II. Mechanism
- Transiently increases Norepinephrine release from nerve terminals (with transient Hypertension and Tachycardia)
- Subsequent decreased Norepinephrine release via depletion of Norepinephrine from nerve stores
- Prevents Norepinephrine release at nerve endings
- Chronic sensitization of nerves to Sympathomimetics
- Poorly crosses blood brain barrier
- No sedation (contrast with Reserpine)
III. Pharmacokinetics
- Bioavailability 30% after oral dose
- Half is Metabolized
-
Half-Life: 5 days (very long)
- Adverse effects persists for weeks after stopping agent
IV. Indications
- Rarely used in United States
- May have a place in Severe Hypertension, but has been replaced by newer agents with fewer adverse effects
V. Contraindications
VI. Dosing: Adults
- Start: 10 mg orally daily
- Titrate to 25 to 50 mg orally daily
VII. Adverse Effects
- Transient Hypertension and Tachycardia (see mechanism above)
-
Orthostatic Hypotension
- Reflex Tachycardia mechanism blocked by loss of Norepinephrine release
- Decreased Cardiac Output
- Bradycardia
- Diarrhea
- COPD Exacerbation
- Nasal congestion (significantly increased)
VIII. Drug Interactions
-
Tricyclic Antidepressants (TCA)
- TCAs block Guanethidine entry into cells
IX. References
- Olson (2020) Clinical Pharmacology, MedMaster, Miami, p. 64-5