Merck Manual

Please confirm that you are a health care professional

honeypot link

Medications for Hypertension

By

George L. Bakris

, MD, University of Chicago School of Medicine

Reviewed/Revised Sep 2023
View PATIENT EDUCATION
Topic Resources

A number of medication classes are effective for initial and subsequent management of hypertension:

Adrenergic Modifiers for Hypertension

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

Table

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 for Hypertension

ACE inhibitors (see table ) 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 Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more . 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 ACE inhibitors references The treatment of hypertension may involve lifestyle modifications alone (eg, dietary modification, weight loss, exercise) or in combination with medications. The decision to treat with medication... read more ). Angioedema Angioedema Angioedema is edema of the deep dermis and subcutaneous tissues. It is usually an acute but sometimes a chronic mast cell–mediated reaction caused by exposure to a drug (eg, angiotensin-converting... read more 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 Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease and those taking potassium-sparing diuretics, potassium supplements, or nonsteroidal anti-inflammatory drugs (NSAIDs).

ACE inhibitors are contraindicated during pregnancy.

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 ACE inhibitors references The treatment of hypertension may involve lifestyle modifications alone (eg, dietary modification, weight loss, exercise) or in combination with medications. The decision to treat with medication... read more ). Spironolactone and eplerenone also appear to enhance the effect of ACE inhibitors.

Table

ACE inhibitors references

  • 1. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med 117(3):234-242, 1992. doi:10.7326/0003-4819-117-3-234

  • 2. Woo KS, Nicholls MG. High prevalence of persistent cough with angiotensin converting enzyme inhibitors in Chinese. Br J Clin Pharmacol 40(2):141-144, 1995.

  • 3. Townsend RR, Holland OB. Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension. Arch Intern Med 150(6):1175-1183, 1990.

  • 4. Lacourcière Y, Poirier L, Lefebvre J, Ross SA, Leenen FH. Increasing the doses of both diuretics and angiotensin receptor blockers is beneficial in subjects with uncontrolled systolic hypertension. Can J Cardiol 26(8):313-319, 2010. doi:10.1016/s0828-282x(10)70442-6

Angiotensin II Receptor Blockers for Hypertension

Angiotensin II receptor blockers (see table ) block angiotensin II receptors and therefore interfere with the renin-angiotensin system Renin-angiotensin-aldosterone system Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Renin-angiotensin-aldosterone 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 Diabetic Nephropathy In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more Diabetic Nephropathy . 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.

Beta-Blockers for Hypertension

Beta-blockers (see table ) 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 Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more (increasing risk of hypoglycemia), chronic peripheral arterial disease Peripheral Arterial Disease Peripheral arterial disease (PAD) is atherosclerosis of the extremities (virtually always lower) causing ischemia. Mild PAD may be asymptomatic or cause intermittent claudication; severe PAD... read more Peripheral Arterial Disease (impairing function), or chronic obstructive pulmonary disease Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more Chronic Obstructive Pulmonary Disease (COPD) (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.

Table

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 references

Calcium Channel Blockers for Hypertension

Dihydropyridines (see table ) 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 Atrioventricular Block Atrioventricular (AV) block is partial or complete interruption of impulse transmission from the atria to the ventricles. The most common cause is idiopathic fibrosis and sclerosis of the conduction... read more Atrioventricular Block or with left ventricular failure.

Table

Calcium channel blocker reference

  • 1. Furberg CD, Psaty BM, Meyer JV.Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation 1995;92(5):1326-1331. doi:10.1161/01.cir.92.5.1326

Direct Renin Inhibitor for Hypertension

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 Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more or renal disease (estimated GFR < 60 mL/minute). It is also contraindicated during pregnancy.

Direct Vasodilators for Hypertension

Direct vasodilators, including minoxidil and hydralazine (see table ), 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.

Table

Direct vasodilators references

  • 1. Handler J. Hydralazine-induced lupus erythematosis. J Clin Hypertens (Greenwich) 2012;14(2):133-136. doi:10.1111/j.1751-7176.2011.00573.x

  • 2. Santoriello D, Bomback AS, Kudose S, et al. Anti-neutrophil cytoplasmic antibody associated glomerulonephritis complicating treatment with hydralazine. Kidney Int 2021;100(2):440-446. doi:10.1016/j.kint.2021.03.029

Diuretics for Hypertension

Main classes of diuretics used for hypertension (see table ) 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 Hypokalemia Hypokalemia is serum potassium concentration < 3.5 mEq/L (< 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common... read more , 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 Stages of chronic kidney disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Stages of chronic kidney disease , chlorthalidone has been shown to be effective in improving blood pressure in patients with glomerular filtration rates < 30 mL/minute (1 Diuretic references The treatment of hypertension may involve lifestyle modifications alone (eg, dietary modification, weight loss, exercise) or in combination with medications. The decision to treat with medication... read more ). 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 Diuretic references The treatment of hypertension may involve lifestyle modifications alone (eg, dietary modification, weight loss, exercise) or in combination with medications. The decision to treat with medication... read more ) 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 Diuretic references The treatment of hypertension may involve lifestyle modifications alone (eg, dietary modification, weight loss, exercise) or in combination with medications. The decision to treat with medication... read more ). 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 Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol (HDL-C) level that contributes to the development of atherosclerosis... read more 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 Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more Overview of Arrhythmias , or develop ectopy or arrhythmias while taking a diuretic.

A hereditary predisposition probably explains the few cases of gout Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more 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 Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more Heart Failure (HF) 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.

Table

Diuretic references

  • 1. Agarwal R, Sinha AD, Tu W: Chlorthalidone for hypertension in Advanced CKD. Reply. N Engl J Med 386(14):1384, 2022.

  • 2. Roush GC, Ernst ME, Kostis JB, Tandon S, Sica DA. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension 65(5):1041-1046, 2015. doi:10.1161/HYPERTENSIONAHA.114.05021

  • 3. Ott SM, LaCroix AZ, Ichikawa LE, Scholes D, Barlow WE. Effect of low-dose thiazide diuretics on plasma lipids: results from a double-blind, randomized clinical trial in older men and women. J Am Geriatr Soc 51(3):340-347, 2003. doi:10.1046/j.1532-5415.2003.51107.x

More Information

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

Drugs Mentioned In This Article

Drug Name Select Trade
GIAPREZA
Aldomet
Catapres, Catapres-TTS, Duraclon, Kapvay, NEXICLON XR
Intuniv, Tenex
Minipress
Hytrin
Cardura, Cardura XL
Aldactone, CAROSPIR
Inspra
Sectral
Tenormin
Betoptic S, Kerlone
Zebeta
KAPSPARGO, Lopressor, Toprol XL
No brand name available
Corgard
Calan, Calan SR, Covera-HS, Isoptin, Isoptin SR, Verelan, Verelan PM
Cardizem, Cardizem CD, Cardizem LA, Cardizem SR, Cartia XT , Dilacor XR, Dilt-CD , Diltia XT, Diltzac, Matzim LA, Taztia XT, TIADYLT ER, Tiamate, Tiazac
Tekturna
Loniten, Rogaine
No brand name available
Demadex, SOAANZ
Thalitone
Lozol
Esidrix, Ezide, HydroDIURIL, Microzide, Oretic, Zide
Dyrenium
Midamor
Digitek , Lanoxicaps, Lanoxin, Lanoxin Pediatric
View PATIENT EDUCATION
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz! 
iOS ANDROID
iOS ANDROID
iOS ANDROID
TOP