pharmacology of insomnia

Question 1

nonREM stages

Answer 1

• Stage 1: Transition phase, EEG like wakefulness.
• Stage 2: Light sleep; short, fragmented thoughts, EEG slower; 50% of total.• Stage 3 and 4 (delta): EEG very slow, deepest level of sleep (described as “best”); stage where somnambulism and night terrors can occur• Stage 1: Transition phase, EEG like wakefulness.
• Stage 2: Light sleep; short, fragmented thoughts, EEG slower; 50% of total.• Stage 3 and 4 (delta): EEG very slow, deepest level of sleep (described as “best”); stage where somnambulism and night terrors can occur

Question 2

How do sedative-hypnotic affect sleep

Answer 2

Decrease latency (promotes onset), increase stage 2 duration (promotes maintenance of sleep), decrease delta sleep (deleterious effect), decrease duration of REM (deleterious)

Question 3

sedative-hypnotics for sleep- tolerance

Answer 3

develops if used >1 week

Question 4

Ideal hypnotic agent characteristics

Answer 4

Rapidly induce sleep , Sufficient duration to maintain sleep, No tolerance development with repeated use, No rebound insomnia with abrupt d/c - influenced by t1/2, High therapeutic index, Normalize disturbed sleep without disturbing normal sleep

Question 5

Which agents are closes to idea hypnotic agents

Answer 5

Z drugs (zolpidem)

Question 6

Benzodiazepines MOA

Answer 6

bind to alpha subunit of GABA channel and intensify action of GABA. Result in slep and anxiolysis

Question 7

Z drugs MOA

Answer 7

bind to alpha1 subunit of GABA channel and intensify action of GABA. Structurally distinct from BDZs. Result in sleep only

Question 8

compare clinical relevance of GABA receptor subunits

Answer 8

alpha1 subunit is in the cortex, where it controls sleep, anticonvusions, amnesia and is bound by BDZs and Z drugs. Alpha 2-5 subunits are in the brain stem and limibc system, bound by BDZs, and have role in anxiolytic, myorelaxant,

Question 9

List benzodiazepines used for insomnia

Answer 9

triazolam, temazepam, flurazepam

Question 10

Triazolam pharmacokinetics

Answer 10

rapid oral absorption, short half life, less hangover, rebound insomnia occurs next day due to rapid elimination, dose reduction in elderly

Question 11

Temazepam pharmacokinetcs

Answer 11

slow absorption, intermediate half life

Question 12

Flurazepam pharmacokinetics

Answer 12

long half life and active metabolites, can accumulate in elderly with impaired hepatic clearance leading to daytime sedation (hangover) or overdose

Question 13

List Z drugs used in insomnia

Answer 13

zolpidem (ambien), zaleplon, and eszopiclone (lunesta)

Question 14

compare pharmacokinetics of the Z drugs

Answer 14

zolpidem (ambien) and zaleplon have short half lives. eszopiclone (lunesta) has longer half life

Question 15

Benzodiazepines side effects

Answer 15

daytime sedation, anterograde amnesia (trizolam > temazepam), rebound insomnia, psychologic and physiologic dependence

Question 16

Z drugs side effects

Answer 16

Tolerance/dependence/withdrawal possible (schedul IV), rebound effects ( more common with eszopiclone)

Question 17

zolpidem function on sleep

Answer 17

reduces sleep latency, reduces nocturnal awakenings,

Question 18

Zaleplon function on sleep

Answer 18

decreases time to sleep onset (rapid oral onset), does NOT reduce nocturnal awakenings (short half life). Best for use as sleep aid for middle of the night awakenings

Question 19

Eszopiclone function on slep

Answer 19

Effective for sleep maintenance (long half life), and safe for long term use

Question 20

Triazolam function on sleep

Answer 20

Rapid oral absorpition decreases time to sleep onset, but more rebound insomnia

Question 21

Temazepam function on sleep

Answer 21

Decreases nocturnal awakenings (intermediate half life), but has minimal effect on sleep latency (slow absorption)

Question 22

Flurazepam function on sleep

Answer 22

Long half life- reduces nocturnal awakenings, but daytime sedation possible

Question 23

Trazodone MOA

Answer 23

•Serotonin receptor antagonist and reuptake blocker. Used as antidepressant, but also very sedating and improves sleep continuity

Question 24

Trazodone side effects

Answer 24

oversedation, orthostasis (a1-block), priapism

Question 25

Ramelteon MOA

Answer 25

•Agonist at melatonin receptors. MT1 (induce sleepiness) and MT2 (regulate circadian rhythms). Reduces sleep latency

Question 26

Ramelteon side effects

Answer 26

dizziness, somnolence, fatigue, nausea

Question 27

Diphenhydramine - Doxylamine MOA

Answer 27

•Antagonist at CNS histamine-H1 and muscarinic receptors

Question 28

Which sleep agents are first line, second line, etc

Answer 28

first line: zolpidem,and eszopiclone for sleep onset and maintenance. Zaleplon, zolpidem and ramelteon for sleep onset alone. Second line: flurazepam, temazepam, triazolam, and trazodone. Adjuncts: melatonin, diphenhydramine. Slow wave sleep: trazodone