Sedatives/Hypnotics

Question 1

Diazepam

Answer 1

Class: Benzodiazepine

Mech: GABAa agonist; binds between a1 and y2 subunits; half-life of 43 hours (active metabolites up to 100 hours)

Thera: Short-term depression treatment; maintenance of bipolar; severe bipolar; anticonvulsant; muscle relaxant

Tox: Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use)

Misc: “Ceiling effect” due to augmenting action of GABA

Question 2

Chlordiazepoxide

Answer 2

Class: Benzodiazepine

Mech: GABAa agonist; binds between a1 and y2 subunits; half-life of 10 hours (active metabolites up to 100 hours)

Thera: Short-term depression treatment; maintenance of bipolar; severe bipolar

Tox: Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use)

Misc: “Ceiling effect” due to augmenting action of GABA

Question 3

Lorazepam (Ativan)

Answer 3

Class: Benzodiazepine

Mech: GABAa agonist; binds between a1 and y2 subunits; half-life of 14 hours

Thera: Short-term depression treatment; maintenance of bipolar; severe bipolar; sedation; anticonvulsant; prevent withdrawal symptoms in alcoholics

Tox: Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use)

Misc: “Ceiling effect” due to augmenting action of GABA; directly conjugated into inactive metabolite

Question 4

Flurazepam (Dalmane)

Answer 4

Class: Benzodiazepine

Mech: GABAa agonist; binds between a1 and y2 subunits; half-life of 74 hours (active metabolites up to 100 hours)

Thera: Short-term depression treatment; maintenance of bipolar; severe bipolar

Tox: Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use)

Misc: “Ceiling effect” due to augmenting action of GABA

Question 5

Alprazolam (Xanax)

Answer 5

Class: Benzodiazepine

Mech: GABAa agonist; binds between a1 and y2 subunits; half-life of 12 hours

Thera: Short-term depression treatment; maintenance of bipolar; severe bipolar; sedation

Tox: Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use)

Misc: “Ceiling effect” due to augmenting action of GABA

Question 6

Midazolam (Versed)

Answer 6

Class: Benzodiazepine

Mech: GABAa agonist; binds between a1 and y2 subunits; half-life of 1.9 hours

Thera: Anesthesia (calming effects, production of anterograde amnesia)

Tox: Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use)

Misc: “Ceiling effect” due to augmenting action of GABA

Question 7

Triazolam (Halcion)

Answer 7

Class: Benzodiazepine

Mech: GABAa agonist; binds between a1 and y2 subunits; half-life of 2.9 hours

Thera: Short-term depression treatment; maintenance of bipolar; severe bipolar; induce sleep

Tox: Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use)

Misc: “Ceiling effect” due to augmenting action of GABA

Question 8

Zolpidem (Ambien)

Answer 8

Class: Non-benzodiazepine receptor agonist

Mech: BDZ-1 selective agonist

Thera: Sedation and hypnosis without muscle relaxation or anticonvulsant activity

Tox: Sleep-walking; next morning impairment

Question 9

Flumazenil

Answer 9

Class: Benzodiazepine antagonist

Mech: Competitive non-selective antagonist

Thera: Benzodiazapine overdose

Tox: Withdrawal (may be life-threatening); seizures in mixed overdoses

Misc: Non uniform in reversal of respiratory depression

Question 10

Thiopental

Answer 10

Class: Barbiturate

Mech: GABAa agonist (binds a or b subunit); highly lipid soluble, fast-on, fast-off

Thera: Induce anesthesia

Tox: Daytime sedation and drowsiness, dose-dependent depression of CNS, pyschologic and physiologic dependence (chronic use)

Misc: Abrupt withdrawal life-threatening; redistribute from brain to muscle and fat, metabolized by liver; dosed based on lean body mass

Question 11

Phenobarbital

Answer 11

Class: Barbiturate

Mech: GABAa agonist (binds a or b subunit)

Thera: Antiepileptic, anticonvulsant

Tox: Daytime sedation and drowsiness, dose-dependent depression of CNS, pyschologic and physiologic dependence (chronic use)

MIsc: Abrupt withdrawal life-threatening

Question 12

Buspirone (Buspar)

Answer 12

Class: N/A

Mech: No GABAa interaction; may be partial agonist at 5HT1A

Thera: Anxiolytic without marked sedation