Effects of guanethidine

The amphetamines and the anorexiants should not be given during or within 14 days after administration of monoamine oxidase inhibitors (see Chap. 31) because the patient may experience hypertensive crisis and intracranial hemorrhage. When guanethidine is administered with the amphetamines or the anorexiants, the antihypertensive effect of guanethidine may decrease. Coadministration of the amphetamines or the anorexiants with the tricyclic antidepressants may decrease the effects of the amphetamines or the anorexiants. 

The answer is b. (Hardman, p 790.) Neuronal uptake is necessary for the hypotensive action of guanethidine. It competes for the norepinephrine storage site and, in time, replaces the natural neurotransmitter. This is the basis of its hypotensive effect. Drugs that prevent reuptake by the neurons, such as cocaine, would destroy the effectiveness of guanethidine... 

Literature on the effect of guanethidine on other natural tissue amines is scanty. In rats, up to about 50 per cent depletion of 5-hydroxytryptamine has been reported in the brain [211], thyroid [333], duodenum [211] and small intestine [334, 335], but no depletion has been observed in the spleen or ileum [21 1,334]. Guanethidine does not affect rat-heart histamine [336]. 

Ephedrine may negate the antihypertensive effects of guanethidine and may potentiate the pressor effects of MAO inhibitors causing hypertensive crisis and intracranial hemorrhage. 

Drug interactions hyperthermia, seizures, coma, and death with MAOIs serotonin syndrome with selective serotonin reuptake inhibitors prevent anti-HTN effect of guanethidine and CNS-acting a2 agonists,... 

The antihypertensive effects of guanethidine may be partially or totally reversed by the mixed-acting sympathomi-metics. Halogenated hydrocarbon anesthetics may sensitize the myocardium to the effects of catecholamines. Use of vasopressors may lead to serious arrhythmias. MAO inhibitors, such as tranylcypromine, increase the pressor response to mixed-acting vasopressors. Possible hypertensive crisis and intracranial hemorrhage may occur. This interaction may also occur with furazolidone, an antimicrobial with MAO inhibitor activity. In obstetrics, if vasopressor drugs are used either to correct hypotension or are added to the local anesthetic solution, some oxytocics may cause severe persistent hypertension in the presence of mephenteramine. The pressor response of mephenteramine may be attenuated by tricyclic antidepressants, which block the uptake of norepinephrine. 

What is the differential postural effect of guanethidine in the therapy of hypertension ... 

The antihypertensive effects of clonidine are reduced by about 50% when it is co-administered with clomipramine or desipramine. The antihypertensive effects of guanethidine can be reduced by doxepin, amitriptyline, or desipramine, but not by maprotiline. 

The antihypertensive effects of guanethidine can be opposed by the concurrent use of haloperidol. 

Clezy TM. Oral contraceptives and hypertension the effect of guanethidine. 1970)... 

The antihypertensive effects of guanethidine can be reduced or abolished by drugs including dexamfetamine, ephedrine, metam-fetamine and methylphenidate. The blood pressure may even rise higher than before treatment with the antihypertensive. 

Flegin OT, Morgan DH, Oates JA, Shand DG. The mechanism of the reversal of the effect of guanethidine by amphetamines in cat and man. BrJPharmacol (1970) 39, 253P-254P. 

Large doses of chlorpromazine may reduce or even abolish the antihypertensive effects of guanethidine, although in some patients the inherent hypotensive effects of the chlorpromazine may possibly predominate. Case reports surest that haloperidol and tiotixene may interact similarly. Molindone is reported not to interact with guanethidine, and a single-dose of prochlorperazine also did not interact with guanethidine. 

However, a single 25-mg dose of prochlorperazine did not significantly antagonise the effect of guanethidine 15 to 20 mg daily in 5 patients. In another study in 7 patients taking guanethidine 50 to 95 mg daily, the addition of molindone 30 to 120 mg daily had no effect on blood pressure. ... 

Phenylbutazone and kebuzone reduce the antihypertensive effects of guanethidine. 

The antihypertensive effects of guanethidine are reduced or abolished by amitriptyline, desipramine, imipramine, nortriptyline and protriptyline. Doxepin in doses of300 mg or more daily interacts similarly, but in smaller doses appears not to do so, although one case is reported with doxepin 100 mg daily. A few case reports surest that maprotiline and mianserin do not interact with guanethidine. 

The manufacturer notes that excessive blood pressure reductions may occur if minoxidil is used in patients taking guanethidine, because of the adrenergic blocking effects of guanethidine. If ex-... 

Gill, J.R., Bartter, F.C. Adrenergic nervous system in sodium metabolism. II. Effects of guanethidine on the renal response to sodium deprivation in normal man. New Engl. J. Med. 275, 1466-1471 (1966)... 

A comparison of the anti hypertensive effect of guanethidine with three of its metabolites in renal hypertensive rats leads to the conclusion that guanethidine per se, and not its metabolites, is responsible for its hypotensive effects. ... 

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