Guanethidine, Ismelin

  • Mechanism
  1. Transiently increases Norepinephrine release from nerve terminals (with transient Hypertension and Tachycardia)
  2. Subsequent decreased Norepinephrine release via depletion of Norepinephrine from nerve stores
  3. Prevents Norepinephrine release at nerve endings
  4. Poorly crosses blood brain barrier
    1. No sedation (contrast with Reserpine)
  • Pharmacokinetics
  1. Bioavailability 30% after oral dose
  2. Half is Metabolized
  3. Half-life: 5 days (very long)
    1. Adverse effects persists for weeks after stopping agent
  • Indications
  1. Rarely used in United States
  2. May have a place in Severe Hypertension, but has been replaced by newer agents with fewer adverse effects
  • Adverse Effects
  1. Transient Hypertension and Tachycardia (see mechanism above)
  2. Hypotension
    1. Reflex Tachycardia mechanism blocked by loss of Norepinephrine release
    2. Decreased Cardiac Output
  3. Bradycardia
  4. COPD Exacerbation
  5. Nasal congestion (significantly increased)
  • Drug Interactions
  1. Tricyclic Antidepressants (TCA)
    1. TCAs block Guanethidine entry into cells
  • References
  1. Olson (2020) Clinical Pharmacology, MedMaster, Miami, p. 64-5