Persistent increase in blood pressure is an important pathological basis for atherosclerosis, and in addition to antihypertensive therapy, vascular endothelial damage should be avoided. Secondary prevention of coronary heart disease is commonly used with pry or sartan drugs, which are associated with blood pressure regulation, water and sodium retention, and water metabolism. Angiotensin II. is a powerful vasoconstrictor substance in the renin-angiotensin-aldosterone system, and its effect on blood pressure regulation is very prominent, so the angiotensin II receptor is considered to be the main target of antihypertensive.
Alisartanyl
Alisartantil, alisartan ester is the latest generation of sartan drugs, that is, angiotensin II receptor blockers, oral absorption is better, half-life is about 10h, peak time is 1.5 ~ 2.5h. It can act on the renin-angiotensin-aldosterone system, inhibit the binding of vascular nervousness II. to the receptor, inhibit the secretion of aldosterone, prevent the proliferation of endothelial cells, and promote the release of vasodifinder substances such as prostacyclin and nitric oxide, and then expand peripheral arterioles, reduce vascular resistance, and reduce blood pressure.
In addition, the drug can effectively delay cardiomyocyte hypertrophy and fibrosis, reduce the left ventricular stress load, and then inhibit ventricular remodeling and improve cardiac function. Alisartan ester hydrolysate is EXP-3174, while binding to the angiotensin II receptor, it has less effect on other hormone receptors or important ion channels in the cardiovascular system, and will not hinder the degradation of angiotensin-converting enzyme on bradykinin, so it will not cause adverse reactions such as cough caused by the enhancement of bradykinin effect, and is suitable for long-term use.
Alisartan ester has a fast onset of action, good consistency of antihypertensive effect at different times, small fluctuations in blood pressure, small adverse drug reactions, and hydrolytic metabolism does not rely on hepatocellular pigment P450 enzyme, which significantly reduces the liver burden of patients and is suitable for long-term use. Alisartantil can also resist atherosclerosis, anti-inflammatory, etc., and can improve endothelial function in patients. Clinical studies have looked at ambulatory blood pressure and found that alisartan ester reduces daytime and nighttime blood pressure levels better than irbesartan.
In addition, hypertension and coronary heart disease are related to vascular endothelial dysfunction, and the hemodynamic changes produced by continuously increasing blood pressure can activate a series of biological factors in the blood and induce endothelial damage. Endothelin-1 (ET-1) and nitric oxide (NO) are a pair of vasoactive substances that antagonize each other. ET-1 is a vasoconstrictive substance that can aggravate atherosclerosis; NO can relax blood vessels and resist platelet aggregation, so both can reflect the degree of damage to vascular endothelial cells. After alisartan ester was treated with hypertension and coronary heart disease, serum ET-1 decreased, NO was elevated, and the total effective rate was significantly better than irbesartan.
Temistartan
Telmisartan, like alisartantil, belongs to the angiotensin II receptor blocker. Clinically, the dose-effect of telmisartan 20~160 mg for mild and moderate hypertension was compared, and the results showed that there was a significant decrease in blood pressure after 4 weeks of medication, the diastolic blood pressure of telmisartan 80 mg per day was the most obvious, and the dose-effect relationship was "ping effect" after more than 80 mg.
Using the similar drug losartan as a control, the efficacy and safety of telmisartan in the treatment of mild to moderate hypertension were observed. The results showed that telmisartan 40 mg or 80 mg once a day orally could effectively reduce blood pressure, and the systolic blood pressure decreased (12.5±14.3) mmHg and the diastolic blood pressure decreased (10.9±7.9) mmHg after treatment, and the onset time was about 4 weeks after treatment, and the antihypertensive effect was better than losartan, and the antihypertensive effect continued to be stable. The good antihypertensive effect of telmisartan is related to its pharmacological properties, its fat solubility is strong, and the effect of blocking angiotensin II receptors is 5 times stronger than that of losartan.
Whether the antihypertensive effect of antihypertensive drugs is long-lasting is related to the half-life of the drug itself, and the half-life of telmisartan is as long as 24 hours to determine that it has a long-lasting antihypertensive effect. In clinical trials, telmisartan 40 mg was taken orally once a day, and the trovanol/peak ratios of systolic and diastolic blood pressure were 66.5% and 76.8%, respectively, both greater than 50%, which reflected that telmisartan is suitable for taking once a day and can maintain a stable antihypertensive effect throughout the dosing interval.
An increase in blood pressure in the early morning is associated with a high incidence of acute cardiovascular and cerebrovascular events at this time. Studies have shown that telmisartan, taken once a day, has a better antihypertensive effect than amlodipine in the early morning of the end of the drug. In clinical trials, it was found that the average blood pressure at night (22:00 to 6:00) and the average blood pressure drop at the end of the drug for 6 hours (early morning) were also very obvious. Therefore, it is shown that the antihypertensive effect of telmisartan once a day can be maintained for 24 hours, especially at night and when the blood concentration is low in the morning, the antihypertensive effect can still be maintained, which may reduce the occurrence of acute cardiovascular and cerebrovascular events.
In conclusion, alisartantil and telmisartan are safe and effective in the treatment of mild to moderate primary hypertension. Compared with general sartan antihypertensive drugs, the antihypertensive effect of 2 drugs is more significant, the trough / peak ratio is high, and oral administration once a day has the effect of smoothly controlling blood pressure for 24h, especially in the early morning and night blood pressure.