Name: Guanethidine (Ismelin)
Class: Adrenergic Neuron Blocking Agent
Mechanism: Taken up at NE nerve terminal by NE transport system. Blocks release of NE by action potential or indirect agents. Eventually depletes NE. Causes ¯ BP, some bradycardia. No adrenal effect.
Absorption: Poor oral.
Dist.: No CNS.
Metabolism.:
Excretion, t½: 5 days.
Toxicity/S.E.s: Marked postural & exercise hypotension, bradycardia, fluid retention, asthma aggravation, diarrhea, inhib. of ejaculation. But no CNS effects. C/I for pheochromocytoma (supersens), impending CHF or partial heart block, bronchial asthma. Not to be used in comb. w/MAO inhibitors or sympathomimetics. TCAs block uptake into nerve terminals.. No CNS effects.
Utility: Mod.-severe hypertension (very effective, but last resort due to severe side effects).
Special Features: Supersensitivity develops ( effect of direct acting, but ¯ effect of indirect). Onset 1-3 wks. No longer considered very useful.