Benzodiazepines Lecture Notes

Structure and Site of Action

• Benzodiazepines have a benzene ring fused to a seven-membered diazepine ring.
• Site of action includes:
  • Thalamus
  • Midbrain
  • Ascending Reticular Formation (regulates wakefulness)
  • Limbic System
  • Brainstem
• Receptor: GABA A with benzodiazepine binding site (BZ1 and BZ2)
  • BZ1: Sedation
  • BZ2: Anxiolytic and cognitive impairment

Classification

• Ultra Short Acting: Triazolam, Midazolam
• Short Acting: Lorazepam, Temazepam
• Medium Acting: Nitrazepam, Alprazolam (Xanax)
• Long Acting: Diazepam, Chlordiazepoxide
  • Produce metabolites with long half-life (e.g., Desmethyldiazepam)

Mechanism of Action

• Acts on GABA-A receptor, increasing frequency of chloride channel opening
• Leads to hyperpolarization and CNS depression
• No GABA mimetic effect (cannot reach toxic levels causing coma)

Pharmacokinetics

• Administration: Oral and IV (Not intramuscular due to erratic absorption)
• High volume of distribution, high redistribution
• Short duration of action
• Metabolism:
  • Metabolized in liver: Mnemonic "Found a CD in the liver"
    • Flurazepam, Alprazolam, Chlordiazepam
  • Not metabolized in liver: Mnemonic "This Lot Not"
    • Lorazepam, Oxazepam, Temazepam

Uses

• Mnemonic: AC-diazepam
  • Alcohol Withdrawal
  • Conscious Sedation
  • Diagnostic procedures
  • Insomnia
  • Anticonvulsant
  • Pre-anesthetic medication
  • Muscle relaxant
• Anxiety Disorders: Lorazepam, Oxazepam, Alprazolam, Diazepam, Chlordiazepoxide
• Insomnia: Fluorazepam, Alprazolam, Nitrazepam, Temazepam, Triazolam, Midazolam

Adverse Effects

• Mnemonic: Diazepam not Pam
  • D: Dizziness, Drowsiness, Disorientation
  • I: Impaired insomnia
  • A: Amnesia, Anorexia
  • Z: Nothing
  • E: Elderly-specific symptoms (hypertension, dose adjustment)
  • P: Psychomotor skill impairment
  • A: Ataxia, Amnesia, Apnea
  • M: Neonatal distress (Floppy baby syndrome)

Important Considerations

• Avoid in respiratory depressed patients.
• Alcohol enhances psychomotor depression and amnesic action of benzodiazepines.