ANTIANXIETY/ANXIOLYTICS

• Anxiety Disorders


  • GAD/Generalized-Anxiety Disorder
  • PTSD/Post-Traumatic Stress Disorder
  • OCD/Obsessive Compulsive Disorder
  • PD/Panic Disorder
  • SP/Social Phobia
• Drugs for Anxiety Disorders

  • Benzodiazepines (BZD)
  • Buspirone
  • Beta-blockers
  • TCAs, MAOIs, SSRIs
  • Barbiturates
• Benzodiazepines (BZD)


  Mechanism of Action: Potentiates the action of the inhibitory neurotransmitter GABA. GABAergic drug → results to opening of Cl- channels → causing hyperpolarization (enhance negative ions intracellular). BZDs → increase duration or prolongation of chloride channel opening.
• 1. DMDZ (N-desmethyldiazepam)


  Common metabolite of benzodiazepines with a half-life of 36-200hrs
• Classification of benzodiazepines by half-life

  • Short-acting: Midazolam, Triazolam
  • Intermediate-acting: Alprazolam, Oxazepam, Lorazepam, Temazepam, Estazolam
  • Long-acting: Chlordiazepoxide, Chlorazepate, Halazepam, Clonazepam, Diazepam, Prazepam
• Side Effects of Benzodiazepines

  • CNS depression-sedation, ataxia, incoordination, weakness, fatigue
  • Anterograde amnesia – inability to recall recent memories
  • Paradoxical reaction
  • Physiologic dependence
  • Withdrawal-induced relapse or rebound
• Buspirone


  Mechanism of Action: Presynaptic 5-HT1A partial agonist and postsynaptic 5-HT1A receptor blocker
• Advantages of Buspirone

  • No interaction with sedative-hypnotics
  • No physical dependence/withdrawal/abuse
  • No marked sedative/hypnotic/euphoric effects
  • No anticonvulsant/muscle relaxant properties
• Side Effects of Buspirone

  • Minimal psychomotor disturbance
  • Tachycardia, palpitations, dizziness, nervousness, GI distress
• Other Drugs for Anxiety Disorders

  • Beta-blockers: Propranolol, Atenolol (used for Panic D/O)
  • TCAs, MAOIs, SSRIs
  • Barbiturates
• Barbiturates


  Mechanism of Action: GABAergic effect (increase duration or prolongation of chloride channel opening)
• Classification of Barbiturates by Duration

  • Ultra-short acting (duration 30 minutes): Thiopental, Thiamylal, Methohexital
  • Short-acting (duration 2 hours): Hexobarbital, Pentobarbital, Secobarbital
  • Intermediate-acting (duration 3-5 hours): Amobarbital, Butabarbital
  • Long-acting (duration > 6 hours): Phenobarbital
• Clinical Uses of Barbiturates


  • Sedative
  • Seizures
  • Adjuncts to surgical anesthetics
  • Treatment of neonatal hyperbilirubinemia (Phenobarbital promotes glucuronidation to form conjugated bilirubin which cannot penetrate blood-brain barrier)
• Toxicity of Barbiturates


  • Over-sedation and suppressed REM sleep
  • Tendency for tolerance to develop rapidly
  • High potential for abuse and physical dependence
  • Frequent drug interaction
  • Acute overdose: coma, respiratory depression, cardiovascular collapse, renal failure