Hypnotics Flashcards
What class of drugs is currently the MOST TYPICAL DRUG used to treat insomnia?
Newer GABAergic hypnotics - ZALEPLON, ZOLPIDEM, ESZOPICLONE
What does it mean to be a “controlled substance” by FDA rules?
The drug has a risk of dependence - both psychological and physiological
What do hypnotics promote? (2)
1) Encourage the ONSET of sleep - DECREASES sleep latency
2) Encourage sleep MAINTENANCE - INCREASES total sleep
CLASS 1 BZ) CLINICAL TOXICOLOGY: How are the withdrawal symptoms of BZ use for hypnosis compared to sedation?
WORSE Rebound hyperanxiety, insomnia/headaches, convulsions
CLASS 2 NEWER GABAergic HYPNOTICS) What is their mechanism of action?
Bind to the same site as BZ, but more specific in terms of the subunit isoform (only alpha1-containing subunits)
What are 2 classes of anxiolytics and 1 class of hypnotics that are NOT controlled substances?
1) Sed - BUSPIRONE
2) Sed - BETA-BLOCKERS
3) Hyp - RAMELTEON
CLASS 2 NEWER GABAergic HYPNOTICS) What are the two therapeutic effects of these drugs?
- All 3 DECREASE sleep latency - decreases the time it takes to fall asleep
ZALEPLON - Does NOT increase total sleep time
ZOLPIDEM + ESZOPICLONE - Do increase total sleep time
CLASS 2 NEWER GABAergic HYPNOTICS) PHARMACOKINETICS: Describe the onset of action and half-life.
Rapid onset of action
Short half-life (DESIRED effect) compared to BZ’s that have long half-lives (except midazolam)
CLASS 2 NEWER GABAergic HYPNOTICS) Can ZALEPLON, ZOLPIDEM, and ESZOPICLONE be used to treat muscle spasms and manage seizures?
NO - Bec of receptor subunit specificity associated with these 3 newer GABAergic hypnotics
Can anxiolytics (sedatives) be used to produce hypnosis?
YES, at higher doses the anxiolytic, calming effects can promote sleep
What are the 3 classes of hypnotics?
CLASS 1) BZ
CLASS 2) NEWER GABAergic Hypnotics
CLASS 3) New non-GABAergic Hypnotics
CLASS 2 NEWER GABAergic HYPNOTICS) Name the 3 GABAergic hypnotics (Hint: Z-drugs)
ZALEPLON
ZOLPIDEM
ESZOPICLONE
What is 1 class of sedatives and 2 classes of hypnotics that are classified as “controlled substances” by FDA and thus have a high risk of dependence?
CONTROLLED SUBSTANCE = RISK OF DEPENDENCY
1) Sed - BZs
2) Hyp - Newer GABAergic Hypnotics - ZALEPLON, ZOLPIDEM, ESZOPICLONE
3) Hyp - SUVOREXANT
CLASS 2 NEWER GABAergic HYPNOTICS) Name the 4 advantages of these drugs: (1 PK, 1 PD, 2 side effects).
1) PHARMACOKINETICS - Act fast, go away fast
2) PHARMACODYNAMICS - Very specific effect of SLEEP
3) SIDE EFFECTS - Very modest psychomotor depression compared to BZs
4) SIDE EFFECTS - NO (few) amnesia
CLASS 2 NEWER GABAergic HYPNOTICS) What are the 2 disadvantages of these 3 drugs?
1) Controlled substance - aka risk of DEPENDENCY (ONLY use in times of crises)
2) Chance of REBOUND INSOMNIA when higher than hypnotic doses are administered
CLASS 3 NEW NON-GABAergic HYPNOTICS) Name the 2 drugs in this category
1) RAMELTEON
2) SUVOREXANT
CLASS 3 NEW NON-GABAergic HYPNOTICS) What is the mechanism of action of RAMELTEON?
Agonist of MELATONIN (M1 and M2) receptors in the BRAIN and has NO GABAergic effects on the CNS
CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the 2 effects of RAMELTEON?
By activating melatonin receptors involved in the sleep-wake cycle, one’s sleep state is promoted.
1) DECREASES Sleep latency
2) INCREASES sleep periods
CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the 3 major advantages of RAMELTEON?
(*Hint: Controlled substance?, Side Effect, Mech of Action)
1) NO DEPENDENCE = Not a controlled substance
2) NO REBOUND INSOMNIA
3) NO PSYCHOMOTOR IMPAIRMENT - No GABAergic effects
CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the 2 disadvantages of RAMELTEON?
(*Hint: drug interactions + effect on body systems)
1) Metabolized mainly by CYP1A2 - should NOT be taken with CYP1A2 inhibitors
2) Adverse effects are not as severe - dizziness + fatigue + endocrine changes [DECREASED testosterone + INCREASED prolactin]
CLASS 3 NEW NON-GABAergic HYPNOTICS) What is the mechanism of action of SUVOREXANT?
Orexin Receptor antagonist in the brain with NO GABAergic CNS effects
* Orexin - stimulating NT promoting “wake” in the sleep-wake cycle
CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the two effects of SUVOREXANT?
1) DECREASES sleep latency
2) INCREASES sleep periods
CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the SEVERE disadvantages of SUVOREXANT?
(*Hint: Controlled substance? Major side effect (1) Other adverse effects (1))
1) HIGH RISK OF ABUSE/DEPENDENCE = controlled substance
2) Can cause “sleep driving” + amnesic effects - no conscious recollection of driving
3) Body System Adverse Effects: Headache + Dizziness + Day-after somnolence
