Hypnotics

Question 1

What class of drugs is currently the MOST TYPICAL DRUG used to treat insomnia?

Answer 1

Newer GABAergic hypnotics - ZALEPLON, ZOLPIDEM, ESZOPICLONE

Question 2

What does it mean to be a “controlled substance” by FDA rules?

Answer 2

The drug has a risk of dependence - both psychological and physiological

Question 3

What do hypnotics promote? (2)

Answer 3

1) Encourage the ONSET of sleep - DECREASES sleep latency

2) Encourage sleep MAINTENANCE - INCREASES total sleep

Question 4

CLASS 1 BZ) CLINICAL TOXICOLOGY: How are the withdrawal symptoms of BZ use for hypnosis compared to sedation?

Answer 4

WORSE Rebound hyperanxiety, insomnia/headaches, convulsions

Question 5

CLASS 2 NEWER GABAergic HYPNOTICS) What is their mechanism of action?

Answer 5

Bind to the same site as BZ, but more specific in terms of the subunit isoform (only alpha1-containing subunits)

Question 6

What are 2 classes of anxiolytics and 1 class of hypnotics that are NOT controlled substances?

Answer 6

1) Sed - BUSPIRONE
2) Sed - BETA-BLOCKERS
3) Hyp - RAMELTEON

Question 7

CLASS 2 NEWER GABAergic HYPNOTICS) What are the two therapeutic effects of these drugs?

Answer 7

• 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

Question 8

CLASS 2 NEWER GABAergic HYPNOTICS) PHARMACOKINETICS: Describe the onset of action and half-life.

Answer 8

Rapid onset of action

Short half-life (DESIRED effect) compared to BZ’s that have long half-lives (except midazolam)

Question 9

CLASS 2 NEWER GABAergic HYPNOTICS) Can ZALEPLON, ZOLPIDEM, and ESZOPICLONE be used to treat muscle spasms and manage seizures?

Answer 9

NO - Bec of receptor subunit specificity associated with these 3 newer GABAergic hypnotics

Question 10

Can anxiolytics (sedatives) be used to produce hypnosis?

Answer 10

YES, at higher doses the anxiolytic, calming effects can promote sleep

Question 11

What are the 3 classes of hypnotics?

Answer 11

CLASS 1) BZ
CLASS 2) NEWER GABAergic Hypnotics
CLASS 3) New non-GABAergic Hypnotics

Question 11

CLASS 2 NEWER GABAergic HYPNOTICS) Name the 3 GABAergic hypnotics (Hint: Z-drugs)

Answer 11

ZALEPLON
ZOLPIDEM
ESZOPICLONE

Question 12

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?

Answer 12

CONTROLLED SUBSTANCE = RISK OF DEPENDENCY

1) Sed - BZs
2) Hyp - Newer GABAergic Hypnotics - ZALEPLON, ZOLPIDEM, ESZOPICLONE
3) Hyp - SUVOREXANT

Question 13

CLASS 2 NEWER GABAergic HYPNOTICS) Name the 4 advantages of these drugs: (1 PK, 1 PD, 2 side effects).

Answer 13

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

Question 14

CLASS 2 NEWER GABAergic HYPNOTICS) What are the 2 disadvantages of these 3 drugs?

Answer 14

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

Question 15

CLASS 3 NEW NON-GABAergic HYPNOTICS) Name the 2 drugs in this category

Answer 15

1) RAMELTEON

2) SUVOREXANT

Question 16

CLASS 3 NEW NON-GABAergic HYPNOTICS) What is the mechanism of action of RAMELTEON?

Answer 16

Agonist of MELATONIN (M1 and M2) receptors in the BRAIN and has NO GABAergic effects on the CNS

Question 17

CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the 2 effects of RAMELTEON?

Answer 17

By activating melatonin receptors involved in the sleep-wake cycle, one’s sleep state is promoted.

1) DECREASES Sleep latency
2) INCREASES sleep periods

Question 18

CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the 3 major advantages of RAMELTEON?
(*Hint: Controlled substance?, Side Effect, Mech of Action)

Answer 18

1) NO DEPENDENCE = Not a controlled substance
2) NO REBOUND INSOMNIA
3) NO PSYCHOMOTOR IMPAIRMENT - No GABAergic effects

Question 19

CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the 2 disadvantages of RAMELTEON?
(*Hint: drug interactions + effect on body systems)

Answer 19

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]

Question 20

CLASS 3 NEW NON-GABAergic HYPNOTICS) What is the mechanism of action of SUVOREXANT?

Answer 20

Orexin Receptor antagonist in the brain with NO GABAergic CNS effects
* Orexin - stimulating NT promoting “wake” in the sleep-wake cycle

Question 21

CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the two effects of SUVOREXANT?

Answer 21

1) DECREASES sleep latency

2) INCREASES sleep periods

Question 22

CLASS 3 NEW NON-GABAergic HYPNOTICS) What are the SEVERE disadvantages of SUVOREXANT?
(*Hint: Controlled substance? Major side effect (1) Other adverse effects (1))

Answer 22

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