Guanethidine And Guanadrel

• 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 effects blocked by N.E. reuptake blockers (tricyclic antidepressants, cocaine, ephedrine, amphetamine, chlorpromazine )

Category: Pharmacology Notes