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Antihypertensive Drugs

Don is an easygoing sixty-six-year-old man who was brought to the emergency department because his son and daughter-in-law found him lying on the floor of his small apartment, too weak to stand on his own. Don has multiple health problems, including heart disease, high blood pressure, type 2 diabetes, an enlarged prostate, depression, and post-traumatic stress disorder (PTSD). He had just returned home after a short rehabilitation stay at a nursing home to recover from hip replacement surgery.

In the emergency department, Don received the “million-dollar workup.” In addition to an array of laboratory tests that ruled out electrolyte imbalances and anemia, he had an electrocardiogram (EKG) and chest x-ray, both normal. He also had a CT scan of his brain, which was reassuringly negative. He was then seen by the stroke team, who felt a stroke was unlikely but suggested that he be admitted to the hospital so that he could be observed and have more imaging done if needed.

The initial plan proposed by the neurology consult team was to consider an MRI to rule out problems with the cerebellum, the part of the brain that helps with balance and sense of position. However, tight spaces trigger severe anxiety for Don, so he would have to be placed under anesthesia to have the MRI.

Fortunately, the staff took time to learn more about Don’s medical history. His blood pressure was slightly elevated, in the 150/90 range, but Don mentioned that he had been too weak to take his blood pressure medications that morning. The team spoke with his primary care physician and learned she had just scaled back two of Don’s four antihypertensive drugs because he was having dizziness and blood pressure measurements as low as 70/50.

Don’s family thought that his medications were to blame for his weakness, especially tamsulosin (Flomax), the one his urologist had prescribed a few months ago for difficulty urinating related to his prostate enlargement. In fact, it is also used to lower blood pressure. The tamsulosin was stopped, and the dose of one of his antihypertensive drugs, lisinopril (Prinivil, Zestril), was lowered. The timing of his medicines was also modified.

When all was said and done, Don’s dizziness vanished with the medication changes. He walked out of the hospital after a costly and stressful three-day stay, symptom-free and not needing to have an MRI under anesthesia. His doctors agreed that his symptoms and subsequent need for hospitalization were due entirely to the adverse effects of medications.

PREVENTING HIGH BLOOD PRESSURE: A MEDICAL REVOLUTION

In 2014, 32.5 percent of American adults had a diagnosis of high blood pressure, also known as hypertension. Hypertension is often referred to as the “silent killer,” because it usually produces no symptoms but is, without a doubt, linked to increased risk of heart attack, stroke, and any number of other debilitating—and deadly—health problems. Research continues to indicate that careful blood pressure control markedly decreases risk.

Hypertension was first described as a disease in 1808, but it was not until 1896, when invention of the sphygmomanometer enabled doctors to measure blood pressure, that it caught their attention. In fact, detection and treatment of high blood pressure resulted in a dramatic shift in Western medical philosophy, motivating health care professionals to focus more on prevention in caring for their patients.

By the 1960s, it was widely understood that high blood pressure correlated with stroke risk. Additional research over the next few decades established a link between hypertension and cardiovascular disease in general. Diagnosis and treatment of hypertension is one reason for the dramatic decline in deaths due to heart attack that were epidemic in the mid-twentieth century. We now know that elevated blood pressure can also impair cognitive function, damage the kidneys, and contribute to erectile dysfunction, loss of vision, heart failure, and the rupture of aneurysms (distended arteries).

In industrialized societies like ours, blood pressure rises with age in most people. Age-related hypertension is associated with stiffening of arteries and is so common as to be considered a normal consequence of growing older. But it does not exist in the few remaining hunter-gatherer societies, suggesting that it is more related to lifestyle than to the aging process. Key lifestyle factors are likely to be diet, physical activity, and stress. Our high consumption of processed and manufactured foods loaded with sodium and quick-digesting carbohydrates is far from the more natural whole-foods diet of hunter-gatherers and probably affects blood pressure for the worse. Regular physical activity keeps arteries more elastic and helps maintain normal weight, both of which correlate with normal blood pressure. And, while hunter-gatherers are not free from stress and anxiety, we seem to experience more of it.

The connection between stress and blood pressure is the autonomic nervous system, which regulates the tone of the smooth (involuntary) muscle that lines the walls of arteries. The sympathetic branch of that system constricts arteries, increasing blood pressure, while the parasympathetic branch relaxes them, lowering pressure. In the fight-or-flight response, sympathetic activity ensures a constant flow of blood to the brain by raising blood pressure. Many people in our population suffer from chronic overactivity of the sympathetic nervous system, as if it were reacting to an emergency that never ends, and this is surely one root of hypertension. The act of measuring blood pressure by a doctor or a nurse often creates anxiety and increases sympathetic nervous tone, distorting readings taken in a medical setting. Such “white-coat hypertension” may not give an accurate picture of a patient’s average pressures. Nevertheless, doctors often prescribe antihypertensive drugs on the basis of such readings.

QUICK FIXES: THE RISE OF ANTIHYPERTENSIVE DRUGS

There is little doubt that blood pressure should be neither too high nor too low. Recent research findings suggest that it is desirable to lower pressures that are even slightly above the 120/80 previously considered normal for most adults.^* Drugs have now displaced all other therapies. In 2010, the United States spent nearly $42.9 billion on the management of hypertension. Some $20.4 billion of that was for medications, $13.0 billion for ambulatory visits, and the rest for emergency department care, inpatient stays, and home health visits. It costs the average American adult with hypertension more than $733 per year to manage it, when costs of medications, doctor visits, and various tests are taken into account.

That said, the most commonly used blood pressure medications are relatively cheap, at least compared to other classes of drugs. Most have been on the market for some time and are available in less expensive generic forms. In fact, a number of them are on the formularies of national pharmacy chains and cost just $4 a month. The question is whether or not that increased availability serves patients’ best interests. The patient in the example above suffered harm because he was given too many medications at once that affect blood pressure.

HOW BLOOD PRESSURE MEDICINES WORK—AND THE PROBLEMS WITH THEM

Because adequate blood flow is vitally important for nearly all functions, the body regulates it carefully with complex nervous and hormonal mechanisms. The various antihypertensive drugs influence these mechanisms in different ways. For example, beta blockers work on the nervous system, while angiotensin-converting enzyme (ACE) inhibitors alter hormonal pathways. Calcium channel blockers relax the smooth muscle that lines blood vessels, and diuretics decrease blood volume by increasing urinary excretion of water. It is common today to treat hypertension by combining multiple medications with different mechanisms of action for a more powerful effect.

Any medication that lowers blood pressure can result in pressure that is too low, especially when used in drug combinations, as was the case with Don. Note that drugs used to treat other problems, like the tamsulosin Don was taking for his prostate-related urinary difficulty, can also lower blood pressure. While there is not a specific number used as a cut-off for dangerously low pressure in older adults, most doctors become concerned when the upper number dips below 100. With very low pressure, blood flow to vital organs like the brain and heart is inadequate, a potentially deadly condition known as “shock.”

Many different classes of medications are used to control hypertension. Here are the most important ones and the adverse effects they can cause.

Thiazide Diuretics (“Water Pills”)

These drugs came into use in 1958. Hydrochlorothiazide (HCTZ, Microzide) and chlorthalidone (Thalitone) are two examples. They reduce the amount of salt and water the kidneys reabsorb from urine, increasing urination and reducing blood volume. Side effects are dose related and tend to be rare: headache, weakness, upset stomach, itching, vision changes, and muscle cramps. Thiazide diuretics can also cause flare-ups in those with gout. People who take them complain about having to urinate frequently, but that is the intended effect. It is best to take these drugs in the morning rather than at bedtime.

Beta Blockers

First developed in 1973, dozens of these drugs are now in use. All block a specific type of receptor (the beta receptor) in the sympathetic nervous system, resulting in relaxation of the smooth muscle in arterial walls. Their generic names end in “-lol.” Common examples are carvedilol (Coreg), atenolol (Tenormin), metoprolol (Lopressor, Toprol), and propranolol (Inderal). Beta blockers frequently cause fatigue, spasm of the airways (thus they should be used with caution in people with asthma), dizziness, erectile dysfunction, and low blood sugar. Metoprolol and propranolol, in particular, can cause insomnia and vivid dreams. Carvedilol can cause edema (retention of fluid in the lower extremities). Recent studies indicate that beta blockers are probably not the best first choice for blood pressure management in most people.

Alpha-2 Agonists

These drugs stimulate alpha-2 receptors in the nervous system, decreasing sympathetic tone. Many, but not all, have names that end with “-idine.” The most common example of an alpha-2 agonist is clonidine (Catapres). All have a number of side effects, the most common of which are sedation, dry mouth, anxiety, constipation, nausea, and vomiting. They can also cause, more than other antihypertensive medications, a dramatic drop in blood pressure associated with changing position, such as when a person stands up after sitting (this is known as postural or orthostatic hypotension). Dizziness and fainting commonly result from postural hypotension.

Alpha-1 Blockers

Blocking alpha-1 receptors also lowers blood pressure. Most drugs in this class have names that end with “-osin,” such as doxazosin (Cardura) and tamsulosin (Flomax). Like alpha-2 agonists, these drugs can cause orthostatic hypotension—a particular risk after a person takes the first dose of one of these medications. (These drugs also help manage prostate enlargement, which is why Don was put on tamsulosin.) Side effects include low heart rate, edema, dizziness, headache, fatigue, anxiety, and a variety of gastrointestinal and urinary effects, including increased urination. Alpha-1 blockers are not usually used as first-line blood pressure treatment.

Calcium Channel Blockers

In order to contract, muscle cells require that calcium ions move into them. Calcium channel blockers (CCBs) prevent calcium ions from moving into the muscle cells in arterial walls, thereby weakening their contractions. More relaxed blood vessel muscle translates into lower blood pressure. CCBs are considered first-line blood pressure drugs. The first CCBs, verapamil (Calan, Verelan, Covera-HS) and nifedipine (Procardia), were developed in 1977; amlodipine (Norvasc) is now widely used. CCBs work well for large blood vessel stiffness, which many elderly patients have. Side effects include constipation, nausea, dizziness, rash, swelling in the legs and feet, and drowsiness.

DRUGS THAT AFFECT THE RENIN-ANGIOTENSIN SYSTEM

The renin-angiotensin system (RAS) regulates blood pressure through hormonal mechanisms. When the kidneys sense that blood flow is decreased, they secrete an enzyme (renin) that increases blood levels of angiotensin I, an inactive precursor. Another enzyme (angiotensin-converting enzyme, or ACE), made by the lungs, acts to convert angiotensin I into angiotensin II, an active hormone that raises blood pressure by causing blood vessels to constrict. Drugs can interfere with this complex pathway in several different ways.

ACE Inhibitors

As their name suggests, these drugs prevent ACE from being released from the lungs, so it can’t then turn angiotensin I into angiotensin II. The names of these drugs all end in “-pril”: lisinopril (Prinivil, Zestril), enalapril (Vasotec), and captopril (Capoten). Like diuretics and CCBs, they are considered first-line blood pressure drugs, and they are particularly useful for people with diabetes because they also protect kidney function. (Kidney damage is a serious long-term complication of diabetes.) Additionally, ACE inhibitors play a vital role in the treatment of heart failure. They can, however, cause a chronic, dry cough in 5 to 25 percent of people. They can also cause rash, diarrhea, drowsiness, headache, weakness, elevation in blood potassium levels, and abnormal taste sensation. A less common side effect is angioedema—swelling of the lips, mouth, and tongue that in some instances can be dangerous.

Angiotensin Receptor Blockers

Another way to decrease the effects of angiotensin II is by preventing it from binding to receptors in blood vessel walls. This is what angiotensin receptor blockers (ARBs) do. The names of these drugs end in “-sartan,” such as losartan (Cozaar), candesartan (Atacand), and irbesartan (Avapro). They are often used when a person cannot tolerate an ACE inhibitor because of cough or angioedema; however, they can cause these same adverse effects, albeit less frequently. More common adverse reactions include first-dose postural low blood pressure, muscle cramping, insomnia, abnormal liver function, and lowered white blood cell counts.

Renin Inhibitors

First developed in 2000, drugs in this relatively new class bind to renin so that it can no longer act to produce angiotensin I. Aliskiren (Tekturna) is the main drug of this type. It should not be taken with an ACE inhibitor or an ARB, and its side effects are similar to those of both classes of drugs. It may also increase gout flares and the formation of kidney stones.

INTEGRATIVE MEDICINE APPROACHES TO LOWERING HIGH BLOOD PRESSURE

If you have been told you have high blood pressure, the first priority is to determine whether it is consistently elevated outside of a medical setting. The only way to do that is to monitor it yourself. Accurate, easy-to-use, reasonably priced digital blood pressure monitors are widely available. Get one and start recording your pressures several times a day at different times. You will find that they vary considerably. After a month or two, take the record to your doctor so that together you can decide whether treatment is necessary. As long as your blood pressure is not extremely high (that is, over 180/100) or associated with clear acute damage to vital organs, your goal should be to reduce it over the long term. Hypertension may be a silent killer, but it is also usually a very slow one. There is almost always time to experiment with lifestyle changes and other measures before starting on antihypertensive drugs. If these measures fail to bring your blood pressure down to the normal range and medication is necessary, ask your doctor to start with the lowest dose of the least powerful drug. Using lifestyle measures and other therapies in combination with medication will often allow you to stay on lower doses of fewer drugs.

There are any number of ways to treat—and prevent—high blood pressure. Many of the methods described below will reduce the upper and lower blood pressure numbers by at least a few points each, and those benefits add up as you try several at a time.

Nutrition

Good evidence shows that both the dietary approaches to stop hypertension (DASH) diet and the Mediterranean diet can lower high blood pressure. Weight loss can make a big difference, too. Eating about 30 grams a day of fiber (at least 14 grams a day for every 1000 calories you eat in total) can also be helpful. (Note that it takes up to eight weeks for fiber to have its full effect.) People who eat more fruits and vegetables have lower risk of hypertension. And several recent studies indicate that eating unsalted nuts can lower blood pressure—especially pistachios, but other nuts as well; the effective dose is a handful a day.

Polyphenols, chemical compounds found in many plants, can also help. Cocoa and dark chocolate are good sources, as are grapes; that may be the reason why limited quantities of wine (red only, and just one glass a day or so, provided it does not lead to other health issues) have been found in some studies to reduce heart disease risk. Omega-3 fats, found in grass-fed animal meats, fatty cold-water fish, supplements, and other sources, also have benefit.

There seems to be a link between low vitamin D levels (under 30 ng/mL, especially) and higher blood pressure. Know your blood level of vitamin D and supplement appropriately.

For a long time, sodium has been associated with hypertension. A 2013 review found that reducing sodium from between 9 and 12 grams daily to between 5 and 6 grams daily has a significant beneficial effect; keeping it to 3 grams might be even better. The easiest way to do this is to reduce intake of processed and manufactured foods. Also, the effects of sodium are opposed by those of potassium, and you can increase your potassium intake simply by eating more fruits and vegetables. But keep in mind that a number of studies suggest, and a number of experts agree, that sodium is not as important an influence on blood pressure as we once thought.

Other Lifestyle Measures

A number of lifestyle factors favorably influence blood pressure. Physical activity, if done prudently, is good for practically all health issues, and hypertension is no exception. Yoga shows promise in what little research we have so far, as does tai chi. Adequate sleep is also important: we know that fewer hours of overall sleep at night and insomnia are tied to an increased risk of hypertension. Finally, quitting smoking is one of the best choices a person can make to improve blood pressure (and overall health). Every cigarette counts; cutting back even by one a day is of some benefit.

Relaxation and Social Connection

Relaxation training, such as breathing exercises, meditation, and biofeedback, lowers blood pressure by increasing activity of the parasympathetic nervous system. These approaches can drop the top blood pressure number by 10 and the bottom number by 7, if practiced regularly. Research indicates that people who are less isolated and more connected with others are less likely to be hypertensive.

Other Nondrug Therapies

A number of supplements have shown promise in lowering blood pressure—for example, hibiscus, coenzyme Q10, garlic, magnesium, and the amino acid L-arginine. Practitioners of Ayurveda and traditional Chinese medicine commonly treat people with hypertension and report success.

BOTTOM LINE

In treating high blood pressure, it is extremely important to take individual uniqueness into account. A doctor trained in integrative medicine will take a detailed history that may suggest ways to bring about more lasting improvements in health than simply depending on pills. How much is stress a contributor? Is there pent-up anger? Is a person living in a perpetual state of fight or flight? What about dietary habits? Or sleep quality? Is there a need to look for other physical contributors, such as the use of over-the-counter products and supplements that can raise blood pressure, particularly cold remedies and energy boosters that contain stimulant drugs (phenylephrine) and herbs (guaraná, ephedra)?

Remember that blood pressure is only one of many different risk factors for heart disease, stroke, and other serious health issues. Treating hypertension is important to these problems, but obesity, diabetes, tobacco dependence, depression, and any number of other contributors should be given attention as well. Medications cannot improve general health in the way that a tailored, thoughtful, and comprehensive treatment plan can. Integrative treatment can include medications but should not be limited to them.