sedative hypnotics - dr austin

idk if we need to know

what is more efficacious?

a. midazolam (benzodiazepine)

b. pentobarbital (barbiturate)

b.

idk if we need to know

what is more potent?

a. midazolam (benzodiazepine)

b. pentobarbital (barbiturate)

a.

idk if we need to know

what is safer?

a. midazolam (benzodiazepine)

b. pentobarbital (barbiturate)

a.

what kind of insomnia lasts days to weeks?

a. transient

b. acute

c. chronic

a.

what kind of insomnia lasts weeks to months?

a. transient

b. acute

c. chronic

b.

what kind of insomnia lasts years?

a. transient

b. acute

c. chronic

c.

what kind of insomnia is difficulty falling asleep upon going to bed and is frequently associated with anxiety disorders?

a. onset insomnia

b. middle insomnia

c. late (terminal) insomnia

a.

what kind of insomnia is difficulty maintaining sleep; waking up during the night and is frequently associated with pain disorders?

a. onset insomnia

b. middle insomnia

c. late (terminal) insomnia

b.

what kind of insomnia is early morning waking and is frequently associated with depression disorders?

a. onset insomnia

b. middle insomnia

c. late (terminal) insomnia

c.

list psychological causes of insomnia

• anxiety

• depression

• psychosis

• behavioral patterns

• substance use/abuse

• stress

list physiological causes of insomnia

• cardiovascular

• endocrine

• autonomic disorders

• pain

• fatigue

• GERD

• apnea

• medications

what lifestyle change is recommended as nonpharm therapy?

reduce stress and anxiety

list ways to improve sleep hygiene

• minimize daytime napping

• eat meals on regular schedule

• practice relaxing behaviors at bedtime and go to bed around the same time nightly

• minimize use of electronic devices in bedroom

what substances should we avoid, especially near bedtime?

• caffeine

• alcohol

• nicotine

list pharm therapies for insomnia

• benzodiazepines

• benzodiazepine receptor agonists

• melatonin receptor agonist

• orexin antagonist

• barbiturates

  • only short term

• OTC/herbal therapies

  • antihistamines

  • lavender

  • melatonin

  • chamomile

  • valerian root

  • passionflower

can we use benzos in pregnancy?

no

idk if we need to know

how do benzos modulate sleep stage distribution?

increase length of stage 2 sleep

decrease length of stage 3, 4, and REM sleep

T/F benzos are not recommended long term

TRUE

benzodiazepines bind to __________ receptor between alpha and gamma subunits

GABA_A

what is the effect of benzodiazepines?

a. increase frequency of chloride channel opening

b. decrease frequency of chloride channel opening

c. increase frequency of sodium channel opening

d. decrease frequency of sodium channel opening

a.

benzodiazepines are weak positive ___________

a. allosteric agonists

b. allosteric antagonists

c. inverse agonists

a.

when does the chloride channel open more frequently?

when all 3 of the sites are bound (2 GABA, 1 BZD)

what are the contraindications of benzodiazepines?

• risks from concomitant use with opioids

• abuse, misuse, and addiction

• dependence and withdrawal reactions

• angle-closure/untreated glaucoma

• pregnancy/lactation

benzodiazepines can be extremely dangerous and sometimes fatal when combined with _______

CNS depressants

(ex: opioids)

what is the antagonist of GABA_A benzodiazepine site, given IV for overdose/anesthesia reversal?

flumazenil (romazicon)

what is the onset and half-life of flumazenil (romazicon)?

onset: 6-10 minutes

t_1/2: 40-80 minutes —> much shorter than agonists because of the ethyl ester

flumazenil (romazicon) is a benzodiazepine antagonist/reversal agent and may cause ________ (SATA)

a. respiratory depression

b. seizures

c. withdrawal

d. flushing

b. c.

ethanol also acts on the GABA_A receptor. should flumazenil be considered for a patient experiencing severe respiratory depression following excessive alcohol consumption?

NO — won’t block that site

which functional group of temazepam (restoril) allows it to undergo conjugation?

hydroxyl group

how is temazepam (restoril) metabolize? major vs minor

major: conjugation

minor: demethylation

which of the following is a benzodiazepine?

a. zolpidem (ambien)

b. zaleplon (sonata)

c. eszopiclone (lunesta)

d. temazepam (restoril)

d.

list the benzodiazepine receptor agonists

• zolpidem (ambien)

• zaleplon (sonata)

• eszopiclone (lunesta)

where do benzodiazepine receptor agonists bind?

GABA_A receptors — selectivity for alpha1 subunits

they require binding of GABA in order to exert effect

benzodiazepine receptor agonists are selective for alpha1 subunit containing GABA_A receptors, which REDUCES _________ effects

• anxiolytic

• antiepileptic

• muscle relaxant

benzodiazepine receptor agonists are selective for alpha1 subunit containing GABA_A receptors, which CONSERVES _________ effects

• sedative

• amnesic

T/F benzodiazepine receptor agonists maintain a risk of tolerance/dependence and are schedule IV controlled substances

TRUE

list the available formulations of zolpidem (ambien)

lowkey he said just to know that there’s multiple formulations available

• tablet

• sublingual CR (approved for terminal insomnia)

• oral spray

idk if we need to know

how is zolpidem (ambien) metabolized?

CYPs

• 3A4

• 2C9

• 1A2

what pregnancy category are the benzodiazepine receptor agonists?

a. Pregnancy A

b. Pregnancy B

c. Pregnancy C

d. Pregnancy D

c.

what benzodiazepine receptor agonist has the fastest onset and shortest half-life? hint: it’s the one that isn’t used for both falling asleep and staying asleep; ONLY for falling asleep

a. zolpidem (ambien)

b. zaleplon (sonata)

c. eszopiclone (lunesta)

b.

idk if we need to know

how is zaleplon (sonata) metabolized?

• CYP 3A4

• aldehyde oxidase

what benzodiazepine receptor agonist is an enantiomer of zopiclone (R or S)?

a. zolpidem (ambien)

b. zaleplon (sonata)

c. eszopiclone (lunesta)

c.

T/F the half life of eszopiclone (lunesta) is LONGER in elderly patients

TRUE - normal is 6 hours

idk if we need to know

how is eszopiclone (lunesta) metabolized?

CYPs

• 3A4

• 2E1

which benzodiazepine receptor agonists help you fall asleep and cause physical dependence? (SATA)

a. zolpidem

b. eszopiclone

c. zaleplon

a. b. c.

what benzodiazepine receptor agonists help you stay asleep and cause rebound insomnia (for sure)? (SATA)

a. zolpidem

b. zolpidem SL

c. zolpidem CR

d. zolpidem spray

e. eszopiclone

f. zaleplon

c. e.

what is melatonin’s role in the body?

• utilizes light-dark information from retina

• synchronizes sleep-wake cycle

• influences circadian rhythm

what dose of melatonin may cause drowsiness in 30 minutes, persisting for about 1 hour?

a. 1-2 mg

b. 2-4 mg

c. 3-5 mg

d. 5-10 mg

c.

list ADRs of melatonin

• next-day drowsiness

• nausea

• irritability

when may melatonin be useful?

• jet lag

• other meds failed/contraindicated

is melatonin an acid or base?

a. acid

b. base

apologies it’s a trick question

it’s neutral!!!! has an amide

what drug class is ramelteon (rozerem)?

a. benzodiazepine

b. benzodiazepine receptor agonist

c. melatonin receptor agonist

d. orexin receptor agonist

c.

rameleteon (rozerem) selectively binds ________ receptors is suprachiasmatic nucleus (SCN) in hypothalamus

a. GABA

b. MT1 and MT2

c. OX1 and OX2 receptors

b.

since ramelteon (rozerem) has no effect on GABA, what effects are NOT seen compared to benzodiazepine receptor agonists?

• no dependence/abuse potential

• not a scheduled drug

• no withdrawal or rebound insomnia

what drug is metabolized by CYP1A2, is not recommended in severe hepatic impairment, and is pregnancy category C?

ramelteon (rozerem)

list ADRs of ramelteon (rozerem)

• dizziness

• fatigue

• depression

idk if we need to know

what is the half life of ramelteon (rozerem)? what is the half-life of the active metabolite?

t_1/2: 1-3 hours

active metabolite: 2-5 hours

what drug blocks wake-promoting neuropeptides orexin A and orexin B by binding OX1 and OX2 receptors?

a. suvorexant (belsomra)

b. ramelteon (rozerem)

c. eszopiclone (lunesta)

d. temazepam (restoril)

a.

what drug is metabolized by CYP3A4, is not recommended in severe hepatic impairment, is pregnancy category C, and is schedule IV?

suvorexant (belsomra)

list ADRs of suvorexant (belsomra)

• drowsiness

• headache

• dizziness

• diarrhea

what is suvorexant (belsomra) contraindicated in?

a. narrow angle glaucoma

b. narcolepsy

c. seizures

d. depression

b.

what antihistamines are used for occasional sleeplessness/insomnia? (SATA)

a. doxylamine

b. diphenhydramine

c. promethazine

d. hydroxyzine

a. b.

what antihistamines are used for operative/situational sedation? (SATA)

a. doxylamine

b. diphenhydramine

c. promethazine

d. hydroxyzine

c. d.

T/F long-term medication-only therapy is recommended for treatment of insomnia

FALSE - long-term med-only is NOT recommended

practice

which statement correctly describes benzodiazepines?

a. structurally similar to GABA

b. structurally similar to glutamate

c. agonist at GABA binding site of GABA_A receptors

d. agonist at allosteric site of GABA_A receptors

d.