II. Mechanism
- Identical mechanism as with Guanethidine, but with faster activity, and shorter Half-Life
- 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
- Poorly crosses blood brain barrier
- No sedation (contrast with Reserpine)
III. Pharmacokinetics
- Incompletely absorbed orally (similar to Guanethidine)
- Half is Metabolized
-
Half-Life: 12 hours
- Contrast with the very long, 5 day half life of Guanethidine
IV. Indications
- Rarely used in United States
- May have a place in Hypertension, but has been replaced by newer agents with fewer adverse effects
V. Contraindications
VI. Adverse Effects
- Effects are less severe than with Guanethidine
- Transient Hypertension and Tachycardia (see mechanism above)
-
Hypotension
- Reflex Tachycardia mechanism blocked by loss of Norepinephrine release
- Decreased Cardiac Output
- Bradycardia
- COPD Exacerbation
- Nasal congestion (significantly increased)
VII. Drug Interactions
-
Tricyclic Antidepressants (TCA)
- TCAs block Guanethidine entry into cells
VIII. References
- Olson (2020) Clinical Pharmacology, MedMaster, Miami, p. 64-5