Sedatives & Hypnotics.pptx

SEDATIVES & HYPNOTICS (SLEEP WAKE DISORDERS) Martha Agbeli, DNP, PMHNP-BC Revised- November, 2022 INSOMNIA/HYPERSOMNIA Sleep Wake Disorders 2 stages of Sleep-wake cycle 1. Rapid eye movement (REM) sleep 2. Non-rapid eye movement (NREM) Initial/sleep-onset Insomnia= Difficulty initiating sleep Middle...

SEDATIVES & HYPNOTICS (SLEEP WAKE DISORDERS) Martha Agbeli, DNP, PMHNP-BC Revised- November, 2022 INSOMNIA/HYPERSOMNIA Sleep Wake Disorders 2 stages of Sleep-wake cycle 1. Rapid eye movement (REM) sleep 2. Non-rapid eye movement (NREM) Initial/sleep-onset Insomnia= Difficulty initiating sleep Middle/sleep maintenance insomnia= frequent nocturnal awakenings Late/sleep offset insomnia= Early morning awakenings Nonrestorative sleep= waking up feeling fatigues and unrefreshed. Insomnia vs Hypersomnia Insomnia= difficulty falling or remaining asleep  Acute insomnia (less than 3 months)  Chronic insomnia (lasts more than 3 months to years) Treatment:  Sleep hygiene measures  Cognitive behavioral therapy (CBT)  Chronotherapy (bright light therapy)  Benzos (use short term)  Non benzos (Melatonin, Ambien, Lunesta, Sonata etc.)= Short term treatment; Ambien in elderly patients  Antidepressants = Trazodone (mostly prescribed sedating antidepressant), Remeron (low doses) Hypersomnia= excessive daytime sleeping. Short-intermediate acting benzo receptor agonists (BzRA: zolpidem, eszopiclone, temazepam) or ramelteon One general sequence for primary insomnia: Alternate from above if first choice not effective Sedating antidepressant (e.g. trazodone, mirtazapine, amitriptyline, doxepin) Combining BzRA or ramelteon + sedating antidepressant Other sedating agents: gabapentin, tiagabine, atypical APs Medications per 2017 guidelines Sleep Onset Sleep Maintenance  Eszopiclone  Suvorexant (Belsomra)  Zaleplon (Sonata)  Eszopiclone (Lunesta)  Zolpidem  Zolpidem (Ambien)  Triazolam (Halcion)  Temazepam (Restoril)  Temazepam  Doxepin (Silenor)  Ramelteon (Rozerem) Eszopiclone (Lunesta) – helps stay asleep Zaleplon (Sonata) GABA-PAM (Positive Allosteric Modulator) Does not appear to cause significant tolerance or dependence over time, though it is a controlled substance; can be used long term Onset within an hour but high fat meals may slow absorption GABA-PAM, alpha 1 agonist GABA-A Approved for short term insomnia Onset less than 1 hour but short half-life Dependence with longer term tx, not intended for longer term use Non-Benzo Hypnotics Zolpidem (Ambien)-Empty stomach Diphenhydramine (Benadryl) Selectively binds to Omega-1 receptor on GABA-A receptor (responsible for sedation) Should be used for short-term of insomnia Less tolerance/dependence occurs with prolonged use (can still occur) Reports of anterograde amnesia, hallucinations, parasomnias (sleep walking, sleep eating) increased fall risk and GI effects Note: Recommended Ambien dose Men=10mg Women= 5mg Ambien: FDA Black Box Warning nighttime complex behaviors Antihistamine w/ moderate anticholinergic effects Most sedating antihistamine (avoid w/ elderly) Ramelteon (Rozerem) Selective Melatonin (MT1 and MT2 agonist) Effective and safe sleep aid d/t no tolerance or dependence. DOES NOT Act on benzodiazepine receptors Knowledge Check  Eszopiclone (Lunesta)= used in which phase of sleep ?? sleep onset vs. maintenance (maintenance)  NOTE: Non-benzo hypnotics do not generally affect REM sleep. NOTE: OTC sedative/hypnotics= tolerance to sedating effects can develop rapidly, True/False? True  MOA of Ramelteon (selective melatonin 1 and 2 agonist; does not act on benzodiazepine receptors) Other Pharmacologic options Melatonin Flurazepam(Dalmane) Long-lasting agent May cause excessive drowsiness Avoid in older adults Temazepam (Restoril) Triazolam(Halcon) – short acting agent Triazolam (Halcion) Temazepam (Restoril) GABA-PAM and benzodiazepine/hypnotic Approved for short term tx of insomnia Quick onset, short halflife Needs to be tapered if using longer term (risk of seizures), not very suitable for long term use, dependence, tolerance issues, dangerous interactions (e.g. ETOH) GABA-PAM and benzodiazepine/hypnotic Approved for short term tx of insomnia Long half life, overdose risk Knowledge Check  Why should Flurazepam be avoided in the elderly? (long-acting and causes excessive drowsiness) Antidepressants -Used for sedating properties  Amitriptyline (Elavil)  Doxepin(Sinequan)  Mirtazapine (Remeron)  Trazodone Consider Armodafinil(Nuvigil) =indicated for daytime sleepiness associated with OSA Knowledge Check  Priapism is commonly associated with which antidepressant commonly used for sleep? Trazodone Sedative hypnotic use in elderly patients  Always consider sleep hygiene as first-line  More likely to cause side effects when used (i.e. memory impairment, ataxia, paradoxical excitement and rebound insomnia) = Trazodone is a safer options NARCOLEPSY Narcolepsy Excessive daytime sleepiness and falling asleep in inappropriate places  Characterized by cataplexy(brief episodes of sudden bilateral loss of muscle tone)  Hallucinations and/or sleep paralysis at the beginning or end of sleep episodes are common  Slightly more in males than females Etiology: Loss of hypothalamic neurons that produce hypocretin Management: Sleep hygiene, scheduled daytime naps, avoid shift work Amphetamines (D-amphetamine, methamphetamine) Modafinil – 1st line pharmacologic treatment Drug of choice for cataplexy= Sodium oxybate (Avoid use with alcohol and other CNS depressants); Others:= TCAs(imipramine, desipramine, clomipramine) REM suppression drugs= SSRI, SNRI (Prozac, Cymbalta, atomoxetine, venlafaxine) Knowledge Check  Treatment for narcolepsy with cataplexy??? Sodium oxybate  Sodium oxybate (GHB)= not to be used with alcohol or other CNS depressants; why? Impairs consciousness and leads to respiratory depression, seizures, coma, death  Treatment of Insomnia in elderly patients (sleep hygiene first, trazadone and Remeron safer especially in depressed patients) RESTLESS LEGS SYNDROME(RLS) Restless legs Syndrome(RLS) Characteristics  The urge to move legs accompanied by unpleasant sensation in the legs, characterized by relief with movement, aggravation with inactivity.  Occurs or worsens in the evening.  1.5 -2 times more likely in males  Risk factors: age, iron deficiency, antidepressants, antipsychotics, dopamine blocking antiemetic, antihistamines; strong familial component Treatment: Remove offending agent; iron replacement 1st line: Dopamine agonists(pramipexole=Mirapex and ropinirole-Requip) and Benzos Gabapentin (Neurontin); pregabalin(Lyrica) Low potency opioids for treatment refractory patients Periodic Limb Movements of sleep (PLMS): RLS associated with involuntary , jerking movements of limbs during sleep Periodic Limb Movement Disorder(PLMD): Impaired sleep and daytime functioning + PLMS in the absence of RLS Knowledge Check  Non-pharmacologic sleep Apnea Treatments=weight loss; avoidance of ETOH; CPAP; Uvulopalatopharyngoplasty  Activating serotonergic agents e.g. Effexor may trigger symptoms consistent with Restless Leg Syndrome (RLS)