Sleep-Wake Pharmacology
Outline I. Drugs that disturb Sleepwake II. Drugs that promote sleep III. Drugs that promote wake
Antidepressants TCA -such as amitriptyline, nortriptyline, etc. Increase TST, PLMs, decrease REM and decrease alertness
NDRI -Bupropion • Can cause – insomnia – Vivid dreams – nightmares
• SSRI – Fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram
• SNRI – venlafaxine
• Cause insomnia • Decrease total sleep time and REM • Cause PLMs
SARI • Trazadone –Improves sleep –Increases TST, SWS –Decreses SL, REM
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NASSA
Anxiolytics • Benzodiazepine
• Mirtazapine (Remeron)
– Diazepam, alprazolam, temazepam, clonazepam
– Improves sleep – Can cause daytime sedation
– – – – –
Buspirone • Slower onset than BZD • Less daytime sedation
Cardiovascular Drugs • Beta blockers – Insomnia, dreams, nightmares – Propranolol, timolol greater than carvedilol and atenolol – Lipophilic greater than hydrophilic
Alpha-Agonist • Clonidine, methyldopa
Help muscle relaxation Anxiolysis Sedation Improve sleep + daytime sedation
Ace Inhibitors • No effect
– Insomnia – Nightmares – sedation
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Reserpine • nightmares
Hypolipidemic Agents • Reported cases of insomnia with atorvastatin and lovastatin
Anti-Histamines • Benadryl – Sedating (lipophilic)
• Terfenadine, cetirizine, loratidine – Less sedating (hydrophilic)
Steroids • • • •
Insomnia Inconsistent Decreased REM Little effect from inhaled
• Cimetidine, rantidine, famotidine – Less sedating (hydrophilic) – Increase levels of theophylline, CMZ, Beta-blockers
Theophylline • Related to caffeine • Disturbs sleep in normal, asthma, CF, OSAs, COPD • Peeks ~ 2 hrs • Half-life 8-9 hrs
Antiparkinsons • Levodopa/Carbidopa – Low dose: can improve sleep – Higher doses: disrupts sleep, nightmares, hallucinations
• Dopamine Agonists – Pramipexole, ropinerole – Increase daytime sleepiness – ?sleep attacks?
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MAOI-B • Selegiline
Amantadine • Insomnia • Hallucinations • Nightmares
– insomnia
Antiepileptics • Older agents caused more sedation – Dilantin, phenobarbital, valproate, mysoline, carbamazepine
• Newer agents have less sedation
Anorectics • INSOMNIA • INSOMNIA • INSOMNIA
– Lamotrigine, levetiracetam, zonisamide
• Gabapentin can increase SWS • Lamotrigine can decrease SWS
Drugs that promote sleep • Match the drug to the problem • Sleep onset vs maintainence
Sleep Onset • Zolpidem – – – –
po ambien, SL edular Onset 30-60 Half life 2.5-3 hr Ambien CR half life 46 hr
• Zolpidem – – – –
SL intermezzo WASO Onset 30 Half life 2.5 hr
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Sonata • Onset 30-45 • Half life 1.5-2 • Doxepin (silenor)
• Escopiclone (lunesta)
– Onset 30-60 – Half life 4-6 hr
– Onset 30 min – Half life 4-6 hr
Sleep Maintanence • Rozerem (remelteon) – Onset 30-45 – Half life 2-5 hr
BZD • Temazepam –Onset 15-30 –Half life 6-8 hr
• Clonazepam –Onset 30 –Half life 8-12 hr
Melatonin • • • •
Gabapentin Barbiturates TCA trazadone
• 0.3-5mg • Insomnia-1 hr prior to bedtime • DSPS-every 6-8 hr
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Drugs to help wake
Ritalin Formulations
• Caffeine – Coffee 70-150mg/cup – Soda < 70 controlled – Energy ?? – Half life 5-6 hrs
Non Ritalins • Provigil (modofinil), Nuvigil (armodafinil) – Onset 1-2 hr – Max 2-4 hr – Half life ~15 hr • Sleep Walking – Take one hour prior to eating
Nightmares • REM sleep • REM suppressants • TCA, Remeron, ventafoxine, BZD
• Night Terrors
– Non REM, SWS – Safety – BZD
– Non REM – Safety – BZD?
REM Behavior Disorder • • • •
REM without atonia Dream enactment Clonazepam, melatonin Parkinsonism
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Light • • • • •
Primary zeitgeber, esp blue wavelength Drives wake-delays sleep Delayed sleep phase Advanced sleep phase Shift work disorder
Hypnogram
Electronic Intrusion • TV, computer, cell phone, etc
Wake-NREM-REM
Abbreviations • • • • • •
TST-Total sleep time BZD-benzodiazepine WASO-Wake after sleep onset RBD-REM behavior disorder SWS-Slow wave sleep DSPS-Delayed sleep phase disorder
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