Benzodiazepine

1. See Also
   1. Benzodiazepine Overdose
2. Indications
   1. Anxiety Disorder
   2. Sedation
      1. Insomnia
      2. Surgical, Medical and Psychiatric procedures
   3. Muscle spasm
   4. Seizure disorder
   5. Alcohol Withdrawal and withdrawal from other drugs
3. Contraindications
   1. Myasthenia Gravis
   2. Acute narrow-angle Glaucoma
   3. Substance Abuse (relative contraindication)
4. Mechanism
   1. Potentiates activity of gamma-aminobutyric acid (GABA)
   2. GABA is an inhibitory neurotransmitter in the CNS
      1. Muscle relaxant
      2. Anticonvulsant
      3. Anxiolytic
      4. Anti-aggressiveness
      5. Sedation
5. Advantages
   1. Rapid onset of action
      1. Anxiolytic effect within 1-2 days
   2. Tolerance develops rapidly to adverse effects
   3. Tolerance does not develop for Anxiolytic effect
   4. Few drug interactions
   5. Good safety profile
6. Preparations
   1. Long Acting Benzodiazepines
      1. Chlordiazepoxide (Librium)
      2. Diazepam (Valium, Valrelease)
      3. Flurazepam (Dalmane)
      4. Chlorazepate (Tranxene)
      5. Clonazepam (Klonopin)
      6. Quazepam (Doral)
      7. Halazepam (Paxipam)
   2. Medium Acting Benzodiazepines
      1. Lorazepam (Ativan)
      2. Temazepam (Restoril)
   3. Short acting Benzodiazepines
      1. Oxazepam (Serax)
      2. Alprazolam (Xanax)
      3. Triazolam (Halcion)
      4. Estazolam (Prosom)
      5. Midazolam (Versed)
7. Absorption
   1. Preparations with most rapid absorption
      1. Diazepam (Valium)
      2. Clorazepate
      3. Alprazolam (Xanax) taken sublingually
   2. Preparations with slowest absorption
      1. Oxazepam (Serax)
      2. Co-administration of Benzodiazepine with medication
         1. Maalox
         2. Gelusil
8. Metabolism
   1. Hepatic Metabolism
      1. Microsomal oxidation
      2. Conjugation by glucuronyl transferases
   2. Renal Excretion
9. Dosing: Strategies
   1. Initiate treatment with low dose Benzodiazepine
   2. Start with 50% of typical dose in at risk cohorts
      1. Elderly
      2. Hepatic dysfunction
      3. Renal dysfunction
   3. Prevent symptoms completely by using a regular regimen
   4. Escalate dose slowly, no more often than every 2 weeks
   5. Maintain lowest effective dose for several months
   6. Periodically attempt to lower dose
   7. Start taper at 25% decrements and slow when below 50%
   8. Decrease dose slowly, no more often than every 4 weeks
   9. Change to longer half-life drug if symptom breakthrough
      1. Example: Switch from Xanax to Klonopin
10. Dosing: Equivalent to Valium 60 mg (for withdrawal)
    1. High Potency Benzodiazepines
       1. Alprazolam (Xanax) 6 mg
       2. Clonazepam (Klonopin) 24 mg
       3. Lorazepam (Ativan) 12 mg
    2. Low Potency Benzodiazepines
       1. Chlordiazepoxide (Limbitrol) 150 mg
       2. Flurazepam (Dalmane) 90 mg
       3. Halazepam (Paxipam) 240 mg
       4. Oxazepam (Serax) 60 mg
       5. Temazepam (Restoril) 60 mg
11. Pregnancy and Lactation
    1. Pregnancy Category: D
    2. Lactation: Not allowed
12. Adverse Effects
    1. Drug Dependence
       1. Risk Benzodiazepine Withdrawal (Seizures may occur, especially if underlying Seizure disorder)
    2. Sedation
    3. Nausea
    4. Blood dyscrasia
    5. Anterograde amnesia
    6. Cognitive Impairment
    7. Respiratory depression
    8. Hyponatremia or Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
13. Monitoring: Consider in patients on longterm therapy
    1. Complete Blood Count
    2. Liver Function Tests
14. References
    1. Tasman (1997) Psychiatry, Saunders, p. 1641-6
    2. Katzung (1989) Pharmacology, Lange, p. 264-7