Blood Pressure Medications: Types, Side Effects, and How to Choose the Right One

High blood pressure (hypertension) is a problem that should be taken very seriously. Although it rarely causes symptoms, high blood pressure weakens the heart muscle and damages blood vessels and valves, increasing the risk of stroke, heart attack, heart failure, and sudden cardiac death. Fortunately, these outcomes are not inevitable, thanks to a multitude of medications.

“The benefits of antihypertensive medications have been shown time and time again,” says Cleveland Clinic preventive cardiologist Luke J. Laffin, MD. “Lowering blood pressure is among the most well-established interventions for reducing the risk of major adverse cardiovascular events (MACE) and death.”

What Are Blood Pressure Medications?

There is no point at which blood pressure suddenly becomes dangerous: The more out-of-control your blood pressure is, the greater your risk. The goal of blood pressure medications is to lower blood pressure into a range that minimizes risk.

“Ideally, systolic blood pressure (the pressure when your heart contracts) should be somewhere in the 120s,” Dr. Laffin says, referring to 120 to 129 milligrams of mercury (mmHg), the units in which blood pressure is measured. “Between 110 mmHg and 120 mmHg is even better. For diastolic blood pressure (the pressure between heartbeats), under 80 mmHg is ideal.”

Because blood pressure is regulated by several complementary biological systems, numerous types (classes) of blood pressure medication have been created to work in different ways. Some eliminate excess water and sodium. Some relax or dilate blood vessels. Others reduce heart rate or prevent adrenaline from raising heart rate.

It takes time for the medications to exert their influence over blood pressure. Consequently, blood pressure lowering requires patience. “You can’t expect to take a pill and, overnight, your blood pressure will be low,” Dr. Laffin says.

For maximum effectiveness, blood pressure medications must be combined with certain nonpharmacologic measures: losing excess weight; eating a healthy diet (the DASH diet is recommended); cutting down on sodium consumption; increasing dietary potassium; getting aerobic, resistance, and isometric exercise; and limiting alcohol use.

“I tell patients that blood pressure management is about 70% lifestyle and 30% medications. If they are not willing to do the lifestyle components, it’s going to be difficult to find an effective medication regimen,” Dr. Laffin says. “If blood pressure remains above 130 mmHg systolic after trying lifestyle measures for three to six months, then we recommend blood pressure medications. We typically start people on medications right away if their blood pressure is over 140 mmHg.”

Main Types of Blood Pressure Medications

The American Heart Association divides blood pressure medications into first-line agents and secondary medications. “If the first-line drugs don’t get someone to these goals, we start adding drugs from the other classes,” Dr. Laffin says.

Four classes of drugs are in the pool of first-line agents for antihypertensive therapy: thiazide-like diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

“These agents have been demonstrated in clinical trials to not only reduce blood pressure, but to reduce the risk of MACE as well,” Dr. Laffin says. “They are well tolerated, inexpensive, available as generics, and often come in combination pills.”

The other drugs are considered second-line agents because they are less effective and have more side effects.

Thiazide-Like Diuretics

Diuretics cause the body to eliminate excess fluid and sodium in the blood through urination. This process reduces the volume of blood in the body, which makes it easier for the heart to pump and lowers blood pressure.

The three types of diuretics for high blood pressure management include thiazide-like, potassium-sparing, and loop. Thiazide-like diuretics are the first choice because they are well tolerated and have a predictable effect. “Hydrochlorothiazide is the most frequently prescribed. However, indapamide and chlorthalidone are more potent, lower blood pressure more effectively, and do a better job at reducing fatal and nonfatal cardiovascular events,” Dr. Laffin says.   

Considerations: Increased urine output can lead to low levels of potassium (hypokalemia) or sodium (hyponatremia) in the blood. Diuretics also can worsen gout (a type of inflammatory arthritis) and increase the risk of gout flare-ups.

Potential side effects: Low blood pressure, dehydration, dizziness, and fatigue

Calcium Channel Blockers (CCBs)

Calcium is necessary for the cells in artery walls to contract. CCBs prevent calcium from entering the cells, allowing the arteries to relax and dilate, thereby lowering blood pressure.

The two types of CCBs include dihydropyridines and nondihydropyridines. Dihydropyridines are more effective for blood-pressure lowering. “Of the six agents in this class, I tend to prescribe amlodipine most often because it comes in combination pills with ARBs,” Dr. Laffin says.

Considerations: CCBs may weaken the lower esophageal sphincter, causing or worsening gastroesophageal reflux disease (GERD). Nondihydropyridine CCBs should not be used in individuals with heart failure with reduced ejection fraction or combined with the antibiotics clarithromycin, erythromycin, or telithromycin, since blood pressure may drop to dangerously low levels.

Potential side effects: The major side effect is swelling (edema) in the lower extremities, which can be blunted by taking CCBs with ACE inhibitors. “Edema, in this instance, is not dangerous, but it can be cosmetically displeasing,” Dr. Laffin says. CCBs also may cause palpitations, nausea, constipation, headache, skin rashes, flushing, and dizziness.

Angiotensin-Converting Enzyme (ACE) Inhibitors

Angiotensin II is a hormone that binds with receptors to constrict blood vessels and increase blood pressure. ACE inhibitors prevent the hormone angiotensin from being converted to angiotensin II. As a result, blood vessels remain relaxed.

Consideration: ACE inhibitors raise potassium levels. 

Potential side effects: Between 5% and 20% of people on ACE inhibitors develop a dry cough. These individuals may be switched to an ARB. Otherwise, ACE inhibitors are generally well tolerated. Some individuals report dizziness, nausea, skin rash, itching, loss of taste, or headache.

Angiotensin Receptor Blockers (ARBs)

Each cell in your body has on its surface tiny receptors, proteins that receive messages from chemical messenger molecules. Angiotensin II must bind with special receptors to constrict blood vessels and increase blood pressure. ARBs block the action of these receptors, thereby preventing blood vessel constriction and reducing blood pressure. Eight ARBs are available, with losartan being the weakest.

ARBs are as effective as ACE inhibitors at lowering blood pressure, and they do not cause a chronic cough. “ARBs are the best-tolerated blood pressure drug,” Dr. Laffin says.

Consideration: Like ACE inhibitors, ARBs can cause potassium levels to rise.

Potential side effects: Dizziness, stuffy or runny nose, gastrointestinal problems, back pain, tiredness, and headache.

Second-Line Blood Pressure Medications

Due to less-effective blood pressure-lowering ability or multiple side effects, or because they apply only in limited situations, these drugs are used less often as antihypertensive agents.

Beta-blockers. These drugs block adrenaline, the hormone responsible for our innate fight-or-flight response to stress. Beta-blockers cause the heart to beat more slowly. They are prescribed when an individual with high blood pressure has had a heart attack or has an arrhythmia such as atrial fibrillation, aneurysm, or heart failure with reduced ejection fraction. Because beta-blockers slow the heart rate, they make some people feel tired.

Loop Diuretics. These diuretics are preferred over thiazide-type diuretics for high blood pressure management in people with symptomatic heart failure and moderate-to-severe kidney disease and used in individuals who develop hyponatremia on thiazide-type diuretics. Three loop diuretics are available, with torsemide preferred for blood pressure lowering.

Potassium-Sparing Diuretics. These drugs have some effect on blood pressure when used alone, but they may be added to therapy if someone experiences hypokalemia (low potassium levels) on thiazide-type diuretics.

Direct Renin Inhibitors. The only drug in this class, aliskiren, works in a similar fashion to ACE inhibitors and ARBs and should not be used in combination with either drug class. In people with kidney disease or taking potassium supplements or potassium-sparing drugs, aliskiren increases the risk of hyperkalemia (potassium overload). Aliskiren also may cause kidney failure in individuals with severe renal artery stenosis.

Alpha-1 Blockers. Alpha-blockers relax smooth muscle cells in arteries to prevent them from constricting and raising blood pressure. They are typically not as effective as other drug classes at lowering blood pressure. These drugs also are prescribed to men with benign prostate enlargement. They should not be used in combination with erectile dysfunction drugs, due to increased risk of low blood pressure (hypotension), or by individuals with, or at risk for, orthostatic hypotension (a drop in blood pressure upon standing). They have many side effects.

Direct Vasodilators. These drugs cause arteries to dilate. Because they encourage the retention of sodium and water, they are used in combination with a diuretic and beta-blocker. Two drugs comprise this class. Hydralazine is usually combined with a nitrate. Minoxidil is given with a loop diuretic and is used in hypertensive crises. In higher doses, hydralazine can cause a lupus-like syndrome. Minoxidil is associated with hirsutism (as such, it is sometimes used in low doses to treat hair loss) and can trigger pericardial effusion.

Alpha-Beta Blocker Combinations. These drugs are primarily given intravenously when blood pressure surpasses 180 mmHg. One medication in this class, carvedilol, is preferred in people with high blood pressure and heart failure with reduced ejection fraction.

Central Alpha-2 Receptor Agonists. These medications ease blood flow and lower blood pressure by blocking signals from the brain that tell the nervous system to increase heart rate and constrict blood vessels. Because these drugs have many undesirable effects on the central nervous system, they are a last choice for blood pressure control.

Aldosterone Antagonists. The two drugs in this class work against the hormone aldosterone. They are used to treat hypertension that remains resistant to three or more antihypertensive medications. They should not be used in conjunction with potassium supplements, potassium-sparing diuretics, or in people with kidney dysfunction. Spironolactone, but not eplerenone, increases the risk of gynecomastia (male breast enlargement) and impotence.

Aldosterone Synthase Inhibitors. This new class of drugs blocks the production of aldosterone in the adrenal glands, significantly reducing the amount of aldosterone circulating in the blood. As a result, less sodium and water are resorbed, decreasing the total volume of blood and lowering blood pressure. Like aldosterone antagonists, these drugs are used in the treatment of resistant hypertension.

Dual Endothelin Receptor Antagonists. Aprocitentan, currently the only drug in this class, blocks endothelin-1 from binding to receptors, thereby preventing blood vessels from narrowing. Aprocitentan may be added when other antihypertensive drugs fail to control blood pressure. The drug is associated with mild fluid retention, but only for the first few weeks of treatment.

How Doctors Choose the Right Blood Pressure Medication

There is no one-size-fits-all blood pressure treatment regimen. Doctors consider many factors when individualizing a treatment regimen, including the known side effects and contraindications of the various medications, the individual’s cardiovascular history, the presence of other comorbid medical conditions, and a person’s age, race, and gender.

“Every patient needs to have a discussion with their doctor about what’s right for them,” Dr. Laffin advises.

Blood Pressure Medication Combinations

Most people with hypertension are started on low-to-medium doses of two or more medications from different classes, an approach that is more effective than using one medication at a higher dose.

The most common antihypertensive combinations are available in a single pill. “These combinations tend to work well together because they have synergistic mechanisms,” Dr. Laffin explains. The single combination pill also provides added convenience, particularly for individuals taking multiple medications.

The majority of fixed-dose combinations are available as generics.

Special Cases

• Several classes of blood pressure medications should not be used during pregnancy, including ACE inhibitors, ARBs, direct renin inhibitors, and aldosterone antagonists. Additionally, the dual endothelin receptor antagonist aprocitentan is toxic to a fetus. “In women who had high blood pressure prior to getting pregnant, we typically prescribe the CCBs and beta-blockers that have been shown to be safe in pregnancy. Occasionally, we use a diuretic, but we prefer not to because there is less data on these drugs,” Dr. Laffin says. “Postpartum, we typically continue the medications they have been on.” For women with gestational hypertension, CCBs are typically prescribed, with beta-blockers added if needed.
• Older Adults. It is not usually necessarily to prescribe different drugs for older individuals with hypertension based on their age alone. “They may be a little more responsive to CCBs and diuretics, but it doesn’t mean you can’t use other classes,” Dr. Laffin says.
• Diabetes and/or Kidney Disease. ACE inhibitors protect the kidneys, so they are a good choice in individuals with hypertension and chronic kidney disease. ACE inhibitors also may help reduce the risk of kidney damage in individuals with diabetes. Like ACE inhibitors, ARBs have been shown to improve outcomes in individuals with high blood pressure and diabetes and/or chronic kidney disease. ACE inhibitors and ARBs are the most effective blood pressure-lowering agents for preventing vascular problems in people with diabetes, and the most effective at preventing diabetes from developing in people with high blood pressure. ACE inhibitors are associated with an increased risk of hyperkalemia (too much potassium), particularly in people with chronic kidney disease and those taking potassium-sparing medications.

Tips for Taking Blood Pressure Medicine Safely

If you have been on the same medication for 10 years, it may be worthwhile to ask your doctor if the dose can be adjusted.

It doesn’t appear to matter what time of day you take your blood pressure drugs. However, taking a diuretic right before bed probably will cause you to wake from sleep several times at night to urinate.  

It’s not important to take blood pressure medications at the same time every day. However, a routine will help prevent you from missing doses. “If you miss a dose in the morning and you don’t remember until the afternoon, take it that afternoon. If you don’t remember until the next day, just take your normal dose for that day. Don’t take double the amount of medication,” Dr. Laffin cautions.

A high-sodium diet will limit or blunt the efficacy of many antihypertensive drugs. That’s why a low-sodium diet is very important.

If you experience side effects from these drugs, let your doctor know, but do not stop taking the drugs unless instructed to do so.

“Everyone wants to know if they will be able to discontinue taking their medications once their blood pressure reaches its goal,” Dr. Laffin says. “If they eat healthy and lose weight, it may be possible. However, hypertension is a disease of aging, so more often than not, once you start antihypertensive therapy, you are on it for life.”