Structurally very similar to dihydralazine which is a mechanism based CYP-1A2 and 3A4 inhibitor. CYP 1A2- inducer. Several references warn against its use.

Antihypertensive, peripheral vasodilator.

Structurally very similiar to dihydralazine which is metabolized in the liver by non-CYP dependent N-acetylation and by CYP-dependent N-oxidation.

Dihydralazine appears to induce CYP1A2. The N-oxidation may theoretically give rise to reactive hydroxylamine and that way to inactivation of hepatic CYPs. In vitro studies with both rat- and human liver microsomes demonstrate that dihydralazine is a mechanism based inhibitor of CYPs 1A2 and 3A4. Effects of hydralazine on the activity of delta-aminolevulinate synthase and on the formation of porphyrins and cytochrome P-450 were examined in the 18-day-old chick embryo liver in ovo. Hydralazine was found to induce delta-aminolevulinate synthase in this system. Hydralazine therefore have the potential to precipitate clinical expression in human hereditary hepatic porphyrias and should be avoided or used with caution in patients with these disorders (Anderson KE. Biochim Biophys Acta 1978).

None

A male hypertensive patient (age 28) is treated with clonidine (Bhadoria). After withdrawal because of non-compliance the patient is treated acutely for severe hypertension with methyldopa and hydralazine. Blood pressure gets normal, but continuous upper abdominal pain, constipation, red urine, and a strongly positive PBG (Walter-Schwartz test) arise upon this treatment. The patient improves on withdrawal of methyldopa and hydralazine, and administration of glucose. In this case two drugs are implicated, but methyldopa is less likely to have contributed (see methyldopa monograph).