Anxiolytics

Question 1

Mechanism of sedative-hypnotic agents

Answer 1

facilitates GABA binding its own receptor –> open Cl channel –> hyperpolarization –> diminished neuronal excitability and neurotransmission

Question 2

alpha 1 GABA subunits

Answer 2

located in cortex –> sleep

Question 3

alpha2/alpha5 GABA subunits

Answer 3

located in limbic system –> myorelaxant, motor impairment, anxiolytic, ETOH-potentiating effect of benzodiazepines

Question 4

Benzodiazepines

Answer 4

intensify effect of GABA; no effect on glutamate

Question 5

Can benzodiazepines maintain surgical anesthesia?

Answer 5

No! Need effect at glutamate and GABA

Question 6

Benzodiazepine receptor action

Answer 6

alpha1 and alpha2/alpha5 –> sleep and anxiolysis. some anticonvulsant effect

Question 7

Barbiturates

Answer 7

prolong effect of GABA. High concentrations –> direct interaction with GABA receptor (no GABA reqd for effect)

Question 8

Can barbiturates maintain surgical anesthesia?

Answer 8

Yes! also depresses glutamate –> greater CNS depression –> full surgical anesthesia

Question 9

lower safety margin between benzodiazepines and barbiturates

Answer 9

barbiturates

Question 10

Non-benzodiazepines that interact with benzo binding site as agonists

Answer 10

“Z drugs” (zolpidem, eszopiclone, zalepon). Bind only a1 –> sleep without anxiolysis

Question 11

reverses CNS effects of benzodiazepines

Answer 11

Flumazenil = benzo binding site antagonist

Question 12

benzodiazepine absorption

Answer 12

IM faster onset than oral

Question 13

Rapid onset oral benzodiazepines

Answer 13

Diazepam, alprazolam, triazolam

Question 14

Slower onset oral benzodiazepines

Answer 14

Oxazepam, temazepam

Question 15

Recommended benzodiazepine for IM administration

Answer 15

lorazepam

Question 16

Benzodiazepine distribution

Answer 16

very lipid soluble –> CNS entry

Question 17

Benzodiazepine metabolism

Answer 17

hepatic
Phase I --> active metabolites (longer half-lives than parent compounds)
Phase II (glucuronidation) --> shorter half-lives

Urinary excretion

Question 18

Barbiturates effect on liver

Answer 18

inducer of CYP450

Question 19

Benzodiazepines requiring phase I metabolism

Answer 19

chlordiazepoxide, diazepam, prazepam, clorazepate, alprazolam, triazolam, flurazepam

Question 20

Which 2 benzos use phase I metabolism, but are rapidly conjugated?

Answer 20

Alprazolam and triazolam. short-lived effects

Question 21

Benzos that only require phase II metabolism

Answer 21

Lorazepam, oxazepam, temazepam. good choices for elderly with impaired phase I metabolism and patients with hepatic dysfunction

Question 22

Benzo side effects seen with high doses or long/intermediate half-life drugs

Answer 22

sedation and performance impairment

Question 23

Benzo drug-drug interactions

Answer 23

additive depressant effects with other CNS depressants

Question 24

why are benzos contraindicated for use in chronic anxiety?

Answer 24

abuse potential

Question 25

Black box warning for benzos

Answer 25

strange sleep behavior, severe anaphylaxis, exacerbated breathing problems with chronic pulmonary disease and symptomatic sleep apnea

Question 26

Why are barbiturates not used in treatment of anxiety?

Answer 26

rapid tolerance, high abuse potential, overdose is lethal, leads to excessive sedation, DDIs

Question 27

Unique pharmacodynamics of buspirone

Answer 27

5HT1A partial agonist (not a benzo), presynaptic on nerve terminal
No sedation, anticonvulsant or myorelaxant action

Question 28

Buspirone use

Answer 28

chronic anxiety (4-6wk for max effect)