Classes of Medication

There are several classes of drugs used to treat hypertension.

Diuretics

Diuretics help the kidneys get rid of excess salt and water. They are the mainstays of anti-hypertensive therapy and are the first drug of choice for most people with hypertension. They are especially helpful for treating the elderly and African-American patients. (African-Americans are more likely to be salt-sensitive, so they respond well to these drugs.) They also work well for patients with diabetes.

Results from the long-term Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), published in the Journal of the American Medical Association in 2005, confirm that thiazide-type diuretics should be the first treatment option for most patients with hypertension. The landmark trial included over 33,000 patients (35% black) with hypertension and at least one other cardiovascular risk factor. Patients were randomized to receive a calcium channel blocker, an ACE inhibitor, or a thiazide-type diuretic.

Results suggested that the diuretic worked just as well as the newer drugs in lowering blood pressure and was more effective in preventing heart failure, heart attack, and stroke. The benefits for the diuretic were even more significant for African-American patients. Other trial results indicated that patients taking the calcium channel blocker had the greatest risk for heart failure, and that the ACE inhibitor was much less effective than the diuretic in lowering blood pressure and preventing stroke in African-American patients.

Diuretic Types and Brands. There are many brands of diuretics. They are generally inexpensive. Some need to be taken once a day, some twice a day. Low doses are usually as effective for lowering blood pressure as higher doses. Diuretics are usually used in combination with other drugs, especially ACE inhibitors and beta blockers.

There are three main types of diuretics:

• Potassium-sparing diuretics. These include amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyrenium).
• Thiazide diuretics. These include chlorothiazide (Diuril), chlorthalidone (Hygroton), indapamide (Lozol), hydrochlorothiazide (Esidrix, HydroDiuril), and metolazone (Mykrox, Zaroxolyn).
• Loop diuretics. Because loop diuretics act faster than other diuretics it is important to avoid dehydration and potassium loss. Loop diuretics include bumetanide (Bumex), furosemide (Lasix), and torsemide (Demadex).

Benefits of Diuretics. Diuretics can:

• Reduce the risk for stroke
• Reduce the risk for heart attack and heart failure
• Protect against blood clots.

Problems with Diuretics. Loop and thiazide diuretics reduce the body's supply of potassium, which, if left untreated, increases the risk for arrhythmias. Arrhythmias are heart rhythm disturbances that can, in rare instances, lead to cardiac arrest. In such cases, doctors will prescribe lower doses of the current diuretic, recommend potassium supplements, or use potassium-sparing diuretics either alone or in combination with a thiazide. Potassium-sparing drugs have their own risks, which include dangerously high levels of potassium in people with existing elevated levels of potassium or in those with damaged kidneys. However, all diuretics are generally more beneficial than harmful.

Common Diuretic Side Effects:

• Fatigue
• Depression and irritability
• Urinary incontinence
• Reduced sexual drive

Beta-Blockers

Beta-blockers help slow heart rate and lower blood pressure. They are usually used in combination with other drugs such as ACE inhibitors and diuretics.

Brands. Propranolol (Inderal), acebutolol (Sectral), atenolol (Tenormin), betaxolol (Kerlone), carteolol (Cartrol), metoprolol (Lopressor), nadolol (Corgard), penbutolol (Levatol), pindolol (Visken), carvedilol (Coreg), and timolol (Blocadren). The drugs may differ in their effects and benefits.

Problems with Beta-Blockers. Evidence presented at the 2005 meeting of the American College of Cardiology suggested that an ACE-inhibitor combined with a calcium channel blocker works just as well as a beta-blocker-diuretic combination in treating hypertension, and poses less risk of diabetes. Other recent studies suggest that beta-blockers may increase the risk of stroke, and should not be a first-line choice for high blood pressure treatment.

• Do not abruptly stop taking these drugs. The sudden withdrawal of beta blockers can rapidly increase heart rate and blood pressure. The doctor may want the patient to slowly decrease the dose before stopping completely.
• Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol may sometimes narrow bronchial airways. These beta blockers should not be used by patients with asthma, emphysema, or chronic bronchitis.
• Beta blockers can lower HDL (“good”) cholesterol.
• These drugs can hide warning signs of low blood sugar (hypoglycemia) in patients with diabetes. When combined with a diuretic, the risk of diabetes may be increased.

Common Side Effects

• Fatigue and lethargy
• Vivid dreams and nightmares
• Depression
• Memory loss
• Dizziness and lightheadedness
• Reduced ability to exercise
• Coldness in extremities (legs, toes, arms, hands)

Check with your doctor about any side effects. Do not stop taking these drugs on your own..

ACE Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors open blood vessels and decrease the workload of the heart. They are used to treat high blood pressure but can also help improve heart and lung muscle function.

These drugs are particularly important for patients with diabetes. A large study reported that patients with diabetes who took these drugs had fewer heart attacks and lower overall mortality rates than patients who took other types of high blood pressure medications. ACE inhibitors may also help slow progression of kidney disease, in addition to controlling blood pressure. They may also be better at preventing the development of diabetes in patients with kidney disease than other types of blood pressure medication. In a 2006 study of African-American patients with high blood pressure and kidney disease, patients who took an ACE inhibitor had a lower risk of developing diabetes than those who took a calcium channel blocker or beta-blocker drug.

Doctors sometimes avoid giving aspirin to patients who are taking ACE inhibitors due to concerns that this drug combination can cause kidney problems. A 2005 study of patients with both coronary artery disease and heart failure indicated that an aspirin and ACE inhibitor combination is not harmful, and that aspirin can significantly reduce mortality risk for these patients.

Brands. ACE inhibitors include captopril (Capoten), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), ramipril (Altace), perindopril (Aceon), and lisinopril (Prinivil, Zestril).

Common Side Effects of ACE Inhibitors:

• Low blood pressure is the main side effect of ACE inhibitors. This can be severe in some patients, especially at the start of therapy.
• Irritating cough is a common side effect, which some people find intolerable. Although all ACE inhibitors can have this side effect, sometimes switching to another brand will reduce this symptom.
• ACE inhibitors can harm a developing fetus and should not be used during pregnancy. While it has long been known that these drugs can cause problems in the second and third trimester, an important 2006 study indicated that ACE inhibitors can also cause major heart birth defects when taken during the first trimester. The FDA and the American Heart Association recommend that women who become pregnant should change from ACE inhibitors to another type of blood pressure drug as soon as possible. Women of child-bearing age who are considering becoming pregnant should also discuss alternative drugs with their doctors.

Uncommon Side Effects of ACE Inhibitors:

• ACE inhibitors protect against kidney disease, but they may also increase potassium retention by the kidneys. If potassium levels become extremely high, they can cause the heart to stop beating (cardiac arrest). This side effect is rare, except in patients with significant kidney disease. Because of this risk, ACE inhibitors are not usually used in combination with potassium-sparing diuretics or potassium supplements.
• A rare but severe side effect is granulocytopenia, an extreme reduction in infection-fighting white blood cells.
• In very rare cases, patients suffer a sudden and severe allergic reaction, called angioedema that causes swelling in the eyes and mouth and may close off the throat.

Patients who have difficulty tolerating ACE inhibitor side effects are usually switched to an angiotensin-receptor blocker (ARB).

Angiotensin-Receptor Blockers (ARBs)

ARBs, also known as angiotensin II receptor antagonists, are similar to ACE inhibitors in their ability to open blood vessels and lower blood pressure. They may have fewer or less-severe side effects than ACE inhibitors, especially coughing, and are sometimes prescribed as an alternative to ACE inhibitors. ARBs are particularly important drugs for patients with diabetes. They may help protect against kidney disease and kidney failure.

A 2006 study in the New England Journal of Medicine suggested that some patients with prehypertension may benefit from treatment with an ARB drug. Patients in the study received candesartan (Atacand).

Brands. Losartan (Cozaar, Hyzaar), olmesartan (Benicar) candesartan (Atacand), telmisartan (Micardis), eprosartan (Teveten), irbesartan (Avapro), and valsartan (Diovan). A combination medication containing candesartan and the diuretic hydrochlorothiazide (Diovan HCT, Atacand HCT) is also available.

Side Effects:

• Low blood pressure
• Dizziness and lightheadedness
• Raised potassium levels
• Drowsiness
• Nasal congestion
• Should not be used during pregnancy

Calcium-Channel Blockers (CCBs)

Calcium-channel blockers (CCBs), or calcium antagonists, help relax blood vessels. Along with diuretics, CCBs may work better than other drug classes for lowering blood pressure in African-Americans. Recent research indicates that newer types of drugs (CCBs, ACE inhibitors) may be a better treatment option for some patients than older drugs (especially beta blockers).

Brands. Diltiazem (Cardizem, Dilacor), amlodipine (Norvasc), felodipine (Plendil), isradipine (DynaCirc), verapamil (Calan, Isoptin, Verelan), nisoldipine (Sular), nicardipine (Cardene), nifedipine (Adalat, Procardia), lercanidipine (Zanidip), lacidipine (Motens), and nitrendipine (Nitrepin). In 2004, a dual-therapy calcium channel blocker-statin combination drug (Caduet) was approved to treat high blood pressure and high cholesterol. Caduet is a fixed-dose combination of amlodipine and atorvastatin.

Side Effects:

• Swelling in the feet
• Constipation
• Fatigue
• Erectile dysfunction
• Gingivitis
• Rash
• Food interactions (do not take CCBs with grapefruit or Seville orange products)

Alpha Blockers

Alpha blockers such as doxazosin (Cardura), prazosin (Minipress), and terazosin (Hytrin) help widen small blood vessels. They are generally not used as first-line drugs for high blood pressure, but are prescribed if other drugs do not work or as add-on medication.

Vasodilators

Vasodilators, which help open blood vessels by relaxing muscles in the blood vessel walls. These drugs are usually used in combination with a diuretic or a beta-blocker. They are rarely used by themselves. Vasodilators include hydralazine (Apresoline), clonidine (Catapres), available in tablets or as a skin patch), and Minoxidil (Loniten). Some of these drugs should be used with caution or not at all in people who have angina or who have had a heart attack.

Other Drugs

Aliskiren (Tekturna). In 2007, the FDA approved aliskiren for treatment of high blood pressure. Aliskiren can be taken either alone or in combination with other blood pressure medication. It should not be used during pregnancy as it can cause injury or death to the fetus. Aliskiren is the first hypertension drug that inhibits renin, a kidney enzyme that is associated with the regulation of blood pressure.

Statins. Statins, common drugs used to lower cholesterol, are proving to have many other health benefits. They include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). In an important 2002 study, patients with high blood pressure but normal or slightly high cholesterol levels had fewer heart attacks and strokes when they took the a statin drug. In 2004, a calcium channel blocker-statin combination drug (Caduet) was approved to treat simultaneously high blood pressure and high cholesterol. Caduet is a fixed-dose combination of amlodipine and atorvastatin.