Ruby Williams, M.D. Drugs, Alcohol and Sleep February 24, 2018
Objectives Describe pharmacology of commonly prescribed drugs for stimulants and hypnotics Brief review of common drugs that affect sleep and by the manner of how they do it either by Inducing sleepiness Inducing insomnia Sleep related side effects (ie RLS, EEG changes and parasomnias Brief review of how alcohol affects our sleep
Sleep and Neurotransmitters Wake Neurotransmitters Dopamine Norepinephrine Serotonin Acetycholine Histamine Orexin Sleep Neurotransmitters Adenosine Gaba
Stimulants Amphetamines Inhibit reuptake of dopamine and release presynaptic vesicles containing NE Leads to more wakefulness, less REM and SWS Bruxism, cardiovascular symptoms Methylphenidates Prevents reuptake of dopamine but does not release Less crash effect Modafinil Thought to be related to dopamine transport inhibition
Drug Comparison adderall Ritalin Provigil Nuvigil
Caffeine Adenosine: Increases as the day increases eventually stimulating sleepiness Caffeine: Antagonizes adenosine receptors Average person needs 200mg to have an effect
Benzo-like Drugs Act on GABA receptors Preferred over benzos less tolerance Decreases TST and sleep latency No clear change in sleep architecture and staging Possible increased sleep spindles SE Amnesia, non REM parasomnias (sleep eating), hallucinations Few respiratory effects
Sonata Ambien Lunesta
Benzodiazepams Modify GABA receptor to potentiate GABA effects Decrease sleep latency and WASO, Inc d TST Decrease REM sleep, Increase N2 Frequent spindles during N2 Suppresses N3 sleep Noteable side effects in the elderly Increased falls in elderly Tolerance and rebound/insomnia Mild respiratory depression
Other Sleep Aides Melatonin Naturally made in the pineal gland Decreases SL 4min and Sleep efficiency 2% Ramelteon Melatonin antagonist, low abuse FDA approved Mild improvement in TST and sleep latency Tasimelteon FDA approved for Non-24hr sleep wake d/o Suvorexant Orexin receptor antagonist FDA approved, decreases sleep latency and WASO Absolutely contraindicated in Narcolepsy
Tricyclic Antidepressants Serotonin and NE reuptake inhibition Muscarinic and histamine antagonist Decrease REM sleep Increase PLMs and RLS symptoms Sedating TCAs (anticholinergic/antihistamine) Decrease TST and sleep latency Amitriptyline, imipramine, doxepin Adrenergic TCAs May increase awakenings and decrease TST Nortriptyline
MAOI Monoamine oxidase inhibitors: prevent dopamine, serotonin and norepinephrine Side effects are daytime sleepiness and insomnia Marked decreased REM sleep
SSRI Selective serotonin reuptake inhibitor Decreased TST, Increased WASO, increased sleep latency Decreased REM, increased stage 1 Increased PLMS REM sleep w/o atonia Prozac eyes on EOG
Most stimulating: Prozac fluoxetine Zoloft- sertraline Paxil- paroxetine celexa- citalopram Lexapro- escitalopram Luvox-fluvoxamine Most sedating
SNRIs Serotonin and norepinephrine reuptake inhibitors Venlafaxine- Effexor Duloxetine- Cymbalta Multiple uses Pain- fibro or neuropathic, depression, anxiety Insomnia very common Watch when this medication is dosed! Dec d TST, Dec d REM, Inc d PLMs, Reports of RBD
Trazodone Serotonin antagonist and reuptake inhibitors Drowsiness is a SE and often used as a hypnotic Dec d SL, Inc d SWS, No change in REM Does not effect PLM or REM SE unwanted prolonged priapism
Buproprion Wellbutrin Inhibits dopamine and NE reuptake Does not really affect REM sleep Dec s PLMS Insomnia (consider depression with EDS)
Mirtazapine Antagonizes 5HT-2 and HT1 receptors Highly sedating Dec d sleep latency and inc d N3 Daytime sleepiness is a SE could use for insomnia RLS can get worse
Antipsychotics Multiple mechanisms Dopamine, 5HT, Ach, Histamine Sedating Inc TST and dec SL Inc SWS and dec REM Exacerbate RLS
Other Drugs Buspirone 5HT1-A partial agonist Non sedating anxiolytic Dec d REM sleep Donepizil Causes vivid dreams Insomnia due to increased cholinergic activity
Beta Blockade Common drug that can affect sleep Daytime fatigue, nightmares, insomnia Impairs melatonin production Propanolol is most associated with sleep disruption The more lipophilic the drug, the more sleep side effects
Alpha-2 Agonists Clonidine and methyldopa Sedation very common Usually goes away with time Nightmares and insomnia
Prazosin Alpha-1 antagonist Inc TST and increased REM sleep Reduces nightmares (key use) Great for PTSD related nightmares
Antihistamines H1 antagonists Benadryl (diphenhydramine),hydroxyzine Lipophilic and crosses blood barrier very easily Certrizine (Zyrtec) and loratadine (Claritin) hydrophilic thus less sedating
Opiates Very decreased amount of N3 sleep No clear effect on TST, however, in chronic users may lead to increase WASO Decreased respiratory drives especially at higher doses Can lead central sleep apneas Can lead to hypercapnia and hypoxia
Respiratory Drugs Prednisone Insomnia with increased doses, dec REM Pseudophedrine Insomnia Theophyline Insomnia and WASO Short acting beta agonists Insomnia
Alcohol and Sleep
Alcohol Alcohol-Related Deaths: An estimated 88,000 8 people (approximately 62,000 men and 26,000 women 8 ) die from alcohol-related causes annually, making alcohol the third leading preventable cause of death in the United States. The first is tobacco, and the second is poor diet and physical inactivity. 9 In 2014, alcohol-impaired driving fatalities accounted for 9,967 deaths (31 percent of overall driving fatalities). 10
Alcohol and Sleep Physiology Patient s given alcohol 30-60min before bedtime Effect: patient s blood alcohol content peaked at lights out Dose ranged from 0.16-1.0 gram per kilogram of body weight 1 Corresponded to 1-6 standard drinks 2 leading to breath alcohol of 0.15 1. WILLIAMS, H., AND SALAMY, A. Alcohol and sleep. In: Kissin, B., and Begleiter, H., eds. The Biology of Alcoholism. New York: Plenum Press, 1972. pp. 435-483. 2. A standard drink is defined as one 12-ounce bottle of beer or wine cooler, one 5-ounce glass of wine, and 1.5 ounces of 80 proof distilled spirits
Findings: Consistently effects the proportions of various sleep stages 1. Dose dependent suppression of REM sleep at the first half of the sleep period 1 Development o f REM rebound 2 during the second half of the night Overall amount of REM sleep in subjects receiving alcohol before sleep did not differ from subjects who did not drink alcohol 1 This was associated with the completed alcohol metabolism and elimination from the body 1 Increase in slow wave sleep with acute ingestion during first half of sleep 1
Recurrent ingestion after 3 nights led to tolerance of alcohol s sedative and sleep stage effects 1 The percentage of SWS and REM returned to normal The discontinuation of nightly alcohol led to REM rebound 1
PSG Effects Acute alcohol ingestion: First part of sleep: dec SOL & WASO, inc REM SL, dec REM Second part of sleep: inc WASO, dec N3, Inc REM Alcohol withdrawal: Inc SOL, Inc WASO, Dec TST, Dec N3, Dec REM SL and Inc REM (REM Rebound) Alcohol abstinence: Inc SOL, Dec TST, Inc WASO, Dec N3 (may be forever in alcoholics who remain sober)
Alcohol and OSA Acute ingestion can make snoring and AHI worse Decreased REM sleep in first part of the night decreases the longer events associated with REM sleep however, more severe desaturations and presumably longer events can occur the second part of the night
Alcohol and Sleep Disturbances Alcohol use: Inc nightmares and vivid dreams. Inc enuresis, RLS, sleep terrors/sleep walking, snoring and osa Acute alcohol withdrawal: Insomnia, frequent awakenings accompanied by headaches and diaphoresis. Vivid disturbing dreams. Alcohol abstinence: Sleep disturbance, including insomnia, can persist for several years. Dec TST with delirium tremens.
Relation to nocturnal sleep to daytime alertness In one study, young pilots drank alcohol between 6 p.m. and 9 p.m. in quantities sufficient to result in blood alcohol concentrations (BACs) of 0.10 and 0.12 percent right before bedtime. 1 The following morning, more than 14 hours after consuming alcohol and with BACs at 0, the performance of pilots in a flight simulator was impaired relative to their performance after consuming a placebo 1 Roehrs and colleagues gave studies alcohol before bedtime, goal of breath 0.06, and studied their performance the next day on MSLT checking their auditory vigilance, in which the participants had to respond to a certain sound, or divided attention tasks, in which the participants had to perform two tasks simultaneously 2 Alertness and divided attention was decreased, showing that alcohol indirectly affects daytime performance by affecting sleep. 2
Bottom Line About Alcohol Makes you feel good when you re drinking it, but you will pay for it later with: Exacerbation of snoring Sleep disturbances with second half of the night REM rebound Exacerbation of OSA Increased WASO Poor performance next day