Today, highly effective medications are available for the treatment of hypertension. Together with measures such as healthy nutrition and weight reduction, these drugs can lower blood pressure to normal or near-normal levels in most cases. This section explains how medications work in hypertension.
Arterial hypertension is a chronic condition that usually cannot be cured. This means that antihypertensive medications must be taken continuously as long-term therapy. This is generally not problematic, as modern medications are usually well tolerated.
Important Points for Long-Term Treatment Success
There are several mechanisms by which blood pressure can be lowered. One important approach is to reduce vascular resistance through vasodilation.
In patients with diabetes, treatment of hypertension should usually begin with two medications, preferably combined in a single tablet.
Initial Therapy – Step 1
Dual therapy consists of a medication that acts on the renin–angiotensin system (RAS), namely either:
combined with either:
ACE inhibitors and ARBs should not be used together because this combination is associated with an increased cardiovascular risk.
Beta-blockers should only be used in Step 1 together with a diuretic if there is a specific indication, such as coronary artery disease, previous myocardial infarction, heart failure, or the need for heart rate control.
Monotherapy with only one drug should be reserved for patients with low risk and stage 1 hypertension with systolic blood pressure below 150 mmHg.
Step 2
If the target blood pressure is not achieved, triple therapy is recommended:
Step 3
In resistant hypertension, spironolactone should be added. If spironolactone is contraindicated or blood pressure targets are still not achieved, beta-blockers or alpha-blockers may be considered.
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Various hormones and enzymes in this system regulate body fluid balance and blood pressure.
When blood pressure falls or when water and salt are lost, renin is released from specific parts of the kidney tissue. Renin cleaves angiotensinogen, a protein produced in the liver, into angiotensin I. Angiotensin I is then converted by angiotensin-converting enzyme (ACE) into angiotensin II.
Angiotensin II acts on receptors in blood vessel walls and causes vasoconstriction. This narrowing of blood vessels raises blood pressure.
ACE inhibitors prevent the conversion of angiotensin I into angiotensin II and thereby lower blood pressure.
Angiotensin receptor blockers (ARBs) block the angiotensin receptor in the vessel wall and also reduce blood pressure.
ACE inhibitor names usually end in “-pril”.
ARBs are also known as sartans.
ACE Inhibitors in the Treatment of Hypertension
Daily dose in milligrams:
Medication | Daily Dose |
Benazepril | 10–40 mg |
Captopril | 12.5–150 mg |
Enalapril | 5–40 mg |
Fosinopril | 10–40 mg |
Lisinopril | 10–40 mg |
Moexipril | 7.5–30 mg |
Perindopril | 4–16 mg |
Quinapril | 10–80 mg |
Ramipril | 2.5–20 mg |
Trandolapril | 1–4 mg |
ACE inhibitors may cause a persistent dry cough. In this case, switching to an ARB should be considered.
ACE inhibitors should not be combined with ARBs or direct renin inhibitors because this increases the risk of cardiovascular complications.
Patients with coronary artery disease, those taking potassium-containing supplements, or those taking potassium-sparing medications have an increased risk of hyperkalemia.
In patients with severe bilateral renal artery stenosis, ACE inhibitors may cause acute kidney failure.
ACE inhibitors should not be used in patients with a history of ACE inhibitor–associated angioedema.
ACE inhibitors are contraindicated during pregnancy.
ARBs / Sartans
Daily dose in milligrams:
Medication | Daily Dose |
Azilsartan | 40–80 mg |
Candesartan | 8–32 mg |
Eprosartan | 600–800 mg |
Irbesartan | 150–300 mg |
Losartan | 50–100 mg |
Olmesartan | 20–40 mg |
Telmisartan | 20–80 mg |
Valsartan | 80–320 mg |
ARBs should not be combined with ACE inhibitors or direct renin inhibitors because this combination is associated with increased cardiovascular risk.
They may increase potassium levels, especially in patients with coronary artery disease, those taking potassium supplements, or those taking potassium-sparing medications.
In severe bilateral renal artery stenosis, ARBs may increase the risk of acute kidney failure.
ARBs should not be used in patients with a history of ARB-associated angioedema.
Patients who developed angioedema while taking an ACE inhibitor may receive an ARB after at least six weeks.
ARBs are contraindicated during pregnancy.
Diuretics
Diuretics increase urine excretion. This reduces the volume of fluid in the vascular system, thereby lowering blood pressure.
Thiazide and Thiazide-Like Diuretics
Daily dose in milligrams:
Medication | Daily Dose |
Chlorthalidone | 12.5–25 mg |
Hydrochlorothiazide | 25–50 mg |
Indapamide | 1.25–2.5 mg |
Hydrochlorothiazide may worsen metabolism and should preferably not be used in patients with diabetes. Thiazide-like diuretics such as chlorthalidone and indapamide are preferred.
Chlorthalidone is often preferred because of its longer half-life and evidence for reduction of cardiovascular events.
During therapy with thiazide or thiazide-like diuretics, sodium, potassium, uric acid, and calcium levels should be monitored.
In patients with a history of acute gout, thiazides should be used with caution unless the patient receives uric acid–lowering therapy.
Dihydropyridine Calcium Channel Blockers
In Step 1 treatment, a RAS-blocking medication is combined with a thiazide diuretic. Alternatively, a calcium channel blocker may be used.
Dihydropyridine calcium channel blockers reduce calcium influx into vascular muscle cells. This decreases contraction of arteriolar smooth muscle, reduces afterload, and lowers blood pressure.
Medication | Daily Dose |
Amlodipine | 2.5–10 mg |
Felodipine | 2.5–10 mg |
Isradipine | 5–10 mg |
Lercanidipine HCl | 10–20 mg |
Nicardipine SR | 60–120 mg |
Nifedipine LA | 30–90 mg |
Nisoldipine | 17–34 mg |
Calcium channel blockers should generally be avoided in patients with heart failure with reduced ejection fraction (HFrEF). If necessary, amlodipine or felodipine may be used.
Calcium channel blockers may cause dose-dependent leg edema, which occurs more often in women than in men. Leg edema occurs more frequently with amlodipine than with lercanidipine.
Non-Dihydropyridine Calcium Channel Blockers
Daily dose in milligrams:
Medication | Daily Dose |
Diltiazem extended release | 120–360 mg |
Verapamil immediate release | 120–360 mg |
Verapamil extended release | 120–360 mg |
Verapamil-type calcium channel blockers reduce heart rate and contractility. Diltiazem-type agents reduce heart rate and also lower afterload through arteriolar vasodilation.
Routine use of diltiazem or verapamil together with beta-blockers should be avoided because of the increased risk of bradycardia and cardiac arrest.
They should not be used in patients with HFrEF.
Diltiazem and verapamil have relevant drug interactions via CYP3A4.
Additional Medications for Resistant Hypertension
In almost all cases, blood pressure can be controlled with the medications listed above. However, some patients have treatment-resistant hypertension.
If blood pressure cannot be controlled with the combinations above, the following medications may be added.
Aldosterone Antagonists
Daily dose in milligrams:
Medication | Daily Dose |
Eplerenone | 50–100 mg |
Spironolactone | 25–100 mg |
Aldosterone antagonists are preferred in primary aldosteronism and resistant hypertension.
A common side effect in men is breast enlargement (gynecomastia). Spironolactone is associated with a higher risk of gynecomastia and impotence than eplerenone.
Aldosterone antagonists should not be used in patients taking potassium supplements, other potassium-sparing diuretics, or in patients with significant kidney dysfunction.
Eplerenone often requires twice-daily dosing for adequate blood pressure reduction.
Loop Diuretics
Daily dose in milligrams:
Medication | Daily Dose |
Bumetanide | 0.5–2 mg |
Furosemide | 20–80 mg |
Torsemide | 5–10 mg |
Loop diuretics are preferred in patients with symptomatic heart failure.
Furosemide and torsemide have short half-lives and are mainly used in patients with chronic kidney disease and a glomerular filtration rate below 30 ml/min, since thiazides and thiazide-like agents lose effectiveness as kidney function declines.
Potassium-Sparing Diuretics
Daily dose in milligrams:
Medication | Daily Dose |
Amiloride | 5–10 mg |
Triamterene | 50–100 mg |
Potassium-sparing diuretics are weak antihypertensive agents when used alone.
Combination therapy with a potassium-sparing diuretic and a thiazide may be considered in patients who develop hypokalemia during thiazide monotherapy.
Potassium-sparing diuretics should not be used in patients with significant chronic kidney disease, for example GFR below 45 ml/min.
Beta-Blockers
Sensors in the central arteries monitor blood pressure and blood gases. These sensors activate the sympathetic nervous system, leading to release of adrenaline and noradrenaline into the bloodstream. These hormones act on alpha and beta receptors and cause vasoconstriction.
Beta-receptor blockers are primarily used to lower blood pressure. Beta-blocker names usually end in “-ol.”
If blood pressure reduction is insufficient, the alpha-1 blocker doxazosin may be used in combination with beta-blockers. Alpha-1 blockers are especially used in men with enlarged prostate.
Beta-blockers may increase insulin resistance and cause weight gain. They may be necessary in patients with heart failure, angina pectoris, after myocardial infarction, in atrial fibrillation, or in younger women who are pregnant or planning pregnancy, for example metoprolol.
If beta-blockers are necessary, metabolically neutral beta-blockers such as carvedilol or nebivolol should preferably be used.
Beta-blockers are not recommended as first-line agents unless the patient has ischemic heart disease or heart failure.
Cardioselective Beta-Blockers
Daily dose in milligrams:
Medication | Daily Dose |
Atenolol | 25–100 mg |
Betaxolol | 5–20 mg |
Bisoprolol | 2.5–10 mg |
Metoprolol tartrate | 100–200 mg |
Metoprolol succinate | 50–200 mg |
Cardioselective beta-blockers are preferred in patients with bronchospastic airway disease who require a beta-blocker.
Bisoprolol and metoprolol succinate are preferred in patients with HFrEF.
Cardioselective and Vasodilating Beta-Blocker
Medication | Daily Dose |
Nebivolol | 5–40 mg |
Nebivolol induces nitric oxide–mediated vasodilation.
Non-Cardioselective Beta-Blockers
Medication | Daily Dose |
Nadolol | 40–120 mg |
Propranolol IR | 80–160 mg |
Propranolol LA | 80–160 mg |
These should be avoided in patients with reactive airway disease.
Beta-Blockers With Intrinsic Sympathomimetic Activity
Medication | Daily Dose |
Acebutolol | 200–800 mg |
Penbutolol | 10–40 mg |
Pindolol | 10–60 mg |
These should generally be avoided, especially in patients with ischemic heart disease or heart failure.
Combined Alpha- and Beta-Receptor Blockers
Medication | Daily Dose |
Carvedilol | 12.5–50 mg |
Carvedilol phosphate | 20–80 mg |
Carvedilol is preferred in patients with HFrEF.
Beta-blockers should be tapered gradually and not stopped abruptly.
Alpha-1 Blockers
Daily dose in milligrams:
Medication | Daily Dose |
Doxazosin | 1–16 mg |
Prazosin | 2–20 mg |
Terazosin | 1–20 mg |
In older adults, alpha-1 blockers are associated with orthostatic hypotension.
Alpha-1 blockers may be considered as second-line agents in patients with concomitant prostate enlargement.
Direct Renin Inhibitor
Medication | Daily Dose |
Aliskiren | 150–300 mg |
Aliskiren should not be used in combination with ACE inhibitors or ARBs.
It has a long duration of action.
Patients with chronic kidney disease, those taking potassium-sparing medications, or those taking potassium supplements have an increased risk of hyperkalemia.
Aliskiren may cause acute kidney failure in patients with severe bilateral renal artery stenosis.
Aliskiren should not be used during pregnancy.
Direct Vasodilators
Daily dose in milligrams:
Medication | Daily Dose |
Hydralazine | 100–200 mg |
Minoxidil | 5–100 mg |
Direct vasodilators are associated with sodium and water retention as well as reflex tachycardia. Reflex tachycardia is a reactive increase in heart rate after a drop in blood pressure.
These medications should be used in combination with a diuretic and a beta-blocker.
Hydralazine at higher doses is associated with drug-induced lupus-like syndrome.
Minoxidil is associated with hirsutism and requires combination with a loop diuretic.
Minoxidil may cause pericardial effusion.
Central Alpha-2 Agonists and Other Centrally Acting Medications
Daily dose in milligrams:
Medication | Daily Dose |
Clonidine oral | 0.1–0.8 mg |
Clonidine patch | 0.1–0.3 mg weekly |
Methyldopa | 250–1000 mg |
Centrally acting medications are generally reserved as last-line agents because of significant central nervous system side effects, especially in older adults.
Abrupt discontinuation of clonidine may cause a hypertensive crisis.
Methyldopa is mainly used for the treatment of hypertension during pregnancy. Metoprolol may also be used during pregnancy. Most other antihypertensive medications are contraindicated.
Blood pressure management during pregnancy should always be performed in hospital. Nifedipine may be additionally used in patients who are breastfeeding.