Medications for Hypertension - Medications for Hypertension - MSD Manual Professional Edition (2024)

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 is based on the blood pressure (BP) level, the presence of atherosclerotic cardiovascular disease (ASCVD) or its risk factors, and other considerations.

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

  • Adrenergic  modifiers

  • Angiotensin-converting enzyme (ACE) inhibitors

  • Beta-blockers

  • Calcium channel blockers

  • Direct renin inhibitors

  • Direct vasodilators

  • Diuretics

Selection and use of medications in the treatment of stable hypertension is discussed elsewhere. For treatment of hypertensive emergencies, see table Parenteral Medications for Hypertensive Emergencies.

(See also Hypertension and Hypertensive Emergencies.)

Adrenergic Modifiers for Hypertension

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

Table

Table

Adrenergic Modifiers for Hypertension

Medication*

Selected Adverse Effects

Comments

Alpha-2-agonists (central acting)

Should be used cautiously in older patients because of orthostatic hypotension

Interferes with measurements of urinary catecholamine levels by fluorometric methods

Should not be combined with an alpha-1-blocker because of a risk of significant orthostatic hypotension.

Guanabenz

Alpha-1-blockers

First-dose syncope, orthostatic hypotension, weakness, palpitations, headache

Should be used cautiously in older patients because of orthostatic hypotension

Relieves symptoms of benign prostatic hyperplasia

* Peripheral-acting adrenergic blockers (eg, guanadrel, guanethidine, reserpine) are no longer available in the United States.

TTS = transdermal therapeutic system.

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.

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. 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

Table

Oral Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin II Receptor Blockers for Hypertension

Medication

Selected Adverse Effects

ACE inhibitors*

Rash, cough, angioedema, hyperkalemia (particularly in patients with renal insufficiency or taking nonsteroidal anti-inflammatory drugs, potassium-sparing diuretics, or potassium supplements), dysgeusia, reversible acute kidney injury if stenosis affecting one or both kidneys threatens renal function, proteinuria (rare at recommended doses), neutropenia (rare), hypotension with initiation of treatment (particularly in patients with high plasma renin activity or with hypovolemia due to diuretics or other conditions)

Angiotensin II receptor blockers

Dizziness, angioedema (very rare); theoretically, same adverse effects as ACE inhibitors on renal function (except proteinuria and neutropenia), serum potassium, and blood pressure

* All ACE inhibitors and angiotensin II receptor blockers are contraindicated in pregnancy (can cause injury or death to the developing fetus).

ACE inhibitors references

  1. 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. 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. 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. 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. 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 withrenovascular hypertension, hypovolemia, and severe heart failure are the same as those for ACE inhibitors (see table ). Angiotensin II receptor blockers are contraindicated during pregnancy.

Beta-Blockers for Hypertension

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 Hypertensiondiabetes (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.

Table

Table

Oral Beta-Blockers for Hypertension

Medication

Selected Adverse Effects

Comments

Contraindicated in patients with greater than 1st-degree atrioventricular block, or sick sinus syndrome

Should be avoided in patients with asthma

Should be used cautiously in patients with COPD with severe disease, heart failure, or who are taking insulin

Should not be stopped abruptly in patients with coronary artery disease

Penbutolol†

* Cardioselective.

† With intrinsic sympathomimetic activity.

§ Can also be given for hypertensive emergencies.

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).

Beta-blockers references

  1. 1. Thomopoulos C, Bazoukis G, Tsioufis C, Mancia G. Beta-blockers in hypertension: overview and meta-analysis of randomized outcome trials.J Hypertens 2020;38(9):1669-1681. doi:10.1097/HJH.0000000000002523

  2. 2. Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH. Beta-blockers for hypertension.Cochrane Database Syst Rev 2017;1(1):CD002003. Published 2017 Jan 20. doi:10.1002/14651858.CD002003.pub5

  3. 3. Morales DR, Jackson C, Lipworth BJ, Donnan PT, Guthrie B. Adverse respiratory effect of acute β-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials.Chest 2014;145(4):779-786. doi:10.1378/chest.13-1235

Calcium Channel Blockers for Hypertension

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 nondihydropyridinesatrioventricular block or with left ventricular failure.

Table

Table

Oral Calcium Channel Blockers for Hypertension

Medication

Selected Adverse Effects

Comments

Nondihydropyridines

Headache, dizziness, asthenia, flushing, peripheral edema, bradycardia; possibly liver dysfunction

Possible gingival hyperplasia with chronic use

Contraindicated in heart failure with reduced ejection fraction due to negative inotropic effects, in sinus node dysfunction, or in greater than 1st-degree atrioventricular block

Headache, dizziness, asthenia, flushing, peripheral edema, bradycardia; possibly liver dysfunction

Constipation

Possible gingival hyperplasia with chronic use

Contraindicated in heart failure with reduced ejection fraction due to negative inotropic effects, in sinus node dysfunction, or in greater than 1st-degree atrioventricular block

Dihydropyridines

Dizziness, flushing, headache, weakness, nausea, heartburn, peripheral edema, tachycardia

Possible gingival hyperplasia with chronic use

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.

Calcium channel blocker reference

  1. 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

As with ACE inhibitors and angiotensin IIAliskiren 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 for Hypertension

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 sodiumand water retention and hypertrichosis, which is poorly tolerated by women. Minoxidil should be reserved for severe, refractory hypertension.

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).

Table

Table

Direct Vasodilators for Hypertension

Medication

Selected Adverse Effects*

Comments

Positive antinuclear antibody test, drug-induced lupus (rare at recommended doses)

Augments vasodilating effects of other vasodilating medication

Sodium and water retention, hypertrichosis; possibly new or worsening pleural and pericardial effusions

Reserved for severe, refractory hypertension

* Both medications may cause headache, tachycardia, and fluid retention and may precipitate angina in patients with coronary artery disease.

Direct vasodilators references

  1. 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. 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 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 <

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 diureticsstage 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, indapamide2) 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.

<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.

Table

Table

Oral Diuretics for Hypertension

Medication

Selected Adverse Effects

Loop Diuretics

Hyperkalemia, hyponatremia, hypomagnesemia, dehydration, postural hypotension, tinnitus, hearing loss

Potassium-sparing diuretics

Bendroflumethiazide

Hypokalemia (which increases digitalis toxicity), hyperuricemia, glucose intolerance, hypercholesterolemia, hypertriglyceridemia, hypercalcemia, sexual dysfunction in men, weakness, rash

Hydroflumethiazide

Methyclothiazide

* Larger doses may be required in patients with renal failure.

† Aldosterone receptor blockers.

Diuretic references

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

  2. 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. 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.

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

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