Sleep Physiology and pharmacotherapy

Question 1

Benzos and non-benzo receptor agonists’ mechanism of action

Answer 1

facilitate GABA at GABAa receptor-chloride channel complex –> membrane hyperpolarization

Question 2

Triazolam pharmacokinetics

Answer 2

1.5-5h half-life, less daytime sedation (hangover). Rapid elimination –> rebound insomnia the next day. rapid absorption

Question 3

Temazepam pharmacokinetics

Answer 3

9-13h half-life. slow absorption. peak effect at 2-3h

Question 4

Flurazepam pharmacokinetics

Answer 4

75-90h half-life. little tolerance. Hepatic clearance (can accumulate in elderly –> daytime sedation, hangover, OD)

Question 5

Zolpidem and zaleplon pharmacokinetics

Answer 5

6-8h duration. rapid oral absorption

Question 6

Eszopiclone (Lunesta) pharmacokinetics

Answer 6

longer half-life than zolpidem and zapelon

Question 7

First line in tx of insomnia

Answer 7

Z drugs. Little effect on sleep stages III and IV

Question 8

Zolpidem role in insomnia tx

Answer 8

reduces sleep latency and nocturnal awakenings –> increased total sleep time and efficiency

Question 9

Zaleplon role in insomnia tx

Answer 9

decreases time to sleep onset, no effect on awakening or total sleep time. Used for patients who fall asleep without sleep aid, but wake up in middle of night.

Question 10

Eszopiclone role in insomnia tx

Answer 10

safest for long-term use

Question 11

Benzo role in insomnia tx

Answer 11

declining use. cheaper than Z drugs. short-term tx of insomnia

Question 12

trazodone side effects

Answer 12

oversedation and orthostasis (alpha adrenergic block)

Question 13

TCAD side effects

Answer 13

antimuscarinic and antiadrenergic activity

Question 14

Ramelteon

Answer 14

melatonin agonist –> induce sleepiness, regulates circadian rhythms

ADRs: dizziness, somnolence, fatigue, nausea

Question 15

Antihistamines

Answer 15

H1 and muscarinic cholinergic antagonist

Question 16

Black box warning for benzos and Z drugs

Answer 16

strange sleep-related behavior, anaphylaxis, facial swelling

Question 17

Benzo side effects

Answer 17

daytime sedation and performance impairment, anterograde amnesia, rebound insomnia, psych and physical dependence

Question 18

Zolpidem side effects

Answer 18

dorwsiness, amnesia, dizziness, headache, GI complaints

Question 19

Zaleplon side effects

Answer 19

dizziness, headache, sonolence

Question 20

Eszopiclone side effects

Answer 20

similar to zolpidem. increased incidence of psychomotor impairment with higher doses

Question 21

Sleep periods at birth

Answer 21

shorter. Consolidate with age

Question 22

Non-REM sleep

Answer 22

stage 1-3. high amplitude, slow brain waves. increased arousal threshold, decreased muscle activity, slow rolling eye movements, decreased heart rate, decreased respirations and metabolism

Question 23

REM sleep

Answer 23

every 90 minutes in adults. EEG similar to awake. Higher arousal threshold than slow-wave sleep. “Active brain in paralyzed body”. 85% of dreams

Question 24

sleep/wake switch

Answer 24

hypothalamus

Question 25

circadian clock. modulates core temp, alertness, cortisol and melatonin secretion

Answer 25

suprachiasmatic nucleus

Question 26

ascending cortical activation and REM/SWS switch

Answer 26

brainstem

Question 27

spindles, slow wave sleep

Answer 27

thalamus

Question 28

inhibit arousal systems during NREM sleep

Answer 28

neurons of ventrolateral preoptic area (GABA and galanin)

Question 29

Drive REM sleep

Answer 29

cholinergic pedunculopontine and laterodorsal tegmental (PPT/LDT) neurons. Inhibited by catecholamines during wake and NREM sleep

Question 30

Neurotransmitters active during wake

Answer 30

Ach in LDT/PPT, serotonin (raphe nucleus), NE (locus ceruleus), histamine (Tubomammillary nucleus), dopamine (VTA/SNc), adenosine (basal forebrain), hypocretin (lateral hypothalamus)

Question 31

Neurotransmitters active during NREM

Answer 31

GABA, galanine (ventrolateral preoptic nucleus), melatonin (pineal gland, SCN, hypothalamus)

Question 32

Neurotransmitters active during REM

Answer 32

Ach (LDT/PPT), DA (VTA/SNc)

Question 33

Homeostatic S drive

Answer 33

the longer we are awake, the sleepier we get. Mediated by adenosine. blocked by caffeine

Question 34

Circadian (C) alerting system

Answer 34

waxing/waning of sleepiness. resides in SCN, linked to core body temp

Question 35

Best sleep

Answer 35

descending curve of core body temp

Question 36

What happens when you stay up 72h?

Answer 36

sleepiness waxes and wanes due to C system

Question 37

Melatonin activity

Answer 37

Light --> SCN --> inhibits pineal gland production of melatonin Dark --> reduced SCN firing --> disinhibition of pineal gland --> melatonin production

Question 38

Evolution of insomnia

Answer 38

3 Ps: Predisposed person (worrier), Precipitant (stress), Perpetuating factors (sleep worry)

Question 39

Two categories of insomnia

Answer 39

Learned and co-morbid