Exam 2: Hypnotics

Question 1

BZD MOA

Answer 1

bind to GABAa receptors, allosteric site

Question 2

BZD AE overview (4)

Answer 2

1. daytime sedation
2. psychomotor impairment
3. cognitive deficits
4. anterograde amnesia

Question 3

BZD cautions (10)

Answer 3

1. older adults
2. tolerance and dependence within 4-6 weeks of use
3. withdrawal
4. rebound insomnia
5. AVOID IN HX OF DRUG USE
6. AVOID W/ ALCOHOL USE OR OPIOD USE
7. BOXED WARNING W OPIODS
8. AVOID IN SLEEP APNEA
9. AVOID IN PREGNANCY
10. can worsen depression, PTSD, suicidal ideation

Question 4

BZD drugs (2)

Answer 4

1. tamezepam
   - 7.5-50mg dose
   - sleep onset/maintenance
   - slow onset
2. Triazolam
   - 0.125-0.25 mg
   - rapid onset
   - sleep onset use

Question 5

BZE Adverse Effects (7)

Answer 5

1. CNS depression
   - sedation
   - respiratory depression
2. psychomotor impairment
   - ataxia
   - falls in elderly
3. Confusion
4. Agression
5. Disinhibition
6. Amnesia
   - anterograde
   - retrograde
7. Dependence and abuse

Question 6

Non-BZD Receptor Agonist

Z-Drugs

MOA

Answer 6

Bind to GABAa receptor, allosteric site

-more selective subunits

Question 7

Z-drugs

Adverse effects (4)

Answer 7

1. Daytime sedation
2. cognitive deficits
3. amnesia
4. complex sleep behaviors

Question 8

Z-drugs

Cautions (6)

Answer 8

1. older adults
2. tolerance and rebound insomnia < BZDs
3. rx for significant withdrawal
4. AVOID concomitant CNS depressants, including alcohol and opioids
5. can worsen depression, suicidal ideation
6. BOXED WARNING:
   April 2019
   -serious injuries or death in 66 patients, caused by parasomnias

Question 9

Z-Drug pearls (1)

Answer 9

Rapid onset; food delays by 1-2 hours

Question 10

Melatonin Agonist

MOA (1)

Answer 10

1. melatonin analogue; binds melatonin 1 & 2 receptors (hypothalamus)

Question 11

Melatonin Agonist Sleep Benefits (3)

Answer 11

1. Regulates circadian rhythms (phase shifting)
2. direct effect on decreasing sleep latency
3. no effect on sleep maintenance

Question 12

Melatonin Agonist AE (4)

Answer 12

1. HA
2. Dizziness
3. daytime somnolence
4. GI upset

Question 13

Melatonin Agonist Caution (2)

Answer 13

1. may increase prolactin level in men & women

2. decreased testosterone levels in men

Question 14

Melatonin Agonist Pearls (5)

Answer 14

1. SAFE in sleep apnea, COPD, hx of substance use disorder
2. may require 3 weeks of nightly use for maximum effect on sleep onset
3. high-fat meal decreased effectiveness
4. affected by CYP1A2 and CYP3A4 inhibition/induction
5. brand-only $$$

Question 15

Orexin Agonist MOA

Answer 15

Antagonism or orexin receptor 1 and 2 in the hypothalamus

-when activated they promote waking

Question 16

Orexin Agonist Adverse Effects (7)

Answer 16

1. daytime solomnce
2. sleep paralysis
3. cataplexy
4. abnormal thinking
5. hallucination
6. CNS depression
7. sleep-related activities

Question 17

Cautions Orexin Agonist (4)

Answer 17

1. potential to worse depression/suicidal ideation
2. CONTRAINDICATED IN NARCOLEPSY
3. Potential for abuse,
   AVOID USE IN ALCOHOL
4. AVOID USE WITH STRONG CYP3A 4 inhibitors

Question 18

Orexin Agonist Pearls

Answer 18

1. onset delayed with food
2. plan for 7 hours of sleep time
3. brand-only $$$

Question 19

Antidepressants MOA (3)

Answer 19

1. Histamine H antagonism, “selective” at low doses
2. serotonin 5HT2c antagonism
3. Alpha-1 blockade (trazodone)

Question 20

Antidepressants benefits/effect on sleep (3)

Answer 20

1. primarily sleep maintenance
2. not dependence, minimal tolerance
3. not well studied in patients without depression

Question 21

Antidepressants cautions (4)

Answer 21

1. side effects vary widely between medications
2. daytime somnolence/sedation is a possible side effect of each of the agents commonly used for sleep
3. sedative effect within 1-2 weeks
4. insomnia doses generally not effective for treatment of depression

Question 22

Antihistamines MOA

Answer 22

1. histamine H1 antagonism

Question 23

Antihistamines benefits

Answer 23

may be effective for transient insomnia; latency and maintenance

Question 24

Cautions Antihistamines (4)

Answer 24

1. Tolerance to hypnotic effect; after 10 days
2. increased dose does not equal increased response
3. anticholinergic; CNS depression, next-day residual effects
4. AVOID: narrow-angle glaucoma, acute asthma, urinary obstruction

Question 25

Pearls Antihistamines (2)

Answer 25

1. in a variety OTC products | 2. some combo products contain antihistamines

Question 26

Melatonin OTC MOA

Answer 26

1. M1, M2, M3 receptors

Question 27

Melatonin OTC Side effects

Answer 27

minimal, some daytime somnolence

Question 28

Valerian OTC MOA

Answer 28

increases GABA

Question 29

Valerican OTC SE

Answer 29

minimal, some diarrhea

Question 30

Kava/chamomile/wuling MOA

Answer 30

*possible effects on GABA, 5HT, or glutamate

Question 31

Kava/chamomile/wuline AE

Answer 31

hapatotoxicity (KAVA) | -rest similar to placebo

Question 32

Gabapentin Role/ Risks

Answer 32

* not recommended 1. role: insomnia with consistent alcohol use disorder 2. Rx: Dizziness, N/V - mortality rx with opioids - Rx dependency and abuse

Question 33

Atypical Antipsychotics role/rx

Answer 33

* NOT recommended 1. quetiapine, olanzapine 2. Role: insomnia with schizophrenia, Bipolar, or depressive d/o 3. rx: - metabolic effects - movement d/o - anticholingeric - QTc prolongation - orthostatic hypotension - increased mortality in elderly patients with dementia-related psychosis