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Hypertension overview

Published: June 19, 2009. Updated: July 29, 2009

Arterial hypertension, or high blood pressure is a medical condition where the blood pressure is chronically elevated. Normal blood pressure is below 120/80; blood pressure between 120/80 and 139/89 is called "pre-hypertension", and a blood pressure of 140/90 or above measured on both arms at two instances (several weeks apart) is considered high blood pressure. The complications of hypertension are often referred to as end-organ damage because damage to these organs is the end result of chronic high blood pressure. Uncontrolled hypertension can cause strokes, which can lead to brain or neurological damage. The strokes are usually due to a hemorrhage or a thrombosis of the blood vessels that supply blood to the brain. The patient's symptoms and signs are evaluated to assess the neurological damage. A stroke can cause weakness, tingling, or paralysis of the arms or legs and difficulties with speech or vision. Multiple small strokes can lead to dementia. The best prevention for this complication of hypertension or, for that matter, for any of the complications, is control of the blood pressure.

Epidemiology

The level of blood pressure regarded as deleterious has been revised down during years of epidemiological studies. A widely quoted and important series of such studies is the Framingham Heart Study carried out in an American town: Framingham, Massachusetts. The results from Framingham and of similar work in Busselton, Western Australia have been widely applied. To the extent that people are similar this seems reasonable, but there are known to be genetic variations in the most effective drugs for particular sub-populations.

High blood pressure does not mean excessive emotional tension, although emotional tension and stress can temporarily increase the blood pressure. While chronic anxiety is associated with poor outcomes in people with hypertension, it alone does not cause it.

Prevalence

Cardiovascular diseases (CVD), most of which are due to atherosclerosis (mainly heart attack and stroke) and often related to arterial hypertension (AH), are responsible for nearly 20% of all deaths world-wide (nearly 10 million). They are the principal cause of death in all developed countries accounting for 50% of all deaths and are also emerging as a prominent public health problem in developing countries, ranking third with nearly 16% of all deaths. It is known that more than 95 % of hypertensive patients in the community are of essential or idiopathic/unknown aetiology, and only a small percentage have an identifiable cause (secondary hypertension).

Essential hypertension affects approximately 75 million Americans, almost 1 in 4 adults in the United States. It is thus a major public health problem. African American patients with poorly controlled hypertension are at a higher risk than Caucasians for most end-organ damage and particularly kidney damage. These differentials are more pronounced in young adult women. Among the very old, race differentials in hypertension prevalence rates are less pronounced. The reasons for the epidemic hypertension rates in the United States are largely environmental: Obesity and physical inactivity probably account for a significant proportion of the premature excess hypertension in African Americans relative to white women.

According to a recent survey, 1.0% of the adult American population use complementary and alternative medicine to treat hypertension.

Age

Mean systolic and diastolic blood pressure and prevalence of AH increase with age throughout childhood, adolescence and adulthood in most populations of developed and developing countries. However, in some isolated populations, this age-related rise of blood pressure (BP) is not evident.

Sex/gender

Men tend to display higher blood pressure than women, more evident in youth and middle-age. Later in life (over 50 years old), the difference narrows and the pattern may be reversed.

Heredity

Although the precise mode of heredity/inheritance has not yet been demonstrated, a high occurrence of hypertension is observed among subjects with a family history of hypertension and it is higher and more severe when both parents are concerned.

Ethnicity/race

Studies have also revealed higher blood pressure levels in the black community than in other ethnic groups, mainly in black Afro-Americans with early onset, severity and appearance of complications.

Causes

Over 90% of all hypertension has no known cause and is therefore called "essential/primary hypertension". Approximately 30 % of cases of essential hypertension are attributable to genetic factors. Often, it is part of the Syndrome X in patients with insulin resistance as it occurs in combination with diabetes mellitus (type 2), combined hyperlipidemia and central obesity.

Important causes of secondary hypertension are:

  • Renal artery stenosis (due to fibromuscular hyperplasia in younger individuals and atherosclerosis in older people)
  • Pheochromocytoma
  • Hyperaldosteronism (Conn's syndrome)
  • Cushing's disease
  • Steroid use
  • Coarctation of the aorta
  • Chronic renal failure
  • Scleroderma crisis

Risk factors

  • African American descendants
  • Obesity and physical inactivity
  • Alcohol
  • High salt intake
  • Psychosocial stress
  • Hereditary (genetic)

Pathogenesis

High blood pressure or hypertension means high pressure (tension) in the arteries. The arteries are the vessels that carry blood from the pumping heart to all of the tissues and organs of the body. The systolic blood pressure represents the pressure in the arteries as the heart contracts and pumps blood into the arteries. The diastolic pressure represents the pressure in the arteries as the heart relaxes after the contraction. The diastolic pressure, therefore, reflects the minimum pressure to which the arteries are exposed. An elevation of the systolic and/or diastolic blood pressure increases the risk of developing heart disease, kidney disease, atherosclerosis or arteriosclerosis, eye damage, and stroke.

The vast majority of patients with essential hypertension have in common a particular abnormality of the arteries. They have an increased resistance (stiffness or lack of elasticity) in the peripheral arteries or arterioles. Just what makes the peripheral arteries become stiff is not known. Yet, this increased peripheral arteriolar stiffness is present in those individuals whose essential hypertension is associated with genetic factors, obesity, lack of exercise, overuse of salt, and aging. Inflammation also may play a role in hypertension since a predictor of the development of hypertension is the presence of an elevated C reactive protein level in some individuals.

Symptoms and signs

Hypertension can progress without symptoms (silently) to finally develop any one or more of the several potentially fatal complications of hypertension such as heart attacks or strokes. As a matter of fact, uncomplicated hypertension may be present and remain unnoticed for many years, or even decades. This happens when there are no symptoms, and those affected fail to undergo periodic blood pressure screening.

Some people with uncomplicated hypertension, however, may experience symptoms such as headache, dizziness, shortness of breath, and blurred vision. The presence of symptoms can be a good thing in that they can prompt people to consult a doctor for treatment and make them more compliant in taking their medications. Not infrequently, however, a person's first contact with a physician may be after significant damage to the end-organs has occurred.

About 1% people with hypertension is diagnosed with severe high blood pressure (accelerated or malignant hypertension) at their first visit to the doctor. In these patients, the diastolic blood pressure (the minimum pressure) exceeds 140 mm Hg! Affected persons often experience severe headache, nausea, visual symptoms, dizziness, and sometimes kidney failure. Malignant hypertension is a medical emergency and requires urgent treatment to prevent a stroke.

Complications

  • Malignant hypertension
  • Hypertensive cardiomyopathy
  • Hypertensive retinopathy
  • Hypertensive nephropathy
  • Atrial fibrillation
  • Hypertension of pregnancy:
    • Pre-eclampsia
    • Eclampsia

Diagnosis

Hypertension is diagnosed using a sphygmomanometer according to the guidelines outlined in the definition above. A blood pressure of 140/90 or above measured on both arms at two instances (several weeks apart) is considered high blood pressure.

Chronic high blood pressure can lead to an enlarged heart, kidney failure, brain or neurological damage, and changes in the retina at the back of the eyes. Examination of the eyes in patients with severe hypertension may reveal damage--narrowing of the small arteries, small hemorrhages in the retina, and swelling of the optic disc.

People with high blood pressure have an increased stiffness or resistance in the peripheral arteries throughout the tissues of the body. This increased resistance causes the heart muscle to work harder to pump the blood through these blood vessels. The increased workload can put a strain on the heart, which can lead to heart abnormalities that are usually first seen as enlarged heart muscle. Enlargement of the heart can be evaluated by chest x-ray, electrocardiogram, and most accurately by echocardiography. Ecocardiography is especially useful in determining the enlargement of the left side of the heart. Heart enlargement may be a forerunner of heart failure, coronary artery disease, and cardiac arrhythmias. Proper treatment of the high blood pressure and its complications can reverse some of these heart abnormalities.

Blood and urine tests may be helpful in detecting kidney abnormalities in people with high blood pressure, although kidney damage can itself be the cause or the result of hypertension. An elevated level of serum creatinine indicates damage to the kidney. In addition, proteinuria may reflect chronic kidney damage from hypertension, even if the kidney function (as represented by the blood creatinine level) is normal. In fact, protein in the urine alone signals the risk of deterioration in kidney function if the blood pressure is not controlled. Even small amounts of protein (microalbuminuria) may be a signal of impending kidney failure and other vascular complications from uncontrolled hypertension. Recent studies have also suggested the angiotensin receptor blocking drugs may offer an additional protective effect against strokes above and beyond control of blood pressure. Other tests include testing blood glucose as hypertension co-exists with diabetes in many instances, and electrolytes (sodium and potassium) in a newly diagnosed hypertension patient, particularly in young patients when secondary hypertension is highly suspected.

Treatment

Lifestyle modifications

Lifestyle modifications refer to certain specific recommendations for changes in habits, diet and exercise. These modifications can lower the blood pressure as well as improve a patient's response to blood pressure medications.

Alcohol

People who drink alcohol excessively (over two drinks per day) have a one and a half to two times increase in the prevalence of hypertension. The association between alcohol and high blood pressure is particularly noticeable when the alcohol intake exceeds 5 drinks per day. Moreover, the connection is a dose-related phenomenon, thus the more alcohol is consumed, the stronger is the link with hypertension.

Smoking

Although smoking increases the risk of vascular complications in people who already have hypertension, it is not associated with an increase in the development of hypertension. Nevertheless, smoking a cigarette can repeatedly produce an immediate, temporary rise in the blood pressure of 5 to 10 mm Hg. Steady smokers however, actually may have a lower blood pressure than nonsmokers. The reason for this is that the nicotine in the cigarettes causes a decrease in appetite, which leads to weight loss. This, in turn, lowers the blood pressure.

Coffee

In one study, the caffeine consumed in 5 cups of coffee daily caused a mild increase in blood pressure in elderly people who already had hypertension, but not in those who had normal blood pressures. What's more, the combination of smoking and drinking coffee in persons with high blood pressure may increase the blood pressure more than coffee alone. Limiting caffeine intake and cigarette smoking in hypertensive individuals, therefore, may be of some benefit in controlling their high blood pressure.

Salt

The American Heart Association recommends that the consumption of dietary salt be less than 6 grams of salt per day in the general population and a lower level (for example, less than 4 grams) for people with hypertension. To achieve a diet containing less than 4 grams of salt, a person should not add salt to their food or cooking. Also, the amount of natural salt in the diet can be reasonably estimated from the labeling information provided with most purchased foods.

Obesity

Obesity is common among hypertensive patients, and its prevalence increases with age. In fact, obesity may be what determines the increased incidence of high blood pressure with age. Obesity can contribute to hypertension in several possible ways. For one thing, obesity leads to a greater output of blood because the heart has to pump out more blood to supply the excess tissue. The increased cardiac output then can raise the blood pressure. For another thing, obese hypertensive individuals have a greater resistance in their peripheral arteries throughout the body. In addition, insulin resistance and the metabolic syndrome described previously occur more frequently in the obese. Finally, obesity may be associated with a tendency for the kidneys to retain salt. Weight loss may help reverse problems related to obesity while also lowering the blood pressure. It has been estimated that the blood pressure can be decreased 0.32 mm Hg for every 1 kg (2.2 pounds) of weight lost down to ideal body weight for the individual.

Some obese people, especially if they are very obese, have a syndrome called sleep apnea. This syndrome is characterized by the periodic interruption of normal breathing during sleep. Sleep apnea may contribute to the development of hypertension in this subgroup of obese individuals. This happens because the repeated episodes of apnea cause hypoxia. The hypoxia then causes the adrenal gland to release adrenalin and related substances. Finally, the adrenalin and related substances cause a rise in the blood pressure.

Exercise

A regular exercise program may help lower blood pressure over the long term. For example, activities such as jogging, bicycle riding, or swimming for 30 to 45 minutes daily may ultimately lower blood pressure by as much as 5 to15 mm Hg. Moreover, there appears to be a relationship between the amount of exercise and the degree to which the blood pressure is lowered. Thus, the more you exercise (up to a point), the more you lower the blood pressure. The beneficial response of the blood pressure to exercise occurs only with aerobic (vigorous and sustained) exercise programs. Therefore, any exercise program must be recommended or approved by an individual's physician.

Medical Treatment

Goals of treatment

High blood pressure is usually present for many years before its complications develop. The idea, therefore, is to treat hypertension early, before it damages critical organs in the body. Accordingly, increased public awareness and screening programs to detect early, uncomplicated hypertension are the keys to successful treatment. Treating high blood pressure successfully early enough can significantly decrease the risk of stroke, heart attack, and kidney failure.

The goal for patients with combined systolic and diastolic hypertension is to attain a blood pressure of 140/85 mm Hg. Bringing the blood pressure down even lower, as mentioned earlier, may be desirable in African American patients, and patients with diabetes or chronic kidney disease. Although life style changes in pre-hypertensive patients (blood pressure between 120/80 and 139/89) is appropriate, it is not well established that treatment with medication of patients with pre-hypertension is beneficial.

Starting treatment for high blood pressure

Blood pressure that is persistently higher than 140/ 90 mm Hg usually is treated with lifestyle modifications and medication. However, if the diastolic pressure remains at a borderline level (usually under 90 mm Hg, yet persistently above 85), more aggressive treatment may be started in certain circumstances. These circumstances include borderline diastolic pressures in association with end-organ damage, systolic hypertension, or factors that increase the risk of cardiovascular disease, such as age over 65 years, African American decent, smoking, hyperlipidemia, or diabetes.

Any one of the several classes of medications may be started, except the alpha-blocker medications. The alpha-blockers are used only in combination with another anti-hypertensive medication in specific medical situations.

In some particular situations, certain classes of anti-hypertensive drugs are preferable to others as the first line (choice) drugs. For example, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocking (ARB) drugs are the drugs of choice in patients with heart failure, chronic kidney failure (in diabetics or non-diabetics), or myocardial infarction that weakens the heart muscle (systolic dysfunction). Also, beta-blockers are sometimes the preferred treatment in hypertensive patients with a resting tachycardia or an acute heart attack.

Furthermore, patients with hypertension may sometimes have a co-existing, second medical condition. In such cases, a particular class of anti-hypertensive medication or combination of drugs may be chosen as the first line approach. The idea in these cases is to control the hypertension while also benefiting the second condition. For example, beta-blockers may treat chronic anxiety or migraine headache as well as the hypertension. Also, the combination of an ACE inhibitor and an ARB drug can be used to treat certain diseases of the heart muscle (cardiomyopathies) and certain kidney diseases where reduction in proteinuria would be beneficial.

In some other situations, certain classes of anti-hypertensive medications are contraindicated. Dihydropyridine calcium channel blockers used alone may cause problems for patients with chronic renal disease by tending to increase proteinuria. However, an ACE inhibitor will blunt this effect. Furthermore, the non-dihydropyridine type of calcium channel blockers should not be used in patients with heart failure or arrhythmias. On the other hand, these drugs may be beneficial in treating certain other arrhythmias. Also, some drugs, such as minoxidil, since it is so powerful, usually are relegated to second or third line choices for treatment. Clonidine is an excellent drug but has side effects such as fatigue, sleepiness, and dry mouth that make it a second or third line choice. That is, it is used only after all of the first and second line drugs have been tried without success.

Treatment with combinations of drugs for high blood pressure

The use of combination drug therapy for hypertension is not uncommon. At times, using smaller amounts of one or more agents in combination can minimize side effects while maximizing the anti-hypertensive effect. For example, diuretics, which also can be used alone, are more often used in a low dose in combination with another class of anti-hypertensive medications. In this way, the diuretic has fewer side effects while it improves the blood pressure-lowering effect of the other drug. Diuretics also are added to other anti-hypertensive medications when a patient with hypertension also has fluid retention and edema.

The ACE inhibitors or angiotensin receptor blockers may be useful in combination with most other anti-hypertensive medications. ACE inhibitors and angiotensin receptor blockers have additive effects in treating patients with cardiomyopathies and proteinuria. Another useful combination is that of a beta-blocker with an alpha-blocker in patients with high blood pressure and enlargement of the prostate gland in order to treat both conditions simultaneously. Caution is necessary, however, when combining two drugs that both lower the heart rate. For example, adding a beta-blocker to a non-dihydropyridine calcium channel blocker (e.g., diltiazem or verapamil) warrants caution. Patients receiving a combination of these two classes of drugs need to be monitored carefully to avoid bradycardia. Combining alpha and beta-blockers may be beneficial for cardiomyopathies and hypertension. Carvedilol (Coreg) is useful for cardiomyopathies and labetalol for hypertension patients.

Emergency treatment of high blood pressure

In a hospital setting, injectable drugs may be used for the emergency treatment of hypertension. The most commonly used agents in this situation are sodium nitroprusside (Nipride) and labetalol (Normodyne). Emergency medical therapy may be needed for patients with severe (malignant) hypertension. In addition, emergency treatment of hypertension may be necessary in patients with short duration (acute) congestive heart failure, dissecting aneurysm (dilation or widening) of the aorta, stroke, and toxemia of pregnancy.

Treatment during pregnancy

Women with hypertension may become pregnant. These patients have an increased risk of developing pre-eclampsia or eclampsia (toxemia) of pregnancy. These conditions usually develop during the last three months (trimester) of pregnancy. In pre-eclampsia (which can occur with or without pre-existing hypertension), affected women have hypertension, proteinuria and edema. In eclampsia convulsions also occur and the hypertension may require prompt treatment. The foremost goal of treating the high blood pressure in toxemia is to keep the diastolic pressure below 105 mm Hg in order to prevent a brain hemorrhage in the mother.

Hypertension that develops before the 20th week of pregnancy almost always is due to pre-existing hypertension and not toxemia. High blood pressure that occurs only during pregnancy, called gestational hypertension, may start late in the pregnancy. These women, however, do not have proteinuria, edema, or convulsions. Furthermore, gestational hypertension appears to have no ill effects on the mother or the fetus. This form of hypertension resolves shortly after delivery, although it may recur with subsequent pregnancies.

The use of medications for hypertension during pregnancy is controversial. The key question is, "At what level should the blood pressure be maintained?" For one thing, the risk of untreated mild to moderate hypertension to the fetus or mother during the relatively brief period of pregnancy probably is not very large. Furthermore, lowering the blood pressure too much can interfere with the flow of blood to the placenta and thereby impair fetal growth. So, some sort of a compromise must be met. Accordingly, not all mild or moderate hypertension during pregnancy needs to be treated with medication. If it is treated, however, the blood pressure should be reduced slowly and not to very low levels, perhaps not below 140/80.

The anti-hypertensive agents used during pregnancy need to be safe for normal fetal development. The beta-blockers, hydralazine (an old vasodilator), labetalol, alpha methyldopa (Aldomet), and more recently, the calcium channel blockers have been advocated as suitable medications for hypertension during pregnancy. Certain other anti-hypertensive medications, however, are contraindicated during pregnancy. These include the ACE inhibitors, the ARB drugs, and probably the diuretics. ACE inhibitors may aggravate a diminished blood supply to the uterus (uterine ischemia) and cause kidney dysfunction in the fetus. The ARB drugs may even lead to death of the fetus. Diuretics can cause depletion of the blood volume and so impair placental blood flow and fetal growth.

Medications used to treat high blood pressure

Angiotensin converting enzyme inhibitors (ACE Inhibitors) and angiotensin receptor blockers

The angiotensin converting enzyme (ACE) inhibitors and the angiotensin receptor blocker (ARB) drugs both affect the renin-angiotensin hormonal system, which, as mentioned previously, helps regulate the blood pressure. The ACE inhibitors work by blocking an enzyme that converts the inactive form of angiotensin in the blood to its active form. The active form of angiotensin constricts or narrows the arteries, but the inactive form cannot. With an ACE inhibitor as a monotherapy, 50 to 60 percent of Caucasians usually achieve good blood pressure control. African American patients may also respond, but they require higher doses and frequently do best when an ACE inhibitor is combined with a diuretic.

As an added benefit, ACE inhibitors may reduce left ventricular hypertrophy in patients with hypertension. These drugs also appear to slow the deterioration of kidney function in patients with hypertension and proteinuria. Moreover, they have been particularly useful in slowing the progression of kidney dysfunction in hypertensive patients with kidney disease resulting from Type 1 diabetes (insulin-dependent). Accordingly, ACE inhibitors usually are the first line drugs of choice to treat high blood pressure in cases that also involve congestive heart failure, chronic kidney failure in both diabetics and non-diabetics, and myocardial infarction that weakens the heart muscle (systolic dysfunction). ARB drugs are currently recommended for first line renal protection in diabetic nephropathy.

Patients who are treated with ACE inhibitors who also have kidney disease should be monitored for further deterioration in kidney function and high serum potassium. In fact, these drugs may be used to reduce the loss of potassium in people who are being treated with diuretics that tend to cause patients to lose potassium. ACE inhibitors have few side effects. One bothersome side effect, however, is a chronic cough.

The ACE inhibitors include enalapril (Vasotec), captopril (Capoten), lisinopril (Zestril and Prinivil), benazepril (Lotensin), quinapril (Accupril), perindopril (Aceon), ramipril (Altace), trandolapril (Mavik), fosinopril (Monopril), and moexipril (Univasc ).

For patients who develop a chronic cough on an ACE inhibitor, an ARB drug is a good substitute. ARB drugs work by blocking the angiotensin receptor on the arteries to which activated angiotensin must bind to have its effects. As a result, the angiotensin is not able to work on the artery. The ARB drugs appear to have many of the same advantages as the ACE inhibitors but without the associated cough. Accordingly, they are also suitable as first line agents to treat hypertension.

ARB drugs include losartan (Cozaar), irbesartan (Avapro), valsartan (Diovan), candesartan (Atacand), olmesartan (Benicar), telmisartan (Micardis), and eprosartan (Teveten).

In patients who have hypertension in addition to certain second diseases, a combination of an ACE inhibitor and an ARB drug may be effective in controlling the hypertension and also benefiting the second disease. For example, while treating hypertension, this combination of drugs can reduce proteinuria in certain kidney diseases and perhaps help strengthen the heart muscle in cardiomyopathies. Note that both the ACE inhibitors and the ARB drugs are contraindicated in pregnant women.

Beta-blockers

The sympathetic nervous system is a part of the nervous system that helps to regulate certain involuntary (autonomic) functions in the body such as the function of the heart and blood vessels. The nerves of the sympathetic nervous system extend throughout the body and exert their effects by releasing chemicals that travel to nearby cells in the body, for example, muscle cells. The released chemicals bind to receptors (molecules) on the surface of the nearby cells and stimulate or inhibit the function of the cells. In the heart and blood vessels, the receptors for the sympathetic nervous system that are most important are the beta receptors. When stimulated, beta-receptors in the heart increase the heart rate and the strength of heart contractions (pumping action). Beta-blocking drugs acting on the heart, therefore, slow the heart rate and reduce the force of the heart's contraction.

Stimulation of beta-receptors in the smooth muscle of the peripheral arteries and in the airways of the lung causes these muscles to relax. Accordingly, beta-blockers cause contraction of the smooth muscle of the peripheral arteries and thereby decrease the blood flow to the tissues throughout the body. As a result, the patient may experience, for example, coolness in the hands and feet. Likewise, in response to the beta-blockers, the airways are squeezed (constricted) by the contracting smooth muscle. This impingement on the airway causes wheezing, especially in individuals with a tendency for asthma. In short, beta-blockers reduce both the force of the heart's pumping action and the blood pressure that the heart generates in the arteries.

Beta-blockers remain useful medications in treating hypertension, especially in patients with a tachycardia, angina, or a recent myocardial infarction. For example, beta-blockers appear to improve long-term survival when given to patients who have had a heart attack. Whether beta-blockers can prevent heart problems (are cardio-protective) in patients with hypertension any more than other anti-hypertensive medications, however, is uncertain. Beta-blockers may be considered for treatment of hypertension because they also may treat co-existing medical problems. For example, beta-blockers can help treat chronic anxiety or migraine headaches in people with hypertension. The common side effects of these drugs include depression, fatigue, nightmares, sexual impotence in males, and increased wheezing in people with asthma.

The beta-blockers include atenolol (Tenormin), propranolol (Inderal), metoprolol (Toprol), nadolol (Corgard), betaxolol (Kerlone), acebutolol (Sectral), pindolol (Visken), and bisoprolol (Zebeta).

Diuretics

Diuretics are among the oldest known medications for treating hypertension. They work in the tubules of the kidneys to remove salt from the body. Fluid also may be removed along with the salt. Diuretics may be used as monotherapy for hypertension. More frequently, however, low doses of diuretics are used in combination with other anti-hypertensive medications to enhance the effect of the other medications.

The diuretic hydrochlorothiazide (Hydrodiuril) works in the distal part of the kidney tubules to increase the amount of salt that is removed from the body in the urine. In a low dose of 12.5 to 25 mg per day, this diuretic may improve the blood pressure-lowering effects of other anti-hypertensive drugs. The idea is to treat the hypertension without causing the adverse effects that are sometimes seen with the higher doses of hydrochlorothiazide. These side effects include potassium depletion and elevated levels of triglyceride, uric acid, and glucose in the blood.

Occasionally, when salt retention causing accumulation of water and edema is a major problem, the more potent, so-called, loop diuretics may be used in combination with other anti-hypertensive medications.

The most commonly used diuretics to treat hypertension include hydrochlorothiazide (Hydrodiuril), the loop diuretics furosemide (Lasix) and torsemide (Demadex), the combination of triamterene and hydrochlorothiazide (Dyazide), and metolazone (Zaroxolyn). For those individuals who are allergic to sulfa drugs, ethacrynic acid, a loop diuretic, is a good option. Note that diuretics probably should not be used in pregnant women.

Calcium channel blockers (CCBs)

Calcium channel blockers inhibit the movement of calcium into the muscle cells of the heart and arteries. The calcium is needed for these muscles to contract. These drugs, therefore, lower blood pressure by decreasing the force of cardiac contraction and relaxing the muscle cells in the walls of the arteries.

Three major types of calcium channel blockers are used. One type is the dihydropyridines, which do not slow the heart rate or cause cardiac arrhythmias. These drugs include amlodipine (Norvasc), sustained release nifedipine (Procardia XL, Adalat CC), felodipine (Plendil), and nisoldipine (Sular).

The other two types of calcium channel blockers are referred to as the non-dihydropyridine agents. One type is verapamil (Calan, Covera, Isoptin, Verelan) and the other is diltiazem (Cardizem, Tiazac, Dilacor, and Diltia). Both the dihydropyridines and the non-dihydropyridines are very useful when used alone or in combination with other anti-hypertensive agents. The non-dihydropyridines, however, are contraindicated in congestive heart failure or with certain arrhythmias. Sometimes, however, these same dihydropyridines are useful in preventing certain other arrhythmias.

Many of the calcium channel blockers come in a short-acting form and a sustained release form. The short-acting forms of the calcium channel blockers, however, may have adverse long-term consequences, such as strokes or heart attacks. These effects are presumably due to the wide fluctuations in the blood pressure and heart rate that occur during treatment. The fluctuations result from the rapid onset and short duration of the short-acting compounds. When the calcium channel blockers are used in sustained release preparations, however, less fluctuation occurs. Accordingly, the sustained release forms of calcium channel blockers are probably safer for long-term use. The main side effects of these drugs include constipation, swelling (edema), and a slow heart rate (only with the non-dihydropyridine types).

Alpha-blockers

Alpha-blockers lower blood pressure by blocking alpha-receptors in the smooth muscle of peripheral arteries throughout the tissues of the body. The alpha-receptors are part of the sympathetic nervous system, as are the beta-receptors. The alpha-receptors, however, serve to narrow (constrict) the peripheral arteries. Accordingly, the alpha-blockers cause the peripheral arteries to widen (dilate) and thereby lower the blood pressure.

Recent evidence, however, suggests that using alpha-blockers alone as a first line drug choice for hypertension may actually increase the risk of heart-related problems, such as heart attacks or strokes. Alpha-blockers, therefore, should not be used as an initial drug choice for the treatment of high blood pressure.

Examples of alpha-blockers include terazosin (Hytrin) and doxazosin (Cardura).

Alpha-blockers are particularly useful in patients with enlargement of the prostate gland (which usually occurs in older men) because these drugs reduce the problems associated with urinating. Alpha-blockers alone, however, have a relatively small blood pressure-lowering effect. Accordingly, when hypertension coexists with prostatic enlargement, another anti-hypertensive medication should be used together with an alpha-blocker. For example, tamsulosin (Flomax) or alfuzosin (Uroxatral) are alpha-blockers that work well in combination with other anti-hypertensive medications.

Clonidine

Clonidine (Catapres) is an antihypertensive drug that works centrally. That is, it works in a control center for the sympathetic nervous system in the brain. The drug is referred to as a central alpha agonist because it stimulates alpha-receptors in the brain. The result of this central stimulation, however, is to decrease the sympathetic nervous system outflow and to decrease the resistance of the peripheral arteries. Clonidine lowers the blood pressure, therefore, by relaxing (dilating or widening) the peripheral arteries throughout the body. This drug is useful as a second or third line drug choice for lowering blood pressure when other anti-hypertensive medications have failed. It also may be useful on an as-needed basis to control or smooth out fluctuations in the blood pressure. This drug tends to cause dryness of the mouth and fatigue so that some patients do not tolerate it. Clonidine comes in an oral form or as a sustained release skin patch.

Minoxidil

Minoxidil is the most potent of the drugs that lower blood pressure by dilating the peripheral arteries. This drug, however, does not work through the peripheral sympathetic nervous system, as do the alpha and beta-blocker drugs, or through the control center in the brain, as does clonidine. Rather, it is a muscle relaxant that works directly on the smooth muscle of the peripheral arteries throughout the body. Minoxidil is used for patients who have not responded to any other medications. It must be combined with a beta-blocker or clonidine to prevent an increase in the heart rate and with a diuretic to prevent retention of fluid. Minoxidil may also increase hair growth.

Patient's compliance with medication regimes

When uncomplicated hypertension has not caused symptoms, as often happens, some patients tend to forget about their medications. Patients also tend to fail to take their medications as prescribed (non-compliance or non-adherence) if they are causing side effects. Quality of life issues are very important, especially with regard to compliance with prescribed blood pressure medications. Certain anti-hypertensive medications may cause such side effects as fatigue and sexual impotence. These side effects understandably can have profound effects on the patient's quality of life and compliance with treatment. Likewise, more resistant cases of hypertension that require more medication may cause more adverse effects, and, therefore, less compliance.

In dosing schedules that require taking medication 2 to 4 times a day (split dose), some patients will remember to take their medicine only some of the times. In contrast, medications that can be given once daily tend to be remembered more regularly.

Expensive blood pressure medications, especially if insurance does not cover the costs, may also reduce compliance. The reason for this is that people attempt to save money by skipping doses of the prescribed medication. The least expensive medication regimes use generic drugs, such as are readily available for some of the diuretics and beta-blockers. Reduced costs of medication may also be achieved by lifestyle changes such as losing weight, reducing dietary sodium, decreasing consumption of alcohol, and exercising regularly. If these changes in lifestyle are effective, the patient may require less medication.

Alternative medicine

Alternative medicine, also called integrative or complementary medicine, features the use of non-traditional (at least in the western world) techniques for treatment. For example, self-relaxation approaches to the therapy of hypertension include yoga, biofeedback, and meditation. These techniques can, in fact, be effective in lowering the blood pressure, at least temporarily. Acupuncture has not yet been established as a standard or proven therapy for hypertension in the western world.

Certain herbal remedies have blood pressure-lowering components that may well be effective in treating hypertension. Most herbal remedies are available as food supplements, and the Food and Drug Administration (FDA) does not approve them as drugs. Therefore, herbal treatments for hypertension have not yet been adequately evaluated in scientifically controlled clinical trials for effectiveness and safety. In particular, their long-term side effects are unknown. Furthermore, a major problem with most herbal treatments is that their contents are not standardized. Moreover, the ways in which herbal treatments work to lower blood pressure are not known. Currently, therefore, herbal remedies are usually not recommended for the treatment of hypertension.

Recent developments

A new class of anti-hypertensive drug, called a vasopeptidase blocker (inhibitor), has been developed. Uniquely, it works on two different systems at the same time. It blocks that part of the renin-angiotensin-aldosterone hormonal system that constricts the peripheral arteries. It also blocks that part of the body's salt regulating system that conserves salt. Accordingly, this class of drug decreases the blood pressure by simultaneously dilating the peripheral arteries and increasing natriuresis.

One such drug that is currently being studied is called omapatrilat. In laboratory animals with high blood pressure, this drug reduces the blood pressure and appears to protect the end-organs (heart, kidney, and brain) from damage by the high blood pressure. Moreover, the drug dilates the peripheral arteries, which increases blood flow to all tissues, and improves cardiac function in hypertensive patients with heart failure. Not yet approved by the FDA, omapatrilat is undergoing further testing to evaluate its effectiveness and safety.


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