Acute systemic and renal haemodynamic effects and long-term antihypertensive action of cadralazine in patients pretreated with beta-blockers and diuretics.
The antihypertensive effects of the hydralazine-related compound cadralazine (2-(3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl)ethyl carbazate, ISF 2469), were investigated in 16 patients with primary hypertension concurrently treated with beta-blockers and diuretics. The protocol included a double-blind placebo controlled haemodynamic evaluation after the first tablet and two 4-week double-blind placebo controlled cross-over periods followed by an open evaluation during 2 months. Cadralazine induced a moderate, prolonged fall in blood pressure that was associated with vasodilatation and slight increases in cardiac output (dye-dilution) and heart rate. Renal plasma flow (PAH) and glomerular filtration rate (51Cr-EDTA) were not significantly influenced, but the filtration fraction was reduced. Plasma concentrations of noradrenaline and adrenaline rose, whereas plasma renin activity was unchanged. The haemodynamic parameters were not correlated with the plasma concentrations of cadralazine. During chronic cadralazine treatment the supine blood pressure was significantly lower than during the double-blind placebo phase (160/93 vs 174/102 mmHg). The compound was generally well tolerated but the body weight increased slightly (1.1 kg), probably because of fluid retention. Several patients who had previously experienced side effects with hydralazine, including one with hydralazine-syndrome, tolerated cadralazine well. This suggests that cadralazine does not cross-react with hydralazine.
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002986:Clinical Trials as Topic; D004232:Diuretics / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011724:Pyridazines / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D011897:Random Allocation; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D004232:Diuretics; D011724:Pyridazines; C031877:cadralazine