Anxiolytics

• Sedative-Hypnotics
• CNS depression
  • Sedation
  • Hypnosis
  • Anesthesia
  • Coma
• Benzodiazepines
• MOA: Activate GABAa receptor binding sites
  • Lorazepam, oxazepam, and temazepam are safe in hepatic dysfunction

• General

  • Anxiolysis, hypnosis, amnesia, no analgesic properties
  • Paradoxical agitation, confusion and aggression within 1 hour of use in elderly
  • Increased cognitive impairment and falls in elderly
  • Withdrawal
  • Life-threatening
    • Increased risk of seizures
    • Anxious and irritable, insomnia, dysphoria, anxiety
    • Begins typically 5-10 days after cessation if long acting, resolve in 2-4 weeks

  • Use Longer half-life benzos to wean off shorter half-life drugs and alcohol

    • "self-taper" by regenerating deficient brain receptors
      • Overdose with alcohol (sedative-hypnotic overdose)
      • Synergistic respiratory depression when combined with opiates
      • Bradycardia, hypotension, respiratory depression, CNS depression, lethargy, somnolence, hyporeflexia
      • Flumazenil to treat OD
    • Short (half-life \<6h):
      • Triazolam (Halcion)
      • Insomnia
      • Oxazepam (Serax)
      • Limited first pass metabolism, "Outside The Liver"
      • Midazolam (Versed)
      • Used for sedation during medical procedures
      • Flumazenil to reverse
      • SE: Decreased RR, hypotension, somnolence, hiccups, bronchospasm
      • Clorazepate (Tranxene)
      • Adjunct in management of partial seizures
    • Intermediate (half-life 6-24h):
      • Alprazolam (Xanax)
      • Tmax: 1-2 hours, Half-Life: 12-15 hours
      • Depression, panic disorder, SAD
      • Medium strength (~1mg of Xanax = 2mg Ativan)
      • Sedation: 0.25-0.5mg BID-TID
      • Lorazepam (Ativan)
      • Tmax: 1-6 hours, Half-Life: 10-20 hours
      • Psychotic agitation, alcohol withdrawal, acute control of seizures
      • Only IM benzodiazepine
      • Weakest
      • Sedation: 1-2mg daily to BID
      • Hypnosis: 2-4mg
      • Limited first pass metabolism, "Outside The Liver"
      • Temazepam (Restoril)
      • Insomnia
      • Alprazolam has more euphoria, less sedation
      • Limited first pass metabolism, "Outside The Liver"
    • Long (half-life ≥24h):
      • Diazepam (Valium)
      • Tmax: 1-2 hours, Half-Life: 20-80 hours
      • Muscle relaxation, analgesia, seizures, alcoholic withdrawal (seizures)
      • Clonazepam (Klonopin)`
      • Seizures, mania, SAD, panic disorder, OCD
      • Strongest strength (~1mg of Klonopin = 2-4mg Ativan)
      • Used for sleep due to longer half life
      • q4hrs prn for CIWA
      • Chlordiazepoxide (Librium)
      • Tmax: 2-4 hours, Half-Life: 15-40 hours
      • Alcohol withdrawal (particularly for agitation)
      • Flurazepam (Dalmane)
      • Insomnia
    • Barbiturates
    • Phenobarbital
      • Can be used in Crigler-Najjar II to induce UDP-glucuronyl transferase
      • Sedation: 15-30mg BID to TID
    • Promethazine (Phenegran)
    • SE: Marked sedation, antiemetic
    • Diphenhydrinate (Dramamine)
    • Diphenhydramine (Benadryl)
    • Hydroxyzine Pamoate (Atarax, Vistaril)
    • SE: Marked Sedation
    • Cyclizine (Marezine)
    • Meclizine (Bonine)
    • Doxylamine
    • Nausea and vomiting in pregnancy
    • Ramelteon (Rozerem)
    • MOA: MT1 agonist (promotes sleep onset), MT2 agonist (shift timing of circadian system) that improves sleep onset
      • Selective melatonin agonist (MT1 and MT2 selective)
    • Use: Insomnia
      • Good for sleep maintenance
      • DELIRIA-J (2014) – Substantial reduction in the risk of developing delirium in elderly inpatients (65-85) when given nightly for 7 days.
    • No tolerance or dependence
    • Suvorexant (Belsomra)
    • Non-Benzo GABA-A Receptor Agonists
    • Non-Benzo GABA-A Receptor Agonists

  • Alpha 1 subunit selective

  • Zaleplon (Sonata)
  • Initial insomnia (non-benzo), 1hour action, sleep onset insomnia
  • Short, insomnia
  • Sleep Initiation
  • Rapid onset, reduces hang-over effect
  • SE: Dizziness and Somnolence
  • Zolpidem (Ambien)
  • Dsoe: Max 5mg females, 10mg males
  • Use: Insomnia
    • ER version good for sleep maintenance
    • Reduces sleep latency, nocturnal awakenings
    • Increases total sleep time
    • 1-4.5 hours, sleep onset or maintenance
  • SE: Anterograde amnesia
    • Can't be used if patient has ever sleepwalked
  • Eszopiclone (Lunsta)
  • Intermediate (6 hours), onset or maintenance
  • Intermediate, insomnia
  • Buspirone (Buspar)
  • Dose: 5mg TID to 20mg TID max
  • MOA: 5HT1a partial agonist
    • Takes 2 weeks to work
    • Increased grapefruit increases buspar concentrations
  • Use: Anxiety, GAD
    • Non-sedating, no anticonvulsant or muscle relaxant properties
    • Useful in alcoholics due to the lack of CNS potentiation
    • Can be used in bruxism and Sexual side effects (inhibits 5HT2 and agonizes DA)
  • SE: headache, nausea, dizziness
    • Can't overdose, so safe