle relaxation
• Anterograde amnesia

Metabolism:

• Metabolized by CYP3A4
• Intermediate time to onset of action
• Intermediate half-life

Interaction:

• Pregnancy category D – teratogenic during 1st trimester, causes cleft palate
• CI: grapefruit juice – inhibits CYP3A4
• Overdose when taken with other CNS depressants (e.g. alcohol)
• Withdrawal sx: insomnia, N&V, twitching, sweating, muscle camps, irritability; hence withdraw drug over a period of weeks

Question 2

Diazepam

-Benzodiazepine

Answer 2

Mechanism:

Bind to allosteric site on the GABA-A receptor to enhance action of GABA by increasing frequency of Cl- channel openings upon stimulation

Use:

• Anxiolytic
• Sedation – induction & maintenance of anesthesia
• Tx of acute EtOH withdrawal (anticonvulsant)
• Status epilepticus
• Muscle relaxant at doses that don’t induce sedation

Toxicity:

• Sedation
• Lightheadedness
• ↑ total sleep time & ↓ latency (but ↓ REM)
• Psychomotor - ataxia & lethargy
• Muscle relaxation
• Anterograde amnesia

Metabolism:

• Metabolized by CYP3A4
• Intermediate time to onset of action
• Intermediate half-life

Interaction:

• Pregnancy category D – teratogenic during 1st trimester, causes cleft palate
• CI: grapefruit juice – inhibits CYP3A4
• Overdose when taken with other CNS depressants (e.g. alcohol)
• Withdrawal sx: insomnia, N&V, twitching, sweating, muscle camps, irritability; hence withdraw drug over a period of weeks

Question 3

Buspirone

non-benzodiazepine anxiolytic

Answer 3

Mechanism:
Partial agonist at 5-HT-1A receptors & DA receptor

Use: Anxiolytic – for long term use (GAD)

Toxicity: * No known potential for abuse
- Dizziness, drowsiness, HA, nervousness, nausea (not bolded)

Metabolism:
Must be taken consistently for 2+ weeks to achieve effect (not for acute use)

Question 4

Propanolol

non-benzodiazepine anxiolytic

Answer 4

Mechanism: β-blocker – suppresses somatic & autonomic symptoms of anxiety

Use: Performance anxiety
Migraine prevention

Metabolism: No effect on emotional symptoms of anxiety

Question 5

Flumazenil

-benzodiazepine receptor antagonist

Answer 5

Mechanism:
Competitive antagonist at the benzodiazepine binding site (allosteric) on GABA-A receptor

Use:

• Reduce sedative effects of benzo’s after anesthesia
• Sedation for brief surgical procedure
• use prior to ECT to decrease seizure threshold
• Tx overdose

Toxicity: 
- Nausea
- Dizziness, HA, blurred vision
- Sweating & anxiety
- Panic attacks
(these were not bolded)

Metabolism:

• Administered IV – activity w/in 1-2 min.
• Short half life ~ 1 hr.

Interaction:
CI: May precipitate convulsions in people who are physically dependent on benzodiazepines & in pts maintained on benzo’s for seizure disorders