Sleep Physiology and pharmacotherapy Flashcards
Benzos and non-benzo receptor agonists’ mechanism of action
facilitate GABA at GABAa receptor-chloride channel complex –> membrane hyperpolarization
Triazolam pharmacokinetics
1.5-5h half-life, less daytime sedation (hangover). Rapid elimination –> rebound insomnia the next day. rapid absorption
Temazepam pharmacokinetics
9-13h half-life. slow absorption. peak effect at 2-3h
Flurazepam pharmacokinetics
75-90h half-life. little tolerance. Hepatic clearance (can accumulate in elderly –> daytime sedation, hangover, OD)
Zolpidem and zaleplon pharmacokinetics
6-8h duration. rapid oral absorption
Eszopiclone (Lunesta) pharmacokinetics
longer half-life than zolpidem and zapelon
First line in tx of insomnia
Z drugs. Little effect on sleep stages III and IV
Zolpidem role in insomnia tx
reduces sleep latency and nocturnal awakenings –> increased total sleep time and efficiency
Zaleplon role in insomnia tx
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.
Eszopiclone role in insomnia tx
safest for long-term use
Benzo role in insomnia tx
declining use. cheaper than Z drugs. short-term tx of insomnia
trazodone side effects
oversedation and orthostasis (alpha adrenergic block)
TCAD side effects
antimuscarinic and antiadrenergic activity
Ramelteon
melatonin agonist –> induce sleepiness, regulates circadian rhythms
ADRs: dizziness, somnolence, fatigue, nausea
Antihistamines
H1 and muscarinic cholinergic antagonist
Black box warning for benzos and Z drugs
strange sleep-related behavior, anaphylaxis, facial swelling
Benzo side effects
daytime sedation and performance impairment, anterograde amnesia, rebound insomnia, psych and physical dependence
Zolpidem side effects
dorwsiness, amnesia, dizziness, headache, GI complaints
Zaleplon side effects
dizziness, headache, sonolence
Eszopiclone side effects
similar to zolpidem. increased incidence of psychomotor impairment with higher doses
Sleep periods at birth
shorter. Consolidate with age
Non-REM sleep
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
REM sleep
every 90 minutes in adults. EEG similar to awake. Higher arousal threshold than slow-wave sleep. “Active brain in paralyzed body”. 85% of dreams
sleep/wake switch
hypothalamus
circadian clock. modulates core temp, alertness, cortisol and melatonin secretion
suprachiasmatic nucleus
ascending cortical activation and REM/SWS switch
brainstem
spindles, slow wave sleep
thalamus
inhibit arousal systems during NREM sleep
neurons of ventrolateral preoptic area (GABA and galanin)
Drive REM sleep
cholinergic pedunculopontine and laterodorsal tegmental (PPT/LDT) neurons. Inhibited by catecholamines during wake and NREM sleep
Neurotransmitters active during wake
Ach in LDT/PPT, serotonin (raphe nucleus), NE (locus ceruleus), histamine (Tubomammillary nucleus), dopamine (VTA/SNc), adenosine (basal forebrain), hypocretin (lateral hypothalamus)
Neurotransmitters active during NREM
GABA, galanine (ventrolateral preoptic nucleus), melatonin (pineal gland, SCN, hypothalamus)
Neurotransmitters active during REM
Ach (LDT/PPT), DA (VTA/SNc)
Homeostatic S drive
the longer we are awake, the sleepier we get. Mediated by adenosine. blocked by caffeine
Circadian (C) alerting system
waxing/waning of sleepiness. resides in SCN, linked to core body temp
Best sleep
descending curve of core body temp
What happens when you stay up 72h?
sleepiness waxes and wanes due to C system
Melatonin activity
Light –> SCN –> inhibits pineal gland production of melatonin
Dark –> reduced SCN firing –> disinhibition of pineal gland –> melatonin production
Evolution of insomnia
3 Ps: Predisposed person (worrier), Precipitant (stress), Perpetuating factors (sleep worry)
Two categories of insomnia
Learned and co-morbid
