Pharmaceutical Management of Hypertension

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 helps regulate blood pressure. ACE inhibitors 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). 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). ACE inhibitors usually are the first line drugs 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 indiabetic nephropathy (kidney disease).

Patients treated with ACE inhibitors who also have kidney disease should be monitored for further deterioration in kidney function and high serum potassium. These drugs may be used to reduce the loss of potassium in people who are being treated with diuretics that cause patients to lose potassium. ACE inhibitors have few side effects. One bothersome side effect 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. (Angiotensin is a hormone that constricts the arteries.) ARB drugs appear to have many of the same advantages as the ACE inhibitors but without the associated cough. 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. This combination of drugs can treat hypertension and 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). Both the ACE inhibitors and the ARB drugs are not to be used (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. 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 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. Beta-blockers cause contraction of the smooth muscle of the peripheral arteries and thereby decrease blood flow to body tissues. As a result, the patient may experience coolness in the hands and feet. 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). 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 is uncertain. Beta-blockers may be considered for treatment of hypertension because they also may treat co-existing medical problems; such as 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 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 adverse effects sometimes seen with 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 '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.

Calcium channel blockers (CCBs)

Calcium channel blockers inhibit the movement of calcium into the muscle cells of the heart and arteries. Calcium is needed for these muscles to contract. Calcium channel blocker 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 isverapamil (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 are not recommended (contraindicated) in congestive heart failure. However, these same dihydropyridines are useful in preventing certain 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 may have adverse long-term consequences, such as strokes or heart attacks. These effects are due to the wide fluctuations in the blood pressure and heart rate that occur during treatment, resulting from the rapid onset and short duration of the short-acting compounds. When the calcium channel blockers are used in sustained release preparations less fluctuation occurs. 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).