High Blood Pressure

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of high blood pressure.

Alternative Names

Beta Blockers; Calcium Channel Blockers; Hypertension

Classes of Medications

There are several classes of drugs used to treat hypertension.

Diuretics

For decades, diuretics, which cause reduction of water and sodium, have been the mainstays of anti-hypertensive therapy. Diuretics are inexpensive and are the 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 and so respond well to these drugs.) A landmark 2002 study reported that patients who take them have a lower incidence of heart failure, heart disease, and stroke after five to six years compared to those who took calcium-channel blocker and an ACE inhibitor. Beta-blockers, which are also often used as first-line therapy, were not studied in this trial.One previous analysis of many studies reported that diuretics were better than beta-blockers on all important points, including reducing heart attacks, strokes, and mortality rates. Of concern, in fact, are studies reporting an increase in the development of type 2 diabetes among people who take beta-blockers.

Diuretics continue to be the best choice for most older adults. A 1999 study reported, in fact, that diuretics may protect against dementia. Combinations may be needed. Because of a concern for drug interactions, some physicians are reluctant to give anti-hypertensive drugs to elderly patients with other risk factors for heart disease. Studies in 2001 reported, however, that the use of diuretics or beta blockers in this population, including those with isolated systolic hypertension, lowered their risks for heart attack, stroke, and heart failure.

Benefits of Diuretics. Some of the benefits reported on diuretics include the following:

• Diuretics significantly reduce the risk for stroke; they may in fact be the most important anti-hypertensive agent for preventing this brain attack. They also appear to protect against stroke in people without hypertension.
• They are associated with lower risk for heart attack (although this is not as significant as their protection against stroke).
• They may protect against blood clots.
• Diuretics may help reduce the risk for dementia and the rate of fractures in elderly people who have taken them for a long time.

Diuretic Types. Diuretics come in many brands and are generally inexpensive. Some need to be taken once a day, others twice a day.

Three primary types of diuretics exist:

• Thiazides. Thiazides often serve as the basis for high blood pressure treatment, either taken alone for mild to moderate hypertension or used in combination with other types of drugs. There are many thiazides and thiazide-related drugs; some common ones are chlorothiazide (Diuril), chlorthalidone (Hygroton), indapamide (Lozol), and hydrochlorothiazide (Esidrix, HydroDiuril).
• Loop diuretics. Loop diuretics block sodium transport in parts of the kidney; they act faster than thiazides and have a great diuretic effect. It is important therefore to control the medication and avoid dehydration and potassium loss. Loop diuretics include bumetanide (Bumex), furosemide (Lasix), and ethacrynic acid (Edecrin).
• Potassium sparing agents. Some potassium-sparing diuretics include amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyrenium).

Problems with Diuretics. The loop and thiazide diuretics deplete 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, physicians will either 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. It should be noted, however, that, in general, all diuretics are more beneficial than harmful.

Common Side Effects. Common side effects of diuretics are fatigue, depression, irritability, urinary incontinence, loss of sexual drive, breast swelling in men, and allergic reactions. Diuretics can trigger attacks of gout. They may also increase the risk of gastrointestinal (GI) bleeding. Diuretics may raise cholesterol level and, used alone, they have no effect on enlarged heart size (hypertrophy). Arrhythmias can also occur as an interaction between diuretics and certain drugs, including some antidepressants, anti-arrhythmic drugs themselves, and digitalis.

Beta-Blockers

Benefits of Beta-blockers. Beta-blockers have the following benefits for people with high blood pressure:

• They affect the force and frequency of heartbeats.
• They slow certain metabolic processes.
• They ease the workload of the heart.

They are very effective in reducing blood pressure and have been associated with the following positive effects on the heart:

• They are now well known for reducing deaths from heart disease.
• In one study, the beta-blocker atenolol (Tenormin) reduced left ventricular hypertrophy and, when used with the diuretic chlorthalidone, was found to significantly reduce the risk for heart failure, particularly in patients at high risk for it.
• Studies are now finding that certain beta-blockers called nonselective beta-blockers (such as carvedilol) may improve heart function, symptoms, and survival in patients with mild to moderate heart failure.

Beta-Blocker Brands. Many beta-blockers are now available, including 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. On the downside, studies are reporting that, when used alone, they may reduce blood pressure, but they do not reduce mortality rates. And, of concern are studies reporting an increase in the incidence of type 2 diabetes in people who take beta blockers. Because they can narrow bronchial airways and constrict blood vessels, patients with asthma, emphysema, and chronic bronchitis should avoid them whenever possible. Some beta-blockers tend to lower HDL cholesterol (the beneficial cholesterol) by about 10%; the effect is most marked in smokers.

Common Side Effects. Fatigue and lethargy are the most common psychologic side effects. Some people experience vivid dreams and nightmares, depression, and memory loss. Dizziness and lightheadedness may occur upon standing. Exercise capacity may be reduced. Other side effects may include coldness in the extremities (that is, legs and toes; arms and hands), asthma, decreased heart function, and gastrointestinal problems. Sexual dysfunction was a problem with older beta-blockers but does not appear to be significant at all in newer agents.

If side effects become very distressing, the patient should call a physician, but it is extremely important not to stop the drug abruptly. Angina, heart attack, and even sudden death have occurred in patients who discontinued treatment without gradual withdrawal.

Angiotensin Converting Enzyme Inhibitors

Angiotensin converting enzyme (ACE) inhibitors block the effects of the angiotensin-renin-aldosterone system, which is thought to have many harmful effects on the heart and blood vessels. ACE inhibitors are expensive, however. In an important 2003 study diuretics, achieved a lower risk for heart failure-and also stroke and angina -- than an ACE inhibitor. However, another 2003 comparison study reported fewer heart attacks and lower risk for death with ACE inhibitors than with diuretics, particularly in elderly Caucasian men. More research is needed to confirm the specific benefits of each agent.

ACE inhibitors are particularly important, in any case, for patients with diabetes. A large study, for example, reported that diabetic patients who took these drugs had fewer heart attacks and lower all-cause mortality rates compared to those who took other anti-hypertensive agents. ACE inhibitors also may help slow progression of kidney disease, independently of their effect on blood pressure. (Some experts believe, in fact, that angiotensin may be the common factor linking diabetes and high blood pressure. This natural chemical not only influences all aspects of blood pressure control but it also interferes with insulin's normal metabolic signaling.)

Some research has also suggested that ACE inhibitors improved heart and lung muscle function, which should be very helpful for patients with existing heart failure. (A 2002 study also indicated that these agents may help preserve general muscle strength in older individuals.) Nevertheless, an important 2003 study suggested that ACE inhibitors might provide less protection against congestive heart failure than diuretics. Other studies have suggested that taking aspirin (or other so-called NSAIDs) may reduce the heart protection of ACE inhibitors. Aspirin is commonly used by patients with heart disease to prevent heart attacks. Studies are needed to clarify all these issues.

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

Side Effects. Side effects include an irritating cough, excessive drops in blood pressure, and allergic reactions. (In some people, the cough is intolerable. Iron supplements or the drug picotamide may prove to help reduce the frequency of coughs.) One rare but severe side effect, granulocytopenia, which is an extreme reduction in white blood cells, has been observed. In rare cases (0.3%), patients suffer a sudden and severe allergic reaction called angioedema that causes swelling in the eyes and mouth and may close off the throat.

Although ACE inhibitors can protect against kidney disease, they also increase potassium retention in the kidneys. This increases the risk for cardiac arrest if levels become too high. Because of this action, they are not generally given with potassium-sparing diuretics or potassium supplements.

They can harm a developing fetus and should not be used during pregnancy, particularly in the second and third trimester.

Calcium-Channel Blockers (CCBs)

Calcium-channel blockers (CCBs), or calcium antagonists, have an immediate effect on reducing blood pressure. Despite this, studies continue to report that they are inferior to the other anti-hypertensive agents in preventing heart events, stroke, or kidney complications. They are also more expensive than diuretics or beta-blockers. A major study also reported that they were not as effective as a diuretic in preventing heart failure. In fact, the drugs may slightly increase the risk. And in another 2002 study, African Americans with hypertensive kidney disease who took them experienced a worsening of their kidney condition. Some experts now believe they should be used only as a last resort. Nevertheless, CCBs have nerve-protecting properties and some of the newer agents may prove to have specific and unique benefits, including helping to reduce the risk for dementia in the elderly.

Calcium-Channel Blocker Brands. CCBs vary widely in their effects and calcium channel blockers used in the US may be categorized into different groups based upon different chemical structures. Those used for hypertension are called dihydropyridines and include diltiazem (Cardizem, Dilacor), amlodipine (Norvasc), felodipine (Plendil), isradipine (DynaCirc), verapamil (Calan, Isoptin, Verelan), nisoldipine (Sular), nicardipine (Cardene), and nifedipine (Adalat, Procardia). Newer CCBs include lercanidipine (Zanidip), lacidipine (Motens) and nitrendipine (Nitrepin). Lercanidipine, for example, is a unique CCP that may be effective and safe for a wider range of patients than with other CCBs.

Side Effects. Side effects vary among different preparations. Most drugs can cause fluid accumulation in the feet, along with constipation, fatigue, impotence, gingivitis, flushing, and allergic symptoms. Interactions with foods and drugs also differ depending on the drug. For example, verapamil interacts with digoxin, but diltiazem does not. Overdose on many of these agents can cause a severe drop in blood pressure.

Note: Grapefruit and Seville oranges boost the effects of calcium-channel blocking drugs, which are often used for hypertension. Seville oranges are often used in marmalade or other condiments. (Regular oranges do not appear to pose any hazard.)

Angiotensin-Receptor Blockers

Angiotensin-receptor blockers (ARBs), also known as angiotensin II receptor antagonists, are similar to ACE inhibitors in their ability to lower blood pressure. ARBs may have fewer or less severe side effects, including cough. Comparison studies with the beta blocker atenolol ACE inhibitor have suggested that it was superior in protection against stroke and in reducing both overall mortality and mortality from heart disease, including in patients with systolic hypertension. In one of the studies, ARBs also appeared to reduce the rate of new-onset diabetes. Other studies have also reported protection against kidney disease even in people with normal blood pressure, making them particularly beneficial for people with diabetes. They may even improve quality of life when added to a drug regimen -- a finding also found with no other anti-hypertensive drugs. In fact, evidence suggests they may improve sexual function in men. These drugs are expensive, however, and additional comparison studies are needed, particularly with diuretics and ACE inhibitors.

Brands. Brands include losartan (Cozaar, Hyzaar), olmesartan (Benicar) candesartan (Atacand), telmisartan (Micardis), eprosartan (Teveten), irbesartan (Avapro), and valsartan (Diovan). A combination medication containing ARBs and the diuretic hydrochlorothiazide (Diovan HCT, Atacand HCT) is also available. Newer agents are proving to be more effective for lowering blood pressure than losartan, but more comparison studies are needed to determine long term benefits.

Side Effects. Side effects may include headache, dizziness, nasal congestion, elevated potassium blood levels, and abnormal kidney function. Sudden hypotension (a drop in blood pressure) can occur. As with ACE inhibitors, these agents can harm a developing fetus and should be not be used during pregnancy.

Alpha Blockers

Alpha blockers, such as doxazosin (Cardura) and prazosin (Minipress), widen arterioles and veins and thereby reduce blood pressure. However, a major study on doxazosin was stopped when it was associated with a higher risk of chest pain, stroke, and congestive heart failure compared with a diuretic. At this time, until more is known, they are still recommended for reducing blood pressure if no other agents are effective.

Vasodilators

Vasodilators, which widen blood vessels, are often used in combination with a diuretic or a beta-blocker. They are almost never used by themselves. Representative 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 with angina or who have had a heart attack.

Newer Agents that Block Chemicals Involved in Hypertension

Aldosterone Blockers. Aldosterone is a hormone that is critical in regulating the body's balance of salt and water. Excessive levels may play important roles in hypertension and heart failure. Additional agents that block this hormone are being developed. Eplerenone (Inspra) is the first to be approved. Its actions are similar to potassium-sparing diuretics, and like these agents, it poses some risk for high potassium levels, which in some cases can be dangerous.

Neutral Endopeptidase Inhibitors (NEPs). Neutral endopeptidase inhibitors (NEPs) are similar to ACE inhibitors. Their primary action is to produce higher levels of an enzyme called atrial natriuretic peptide, which has the following effects:

• It opens blood vessels.
• Induces fluid elimination.
• Opposes the actions of the compensating systems responsible for ongoing damage of the failing heart.

Agents under investigation include omapatrilat (Vanlev), candoxatril, and ecadotril. Important studies of omapatrilat, however, are reporting little advantages compared to ACE inhibitors, although may have some benefits in patients with heart failure. Unfortunately, in patients with hypertension, the drug poses a risk (0.7%) for angioedema, a sudden and severe allergic reaction that causes swelling in the eyes, mouth, and may close off the throat. (ACE inhibitors also can cause this reaction but the risk is lower.) Other side effects are very similar to those of ACE inhibitors, including coughing.

Statins

Statins are common drugs used to lower cholesterol that are proving to have many other health benefits as well. They include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), luvastatin (Lescol) and atorvastatin (Lipitor). 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 statin atorvastatin. The study was stopped so all subjects could take statins. An earlier study had shown similar benefits with the statin simvastatin.