indication

For the treatment of moderate and severe hypertension, either alone or as an adjunct, and for the treatment of renal hypertension.

pharmacology

High blood pressure can cause the heart and arteries to not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Guanethidine works by decreasing the heart rate and relaxing the blood vessels so that blood can flow more easily through the body, thereby reducing these risks. It is a postganglionic sympathetic nerve terminal blocker that prevents the release of norepinephrine from nerve terminals.

mechanism of action

Guanethidine acts at the sympathetic neuroeffector junction by inhibiting or interfering with the release and/or distribution of norepinephrine, rather than acting at the effector cell by inhibiting the association of norepinephrine with its receptors. It is taken up by norepinephrine transporters. It becomes concentrated in NE transmitter vesicles, replacing NE in these vesicles. This leads to a gradual depletion of NE stores in the nerve endings. Once inside the terminal it blocks the release of noradrenaline in response to arrival of an action potential. In contrast to ganglionic blocking agents, Guanethidine suppresses equally the responses mediated by alpha-and beta-adrenergic receptors but does not produce parasympathetic blockade. Since sympathetic blockade results in modest decreases in peripheral resistance and cardiac output, Guanethidine lowers blood pressure in the supine position. It further reduces blood pressure by decreasing the degree of vasoconstriction that normally results from reflex sympathetic nervous activity upon assumption of the upright posture, thus reducing venous return and cardiac output more.

toxicity

Side effects include drowsiness, dizziness, tiredness or confusion. LD₅₀=1000 mg/kg (mouse, oral)

biotransformation

Guanethidine is converted by the liver to three metabolites, which are excreted in the urine. The metabolites are pharmacologically less active than the parent compound.

absorption

3-30% of oral dose (poor and highly variable)

half life

1.5 days

route of elimination

Ismelin is converted by the liver to three metabolites, which are excreted in the urine.

drug interactions

Acetophenazine: Acetophenazine may decrease the effect of guanethidine.

Amitriptyline: The tricyclic antidepressant, amitriptyline, decreases the effect of guanethidine.

Amoxapine: The tricyclic antidepressant, amoxapine, decreases the effect of guanethidine.

Amphetamine: Amphetamine may decrease the effect of guanethidine.

Benzphetamine: Benzphetamine may decrease the effect of guanethidine.

Chlorpromazine: Chlorpromazine may decrease the effect of guanethidine.

Chlorprothixene: Chlorprothixene may decrease the effect of guanethidine.

Clomipramine: The tricyclic antidepressant, clomipramine, decreases the effect of guanethidine.

Desipramine: The tricyclic antidepressant, desipramine, decreases the effect of guanethidine.

Dexfenfluramine: Dexfenfluramine may decrease the effect of guanethidine.

Dextroamphetamine: Dextroamphetamine may decrease the effect of guanethidine.

Diethylpropion: Diethylpropion may decrease the effect of guanethidine.

Dobutamine: Dobutamine may decrease the effect of guanethidine.

Dopamine: Dopamine may decrease the effect of guanethidine.

Doxepin: The tricyclic antidepressant, doxepin, decreases the effect of guanethidine.

Ephedra: Ephedra may decrease the effect of guanethidine.

Ephedrine: Ephedrine may decrease the effect of guanethidine.

Epinephrine: Epinephrine may decrease the effect of guanethidine.

Ethopropazine: Ethopropazine may decrease the effect of guanethidine.

Fenfluramine: Fenfluramine may decrease the effect of guanethidine.

Fluphenazine: Fluphenazine may decrease the effect of guanethidine.

Haloperidol: Haloperidol may decrease the effect of guanethidine.

Imipramine: The tricyclic antidepressant, imipramine, may increase the sympathomimetic effect of guanethidine.

Isocarboxazid: Isocarboxazid may decrease the effect of guanethidine.

Mazindol: Mazindol may decrease the effect of guanethidine.

Mesoridazine: Mesoridazine may decrease the effect of guanethidine.

Metaraminol: Metaraminol may decrease the effect of guanethidine.

Methamphetamine: Methamphetamine may decrease the effect of guanethidine.

Methdilazine: Methdilazine may decrease the effect of guanethidine.

Methotrimeprazine: Methotrimeprazine may decrease the effect of guanethidine.

Methoxamine: Methoxamine may decrease the effect of guanethidine.

Methylphenidate: Methylphenidate may decrease the effect of guanethidine.

Norepinephrine: Norepinephrine may decrease the effect of guanethidine.

Nortriptyline: The tricyclic antidepressant, nortriptyline, decreases the effect of guanethidine.

Pargyline: Pargyline may decrease the effect of guanethidine.

Perphenazine: Perphenazine may decrease the effect of guanethidine.

Phendimetrazine: Phendimetrazine may decrease the effect of guanethidine.

Phenelzine: Phenelzine may decrease the effect of guanethidine.

Phenmetrazine: Phenmetrazine may decrease the effect of guanethidine.

Phentermine: Phentermine may decrease the effect of guanethidine.

Phenylephrine: Phenylephrine may decrease the effect of guanethidine.

Phenylpropanolamine: Phenylpropanolamine may decrease the effect of guanethidine.

Prochlorperazine: Prochlorperazine may decrease the effect of guanethidine.

Promazine: Promazine may decrease the effect of guanethidine.

Promethazine: Promethazine may decrease the effect of guanethidine.

Propericiazine: Propericiazine may decrease the effect of guanethidine.

Propiomazine: Propiomazine may decrease the effect of guanethidine.

Protriptyline: The tricyclic antidepressant, protriptyline, decreases the effect of guanethidine.

Pseudoephedrine: Pseudoephedrine may decrease the effect of guanethidine.

Thiethylperazine: Thiethylperazine may decrease the effect of guanethidine.

Thioridazine: Thioridazine may decrease the effect of guanethidine.

Thiothixene: Thiothixene may decrease the effect of guanethidine.

Tranylcypromine: Tranylcypromine may decrease the effect of guanethidine.

Trifluoperazine: Trifluoperazine may decrease the effect of guanethidine.

Triflupromazine: Triflupromazine may decrease the effect of guanethidine.

Trimeprazine: Trimeprazine may decrease the effect of guanethidine.

Trimipramine: The tricyclic antidepressant, trimipramine, decreases the effect of guanethidine.