Guanethidine (Ismelin)& Guanadrel (Hylorel) 
  • Guanethidine (Ismelin) inhibits the function of postganglionic adrenergic neurons, thus inhibiting sympathetic function.
  • Guanethidine (Ismelin) uses the norepinephrine (N.E.) re-uptake transporter to reach its site of action, the neurosecretory vesicles.
    • Guanethidine (Ismelin) replaces norepinphrine in the vesicle and is released instead of the normal transmitter.
    • Guanethidine (Ismelin) is an inactive transmitter and the replacement of N.E. by an inactive agent is responsible for its antihypertensive effects (maintenance dosing).
  • Adrenergic blockade by guanethidine (Ismelin) results in post-synaptic supersensitivity.
  • Sympathetic blockade by guanethidine (Ismelin) produces:
    •  venodilatation
    •  reduction in cardiac output due to inhibition of cardiac sympathetic innervation
    •  blockade of  the sympathetic reflex arteriolar response to the reduction in cardiac output.

 

 

 Adverse Effects
  • Symptomatic hypotension (due to sympathetic reflex blockade)
  • Sexual dysfunction (delayed ejaculation)
  • Diarrhea
  • Guanethidine (Ismelin) effects blocked by N.E. reuptake blockers (tricyclic antidepressants, cocaine, ephedrine, amphetamine, chlorpromazine (Thorazine))