Résumé
This work included evaluation and comparison of isradipine and dilitiazem on the cardiovascular system and smooth muscles of experemintal animals. Clinical studies were also performed on hypertensive patients undergoing surgery. Isradipine [50-800 micro g/kg] and dilatiazem [0.75-12 mg/kg] produced sudden and transient fall in blood pressure of anaesthetized cats and this drop was shown to be peripherally. Isradipine was found to be superior in its hypertensive action. No abnormality in the ECG pattern was observed apart from the bradycardia which happended only with high doses of both drugs. Isradipine only in doses ranging from 4-16 micro g while all concentrations of diltiazem [12.5-200 micro g], in the present study, included a significantly dose dependent cardio-inhibitory effect, probably due to a direct action. On isolated rabbit's aortic spiral strip, both isradipine [0.2-3.2 micro g/ml] and diltilazem [2.5-40 micro g/ml] did not alter the basal tone of the strip but they reduced the amplitude of noradrenaline induced aortic contractions significantly. The effect of isradipine was greater than that of diltiazem. On smooth muscles, isradipine and diltiazem elicited a direct spasmolytic action on rabbit's intestinal contractions. This was confirmed by the relief of the drugs to barium chloride-induced spasm of the smooth muscles. The antispasmodic effect of isradipine was found to be highly superior than that of diltiazem and the difference was found to be significant. As regards the effect on tracheal preparations, isradipine [0.25-4 micro g/ml] and diltiazem [2.540 micro g/ml] did not alter the basal tone of tracheal preparations, but in case of histamine-induced contractions, only diltiazem reduced that response. The clinical study was conducted, in the present study, on patients of ASA grade I and II. By comparing the haemodynamic effects of isradipine and diltiazem with the control group of patients, it was found that the reduction of systolic and mean arterial blood pressure was greater in the isradipine treated patients than in those receiving dilitiazem; whereas the decrease of diastolic blood pressure was not different. The cardiac output is slightly increased in both groups. The heart rate remained unchanged in patients treated with isradipine but it was decreased significantly in those receiving diltiazem. As regards the metabolic effect, isradipine produced a decrease in total serum cholesterol with no significant effect on blood sugar level, however diltiazem increased both. Isradipine, in the present study, was better tolerated tam diltiazem and patients under isradipine therapy complained of fewer side effects. So it can be concluded that isradipine can be safely administered to hypertensive patients, regardless of concomitant disease. Unlike diltiazem, it preserves cardiac function and has no negative impact on lipids or blood chemistry. So it can be safely administered to hyperetensive patients with asthma, diabetes or congestive heart failure