By John Messmer, MD

Diagnosing hypertension is complicated. However, treating it is even more complicated. Although simple, essential hypertension in an otherwise healthy person is straightforward, as people age or develop other health issues, treating it can be very tricky.

Why combine drugs to treat hypertension?

To treat hypertension, physicians don't simply pick a drug from a list. They must also consider the patient's preexisting medical problems, his age, ethnicity, and other medications, as well as the cost of medications. Approximately one third of all people suffering from hypertension can control their condition using one medication. However, most people will eventually need to use several medications at once.

Here are five reasons for combining medications:

1. Higher doses of one medication may increase the risk of side effects.
2. Combining medications balances the effects on the organs being protected by treatment.
3. Some medical problems, such as diabetes or heart failure, improve with the use of certain medications, so these are often used even in small doses to get these benefits.
4. Some medications will counteract the adverse effects of another blood pressure medication.
5. Adding a medication may lower the pressure more than by increasing the dose.

Drugs for hypertension

1.   Diuretics elimate water

Diuretics eliminate some water from the body. However, this function is unrelated to their blood pressure lowering mechanism (which is unknown). They are inexpensive, but some people find the increased urination inconvenient. Diuretics deplete sodium and potassium, which can cause weakness and heart rhythm disturbances. As a result, many doctors add a potassium supplement or a second, potassium-sparing diuretic to counter this effect. Adding more sodium to the diet does not counter the sodium loss-it makes it worse. The risk of low sodium increases with age and the potency of the diuretic. Sometimes, doctors will add a tiny dose of diuretic to increase the effect of other blood pressure medications.

2.   Beta blockers reduce blood pressure

Epinephrine (adrenaline) and norepinephrine increase heart rate and blood pressure by stimulating a cellular receptor called a "beta" receptor. Beta blockers reduce blood pressure by inhibiting this effect. The adrenaline-like chemicals also stimulate another group of receptors called "alpha" receptors causing arteries to constrict. Some beta blockers also block alpha receptors with even greater blood pressure lowering effects. Some even partially stimulate the beta receptor to counteract some of the adverse effects of beta blockade.

The potential adverse effects of beta and/or alpha blockade are weakness, shortness of breath, fainting, slow heart rate, cold extremities and sometimes depression and erectile dysfunction.

3.   Calcium channel blockers lower blood pressure and can reduce angina

Muscles in the walls of arteries contract, narrowing the artery to raise blood pressure. The muscles are activated by calcium flowing through channels in the muscle cells. Calcium channel blockers reduce this effect, allowing arteries to relax. In addition to lowering blood pressure, calcium channel blockers can allow increased flow in the heart's arteries, relieving angina, the chest pain from coronary artery disease.

Muscles in the heart can also relax, slowing the heart's rate and strength of contraction. Relaxed arteries allow blood to pool in the legs, leading to swelling. Relaxed muscles in the intestines slow intestinal movement. Heart rate abnormalities, swelling in the legs and constipation are the most common side effects of this class of drug.

4.   Angiotensin Converting Enzyme inhibitors (ACE inhibitors)

Angiotensin is a potent and dangerous chemical in our bodies. It is important in blood pressure regulation through salt and water management, but if too much is around it can damage kidneys, arteries, and more. Angiotensin is made from a precursor chemical by the action of the angiotensin converting enzyme. When that enzyme is inhibited less angiotensin is made, lowering blood pressure and protecting the heart and kidneys.

Inhibition of angiotensin is very beneficial for diabetics and people with heart failure. However, we make angiotensin a second way, so ACE inhibitors are not perfect. When angiotensin is made the alternate way, other chemicals are also created which can have adverse effects, such as, a cough or hives which rarely can be life threatening. Also ACE inhibitors cause the kidneys to retain potassium so they can be used in combination with a diuretic to offset the latter's potassium loss, but sometimes they can cause potassium levels to become dangerously high.

5.   Angiotensin receptor blockers

Rather than inhibit angiotensin production, angiotensin receptor blockers (ARB's) block the effect angiotensin has on the kidney and blood vessels. They eliminate the cough that ACE inhibitors can cause, but they promote the retention of potassium and can lead to elevated potassium levels. Otherwise, they tend to be very well tolerated. They are beneficial to diabetics and people with heart failure, much like ACE inhibitors.

6.   Alpha blockers as a combination drug

These inhibit the constricting effect epinephrine and norepinephrine have on the blood vessels. They are rarely used alone for blood pressure as they cause the heart to work harder and can increase the pressure inside the kidneys. When used for blood pressure, they are commonly used with other medications for additive effect.

7.   Sympatholytics to manage hypertension

Epinephrine and norepinephrine are released by a part of the nerve complex called the "sympathetic" nervous system. The term "lysis" means to break apart or inhibit. Thus, sympatholytics interfere with the part of the nervous system that uses norepinephrine to raise blood pressure. The most common one used these days is clonidine which can be taken orally or applied as a weekly patch. Dry mouth and sedation are possible with clonidine.

8.   Vasodilators (dilate the arteries/veins)

These are older medications that act directly on the arteries or veins to dilate them. They are sometimes used in conjunction with other blood pressure medications to augment their effect or for short term use to lower blood pressure quickly in an emergency. They have not been as well tolerated as newer medications; they often require multiple doses daily and typically are not used alone because, like alpha blockers, they make the heart work harder.

High blood pressure requires regular check-in with your doctor

No matter what drug is used, it is important to have periodic re-evaluation by your physician to assess how well the pressure is controlled and to look for signs of side effects or impairment of the organ systems being protected by blood pressure treatment. Periodic home measurement of blood pressure monitors it under "real world" conditions.

No blood pressure medication should ever be stopped or the dose changed by the patient without consulting the physician. This leads to potentially dangerous under- or over-treatment and can cause a stroke or heart attack. Working with one's physician, it is possible to avoid the damage hypertension can cause and thereby to be fit and active for a long time.