pharmacological action
It is a dihydropyridine calcium channel blocker, which selectively inhibits calcium ion from crossing the membrane into smooth muscle cells and myocardial cells, but does not affect plasma calcium concentration, and its effect on smooth muscle is greater than that on myocardium. Its interaction with calcium channels is determined by the gradual rate of its binding and dissociation with the receptor site, so its pharmacological action is gradually produced. Directly acting on the smooth muscle of peripheral artery, reducing peripheral vascular resistance, thus lowering blood pressure. At the therapeutic dose, negative inotropic effect can be observed in vitro, but not in the whole animal experiment. Taking 1 time a day for patients with mild to moderate hypertension can reduce 24-hour blood pressure in lying position and standing position, and long-term use does not cause obvious changes in heart rate or plasma catecholamine. The antihypertensive effect is stable. The antihypertensive effect is related to the dose, and the antihypertensive extent is related to the blood pressure before treatment. The curative effect of patients with moderate hypertension is higher than that of patients with mild hypertension, and those with normal blood pressure have no obvious effect after taking the medicine. The effect of reducing diastolic blood pressure in elderly patients and young patients is similar, and the effect of reducing systolic blood pressure in elderly patients is stronger. This product can reduce the product of cardiac work, heart rate and blood pressure, reduce myocardial oxygen demand and treat fatigue angina pectoris by reducing peripheral resistance (afterload). By inhibiting the contraction of coronary artery and arteriole caused by calcium ion, adrenaline, 5- hydroxytryptamine and thromboxane A2, the blood supply in ischemic area can be restored, and spontaneous angina pectoris can be treated. Clinical trials show that this product significantly prolongs the time of exercise-induced angina pectoris; Studies have shown that this product can prolong the ST segment decline time by 65438±0mm and reduce the frequency of angina pectoris. This effect is lasting and will not significantly affect blood pressure and heart rate. This product does not change the electrocardiogram of patients with angina pectoris and does not aggravate atrioventricular block. After taking this product, patients with normal cardiac function measured the hemodynamics at rest and during exercise, and the cardiac ejection fraction increased, but it had no obvious effect on dp/dt or left ventricular end-diastolic pressure/volume. At the therapeutic dose, this product alone or in combination with beta blockers will not cause negative inotropic effect. This product does not affect sinus node function and atrioventricular conduction. Patients with hypertension or angina pectoris were combined with β -blockers and no ECG abnormalities were found. After taking the medicine, the renal vascular resistance of hypertensive patients with normal renal function decreased, the glomerular filtration rate and renal blood flow increased, but the filtration fraction or urinary protein remained unchanged.
pharmacokinetics
After oral administration, the absorption was complete but slow, and the Tmax was 6 ~ 12h. The single oral dose was 5mg and 10mg, and the Cmax was 3.0 and 5.9ng/ml, respectively. The absolute bioavailability is 64% ~ 90%, which is not affected by diet. The binding rate of plasma protein is over 95%, and the distribution volume is 2 1L/kg. After continuous administration, the plasma protein concentration reached a steady state within 7 ~ 8 days. This product is widely metabolized in the liver as an inactive metabolite (90%). T 1/2 is about 35 hours for healthy people, 50 hours for patients with hypertension, 65 hours for elderly patients and 60 hours for patients with impaired liver function, and renal insufficiency is not affected. 10% of this product is excreted in urine, 60% in the form of metabolites, and 20% ~ 25% in bile or feces. This product cannot be removed by hemodialysis. The clearance rate of this product decreased in elderly patients and patients with liver dysfunction, and AUC increased by 40% ~ 60%. The increase of AUC in patients with moderate and severe heart failure is similar.