It’s considered among specialists that with a persistent increase in diastolic blood pressure (more than 90 mmHg), and after 65 years – even with only an increasing systolic pressure (more than 160 mmHg), the cause of the disease should be determined to start treatment. It should be noted that with the same level of blood pressure, the risk of complications in men is higher than in women, and in young people it’s higher than in older people.
Treatment itself has a risk of side effects that arise from antihypertensive medications, e.g. 35% of affected men suffer from different degrees of impaired potency. That is why some clinicians consider this risk to be unjustified, e.g. for women older than 70 years with an asymptomatic increase in diastolic blood pressure to 90 mmHg.
At the same time, for a 30-year-old man with diastolic blood pressure over 90 mmHg, antihypertensive therapy is vital.
The choice of antihypertensive treatment is very wide, which is why it’s possible for most of the patients (in 95% cases) to choose a treatment regimen with minimal side effects. Patients with hypertension for any reason that aren’t receiving antihypertensive therapy need to be examined by a doctor every three months. For patients with angina pectoris, or diabetes with confirmed ischemic heart disease, or risk factors for atherosclerosis, antihypertensive therapy is indicated even with a slightly increased blood pressure. In such cases, it’s prescribed even with diastolic blood pressure 85-90 mm Hg.
Medication-free treatment with arterial hypertension is indicated for all patients without any exception. It includes:
Reducing emotional stress.
An appropriate diet (reduced salt consumption).
Weight loss (with proper diet).
As much as possible, elimination of risk factors for atherosclerosis.
Although emotional stress cannot be completely excluded, patients are advised to avoid it in every possible way. Because of this, it’s sometimes recommended to even change jobs and their lifestyle.
It’s been proved that a low-salt diet reduces blood pressure; therefore, patients are advised to drastically reduce the use of table salt. From the results of several studies of past years it’s known that reduced sodium consumption of less than 4.0 g/day reduces systolic blood pressure by 5 mm Hg, and diastolic by 2.6 mm Hg. It’s known that a low salt diet by itself has little effect on blood pressure, but it strengthens the effect of all antihypertensive drugs. This allows for a reduction in dosage, and thus reduces the risk of side effects. In some cases, a low-salt diet directly reduces blood pressure. Since it’s harmless, patients are advised to reduce the consumption of salt to 5 g/day, this means you should not add salt to food at the table.
In professional literature, several studies have been published showing that blood pressure decreases with high calcium and potassium consumption. Some studies showed that adding potassium to foods (50-120 mmol/day) reduced systolic blood pressure by 6 mmHg, and diastolic by 3.4 mmHg (like a low-salt diet). In addition, increased calcium consumption (1.5 g/day) helps with senile osteoporosis.
In the presence of obesity, patients with arterial hypertension are given a low-calorie diet because sometimes it’s enough to lose weight in order to significantly reduce blood pressure.
A clinical study named TAIM (Trial of Antihypertensive Interventions and Management) showed that weight loss (about 4.4 kg during 6 months) reduced blood pressure by 2.5 mmHg. Limiting the consumption of cholesterol and saturated fatty acids also reduces the risk of atherosclerosis. In addition, alcohol consumption should be limited because it causes an increase in blood pressure, especially if there is overconsumption of it.
According to the capabilities of the patient, an appropriate set of physiotherapy exercises is selected. It helps not only to reduce weight, but it can also decrease blood pressure thanks to improved tissue oxygenation. Isotonic loads (jogging, swimming) are indicated for such patients, but not isometric (weightlifting), because they increase blood pressure. The diet should be combined with the elimination of other risk factors, such as smoking.
Medication (Drug Treatment)
For an efficient use of antihypertensive drugs, it’s necessary to understand the mechanisms of their action. Nowadays, six main drug groups are used for treatment of arterial hypertension:
II. drugs lowering the activity of the sympathoadrenal system
III. direct vasodilators
IV. calcium antagonists
V. ACE blockers
VI. angiotensin receptor blockers.
The most studied and that have accumulated the largest clinical research experience are thiazide diuretics. They lower blood pressure quickly (in 3-4 days) due to sodium excretion and reduction of circulating blood volume. Existing observations report that diuretics also reduce total peripheral vascular resistance. According to long-term clinical trials, thiazide diuretics significantly reduce mortality and risk of hypertension complications (Disothiazid is used in Israel). In recent years, they have been prescribed less frequently; first of all, due to their negative effect on electrolyte metabolism. Their long-term use can cause hyperkalemia (excretion of potassium), hyperuricemia (uric acid retention), and hyperlipoproteinemia.
Stronger drugs, such as the loop diuretics "furosemide" and "bumetanide", also reduce blood pressure well enough, but their use is limited primarily due to their short action duration.
The competitive aldosterone antagonist spironolactone is sold in Israel under the name "Aldactone". Its Russian counterpart "Veroshpiron" increases sodium excretion, therefore, it is most effective in hyperaldosteronism (primary and secondary). Two other potassium-sparing diuretics, "triamteren" and "amiloride", affect the same nephron departments inhibiting sodium reabsorption, but their action is not related to aldosterone. "Triamteren" and "amiloride" have the same indications as "spironolactone". "Triamteren" also produces a hypotensive effect. The main disadvantage of potassium-sparing diuretics is the risk of hyperkalemia, especially with chronic renal failure, but they can be combined with thiazide diuretics to reduce potassium accumulation.
II. Drugs lowering the activity of the sympathoadrenal system
They affect the vasomotor center of the medulla oblongata, sympathetic postanglionic neurons, and peripheral adrenoreceptors. They usually also reduce cardiac output and heart rate, but the baroreflex is not affected. Therefore, they do not cause orthostatic hypotension. Due to risk of side effects, ganglionic blockers have been rarely used in the last decade and only in urgent cases for a rapid decrease in blood pressure. Due to side effects, sympatholytics are also rarely used. "Guanethidine" and its short-term analogue "guanadrel" block norepinephrine release from sympathetic nerve endings. As a result, cardiac output is reduced, and systolic blood pressure drops more than the diastolic. Orthostatic hypotension occurs more often and is more pronounced than when using another sympatholytic like reserpine. Peripheral adrenoreceptors are affected by both α- and β-blockers which are produced in Israel, such as:
These drugs block the effect of catecholamines on the heart, so they especially reduce cardiac output and blood pressure when the sympathetic tone is raised. They also inhibit catecholamine-stimulated renin release from juxtaglomerular cells leading to decrease in blood pressure.
Beta-blockers are well prescribed together with direct vasodilators, which cause a reflex increase of heart rate, and with diuretics which increase plasma renin activity. In general, β-blockers even help with a normal sympathetic tone. After their prescription, blood pressure decreases in about half of patients with hypertension. Clinical trials have shown that, like diuretics, β-blockers reduce mortality and the risk of complications. The main side effects include bronchospasm and exacerbation of heart failure. In patients with a sugar-reducing therapy, β-blockers should be used with caution, as they have hypoglycemic effects.
The beta1-blockers (cardio selective) metoprolol and atenolol are possibly less dangerous in chronic obstructive pulmonary diseases than non-selective drugs (propranolol, timolol). The non-selective drugs, pindolol and acebutolol, have a small β2-adrenostimulating activity, so they hardly cause bradycardia by themselves. The hypotensive action of labetalol is due to a reduction of total peripheral vascular resistance as they have characteristics of both α-, and β-blockers. It acts faster than other β-blockers but causes orthostatic hypotension more often as well as impotence.
Hydralazine is the drug most often used among those in this group. It’s prescribed parenterally, and basically acts on arterioles; therefore, it doesn’t cause orthostatic hypotension. However, the reduction of total peripheral vascular resistance is partly balanced by the increase in the sympathetic tone, leading to increased heart rate and cardiac output. Because of this, hydralazine use is restricted, especially in severe ischemic heart disease (IHD).
To prevent the rise of sympathetic tone, hydralazine is best prescribed along with β-blockers, methyldopa and clonidine. Minoxidil reduces blood pressure more pronouncedly than hydralazine, but it can lead to fluid retention. Therefore, it’s used only for severe hypertension with chronic renal failure. It’s sold in Israel under the name "Nipruss". Diazoxide is close to thiazide diuretics structurally, but it has no diuretic effect and even causes sodium retention. Like thiazide diuretics, diazoxide reduces glucose tolerance. In the past decade, direct vasodilators have rarely been used.
IV. ACE inhibitors (inhibitors of angiotensin converting enzyme)
Synthesis of angiotensin II can be reduced at different levels: some antihypertensives (clonidine, reserpine, methyldofa, β-blockers) reduce renin secretion, others (ACE inhibitors) inhibit conversion of angiotensin I into angiotensin II.
In addition, ACE inhibitors inhibit the destruction of a powerful vasodilator, bradykinin, and affect prostaglandin synthesis (especially captopril) and sympathetic tone.
ACE inhibitors are the drugs of choice for renovascular hypertension, hypertension with kidney diseases, and for progressive and malignant hypertension. However, with bilateral renal artery stenosis, their use may cause a rapid deterioration in renal function. With mild, uncomplicated arterial hypertension, ACE inhibitors are as effective as β-blockers and thiazide diuretics, but they have less side effects, especially those worsening the normal life of patients. Benzepril and Cilaril are used in Israel for this purpose.
VI. Angiotensin receptor blockers
They are close to ACE inhibitors in terms of efficiency. They don’t affect the formation of angiotensin II, but instead compete with it for type I angiotensin receptors. Efficacy and side effects are about the same as those of ACE inhibitors but cough does not happen. СО-Diovan is used in Israel in different dosages, since diuretics are part of the medication.
VI. Calcium Channel blockers
They are divided into:
The last are divided into first (nifedipine) and second generation. All calcium antagonists affect calcium flow into cells by binding to certain parts of α1 subunits of the L-type potential dependent calcium channels. Since there are T- and N-types of calcium channels as well, calcium antagonists affect only part of calcium transport into cells. Features of the action of some drugs depend on the fact that each subgroup of calcium antagonists has their own binding sites for α1 subunit, and different tissues have different levels of such binding sites.
All of the calcium antagonists have vasodilating effects, but only dihydropyridines cause reflex tachycardia. Diltiazem and verapamil inhibit AV-conduction. In Israel they are sold under the names Vasodip, Norvasc, Lercapress, and Lercanidirine. Due to their negative inotropic effect, calcium antagonists are indicated for angina pectoris, but they should be prescribed with caution for arterial hypertension with heart failure.
General principles of drug treatment
The purpose of treatment is to normalize blood pressure with one of the listed drugs or a combination with the least amount of side effects. The ideal blood pressure when taking medications should be 120/80 mmHg. Treatment should be directed at the pathogenesis as much as possible. If the pathogenesis of increased blood pressure in this patient is unknown (that is characteristic for the majority of cases), therapy is prescribed empirically due to the patient’s willingness to be treated, efficiency, safety, ease of use of medications and their effect on working ability.
If only diastolic blood pressure remains below 130 mmHg, treatment starts with monotherapy. For combined therapy, drugs with different action mechanisms are preferable. There are a lot of antihypertensive drugs and schemes for their use, but these schemes are not universal. 10 years ago, treatment almost always started with diuretics or β-blockers due to their efficiency in the beginning of treatment. However, they are as effective as ACE inhibitors or calcium antagonists.
Usually, a drug from one of these four groups is empirically prescribed. We prefer to start with ACE inhibitors or calcium antagonists as they have less side effects. The advantage of ACE inhibitors is that they are more convenient to take and have longer effects. Treatment can also be started with angiotensin receptor blockers. The need to add potassium supplements or potassium-sparing diuretics show an eight-to-tenfold increase in treatment costs. With increased sympathetic tone (evidenced by tachycardia), the best option to start with is β-blockers, in the rest of the cases –ACE inhibitors or calcium antagonists are preferred.
Medications begin with small doses: e.g. atenolol is prescribed at a dose of 25 mg/day, captopril – 25 mg/day, enalapril – 5 mg/day, diltiazem – 120 mg/day with dosage divided into several intakes. If blood pressure gets lower than 140/90, the dosage should not be changed. If it doesn’t decrease after 1-3 months, the dosage should be doubled. If this still doesn’t help, hydrochlorothiazide 25 mg/day, or any other thiazide diuretic, should be added. Thiazide diuretics enhance ACE inhibitors’ effect and possibly β-blockers’ effect; in combination with calcium antagonists, the hypotensive effect adds up.
The best option is a combination of thiazide diuretics with ACE inhibitors, as they balance the negative effect of diuretics on metabolism. β-blockers and calcium antagonists don’t have such effects; moreover, β-blockers can even increase side effects of thiazide diuretics (hypokalemia and hypercholesterolemia). If these drugs cannot normalize blood pressure, the daily dose of the first main drug should be adjusted to the maximum.
Higher doses than those usually recommended can be given, but it’s thought that changing the main drug is a better option. If blood pressure does not decrease, symptomatic hypertension must be ruled out. If the reason is not found, the patient’s diet should be checked. Restricted salt consumption (less than 5 g/day) often decreases blood pressure. Otherwise, the main drug should be changed, keeping the same diuretic. If a patient did not receive ACE inhibitors earlier, their prescription, along with diuretics, can dramatically lower blood pressure. If changing the main drug doesn’t help, calcium antagonists with ACE inhibitors are prescribed or a combination of three drugs are used: diuretics, ACE inhibitors and hydralazine. If blood pressure has decreased, medications should be gradually removed or their doses should be lowered to the minimum to maintain a blood pressure level that doesn’t exceed 140/90 mmHg.
Nearly 5% of patients still have high blood pressure, despite all the treatments. In this case, everything that could reduce therapy effectiveness should be eliminated. Then, a direct vasodilator (hydralazine, prazosin or clonidine) should be added. After blood pressure has decreased, medications should be gradually removed while making sure blood pressure remains normal. This treatment plan helps in most cases, but it’s not universal because drugs and their combinations can affect patients differently. If the final scheme includes several drugs, ready-made combination drugs can be used since they are easier to take. Patients should do everything possible to follow the doctor’s orders and continue their usual daily activities. Treatment is life-long, and since patients don’t have troublesome symptoms, it can be difficult to convince them to take several medications, especially if they have side effects. A special approach is required and applied in the following cases.
After treatment, a decrease in blood pressure in the presence of impaired renal function can often lead to an increase in blood creatinine.
This is usually not associated with further kidney damage, and treatment should not be stopped: over time, creatinine levels return to baseline. An increase in creatinine levels secondary to taking ACE inhibitors requires special attention.
In such situations, stenosis of both renal arteries should be ruled out, since treatment of such patients will only lead to a deterioration of kidney function. Therefore, with kidney damage, ACE inhibitors are used with caution, and during first three weeks kidney function should be tested every 4-5 days. ACE inhibitors are contraindicated in bilateral renal artery stenosis (remaining one of the drugs of choice in unilateral stenosis, if the other kidney works fine) and in chronic renal failure (including patients with diabetes mellitus).
With IHD, especially if cardiac glycosides are taken (when IHD is accompanied by heart failure), thiazide diuretics are used with caution and while monitoring blood potassium levels. With IHD, β-blockers are not stopped or are removed very gradually. Calcium antagonists and ACE inhibitors are indicated, they reduce side effects from other drugs, especially from direct vasodilators.
Treatment of hypertension with diabetes is difficult, as many antihypertensive drugs disrupt glucose metabolism. The best way to treat is to use ACE inhibitors, which don’t affect the metabolism of glucose and lipoproteins, and inhibit the development of diabetic nephropathy as they reduce renal blood vessel tone and renal perfusion pressure.
During pregnancy, arterial hypertension (including preeclampsia and eclampsia) is hard to treat. It’s unknown if there’s self-regulation of uterine blood flow during antihypertensive therapy; therefore, a decrease in blood pressure can cause ischemia of the placenta and fetus. The best option is to manage it using a treatment without medications. Antihypertensive drugs are usually not prescribed in the second and third trimesters, unless diastolic blood pressure exceeds 95 mmHg. A salt-free diet and diuretics increase the risk of preterm birth, so they’re not commonly used. Use of β-blockers is restricted due to these same reasons. Metildopa and hydralazine are typically used, as well as calcium antagonists, though less commonly. Not all of them have adverse effects on the fetus. Very little is known about the safety of other drugs. ACE inhibitors negatively affect the fetus, and are therefore contraindicated during pregnancy.
Advanced (old) age
Clinical trials have shown a reduction in risk and mortality for stroke in otherwise healthy older people of both sexes suffering from arterial hypertension, when moderate doses of antihypertensives are used. This is also true for isolated systolic hypertension.
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