Лікарські препарати для лікування гіпертензії

Adrenergic modifiers include central alpha-2-agonists, postsynaptic alpha-1-blockers, and peripheral-acting non-selective adrenergic blockers (see table Adrenergic Modifiers for Hypertension).

Alpha-2-agonists (eg, methyldopa, clonidine, guanabenz, guanfacine) stimulate alpha-2-adrenergic receptors in the brain stem and reduce sympathetic nervous activity, lowering blood pressure (BP). Because they have a central action, they are more likely than other antihypertensives to cause drowsiness, lethargy, and depression; they are no longer widely used. Clonidine can be applied transdermally once a week as a patch; thus, it may be useful for patients who have difficulty adhering to treatment (eg, those with dementia). Rebound hypertension can occur with abrupt discontinuation.

Postsynaptic alpha-1-blockers (eg, prazosin, terazosin, doxazosin) are no longer used for primary treatment of hypertension because evidence suggests no reduction in mortality. Also, doxazosin used alone or with antihypertensives other than diuretics increases risk of heart failure. Other adverse effects include first-dose syncope, orthostatic hypotension, weakness, palpitations, and headache. However, they may be used in patients who have prostatic hypertrophy and need a 4th antihypertensive or in people with high sympathetic tone (ie, with high heart rate and spiking blood pressures) already on the maximum dose of a beta-blocker.

ACE inhibitors (see table Oral ACE Inhibitors and Angiotensin II Receptor Blockers for Hypertension) reduce blood pressure by interfering with the conversion of angiotensin I to angiotensin II and by inhibiting the degradation of bradykinin, thereby decreasing peripheral vascular resistance without causing reflex tachycardia. These medications reduce BP in many hypertensive patients, regardless of plasma renin activity. Because these medications provide renal protection, they are the medications of choice for patients with diabetes. They are not recommended for initial treatment in patients with African ancestry, in whom they appear to increase the risk of stroke when used for initial treatment.

A dry, irritating cough is the most common adverse effect, with estimates of up to 20% in North American and Europe populations and up to 40% in Asian populations (1, 2). Angioedema is the most serious adverse effect and, if it affects the oropharynx, can be fatal. Angioedema is most common among patients with African ancestry and those who smoke.

ACE inhibitors may increase serum potassium and creatinine levels, especially in patients with chronic kidney disease and those taking potassium-sparing diuretics, potassium supplements, or nonsteroidal anti-inflammatory drugs (NSAIDs).

ACE inhibitors are contraindicated during pregnancy.

In patients with a renal disorder, serum creatinine and potassium levels are monitored at least every 3 months. Patients who have stage 3 nephropathy (estimated glomerular filtration rate [GFR] of  < 60 mL/minute to > 30 mL/minute) and are given ACE inhibitors can usually tolerate up to a 30 to 35% increase in serum creatinine above baseline. ACE inhibitors can cause acute kidney injury in patients who have hypovolemia, severe heart failure, severe bilateral renal artery stenosis, or severe stenosis in the artery to a solitary kidney.

Thiazide-type diuretics enhance the antihypertensive activity of ACE inhibitors and angiotensin II receptor blockers more than that of other classes of antihypertensives (3, 4). Spironolactone and eplerenone also appear to enhance the effect of ACE inhibitors.

Angiotensin II receptor blockers (see table Oral ACE Inhibitors and Angiotensin II Receptor Blockers for Hypertension) block angiotensin II receptors and therefore interfere with the renin-angiotensin system. Angiotensin II receptor blockers and ACE inhibitors are equally effective as antihypertensives. Angiotensin II receptor blockers may provide added benefits via tissue ACE blockade. The 2 classes have the same beneficial effects in patients with left ventricular failure or with nephropathy due to type 1 diabetes. An angiotensin II receptor blocker should not be used together with an ACE inhibitor, but when used with a beta-blocker may reduce the hospitalization rate for patients with heart failure. Angiotensin II receptor blockers may be safely used in anyone with an estimated GFR > 30 mL/minute to reduce cardiovascular risk and kidney disease progression.

Incidence of adverse events is low; angioedema occurs but much less frequently than with ACE inhibitors. Precautions for use of angiotensin II receptor blockers in patients with renovascular hypertension, hypovolemia, and severe heart failure are the same as those for ACE inhibitors (see table Oral ACE Inhibitors and Angiotensin II Receptor Blockers for Hypertension). Angiotensin II receptor blockers are contraindicated during pregnancy.

Beta-blockers are no longer first line agents for treatment of hypertension. However, they may be useful in patients with hypertension who have other disorders that may benefit from a beta-blocker, such as angina, previous myocardial infarction, or heart failure. Otherwise, beta-blockers are less protective against stroke and overall mortality than some other antihypertensives (1, 2).

Beta-blockers (see table Oral Beta-Blockers for Hypertension) slow heart rate and reduce myocardial contractility, thus reducing blood pressure. All beta-blockers are similar in antihypertensive efficacy. Cardioselective beta blockers (eg, acebutolol, atenolol, betaxolol, bisoprolol, metoprolol) are often preferred over nonselective agents because of potentially less bronchodilation and peripheral vasodilation, which is particularly relevant for patients with diabetes (increasing risk of hypoglycemia), chronic peripheral arterial disease (impairing function), or chronic obstructive pulmonary disease (COPD, by potentiating bronchospasm). However, cardioselectivity is only relative and decreases as dose increases. Even cardioselective beta-blockers should be used with caution in patients with COPD with a prominent bronchospastic component.

Beta-blockers with intrinsic sympathomimetic activity (eg, acebutolol, pindolol) do not adversely affect serum lipids; they are less likely to cause severe bradycardia.

Beta-blockers have central nervous system (CNS) adverse effects (sleep disturbances, fatigue, lethargy) and exacerbate depression. Nadolol affects the CNS the least and may be best when CNS effects must be avoided. Beta-blockers are contraindicated in patients with 2nd- or 3rd-degree atrioventricular block or sinus node dysfunction. Beta-blockers should generally be avoided in patients with asthma because in addition to bronchospasm, they can also cause resistance to the effects of inhaled or oral beta receptor agonists (3).

Dihydropyridines (see table Oral Calcium Channel Blockers for Hypertension) are potent peripheral vasodilators and reduce blood pressure by decreasing total peripheral vascular resistance (TPR); they sometimes cause reflexive tachycardia.

The nondihydropyridines verapamil and diltiazem slow the heart rate, decrease atrioventricular conduction, and decrease myocardial contractility. These medications should not be prescribed for patients with second- or third-degree atrioventricular block or with left ventricular failure.

Use of short-acting calcium channel blockers should be avoided because of an increased risk of  acute myocardial infarction (1).

A calcium channel blocker is preferred to a beta-blocker in patients with angina pectoris, with a bronchospastic disorder, with coronary spasms, or with Raynaud syndrome.

Aliskiren, a direct renin inhibitor, is used in the management of hypertension.

As with ACE inhibitors and angiotensin II receptor blockers, aliskiren causes elevation of serum potassium and creatinine. Aliskiren should not be combined with ACE inhibitors or angiotensin II receptor blockers in patients with diabetes or renal disease (estimated GFR < 60 mL/minute). It is also contraindicated during pregnancy.

Direct vasodilators, including minoxidil and hydralazine (see table Direct Vasodilators for Hypertension), work directly on blood vessels, independently of the autonomic nervous system. Minoxidil is more potent than hydralazine but has more adverse effects, including sodium and water retention and hypertrichosis, which is poorly tolerated by women. Minoxidil should be reserved for severe, refractory hypertension.

Hydralazine may be used during pregnancy (eg, for preeclampsia) and as an adjunct antihypertensive. Hydralazine (particularly at doses > 200 mg/day) has been associated with drug-induced lupus, which resolves when the medication is stopped (1). It is also associated with drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (2).

Main classes of diuretics used for hypertension (see table Oral Diuretics for Hypertension) are

• Loop diuretics

• Potassium-sparing diuretics

• Thiazide diuretics

Diuretics modestly reduce plasma volume and reduce vascular resistance, possibly via shifts in sodium from intracellular to extracellular loci.

Loop diuretics are used to treat hypertension only in patients who have an estimated GFR < 30 mL/minute; these diuretics are given at least twice a day (except for torsemide which can be given once a day).

Although the potassium-sparing diuretics do not cause hypokalemia, hyperuricemia, or hyperglycemia, they are not as effective as thiazide-type diuretics in controlling hypertension and thus are not used for initial treatment. Potassium-sparing diuretics or potassium supplements are not needed when an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker is used because these medications increase serum potassium.

Thiazide-type diuretics (thiazide diuretics and thiazide-like diuretics) are most commonly used. Common medications in this class with mortality benefits include chlorthalidone and indapamide. Although thiazide diuretics had previously been thought to be ineffective in patients with stage 4 chronic kdney disease, chlorthalidone has been shown to be effective in improving blood pressure in patients with glomerular filtration rates < 30 mL/minute (1). In addition to other antihypertensive effects, thiazide diuretics cause a small amount of vasodilation as long as intravascular volume is normal. Thiazide-like diuretics (ie, chlorthalidone, indapamide) are preferred over hydrochlorothiazide because of their higher potency (2) and longer duration of action. Thiazide-type diuretics can increase serum cholesterol slightly (mostly low-density lipoprotein cholesterol) and also increase triglyceride levels, although these effects may not persist > 1 year (3). Furthermore, levels seem to increase in only a few patients. The increase is apparent within 4 weeks of treatment and can be ameliorated by a low-fat diet. The possibility of a slight increase in lipid levels does not contraindicate diuretic use in patients with dyslipidemia.

All diuretics except the potassium-sparing distal tubular diuretics (eg, spironolactone) cause significant potassium loss, so serum potassium is measured monthly until the level stabilizes. Unless serum potassium is normalized, potassium channels in the arterial walls close and the resulting vasoconstriction makes achieving the blood pressure (BP) goal difficult. Patients with potassium levels < 3.5 mEq/L (< 3.5 mmol/L) are given potassium supplements. Supplements may be continued long-term at a lower dose, or a potassium-sparing diuretic (eg, spironolactone, triamterene, amiloride) may be added. Potassium supplements or addition of a potassium-sparing diuretic is also recommended for any patients who are also taking digoxin, have a known heart disorder, have an abnormal ECG, have ectopy or arrhythmias, or develop ectopy or arrhythmias while taking a diuretic.

In most patients with diabetes, thiazide-type diuretics do not affect control of diabetes. Uncommonly, diuretics precipitate or worsen type 2 diabetes in patients with metabolic syndrome.

A hereditary predisposition probably explains the few cases of gout due to diuretic-induced hyperuricemia. Diuretic-induced hyperuricemia without gout does not require treatment or discontinuation of the diuretic.

Diuretics may slightly increase mortality in patients with a history of heart failure who do not have pulmonary congestion, particularly in those who are also taking an ACE inhibitor or angiotensin II receptor blocker and who do not drink at least 1400 mL (48 oz) of fluid daily. The increased mortality is probably related to diuretic-induced hyponatremia and hypotension.

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

1. 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.