anxiolytic agents

Question 1

List drug categories used in treatment of anxiety

Answer 1

1. Antidepressants [SSRIs - SNRIs]: 1st line agents for most anxiety disorders. 2. Benzodiazepines: Declining use due to abuse potential - used in acute and situational anxiety. 3. Buspirone: Weaker anxiolytic effect than benzodiazepines, but fewer side effects. 4. Barbiturates: Rarely used for anxiety - low safety margin - drug interactions - high abuse potential

Question 2

benzodiazepines and barbituates MOAs

Answer 2

Produce graded dose-dependent CNS depressant effects (sedation and hypnotic) Distinct mechanism of depressant action: augment GABA inhibition and/or inhibit glutamate excitation

Question 3

what do sedative drugs do

Answer 3

decrease activity, moderate excitement, and calm the recipient

Question 4

what do hypnotic drugs do

Answer 4

Produce drowsiness and facilitate the onset and maintenance of sleep. Resembles natural sleep and from which the recipient can be easily aroused

Question 5

barbiturates and benzodiazepines have what effects in therapeutic range

Answer 5

antianxiety, anticonvulsant, muscle relaxant, sedative, and hypnotic

Question 6

Barbiturates effects from doses above therapeutic range

Answer 6

leads to state of general anesthesia - can progress to depression of respiratory and vasomotor centers, ultimately resulting in coma and death

Question 7

Benzodiazepines effects from doses above therapeutic range

Answer 7

much greater dosage increments are required to achieve CNS depression more profound than hypnosis- greater margin of safety

Question 8

sedative-hypnotic drugs MOA

Answer 8

Indirectly increase GABAergic effect at the GABAa receptor-chloride channel complex. This results in membrane hyperpolarization that diminishes neuronal excitability and neurotransmission.

Question 9

What are Z drugs

Answer 9

Zolpidem - eszopiclone - zaleplon are non-benzodiazepines that interact with the benzodiazepine binding site as agonists and result in sleep without anxiolysis

Question 10

What drug reverses the CNS effects of benzodiazepines

Answer 10

flumazenil- antagonist at benzo binding site

Question 11

GABA receptor subunits and functions/locations

Answer 11

alpha1 subunits: in cortex, mediate sedative, amnesia, action of benzos. Alpha2/5 subunits: in limbic system and brain stem, mediate anxiolytic, tolerance, addiction effects of benzos

Question 12

Which sedative-hypnotics are capable of inducing/maintaining surgical anesthesia

Answer 12

Short-acting barbiturates, NOT benzos

Question 13

which drug is used for status epilepticus

Answer 13

diazepam- anticonvulsant effects

Question 14

List benzodiazepines

Answer 14

Diazepam - Alprazolam - Lorazepam - Oxazepam - Flumazenil - Midazolam

Question 15

list barbiturates

Answer 15

Pentobarbital - Phenobarbital

Question 16

Compare absorption of different benzodiazepines

Answer 16

Diazepam, alprazolam, and triazolam have rapid oral absorption. • Lorazepam has consistent and reliable intramuscular absorption

Question 17

benzodiazepine elimination

Answer 17

Most benzodiazepines undergo CYP450 oxidations (phase I [N-dealkylation and aliphatic hydroxylation]) with subsequent inactivation via conjugation by glucuronidation (phase II), then elimination in the urine

Question 18

Which benzos have long vs short half lives

Answer 18

diazepam, chlordiazepoxide, flurazepam has phase 1 metabolites which are active with long half lives. Alprazolam and triazolam are metabolized to active metabolites, but these are rapidly conjugated so their effects are short-lived. • Lorazepam and oxazepam (and temazepam) are metabolized directly to the inactive glucuronides (NO P450 step) and as a result have shorter half-lives

Question 19

Which benzos are best for elderly

Answer 19

Lorazepam and oxazepam (and temazepam) are good choices for use in the elderly with impaired phase I metabolic pathways and in patients with hepatic dysfunction, b/c they are metabolized to inactive compounds

Question 20

barbiturates drug interactions

Answer 20

Barbiturates are classic inducers of CYP450 enzymes and represent a major source of clinically significant drug interactions that has contributed to their declining use

Question 21

benzodiazepines adverse reactions

Answer 21

can exacerbate breathing problems in pts with COPD and sleep apnea, daytime sedation, anterograde amnesia (beneficial for uncomfortable procedures), pscyhologic and psyiologic dependence

Question 22

Can flumazenil be used in barbiturate or ethanol toxicity

Answer 22

no- only useful to reverse benzo effects

Question 23

acute management of anxiety

Answer 23

Benzodiazepines (alprazolam, clonazepam are best b/c high potency)

Question 24

Function of buspirone

Answer 24

alternative anxiolytic- 5HT1A partial agonist. NO sedation, anticonvulsant or myorelaxant action.