ACE Inhibitors Beta Blockers Diuretics Calcium channel blockers
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 (inhibiting) 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 single drug treatment (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. (Diuretics are discussed below.)
As an added benefit, ACE inhibitors may reduce an enlarged heart (left ventricular hypertrophy) in patients with hypertension. These drugs also appear to slow the deterioration of kidney function in patients with hypertension and protein in the urine (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 heart attack (myocardial infarction) that weakens the heart muscle (systolic dysfunction). ARB drugs are currently recommended for first line renal protection in diabetic nephropathy (kidney disease).
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 (binder) 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. (Recall that angiotensin is a hormone that constricts the arteries.) 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 the loss of protein in the urine (proteinuria) in certain kidney diseases and perhaps help strengthen the heart muscle in certain diseases of the heart muscle (cardiomyopathies). Note that both the ACE inhibitors and the ARB drugs are not to be used (are contraindicated) in pregnant women. (See the section above on pregnancy.)
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 squeezing (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 fast heartbeat while resting (tachycardia), cardiac chest pain (angina), or a recent heart attack (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 tiny tubes (tubules) of the kidneys to remove salt from the body. Water (fluid) also may be removed along with the salt. Diuretics may be used as single drug treatment (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 far end (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 (fat), uric acid, and glucose (sugar) in the blood.
Occasionally, when salt retention causing accumulation of water and swelling (edema) is a major problem, the more potent, so-called, loop diuretics may be used in combination with other anti-hypertensive medications. (The loop diuretics are so called because they work in the loop segment of the kidney tubules to eliminate salt.) 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. (See the section above on pregnancy.)
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 the heart's pumping action (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 other abnormal heart rates or rhythms (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 not recommended (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 long-acting (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). For more information, please see the article on Calcium Channel Blockers.
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 stiffness (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. For more information, please see the drug monograph on Clonidine.
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 (swelling). Minoxidil may also increase hair growth. For more information, please see the drug monograph on Minoxidil.