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