In 2002, the national nutrition survey shows that China has suffered from hypertension has reached 160 million patients, hypertension is the number one killer of our national health or “hypertension power” is not too much. It is a very difficult task to strengthen the publicity of the dangers of hypertension and to effectively control the blood pressure of hypertensive patients.
1, the clinical typing of hypertension
Hypertension has a lot of typing, in general, from three aspects, namely, etiology, pathology and clinical three types of typing, in practice, commonly used is the clinical typing, it has a strong target, good practicality, convenient and feasible characteristics.
1.1 Simple systolic blood pressure increase type (high vascular resistance type)
This is the most common type of hypertension in the elderly, accounting for more than 65% of the hypertensive population. For elderly patients, according to the criteria of the 1999 WHO/ISH guidelines for the prevention and treatment of hypertension, the blood pressure of both upper arms is measured in a sitting position by the cuff method, and those with systolic blood pressure (SBP) > 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg are called pure systolic hypertension. In addition to vascular sclerosis, most patients have varying degrees of small-vessel spasm, and at the same time as SBP increases, DBP decreases and pulse pressure widens. Patients often have headache, dizziness, fear of cold, polyuria, thirst, cold hands and feet, and even numbness. If this type is not treated in time, some may induce hypertensive crisis, transient cerebral ischemia, cerebral infarction or cerebral hemorrhage, while the increase in SBP increases the left ventricular ejection load and increases the risk of left ventricular failure and sudden death.
1.2 Increased diastolic blood pressure alone (hypervolemic type)
This type is relatively rare in the elderly, mainly due to increased diastolic blood pressure, some of which can reach or exceed 120 mmHg, while the increased systolic blood pressure is not obvious and the pulse pressure difference is relatively small. Patients of this type are generally fat, and their clinical manifestations are mostly dizziness, dizziness, dizziness, lightness of the head and feet, and sunken edema in front of the shins.
1.3 Systolic and diastolic blood pressure combined increase type (mixed type)
Patients of this type are mostly obese and complain of headache and dizziness, or have different symptoms with the degree of increase in systolic and diastolic blood pressure.
2.Principles of hypertension drug treatment
There are six major categories of anti-hypertensive drugs recommended by the World Health Organization: diuretics, calcium antagonists (CCB), β-blockers, α1-blockers, angiotensin-converting enzyme inhibitors (ACEI), and angiotensin II receptor antagonists (ARB). The principles of application are as follows: ① For grade 1 and 2 hypertension, any drug should be started at a small dose to reduce side effects when starting treatment. (2) Try to apply long-acting drugs that work once a day and last 24 hours. ③Rational choice of combination drugs to achieve the maximum antihypertensive effect, the least side effects, in general prefer to apply a second drug in combination with a non-identical drug, without increasing the dose of the first drug. ④The goal of blood pressure reduction is to reduce to normal or “ideal” level. That is, for middle-aged and young patients or patients with combined diabetes, blood pressure should be lowered to 135/85 mmHg or within the normal range; for elderly patients ≥ 60 years old, blood pressure should be lowered to 140/90 mmHg or below. ⑤ To adhere to the medication.
3.Clinical application of anti-hypertensive drugs
3.1 Diuretics
Thiazide diuretics, whether used alone or in combination, have clear efficacy, in recent years, its side effects such as hypokalemia, insulin resistance and abnormal lipid metabolism, etc. are increasingly receiving clinical attention, currently less used alone and try to apply in small doses. The new diuretic indapamide is only slightly diuretic and mainly vasodilatory in common doses, with an antihypertensive efficiency of about 70% and without the side effects of metabolic abnormalities that are easily caused by traditional diuretics.
3.2 β-blockers
β-blockers are safe and effective in lowering blood pressure, and can generally reduce systolic blood pressure by 15-20 mmHg when used alone. Among them, bisoprolol is a new type of highly selective beta-blocker once a day, which is easy to take, has little side effects and does not affect the glycolipid metabolism. The third-generation beta-blocker carvedilol has fewer side effects and has a downregulating effect on blood glucose and lipids, and is used by many patients with blood glucose and lipid abnormalities. beta-blockers are mainly used for mild to moderate hypertension, especially in young and middle-aged patients with a fast resting heart rate (>80 beats/min) or in combination with angina pectoris. Side effects are bradycardia, atrioventricular block, inhibition of myocardial contraction, and abnormal glycolipid metabolism.
3.3 Calcium antagonists (CCB)
Calcium antagonists used for hypertension can be divided into three categories, namely: dihydropyridines, represented by nifedipine, the first generation of short-acting preparations of nifedipine has been less used, the clinical use of extended-release and controlled-release preparations or the second and third generation of nifedipine, felodipine, amlodipine, etc.; benzothiazoles, represented by diltiazem; benzalkamides, represented by verapamil. The latter two classes, also known as non-dihydropyridines, are mostly used in patients with hypertension combined with coronary artery disease and supraventricular arrhythmias. Calcium antagonists have good antihypertensive effect and can significantly reduce the incidence of cardiovascular and cerebrovascular complications and death rate, slow down the process of atherosclerosis, and have no adverse effects on electrolytes, glucose and lipid metabolism and uric acid. The first generation of short-acting preparations of nifedipine is inconvenient to take, poor compliance, unstable blood pressure control, reflex heart rate acceleration, sympathetic nerve activation, headache, red face, ankle edema and other side effects, so it has been less used.
3.4 Angiotensin-converting enzyme inhibitors (ACEI)
Most of these drugs appear within 1 hour of oral administration, but it may take several days or even weeks to achieve the maximum antihypertensive effect. ACEI can safely and effectively lower blood pressure and can be used to treat all levels of hypertension. It is particularly effective in reducing the incidence of heart failure and death in hypertensive patients and in slowing the progression of renal damage in insulin-dependent diabetic patients, especially in the presence of proteinuria. It does not affect heart rate and glucose and lipid metabolism, and more importantly, it can protect and reverse target organ damage. The main side effects are dry cough, hyperkalemia, and angioneurotic edema.
3.5 Angiotensin II receptor antagonists (ARBs)
ARB is a new class of anti-hypertensive drugs that act on the renin-angiotensin system (RAS) after ACEI with good effects on hypertension, atherosclerosis, cardiac hypertrophy, heart failure, diabetic nephropathy, etc. Long-term use is beneficial to patients. Compared with ACEI, it blocks ARS more fully and selectively, and does not have side effects such as dry cough and angioneurotic edema, and also promotes blood uric acid excretion. It is indicated for patients who cannot tolerate ACEI. It has a good protective effect on the target organs of hypertension, which can reduce the occurrence of cardiac and cerebral emergencies and reduce the death rate of heart failure patients. Currently, valsartan and coxsartan are more commonly used in China, followed by irbesartan and telmisartan.
3.6 α1 receptor blockers
This class of drugs is not widely used clinically, the reason is: it can lead to upright hypotension, syncope, vertigo, palpitations, etc., so it requires the first half of the bedtime dose (its incidence is less than 1%). Long-term use alone is likely to lead to water and sodium retention reducing the efficacy. It has the effect of improving abnormal lipid metabolism and abnormal glucose tolerance and can relieve symptoms caused by prostatic hypertrophy, so it can be considered preferred by elderly people with prostatic hypertrophy. The representative drugs are prazosin, terazosin and doxazosin.
3.7 There are also the following new hypertensive agents.
Dual-acting ACE and NEP vasopeptidase inhibitors, dual receptor blockers, hypertension vaccines, endothelin receptor antagonists, CCB- Cilnidipine, new highly selective β-B-Nebivolol. of current interest: direct renin inhibitors (DRI), which are another type of RAS inhibitor. The existing RAS inhibitors (ACEIs, ARBs) inhibit AT1R and lose feedback mechanism on renin, resulting in increased PRA, while DRI directly inhibits the effect of renin, which is an ideal RAS inhibitor. Rasilez has been shown in animal models of hypertension to reduce proteinuria, prevent LVH, i.e., cardioprotective effects, dose-dependent PRA reduction compared with ACEIs, reduce Ang I and Ang II, and reduce aldosterone excretion.
4. Commonly used combinations of antihypertensive drugs in clinical practice
The fundamental goal of hypertension treatment is to prevent and control hypertension and complications, reduce disability and mortality, and improve the quality of life of patients. The efficiency of treating hypertension with a single drug is only 50% to 70% even in mild essential hypertension, although increasing the dose can improve the efficacy, but also increases the incidence of adverse reactions. Clinically, in order to increase the efficacy and reduce adverse reactions, combination drug therapy is usually used to treat hypertension, and the combination drug regimen can be reasonably selected according to the patient’s blood pressure and different comorbidities. The recommended diphasic regimens are as follows.
4.1 Diuretics in combination with ACEI
Diuretics can activate the renin-angiotensin-aldosterone system (RAAS), thus making the effect of ACEI more obvious, while diuretics can reduce blood volume and reduce the burden on the heart; ACEI can reverse left ventricular hypertrophy and have a protective effect on the kidney.
4.2 Combination of CCB and ACEI
These two types of antihypertensive drugs have different mechanisms of action, but both can reduce calcium levels in cardiovascular cells, enhance vasodilator effects, and also have the characteristics of protecting target organs, reversing cardiovascular remodeling, reducing CCB edema, and not affecting glucose and lipid metabolism.
4.3 Dihydropyridine CCB in combination with β-blockers
Dihydropyridine CCB has the effect of vasodilatation and mild increase of cardiac output, which can offset the vasoconstrictive effect of β-blockers and reduce cardiac output while lowering blood pressure; the effect of β-blockers in slowing down heart rate can antagonize the side effect of accelerated heart rate of dihydropyridine CCB. Non-dihydropyridine CCBs (diltiazem and verapamil) should not be used in combination with β-blockers.
4.4 Combination of ARB and diuretics
The combination of these two classes of drugs can enhance the blockade of RAAS, especially in the manifestation of low potassium, low magnesium and blood uric acid, blood glucose complement each other’s effects.
4.5 β-blockers in combination with diuretics
Beta-blockers can antagonize diuretics to increase renin secretion and renin activity, while the sodium excretion of diuretics and the effect of reducing blood volume can offset the vasoconstrictive and sodium retention effects of beta-blockers, increasing the antihypertensive efficacy. Because of the effect of both types of drugs on lipid and blood glucose metabolism, long-term clinical use is not recommended.
4.6 Combination of α1-blockers and diuretics
The combination of the two types of drugs can strengthen the vasodilator effect, which is beneficial to reduce the renal sodium retention effect of α1-blockers.
4.7 CCB in combination with ARB
In recent years, the development of ARB is rapid, and new types of preparations are appearing, which greatly increase the choice of clinical application. The combined application of CCB and ARB enhances the vasodilating effect and reduces the edema caused by CCB, and also has a balancing effect on the effect of blood sugar.
4.8 If patients with renal insufficiency, it is recommended to avoid the combined use of ACEI and ARB.
In conclusion, hypertension drug therapy should be individualized according to the patient’s specific situation and different blood pressure types, while the drug selection follows the principles of increasing antihypertensive efficacy, counteracting adverse effects, and incompatibility of similar drugs and drugs with the same effect. If the diphasic regimen is unsatisfactory, multiple regimens can be used, such as diuretics + ACEI (ARB) + β1 receptor blocker (or CCB), diuretics + ACEI (ARB) + CCB + α1 receptor blocker (or central α1 receptor agonist). The clinical treatment of hypertension can then achieve a satisfactory outcome.