Guanethidine Desipramine

The tricyclic antidepressants (e.g., desipramine and amitriptyline) and some phenothiazines block the sympathetic neuronal amine uptake system they thereby would also block the uptake of guanethidine and thus reduce its hypotensive effectiveness. Conversely, guanethidine competitively inhibits the uptake of drugs that are substrates for neuronal uptake, such as the indirectly acting adrenomimetics, or sympathomimetics (see Chapter 10). 

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 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. 

Five hypertensive patients taking guanethidine sulfate 50 to 150 mg daily had a mean arterial blood pressure rise of 27 mmHg when they were also given desipramine 50 or 75 mg or protriptyline 20 mg daily for 1 to 9 days. The full antihypertensive effects of the guanethidine were not reestablished until 5 days after the antidepressants were withdrawn. ... 

The same interaction has been described in other reports, with guanethidine and desipramine, imipramine, amitriptyline, protriptyline or nortriptyline. The interaction may take seveid days to develop fully and can last an average of 5 days after discontinuation of the tricyclic. Some studies, and clinical experience suggests that doxepin does not begin to interact until doses of about 200 to 250 mg daily are used, then at 300 mg or more daily it interacts to the same extent as other tricyclics. " However, in one case excessive hypertension occurred in a man taking guanethidine and doxepin 100 mg daily. ... 

Mitchell JR, Arias L, Oates JA. Antagonism of the antihypertensive actions of guanethidine sulfate by desipramine hydrochloride. (1967) 202, 973-6. 

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