Angiotensin converting enzyme inhibitor (ACEI)
Application of Angiotensin Converting Enzyme Inhibitor (ACEI)
ACEI can safely and effectively lower blood pressure, and there are many kinds at present. It is particularly effective in reducing the morbidity and mortality of patients with heart failure and delaying the progress of renal damage in patients with insulin-dependent diabetes, especially when proteinuria exists. The main side effect is dry cough, the incidence rate is 15 ~ 20%, and occasionally fatal vascular edema.
(A) the mechanism of action
Renin-angiotensin-aldosterone system (RAS) plays an important role in the occurrence and development of hypertension, in which angiotensin II is the main effector peptide. ACEI inhibits the transformation of angiotensin I into angiotensin II, does not inactivate bradykinin, and has antihypertensive effect. The mechanism is as follows: ① inhibiting the circulation of RAS; Inhibition of RAS; In the organization; ③ Reduce the release of norepinephrine from nerve endings; ④ Reduce the production of endothelin in endothelial cells; ⑤ Increase the formation of bradykinin and vasodilator prostaglandin; ⑥ Decreased aldosterone secretion and/or increased renal blood flow to reduce sodium retention.
(II) Types and dosages of ACEI drugs
Although the mechanism of action of ACEI is the same, the binding mode, strength, precursor state, action time and elimination or excretion mode of ACEI are different. Among them, captopril has the shortest action time and needs 2 ~ 3 times a day. Other ACEI can be used once a day.
Application of common angiotensin converting enzyme inhibitors in hypertension
The equivalent dosage of ACEI is as follows: enalapril 10mg, cilazapril 2.5mg, quinapril 15mg, ramipril 2.5mg, benazepril 7.5mg, perindopril 4mg, spironolactone 6mg and fosinopril 15mg, all equivalent to captopril 50mg.
(3) Clinical application
1, ACEI is used as a single drug in clinical trials, and its antihypertensive effect is equivalent to that of diuretics or beta blockers. Single drug is effective in treating about 60 ~ 70% patients with hypertension. Most of them have antihypertensive effect within 1 hour, but it may take several weeks to reach the maximum antihypertensive effect. Salt restriction or diuretics can increase the effect of ACEI. The combination of ACEI with calcium antagonists and α 1 receptor blockers can also increase the effect, but it has little effect with β-receptor blockers.
2.ACEI can be used for patients with mild, moderate and severe hypertension, especially for the treatment of severe or rapid hypertension.
3.ACEI is also effective for senile hypertension without orthostatic hypotension. It may be because these drugs do not damage the autonomic nervous system. Although blood pressure drops, they can maintain cerebral blood flow by restoring the automatic regulation of cerebral blood flow.
(D) Clinical advantages of ACEI application
It is known that ACEI has no effect on the central nervous system and autonomic nervous system, nor does it affect sexual function. Unlike other direct vasodilators, ACEI produces antihypertensive effects without reflex tachycardia. ACEI can prevent secondary aldosteronism caused by diuretics.
ACEI has no effect on metabolism, blood potassium is stable, plasma uric acid may decrease, and blood cholesterol and blood lipid have no obvious changes. Therefore, the influence on the risk factors of coronary artery disease and vascular injury is neutral or beneficial. Some studies show that ACEI can reduce insulin resistance and is beneficial to glucose metabolism. It can be safely used for patients with the following diseases: ① asthma or chronic obstructive respiratory disease; ② Peripheral vascular diseases, including Raynaud's phenomenon; ③ Depression; ④ Diabetes.
(5) Special indications for clinical application of 5)ACEI.
ACEI can not only be used to treat mild to moderate or severe hypertension, but also be particularly useful in some cases: ① hypertension with left ventricular hypertrophy; ② Left ventricular dysfunction or heart failure; ③ Ventricular remodeling after myocardial infarction; ④ Diabetes with microalbuminuria; ⑤ Hypertension patients are accompanied by peripheral vascular diseases or Raynaud's syndrome, chronic obstructive respiratory diseases and depression; ⑥ Scleroderma hypertensive crisis; ⑦ Dialysis can resist renal hypertension.
1. Ventricular hypertrophy: Left ventricular hypertrophy is an important independent risk factor for cardiovascular events in patients with hypertension, so it is necessary not only to lower blood pressure, but also to reduce ventricular hypertrophy. In a meta-analysis of different hypertension treatment schemes, ACEI drugs can reduce left ventricular hypertrophy, which is twice as effective as other antihypertensive drugs. This effect is also effective for vascular hypertrophy.
2. Left ventricular dysfunction or heart failure: In the first study of Enalapril, ACEI reduced the mortality of patients with symptomatic congestive heart failure by 27%. In the study of left ventricular dysfunction, for patients with mild symptomatic heart failure, the mortality and mortality of cardiovascular diseases are also significantly reduced. Therefore, ACEI is also beneficial to patients with mild congestive heart failure. In the study of preventing left ventricular dysfunction, survival and ventricular enlargement, it has been proved that asymptomatic patients with LVEF < 40% benefit greatly from enalapril or captopril after myocardial infarction. This seems to be related to the prevention of myocardial dilatation and progressive ventricular remodeling.
3. Diabetes and diabetic nephropathy: ACEI can be used to treat insulin-dependent or independent hypertensive diabetic patients. Captopril has been proved to increase insulin sensitivity, but its clinical significance has not been determined. Several studies (captopril, lisinopril, perindopril and ramipril) can reduce microalbuminuria in hypertensive patients with normal blood pressure and diabetic nephropathy. ACEI can slow down the decrease of creatinine clearance rate in these patients. Long-term clinical trials also show that diabetic patients can slow down the progress of chronic renal failure.
4. Kidney diseases: ACEI can reduce proteinuria in other types of kidney patients with decreased glomerular filtration rate. It is reported that long-term ACEI treatment can increase the filtration rate and renal plasma flow. But patients with unexplained renal failure should be especially careful, because bilateral renal artery stenosis can promote acute renal failure.
(6) Contraindications and careful use of 6)ACEI.
ACEI is absolutely forbidden in pregnancy-induced hypertension, because it will lead to fetal malformation. Therefore, women of childbearing age should use it with caution. For patients with severe hypovolemia or low salt and high plasma renin level (excessive diuresis), blood pressure often drops when taking ACEI for the first time. The patient stopped using diuretics 1 ~ 2 days earlier.
Similarly, patients with fixed cardiac output can significantly reduce severe aortic or mitral stenosis, because the reduction of peripheral resistance caused by ACEI cannot be compensated by the increase of cardiac output.
ACEI should be used with caution in the following situations: severe hypovolemia; Severe aortic and mitral stenosis; Restrictive pericarditis; Severe congestive heart failure (NYHA4 grade); Renal hypertension, especially bilateral renal vascular disease or solitary kidney with renal artery stenosis; Unexplained renal insufficiency; Elderly smokers with vascular murmurs; Patients with renal insufficiency take nonsteroidal anti-inflammatory drugs.
Drug interaction: Elderly patients often have renal insufficiency, and arthritis can be treated with non-steroidal anti-inflammatory drugs. If ACEI is used together, hyperkalemia will occur, and ACEI combined with non-steroidal anti-inflammatory drugs will often aggravate renal failure. ACEI is not usually used with potassium-preserving diuretics to avoid the risk of hyperkalemia.
(7) Side effects of 7)ACEI:
The incidence rate is low. In large-scale clinical research, the incidence of adverse reactions is lower than 10%, which is lower than other drugs.
Dry cough is the most common, the incidence rate is 1 ~ 30%, which is often in the initial stage of medication (days to weeks) and may accumulate. The most serious and rare side effect is angioneurotic edema. These two side effects may occur in all kinds of ACEI, so they are considered to be related to bradykinin.
Because ACEI has no central and autonomic nervous function and sympathetic nerve activity, ACEI has no adverse effect on the quality of life. In fact, it is reported that patients receiving treatment can improve their quality of life.