Pharm: Sedative Hypnotics

Question 1

How do benzodiazepines distribute through the body and how are they metabolized?

Answer 1

• Widely distributed throughout body: CNS, placenta, breast-milk
• Hepatic metabolism (CYP3A4) and excretion via kidney

Question 2

What are the benefits of using benzodiazepines for anxiety states?

Answer 2

• High therapeutic index; antagonist available for OD (flumazenil)
• Low-risk of drug-drug interactions
• Minimal effect of cardiovascular or autonomic function

Question 3

Which benzodiazepine has the fastest rate of onset?

Answer 3

Diazepam

Question 4

How does Diazepam differ from Alprazolam in terms of half-life, active metabolites and rate of onset?

Answer 4

• Diazepam: long half-life (>100 hr); has active metabolite; very fast onset
• Alprazolam: short half-life (12-15); no active metabolite; fast onset

Question 5

Which benzodiazepine has a short half-life (5-14 hr), no active metabolite, and the slowest rate of onset?

Answer 5

Oxazepam

Question 6

Which 2 benzodiazepines have the shortest half-lifes?

Answer 6

Triazolam and Midazolam

Question 7

Which 4 benzodiazepines have the longest half-lives all >100 hr and all have active metabolites?

Answer 7

• Chlordiazepoxide
• Clorazepate
• Diazepam
• Flurazepam

Question 8

List 5 benzodiazepines that are short to intermediate acting?

Answer 8

• Alprazolam
• Temazepam
• Triazolam
• Oxazepam
• Midazolam

Question 9

What is the effect of barbituates on CYP450 enzymes?

Answer 9

Can induce CYP450 enzymes

Question 10

What is the prototype ultra-short acting barbituate used in anesthesia?

Answer 10

Thiopental

Question 11

What is the prototype short-acting barbituate that is used for insomnia?

Answer 11

Secobarbital

Question 12

What is the prototype long-acting barbituate that is used for seizures?

Answer 12

Phenobarbital

Question 13

What are 3 of the newer sedative hypnotics that are used as sleep aids?

Answer 13

• Eszopiclone (Lunesta)
• Zolpidem (Ambien)
• Zaleplon (Sonata)

Question 14

Which newer sedative hypnotic has the advantage of coming in a biphasic release formulation for sustained sleep maintenance?

Answer 14

Zolpidem (Ambien)

Question 15

Which newer sedative hypnotic has the longest half-life?

Answer 15

Eszopiclone (Lunesta)

Question 16

What are 4 AE’s associated with the sedative drug, Ramelteon?

Answer 16

• Dizziness
• Somnolence
• Fatigue
• Endocrine changes –> ↓ testosterone and ↑ prolactin

Question 17

What is Buspirone used for and what must you keep in mind when prescribing this drug?

Answer 17

• Approved for tx of generalized anxiety disorder
• Anxiolytic effects may take more than a week to become established (less effective in acute panic disorders)

Question 18

What are CIs of Alprazolam?

Answer 18

acute narrow angle glaucoma

HS rxn

Question 19

What is the Black Box Warning of Midazolam?

Answer 19

respiratory depression/arrest

use: pre-op sedation/anxioysis/amnesia

Question 20

CIs of Diazepam

Answer 20

HS

pts under 6 y/o

MG

severe respiratory insufficiency

severe hepatic insufficiency

sleep apnea syndrome

acute narrow angle glaucoma

Question 21

What benzo can aid in insomnia with difficulty falling asleep, frequent awakenings, and/or early morning awakenings?

Answer 21

flurazepam

Question 22

What are the indications, and CIs of secobarbital?

Answer 22

indications - short term tx of insomnia

CIs - HS, hx of manifest or latent porphyria, marked impairment of liver function, respiratory disease with dyspnea or obstruction

Question 23

What tx for insomnia due to difficulties with sleep initiation can also worsen depression or inc suicidal thinking?

Answer 23

zolpidem