DSA28 - Drugs for Sleep Disorders

While most BZD are effective as Hypnotics, what are the main issues that they can cause?

-Short Acting = Rebound Insomnia & Anxiety

-Interm Acting = Early Mornin Awakening

-Long Acting = Hangover (Grogginess)

-Tolerance/Dependence/Withdrawal potential

Triazolam MoA

BZD; Short Elim T1/2 (3-4 hrs)

Triazolam Tx

Hypnotic (for Sleep) - induce sleep W/O HANGOVER

Triazolam S/E

REBOUND INSOMNIA AND/OR ANXIETY, Withdrawal , Amnesia, Tolerance if continued

Zolpidem MoA

BZD1 Receptor Agonist = BZD that binds to GABA receptors w/ Alpha 1 subunit (BZD1 subtype); Short Elim T1/2 (3-5 hrs)

Zolpidem Tx

Hypnotic (induces sleep) - less anxiolyic, anticonvulsant, or muscle relaxant; Less hangover, dependence, or rebound insomnia

Zaleplon MoA

BZD1 Receptor Agonist = BZD that binds to GABA receptors w/ Alpha 1 subunit (BZD1 subtype); SHORTEST Elim T1/2 (1 hr) --> little change of hangover

Zaleplon Tx

PRN for Awakening in middle of night (if more than 4 hr remains) + MORE if TROUBLE FALLING ASLEEP

Eszopiclone MoA

BZD1 Receptor Agonist = BZD that binds to GABA receptors w/ Alpha 1 subunit (BZD1 subtype)

Eszopiclone Tx

Long Term use Hypnotic (Non-existent Rebound Insomnia)

Melatonin MoA

Pineal gland hormone that regulates sleep/wake cycle - binds to MT1 (sleepiness) & MT2 (sync circadian cycle)

Melatonin Tx

Jet-lag OR Changing Day/Night Working hours

Melatonin S/E

C/I Hx of Depression

Ramelteon MoA

Binds Melatonin receptors (MT1, MT2) - No dependence or Rebound

Ramelteon Tx

Circadian rhythm sleep-wake disorders (Off-Label)

Ramelteon S/E

DDI w/ Fluvoxamine (binds to CYP1A2 --> inhibits metabolism); C/I w/ Hx of Depression

Tasimelteon MoA

Binds Melatonin receptors (MT1, MT2) - No dependence or Rebound

Tasimelteon Tx

Circadian rhythm sleep-wake disorders (Specific Approval)

Tasimelteon S/E

HA, elevated ALT, Nightmares, Vivid Dreams, Suscept to URI/UTI

Suvorexant MoA

Orexin (Hypocretin) Antagonist - stops effect of wakefulness hormone

Suvorexant Tx

Insomnia (difficulty falling or staying asleep)

Suvorexant S/E

Wt Loss (may be positive if obesity), Drowsiness, Decreased alertness, Amnestic, C/I = Narcolepsy

Secobarbital MoA

Barbituate - GABA(A) Agent = BZD effects + CNS Depression

Secobarbital Tx

ONLY Under Supervision = Anesthesia, Sleep

Secobarbital S/E

SCHEDULE II; Abuse Potential, Poor Therapeutic Index = Coma, Respiratory Depression

Pentobarbital MoA

Barbituate - GABA(A) Agent = BZD effects + CNS Depression

Pentobarbital Tx

ONLY Under Supervision = Anesthesia, Sleep

Pentobarbital S/E

SCHEDULE II; Abuse Potential, Poor Therapeutic Index = Coma, Respiratory Depression

Phenobarbital MoA

Barbituate - GABA(A) Agent = BZD effects + CNS Depression

Phenobarbital Tx

Seizure Control, Anestheia, Sleep; Only Under Supervision

Phenobarbital S/E

Abuse Potential, Poor Therapeutic Index

While both BZDs and Barbituates facilitate GABA's effects, what is the main difference between them?

-At high doses, barbiturates directly increase Cl- flux

-In contrast, BZDs only facilitate GABA.

Diphenhydramine MoA

Antihistamine w/ Antimuscarinic properties

Diphenhydramine Tx

Sedative at recommended doses

Diphenhydramine S/E

O/D = CNS Excitation, Delirium

Modafinil MoA

DA mechanisms likely

Modafinil Tx

Narcolepsy, Sleep Apnea, Shift-Work Disorder; Promotes vigilance (increases ability to perform repetitive tasks)

Modafinil S/E

Abuse Potential (off label use); DEA C-IV (Weak Amphetamine type effect --> Chronic high dose = Crash if stopped)

Armodafinil MoA

R-enantiomer of Modafinil; Weak DA agonist + Weak DA Re-uptake blocking

Armodafinil Tx

PREFERRED over Modafinil for Narcolepsy, Sleep Apnea, Shift-Work Disorder

Oxybate (Gamma Hydroxybutyrate, GHB) Tx

Cataplexy (decreases number of events significantly), Daytime Sleepiness, Narcolepsy - ONLY give at bedtime

Oxybate (Gamma Hydroxybutyrate, GHB) S/E

Abuse potential - body builders, potential SA; Somnolence/Drowsiness, Bedwetting (profound CNS depression), Mood Changes (confusion, depression, suicidality); O/D = CNS Activation

What disorder is C/I with Oxybate specifically and why?

Succinic Semialdehyde Dehydrogenase deficiency:

> Rare genetic disorder

> Failure to metabolize GABA --> 30-fold excess of GHB

> Patients with this condition have excess sedation, but also cognitive impairment and seizures