The Drugs Used to Treat High Blood Pressure
Many people with high blood pressure need two or more blood pressure-lowering drugs to reach the goal of less than 140/90 mm Hg. Because hypertension is a chronic condition, you will most likely need to take your medication indefinitely.
There are 10 classes of blood pressure drugs—diuretics, ACE inhibitors, angiotensin II receptor blockers (ARBs), calcium-channel blockers, beta-blockers, alpha-blockers, central alpha agonists, direct vasodilators, peripheral-acting adrenergic antagonists and direct renin inhibitors. Each class lowers blood pressure in a different way. The first line of treatment for hypertension usually involves a thiazide diuretic, such as chlorthalidone. Then, depending on how well you respond to the diuretic and whether you have any other health conditions such as diabetes, heart disease or kidney disease, your doctor may add an ACE inhibitor, ARB, beta-blocker or calcium-channel blocker. Less commonly, an alpha-blocker, central alpha agonist, direct vasodilator, peripheral-acting adrenergic antagonist or direct renin inhibitor may be added to help lower blood pressure.
Often referred to as fluid or water pills, diuretics help reduce blood pressure by increasing the removal of sodium and fluid from the blood into the urine by the kidneys. Diuretics also lower blood pressure by promoting dilation of small blood vessels. There are three types of diuretics, each one acting on a different site in the kidney.
• Thiazide diuretics. These are the most commonly used diuretics. In fact, nearly everyone who has hypertension should be taking a thiazide diuretic as first line for treatment. These drugs are inexpensive, often need to be taken only once a day, and are at least as effective—if not more effective—than other classes of blood pressure drugs at lowering blood pressure and reducing the risk of stroke and heart attack. Hydrochlorothiazide (Microzide) and chlorthalidone are two commonly prescribed thiazide diuretics.
The benefits of chlorthalidone was shown in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which followed about 33,000 people with hypertension who had at least one risk factor for heart disease (for example, type 2 diabetes or smoking). The participants were randomly assigned to receive the thiazide diuretic chlorthalidone or one of two other drugs—the ACE inhibitor lisinopril (Prinivil, Zestril) or the calcium-channel blocker amlodipine (Norvasc).
In ALLHAT, chlorthalidone was superior to the ACE inhibitor and calcium-channel blocker for the prevention of certain types of cardiovascular events. Specifically, people on chlorthalidone had a lower risk of heart failure than those taking the calcium-channel blocker as well as a lower risk of stroke, heart failure and angina (chest pain) than people treated with the ACE inhibitor.
Thiazide diuretics are not the best first-choice drugs for everyone—particularly those with certain health conditions. A beta-blocker may be the preferred option for someone with coronary heart disease and an ACE inhibitor may be the first choice for a person with kidney disease. Still, if you have hypertension and are not taking a thiazide diuretic, you should ask your doctor why.
• Loop diuretics. These diuretics, such as furosemide (Lasix), are better at removing excess fluid and are most commonly used in people with heart failure or kidney disease.
• Potassium-sparing diuretics. These medications are used along with a thiazide diuretic to counteract potassium loss. Some examples are triamterene (Dyrenium), spironolactone (Aldactone) and eplerenone (Inspra).
Diuretics are well tolerated, particularly at lower dosages, but side effects can sometimes occur—dizziness, lightheadedness, headache, blurred vision, loss of appetite, stomach upset, diarrhea and constipation. Thiazide and loop diuretics can cause a loss of potassium from the blood, which can lead to abnormal heart rhythms. If this happens, your doctor may recommend eating foods rich in potassium, a potassium supplement, or may prescribe a potassium-sparing diuretic.
2. ACE inhibitors
These medications decrease blood pressure by reducing the production of angiotensin II, a potent constrictor of blood vessels. They are often prescribed for people with hypertension who also have kidney damage, heart failure or diabetes. Commonly prescribed ACE inhibitors include benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), lisinopril (Prinivil, Zestril), and ramipril (Altace).
A dry cough occurs in about 10 percent of people on ACE inhibitors, especially women. If you experience this side effect and find it intolerable, tell your doctor. He or she may switch you to an angiotensin II receptor blocker. Other possible side effects of ACE inhibitors include dizziness, lightheadedness, fatigue, nausea, blurred vision, or an increase in concentration of potassium in the blood.
3. Angiotensin II receptor blockers (ARBs)
These drugs, such as irbesartan (Avapro), losartan (Cozaar), and valsartan (Diovan), work by decreasing the activity of angiotensin II, a hormone that raises blood pressure by constricting small blood vessels and stimulating the adrenal glands to produce the sodium-retaining hormone aldosterone. ARBs may also halt overgrowth of smooth muscle cells in blood vessel walls. In addition, ARBs slow the progression of kidney disease in people with diabetes (and possibly in those without diabetes). Potential side effects include dizziness, lightheadedness, blurred vision, or an increase in concentration of potassium in the blood.
4. Calcium-channel blockers
This class of medications lowers blood pressure by dilating the arteries and, depending on the type of calcium-channel blocker, by lowering the heart rate. Like beta-blockers, they help alleviate symptoms of angina (chest pain). Commonly used calcium-channel blockers include verapamil (Calan and other brands), nifedipine (Adalat and other brands), diltiazem (Cardizem and other brands), and amlodipine (Norvasc). Potential adverse effects include headache, dizziness, facial flushing and constipation. These side effects tend to subside with continued use, however.
Beta-blockers are one of the older classes of medications used to lower blood pressure, and they include atenolol (Tenormin), metoprolol (Lopressor, Toprol XL) and propranolol (Inderal LA, Innopran XL). They are commonly prescribed as “add-on” therapy, when people need more than one drug to keep blood pressure under control.
Beta-blockers block the action of the hormone epinephrine and lower blood pressure by slowing heart rate. These medications offer the additional benefit of lowering the heart’s need for oxygen, which can help control angina (chest pain). Thus, hypertensive people with angina or a previous heart attack often receive a beta-blocker to treat both high blood pressure and their heart condition.
These medications, which include doxazosin (Cardura), prazosin (Minipress) and terazosin (Hytrin), lower blood pressure levels by blocking nerve impulses that constrict small arteries. As a result, small arteries dilate, facilitating blood flow and reducing blood pressure.
Alpha-blockers are used only in people with difficult-to-control blood pressure. They are not recommended as first-choice therapy for hypertension because they can increase the risk of certain heart conditions.
7. Central alpha agonists
Like alpha-blockers, these drugs lower blood pressure by blocking nerve impulses that constrict the small arteries, relaxing peripheral arteries throughout the body (including the arteries leading to the arms and legs). Clonidine (Catapres), guanabenz, guanfacine (Tenex), and methyldopa are examples of central alpha agonists. Common side effects of these drugs include drowsiness, fatigue, sleep problems, depression, dry mouth, constipation, dizziness and erectile dysfunction. These drugs should not be stopped abruptly since doing so can lead to rebound hypertension and angina (chest pain). Central alpha agonists usually are used only when other medications are unable to control blood pressure adequately.
8. Direct vasodilators
These drugs act directly on the blood vessel walls, relaxing muscles to allow blood to flow more easily. Direct vasodilators such as minoxidil are used only in individuals with hypertension that is extremely difficult to control. Hydralazine is typically used in patients with heart failure. To prevent fluid retention and a rapid heartbeat, they must be used in combination with a diuretic and a beta-blocker. Vasodilators can also cause headaches and joint pain.
9. Peripheral-acting adrenergic antagonists
These medications reduce resistance to blood flow in small arteries by inhibiting the release of epinephrine and norepinephrine. Reserpine (Serpalan) is the only available drug in this class. Potential side effects include dizziness, lightheadedness, diarrhea, heartburn, and a stuffy nose. Reserpine is commonly used in people with severe hypertension and is often prescribed in combination with a diuretic and a beta-blocker (or another medication that slows the heart rate).
10. Direct renin inhibitors
Aliskiren (Tekturna) is the first drug approved in this class. (A combination of aliskiren and amlodipine called Tekamlo is also available.) It reduces blood pressure by blocking the activity of renin, an enzyme that converts angiotensinogen to angiotensin I. When angiotensin I is converted to angiotensin II, arteries constrict and blood pressure rises.
Studies show that Tekturna produces modest reductions in blood pressure, but there’s no evidence that it reduces the risk of heart attack, stroke or kidney disease like diuretics, ACE inhibitors and ARBs do. Therefore, Tekturna is not considered first-line therapy.
Most people with hypertension require two or more blood pressure medications to control their blood pressure. By combining drugs from different classes, you’ll likely be able to reduce your blood pressure more than if you use a single drug.
Studies have found that combining two different drugs worked better than doubling the dosage of a single drug. That’s because the actions of two medications can complement each other. For example, diuretics reduce blood pressure by increasing the excretion of sodium and water by the kidneys. In some people, this effect stimulates hormones to compensate for the drop in blood volume. Adding an ACE inhibitor blocks the actions of these hormones and improves blood pressure control.
Combination therapy involves taking either a separate dose of each medication or a single pill that contains two or more different medications (a fixed-dose combination drug). Most fixed-dose combination drugs contain a thiazide diuretic and an ACE inhibitor, ARB or beta-blocker. Some examples are Capozide (hydrochlorothiazide plus captopril), Diovan HCT (hydrochlorothiazide plus valsartan), Inderide (hydrochlorothiazide plus propranolol) and Lotensin HCT (hydrochlorothiazide plus benazepril).
Fixed-dose combination drugs are more convenient (there are fewer pills to take each day). In addition, the risk of side effects may be reduced because the fixed-dose combination typically contains smaller doses of each medication than when the drugs are taken separately.
However, fixed-dose combinations may be more expensive than taking a generic version of each drug individually. Also, fixed-dose combinations reduce dosing flexibility—the dosage of each medication in the combination cannot be adjusted separately. Thus, fixed-dose combination drugs are most appropriate for people who have found that the combination of the two drugs effectively controls their blood pressure when taken separately at the same dosages as in the combination pill.