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This topic will review the appropriate therapy of essential hypertension. The definition of hypertension and the indications for both non-drug and drug therapy are discussed separately. ( See "Patient information: Hypertension: What is it, who should be treated, and why" and see "Patient information: Hypertension and diet and weight" ).

INTRODUCTION ? Hypertension is the medical term for high blood pressure. Blood pressure refers to the pressure exerted by circulating blood on the inner walls of the arteries. It is measured based upon two values: the arterial pressure both as the heart contracts and as it relaxes between beats (ie, systolic pressure/diastolic pressure).

Most adults with hypertension have what is called essential or primary hypertension, because the cause is not known. A small subset of adults have secondary hypertension, in which an underlying and potentially correctable cause can be identified.

Blood pressure varies naturally over the course of a day, and usually increases with age. In addition, activity affects blood pressure, which rises as a normal response to physical exertion and stress. However, patients with hypertension have high blood pressure even at rest. Untreated hypertension puts strain on the heart and arteries, eventually damaging such tissues, and is a key risk factor for heart failure, heart attack (myocardial infarction), and stroke.

Making appropriate lifestyle changes under a doctor's guidance is an important initial part of any treatment plan for high blood pressure. In some patients, such modifications ? such as lowering sodium and alcohol intake, keeping weight in the ideal range, engaging in regular aerobic exercise, and stopping smoking ? may be sufficient to control hypertension.

However, many patients also require therapy with medications known as "antihypertensive drugs" to lower the blood pressure. The following is an overview of the different types of drugs that may initially be prescribed for patients who require antihypertensive therapy for essential hypertension. (For information on proper lifestyle modifications and who should receive antihypertensive therapy, see "Patient information: Hypertension and diet and weight" and see "Patient information: Hypertension: What is it, who should be treated, and why" ).

ANTIHYPERTENSIVE DRUGS ? There are various classes of antihypertensive agents that are commonly used to reduce high blood pressure. Following is a brief description of the major antihypertensive drug classes, with the generic names of certain medications that are commonly prescribed. Clicking on the name of a drug will call up information on that drug. (Please note that listings of such medications within this review are not all inclusive and are meant for information purposes only.)

Although generally well tolerated, antihypertensive drugs can cause side effects that vary with the specific drug given, dosage, and other factors. In addition, many patients will respond well to one drug but not to another. Therefore, it may take time to determine the right drug(s) and proper dosage levels in your case to most effectively lower blood pressure with a minimum of side effects.

The following discussion includes a general description of the types of side effects that may be associated with certain classes of antihypertensive medications. If you develop any side effects from drug treatment, be sure to inform your doctor so that your medication may be adjusted.

Diuretics ? Diuretics lower blood pressure mainly by causing the kidneys to increase their excretion of water and sodium, reducing fluid volume throughout the body, and also serve to widen (dilate) blood vessels.

The diuretics used to treat hypertension are thiazides, eg, chlorthalidone , hydrochlorothiazide , and indapamide . In some cases, a potassium-sparing diuretic, eg, amiloride , spironolactone , or triamterene or potassium supplements are given in combination with a thiazide diuretic because the thiazides can produce potassium deficiency due to increased excretion of potassium in the urine.

Side effects ? Side effects are uncommon at the low doses of thiazide diuretics that are now recommended. Fatigue, dizziness, weakness, and other symptoms can result from the loss of sodium and water and from the loss of potassium. Other symptoms that can occur include reversible impotence and gout attacks. Also, in patients with diabetes, higher doses than currently recommended may make control of blood sugar (glucose) levels more difficult.

ACE inhibitors ? Angiotensin converting enzyme (ACE) inhibitors block production of the hormone angiotensin II, a compound in the blood that causes narrowing of blood vessels (vasoconstriction) and increases blood pressure. By reducing angiotensin II production, ACE inhibitors allow blood vessels to widen, lowering blood pressure, and improving heart (cardiac) output.

The available ACE inhibitors include benazepril , captopril , enalapril , fosinopril , lisinopril , moexipril , perindopril , quinapril , ramipril , and trandolapril .

Side effects ? In some patients, ACE inhibitors may cause a persistent dry hacking cough that is reversible with discontinuation of therapy. Less common side effects include dry mouth, nausea, lightheadedness, postural dizziness, rash, muscle pain, or, occasionally, kidney dysfunction.

A potentially serious complication is angioedema, which occurs in 0.1 to 0.7 percent of treated patients. Angioedema refers to the relatively rapid onset over minutes to hours of swelling of the lips, tongue, and throat, which can interfere with breathing. Thus, the development of these symptoms should be considered a medical emergency. Such patients should not continue therapy with an ACE inhibitor.

Angiotensin II receptor blockers ? The angiotensin II receptor blockers (ARBs) block the effects of angiotensin II on cells in the heart and blood vessels, rather than inhibiting angiotensin II production as with ACE inhibitors.

The available ARBs include candesartan , irbesartan , losartan , telmisartan , and valsartan .

Side effects ? From the viewpoint of side effects, the main difference between ARBs and ACE inhibitors is that ARBs do not produce cough. A few patients who receive angiotensin II receptor blockers may experience dizziness, drowsiness, headache, nausea, dry mouth, abdominal pain, or other side effects. Angioedema is even less common with ARBs than with ACE inhibitors.

Calcium channel blockers ? Calcium channel blockers drugs reduce the amount of calcium that enters the smooth muscle in blood vessel walls and heart muscle. Muscle cells require calcium to contract. Thus, by inhibiting the flow of calcium across muscle cell membranes, calcium channel blockers cause muscle cells to relax and blood vessels to dilate, reducing blood pressure as well as reducing the force and rate of the heartbeat.

There are two major categories of calcium channel blockers: drugs known as "dihydropyridines" (including amlodipine , felodipine , isradipine , nicardipine , nifedipine , and nisoldipine ); and the nondihydropyridines diltiazem and verapamil . Diltiazem and verapamil are less potent vasodilating agents, but may provide additional effects on cardiac contractility and conduction.

Side effects ? The side effects that may be seen with calcium channel blockers vary with the specific agent used. Patients who take dihydropyridines may develop headache, dizziness, flushing, nausea, overgrowth of the gum tissue (gingival hyperplasia), or swelling of the extremities (peripheral edema).

The side effects are different with the nondihydropyridines, diltiazem or verapamil . These drugs can cause the heart rate to slow too much. Other side effects include headache and nausea with diltiazem or constipation with verapamil.

Beta blockers ? Beta blockers block some of the effects of the sympathetic nervous system, which stimulates particular involuntary functions at times of stress, increasing the heart rate and raising blood pressure. Beta blockers lower blood pressure in part by decreasing the rate and force at which the heart pumps blood into the circulation.

The available beta blockers include acebutolol , atenolol , betaxolol , bisoprolol , carteolol , metoprolol , nadolol , penbutolol , pindolol , propranolol , and timolol .

Some beta blockers have combined activity, blocking both the beta and alpha receptors (see next section). These include labetalol and carvedilol .

Side effects ? Beta blockers may worsen symptoms of asthma, other lung diseases, or abnormal conditions affecting certain blood vessels outside the heart (such as peripheral vascular disease). As a result, they normally are not prescribed for patients with such conditions. In addition, they may mask symptoms of low blood sugar (hypoglycemia) in patients with diabetes who are treated with insulin . Beta blockers can also cause fatigue, dizziness, insomnia, decreased exercise tolerance, a slow heart rate, rash, and cold hands and feet due to reduced blood flow to the limbs.

Alpha blockers ? Alpha blockers relax or reduce the tone of involuntary (ie, smooth) muscle in the walls of blood vessels (vascular smooth muscle), allowing the vessels to widen, thereby lowering blood pressure. An increase in blood vessel diameter is known as "vasodilation." The available alpha blockers include doxazosin , prazosin , and terazosin .

Side effects ? Alpha blockers can cause dizziness, particularly when standing up, headache, weakness, drowsiness, postural hypotension, or other side effects. They also may increase the risk of developing heart failure. For these reasons, they are not frequently used for first-line treatment of essential hypertension. A possible exception is in an older man with symptoms related to enlargement of the prostate; such symptoms may be relieved by alpha blocker therapy.

Direct vasodilators ? Direct vasodilators relax or reduce the tone of blood vessels. The two drugs in this class are hydralazine and minoxidil . Minoxidil is typically used in only severe and resistant hypertension.

Side effects ? Side effects associated with direct vasodilators include headache, weakness, nausea, constipation, peripheral edema, and rapid heartbeat. These effects are usually minimized by combined therapy with a beta blocker, but are more prominent with minoxidil , which is more powerful. Minoxidil also may cause excessive hair growth. Rogaine, which is used to treat baldness, is the topical preparation of minoxidil.

Centrally acting agents ? Sympathetic activity can also be reduced by centrally acting agents, such as clonidine , guanabenz , guanfacine , and methyldopa . These drugs, which act in the brain, are now infrequently used because of a worse side effect profile than the drugs listed above.

Side effects ? Centrally acting drugs can cause postural dizziness, drowsiness, impaired judgment, dry mouth, nausea, constipation, and reversible decrease in sexual function.

Important ? Before taking any medication, be sure to read all drug labels and any additional information provided by your pharmacist or doctor. It is important that you take the medication exactly as instructed. As mentioned above, if you do develop side effects, speak with your doctor, in order to adjust your dosage or change your medication. In addition, if you experience lightheadedness, dizziness, drowsiness, or impaired judgment when first taking such medication, use caution when driving or engaging in other tasks that require alertness until you know how you are affected by the drug.

THE PROPER MEDICATION FOR YOU ? Your doctor will take several factors into account when determining which antihypertensive drug should initially be prescribed. In addition to considering the documented effectiveness and potential side effects, your doctor will take into consider your general health, sex, age, and race; the severity of the hypertension; any additional, underlying (coexistent) conditions that are present; and whether particular drugs are inadvisable (ie, contraindicated) in your specific case.

Certain antihypertensive drugs are specifically recommended for the treatment of particular conditions independent of the blood pressure, although such conditions often coexist with hypertension. As examples:

• There are also certain antihypertensive agents that are contraindicated in some patients. Some examples include:

• Finally, certain coexistent conditions may be worsened by treatment with particular antihypertensive drugs. As an example, diuretics can worsen gout.

Thus, a complete history is essential to enable your doctor to determine the appropriate drug therapy for the control of your hypertension. The patient history should include any coexistent conditions, current medications, known drug allergies, and past adverse effects to certain drugs.

Effectiveness and cardiovascular protection ? Since various antihypertensive medications have documented effectiveness, there is currently no uniform agreement concerning which class of drug should initially be prescribed for the treatment of high blood pressure in most patients. Evidence suggests that each of the four major classes of antihypertensive drugs ? diuretics, ACE inhibitors, calcium channel blockers, and beta blockers ? is roughly equally effective, resulting in a good response in about 40 to 60 percent of cases. Blood pressure lowering protects against complications such as heart failure, stroke, and a heart attack.

As mentioned above, many patients will respond well to a particular antihypertensive drug but not to another. Therefore, identification of the specific drug class to which you are more likely to respond is a major element in determining which agent your doctor prescribes.

In addition, the use of particular drugs may be associated with better outcomes in certain clinical settings. This was best illustrated in the ALLHAT trial, which is the largest controlled trial ever performed in the treatment of hypertension and had the additional advantage of comparing four different classes of antihypertensive drugs, In this trial of patients at increased risk for coronary artery disease, a low-dose thiazide diuretic produced better outcomes than ACE inhibitors, calcium channel blockers, and beta blockers.

Recommendations ? For patients with hypertension without any significant underlying disorder or complications (that is, uncomplicated hypertension), we recommend beginning drug therapy with a low dose of a thiazide diuretic, based upon their proven long-term benefit, improved outcomes compared to other drugs, and low cost. This recommendation assumes that a different antihypertensive class is not specifically indicated for the treatment of a coexistent condition.

If low-dose thiazide monotherapy proves ineffective, experts recommend that an ACE inhibitor, ARB, calcium channel blocker, or beta blocker may then be sequentially added or substituted. Evidence suggests that a calcium channel blocker is likely to be most effective in black or elderly patients. However, patients who are unresponsive to a diuretic may have a similar lack of response to a calcium channel blocker; thus, an ACE inhibitor, ARB, or beta blocker may be preferable as second-line antihypertensive therapy.

As noted earlier, these general recommendations for initial therapy are altered for certain patients in whom specific agents may offer particular benefits (eg, both an ACE inhibitor and a beta blocker in patients with heart failure or a prior heart attack). In addition:

A diuretic is also indicated for fluid control in patients with heart failure and in elderly patients with isolated systolic hypertension. In the latter setting, certain long-acting dihydropyridine calcium channel blockers may be an appropriate alternative.

Combination drug therapy ? If patients have an insufficient response to initial drug treatment, your doctor will probably recommend early addition of a second drug. Alternatives include raising the dosage of the first drug to the recommended maximum dosage or adding a second drug after reaching moderate dosage. Early addition of a second drug may be:

If two drugs are in fact required, using low-dose therapy with a thiazide diuretic as one of the medications tends to increase the response to other antihypertensive agents. As an example, combining a thiazide diuretic with an ACE inhibitor or a beta blocker or an ACE inhibitor has a "cooperative" (synergistic) effect, controlling blood pressure in up to 85 percent of patients.

WHERE TO GET MORE INFORMATION ? Your doctor is the best resource for finding out important information related to your particular case.