What are the 3 "newer hypnotics?"
Do benzodiazepines or "newer hypnotics" bind more selectively?
When taking "newer hypnotics," what drug can antagonize CNS depressant effects?
What is a barbiturate that is not available in the US, is an adjunct to anesthesia (rapid / short acting) and is used as a truth serum?
- Facilitates / prolongs inhibitory effects of GABA and glycine
- Binds to receptor site different from benzodiazepines
- Actions not antagonized by flumazenil
- May also block excitatory transmitter glutamic acid & at high concentrations (sodium channels)
3 uses for Barbiturates
Insomnia / Sedation (secobarbital)
Seizure disorders (phenobarbital)
- Extension of CNS depressant actions
- Dependence liability > benzodiazepine
Toxicities of Barbiturates
- Which drug leads to coma/death?
- Which drug leads to just medullary depression/anesthesia?
- Barbiturates (coma)
- Benzodiazepines (anesthesia)
______ & _____ induce liver enzymes causing drug interactions.
Barbiturates and carbamates induce liver enzymes causing drug interactions.
- Enzyme induction
- Can precipitate acute intermittent _____ in susceptible patients
- ___ ____ may displace coumarins from plasma protein binding sites and increase anticoagulant effects
- Chloral hydrate
- exhibit sedating properties
- effective in tx of mild insomnia & are generally safe
- tolerance develops to sedative effects
- increasing the dose will not produce linear increase in response
- Disadvantage of ______ side effects
- Histamine 1 receptor
- Diphenhydramine & doxylamine are more sedating than ______.
- Are effective for inducing "sleep continuity"
- anticholinergic activity
- adrenergic blockade
- cardiac conduction prolongation adverse effects
Low dose ____ has FDA approval for tx of sleep maintenance insomnia.
What are the 2 sedating antidepressants?
- ___ may promote sleep (cause daytime sedation/weight gain)
- ____ at bedtime is sedating and can improve sleep continuity
Which antidepressant should you prescribe for:
- pts prone to substance abuse (dependence is NOT a problem)
- pts w. selective serotonin reuptake inhibitor & buproprion-induced insomnia
Which drug's side effects?
- Carryover sedation
- alpha adrenergic blockage --> orthostasis can occur at any age, but is more dangerous in elderly
- Priapism is a rare but serious side effect (prolonged erection)
Which antidepressant turns off wake signaling orexin (hypocretin)?
What is the primary role of Orexin?
control of sleep and arousal
Instead of inducing sleepiness, Suvorexant does what?
Turns off wake signaling
What are the 4 most commonly reported side effects of Suvorexant?
- Somnolence (MC)
- Sleep paralysis
- Narcolepsy-like sxs
- What drug is approved for tx of sleep onset insomnia?
- Selective MT1 & MT2 receptors
- Regulates circadian rhythm & sleep onset
Remelteon (a melatonin receptor agonist)
Ramelteon is a melatonin receptor agonist
- forms _____ via CYP1A2
- Generally well tolerated
- What are the 3 MC adverse events?
- active metabolite
- HA, dizziness, somnolence
Ramelteon (melatonin receptor agonist) effectively treats ____ in patients w/ which 2 conditions?
- sleep onset difficulties
- COPD & sleep apnea
- herbal sleep remedy
- studied for its sedative-hypnotic properties in pts w/ insomnia
- MOA not fully understood
- May involve increasing concentrations of _____.
Pts complain bc this drug smells like old gym socks
Valerian (herbal sleep remedy)
What 4 characteristic sxs differentiate narcolepsy from other sleep disorders?
- Excessive daytime sleepiness
- Sleep paralysis
- Impairment of both onset and offset of REM/NREM sleep
- Arousals & disturbed sleep during the night
Excessive Daytime Sleepiness
(Part of Narcolepsy Tetrad)
- Sudden bilateral loss of muscle tone varying severity / duration w/o loss of consciousness
- Often precipitated by highly emotional situations
- Brief, lasting ___ to ____
- Seconds to several minutes
- Falling asleep (hypnagogic) & on awakening (hypnopompic)
- Brief, dream-like experiences that intrude wakefulness
- 70% of narcoleptics experience this
(1 of 4 characteristics of Narcolepsy)
- Episodic loss of voluntary muscle tone that occurs when the individual is falling asleep or waking
- Conscious but not able to move or speak
Narcolepsy is dysfunction of _____ system
hypocretin / orexin neurotransmitter system
Vaccines licensed in US w/o adjuvants are or are not associated w/ increased risk of narcolepsy?
Wake Disorder Tx options include
- encouragement of good sleep hygiene and __ or more daytime naps daily (as little as 15 mins)
- Pharmacotherapy focuses on ____ and ____ sleep abnormalities
- EDS (Excessive Daytime Sleepiness) & REM sleep
3 tx for EDS (Excessive Daytime Sleepiness)
Tx for Cataplexy?
Tricyclic antidepressants (TCA)
SNRI, SSRI, MAOI
Tx for EDS, Cataplexy, Hallucinations
What is the standard of tx for EDS?
Which other drug is FDA approved?
4 SE of Modafinil
Which 2 drugs?
- Fast onset of effect
- One has more risk of abuse/tolerance
- SE: insomnia, HTN, palpitations, irritability
Amphetamines & Methylphenidate
(Amphetamines have more risk of abuse/tolerance)
Drug tx for what condition?
- MOA: blockade of serotonin & norepinephrine reuptake in locus coeruleus & raphe and subsequent suppression of REM sleep
- Tricyclic antidepressants
What is the drug tx for Hypersomnolence and Cataplexy?
(REM suppression & increase in REM latency)
- Tx for EDS, sleep paralysis, cataplexy, & hypnagogic hallucinations
- Potent sedative (hypnotic)
- Should NOT be used concomitantly w/ any other sedating medications
- Changes "sleep architecture" to resemble normal sleep
5 SE of Sodium oxybate
(used to tx EDS, sleep paralysis, cataplexy, hypnagogic hallucinations)