High Blood Pressure (Hypertension)

What Medications Are Used To Treat High Blood Pressure?

Although changes in lifestyle and diet are essential steps to take in controlling high blood pressure, many people also need to use medications to keep their blood pressure in control. Drug treatment has been shown to protect against stroke, heart failure, coronary events such as a heart attack, progression of kidney failure, and progression to severe hypertension.

Medications that lower blood pressure are often referred to as antihypertensive drugs, antihypertensive agents, or just antihypertensives. Generally these drugs are classified by how they work.

Many medications are available for effective blood pressure control. Currently, more than 100 drug preparations are available, and the list is growing. They include:

• Diuretics (“Water pills”)
• Beta-adrenergic blocking agents
• Calcium channel blockers
• Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers
• Vasodilators

Diuretics (“Water Pills”)

Diuretics, commonly called “water pills,” cause the body to excrete water and salt. Diuretics are often the first-choice drug in the treatment ofessential hypertension, and have been shown to reduce the occurrence of stroke by 40 percent and hypertension-related heart attacks by 16 percent.

Diuretics are often prescribed for blacks and elderly individuals, who are considered salt-sensitive. They are the preferred treatment for people with heart failure or isolated systolic hypertension. Diuretics can be used alone or in combination with other medications.

How diuretics work

• Thiazide diuretics are most commonly used to treat mild hypertension. Over a short period of time, thiazide diuretics reduce blood volume by causing the kidney to excrete more sodium. Water follows the sodium. This, in turn, means that the heart pumps less blood each minute (cardiac output), which lowers blood pressure.

  Over a longer period of time, thiazide diuretics cause the smooth muscle in arterial walls to relax. The blood vessels dilate, making it easier for blood to pass through them, which lowers blood pressure.

• Potassium-sparing diuretics are used in people with mild-to-moderate high blood pressure. These agents work by blocking the actions of the chemical messenger aldosterone on the kidney, which leads to the excretion of sodium but the retention of potassium.
• Loop diuretics are sometime used in people with impaired kidney function. Loop diuretics cause more urine to be excreted than thiazide diuretics, but are less effective at lowering blood pressure and can cause severe electrolyte imbalances.

What are the adverse effects of diuretics?

Although diuretics effectively reduce cardiovascular disease and death, they do have some drawbacks, including:

• Decreased (e.g., thiazides) or elevated (e.g., potassium-sparing) levels of potassium
• Elevated levels of blood sugar
• Elevated cholesterol levels of cholesterol
• Elevated levels of lipids
• Elevated levels of uric acid
• Occasional sexual dysfunction

Fortunately, when prescribed at low doses with careful electrolyte monitoring, these undesirable effects can usually be minimized.

Beta-Adrenergic Blocking Agents (Beta-Blockers)

Beta-adrenergic blocking agents, or beta-blockers, are frequently used to start treatment of hypertension. Beta-blockers lessen the heart’s workload by decreasing the strength and frequency of heartbeats, slowing certain metabolic processes, and reducing blood pressure.

How do beta-blockers work?

These drugs work by blocking beta-receptors. Receptors are specialized sites at the nerve endings that are sensitive to certain chemical messengers in the body. These chemical messengers attach to the receptor sites and cause certain reactions.

Normally, the chemical messengers norepinephrine and epinephrine, commonly known as adrenaline, bind to these beta-receptors. These act to increase heart rate and make the heart pump harder, and also affect the lungs, kidneys, and blood vessels.

Beta-blockers are medications that reduce blood pressure by binding to the same site where these chemical messengers normally bind, much like someone taking your designated parking space. If the chemical messengers are unable to bind to the receptor site, they cannot exert their blood pressure-increasing effects, and so the blood pressure drops.

Beta-blockers:

• Slow the heart rate
• Reduce the strength of the heart’s contractions, directly causing blood pressure to drop
• Can also indirectly lower blood pressure by slowing the kidney’s production of a protein called renin. Renin normally causes the release of a powerful blood vessel constrictor calledangiotensin II, which makes it harder for blood to flow through the arteries (thus raising blood pressure) and also causes secretion of hormones that cause water retention (which increases the amount of fluid in the blood).

What are the adverse effects of beta-blockers?

Beta-blockers are effective and useful drugs in the treatment of high blood pressure. However, they might not be right for everybody. Two of the hormones that beta-blockers interfere with – norepinephrine and adrenaline – also bind to beta-receptors in other regions of the body. In the lungs, these hormones cause smooth muscle in the walls of lung airways to relax, opening the airway and making it easier to breathe.

Beta-blockers interfere with this airway relaxation, instead causing the airways to narrow. This phenomenon, known as bronchoconstriction, can be particularly problematic for people with asthma or chronic obstructive pulmonary disease.

If you suffer from asthma or COPD, your doctor may prescribe a cardioselective beta-blocker. Cardioselective beta-blockers decrease blood pressure by confining their actions to the heart and kidneys, and do not block beta-receptors in lung airways.

There are also several combined alpha- and beta-blocker agents available to treat high blood pressure. These agents block alpha-receptors, which influence blood vessel constriction, as well as both types of beta-receptors.

Although beta-blockers are useful for controlling blood pressure in many people, they tend to be less effective than thiazide diuretics in older people and blacks. In addition, some people experience:

• Fatigue
• Depression
• Impotence
• High blood sugar level, or hyperglycemia
• Undesirable changes in blood fats
• Increased airway resistance (non-cardioselective beta-blockers)

If you are taking beta-blockers, your doctor should monitor you closely for signs of:

• Low blood pressure
• An abnormally low heart rate
• Worsening heart failure
• Increases in heart rate or blood pressure with sudden discontinuation of treatment

Calcium Channel Blockers

Calcium channel blockers help lower blood pressure by relaxing blood vessels and reducing blood flow. They are effective in people with essential hypertension and have few side effects, but should not be used in people with heart failure or disturbances in the electrical conduction system of the heart.

How calcium channel blockers work

Calcium channel blockers cause blood vessels to relax, which makes it easier for blood to flow and lessens blood pressure. Some calcium channel blockers also slow the heart rate and reduce the strength of the heart’s pumping action, causing blood pressure to fall.

Calcium ions are needed for muscles to contract. Calcium channel blockers inhibit the entry of calcium ions into the heart muscle and smooth muscle of blood vessels walls, reducing the force of heart muscle contraction and causing blood vessels to dilate.

There are four main types of calcium channel blockers:

• Dihydropyridines (such as felodipine-type)
• Phenylalkylamines (such as verapamil-type)
• Benzothiazepines (such as diltiazem-type)
• Tetralol (T-channel blocker)

Calcium channel blockers have different chemical structures, which means that the different types of calcium channel blockers affect the cardiovascular system differently. For example, all calcium channel blockers dilate arteries, but some dilate arteries in certain parts of the body to a greater degree than others.

Some types of calcium channel blockers slow heart rate more than others do. These differences reflect the different types of calcium channels, located in membranes of cells, that these agents block. Long-acting dihydropyridine calcium channel blockers are particularly useful in the treatment of isolated systolic hypertension.

Adverse effects of calcium channel blockers

Calcium channel blockers can have some serious adverse effects on the cardiovascular system, including:

• Hypotension (low blood pressure)
• Disturbances in the heart rhythm
• Heart failure

Calcium channel blockers are not appropriate drug therapy for people with these heart conditions. Your physician should also obtain a record of the electrical activity of your heart (electrocardiogram or EKG) before prescribing a calcium channel blocker. The EKG is used to screen for certain heart disturbances.

These risks can be minimized with careful monitoring, patient selection, and use of long-acting medications.

Other side effects of calcium channel blockers include:

• Flushing of the face
• Headache
• Dizziness
• Mild edema (swelling due to watery fluid outside of blood vessels)
• Constipation

The relatively low incidence of other side effects is an appealing feature. Your doctor can help you to decide whether calcium channel blockers represent a good treatment choice for you.

Angiotensin Converting-Enzyme (ACE) Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors have been used successfully in people with all types of high blood pressure. ACE inhibitors have gained popularity in recent years. In addition to being used in the treatment of mild-to-moderate high blood pressure, they are also used in the treatment of heart failure, heart attack, and kidney disease due to diabetes.

ACE inhibitors can provide safe and effective blood pressure control for many people. Your doctor may prescribe ACE inhibitors if you have:

• Heart failure
• A history of heart attack
• Type 1 diabetes with protein in the urine

How ACE inhibitors work

ACE inhibitors interfere with the renin-angiotensin aldosterone system (RAAS). The RAAS regulates blood volume, blood vessel contraction, sodium and water balance, and the development of cells in the heart.

Angiotensin-converting enzyme (ACE) is a protein that converts the inactive hormone angiotensin into the active hormone angiotensin II. Angiotensin II increases blood pressure because it:

• Causes blood vessels to narrow
• Stimulates the release of a hormone called aldosterone, which causes the kidneys to retain sodium
• Stimulates the release of a hormone calledantidiuretic hormone, which causes the kidneys to retain water
• Increases blood volume and cardiac output increase the kidneys retain more sodium and water

ACE inhibitors block the conversion of the inactive angiotensin I to active angiotensin II. With less angiotensin II circulating in the body, blood pressure drops because:

• Blood vessels relax
• Blood volume and cardiac output lessen because the kidneys retain less sodium and water

ACE also slows the breakdown of a substance produced by the inner lining of blood vessels, called bradykinin. Bradykinin causes blood vessels to dilate, and causes the release of two other substances that also make blood vessels dilate: nitric oxide and prostacyclin.

Because ACE inhibitors slow the breakdown of bradykinin, they could raise the relative levels of all three of these blood-vessel-relaxing substances.

Large studies have shown that ACE inhibitors:

• Effectively lower blood pressure in individuals with high blood pressure
• Improve the function of the inner lining of blood vessels, orendothelium
• Reduce the frequency of future heart attacks in people with heart disease
• Reduce death in individuals with a history of left ventricular dysfunction, heart failure, or heart attack
• Slow the progressive loss of kidney function in individuals withdiabetic nephropathy
• Reduce the risk of stroke and heart disease in people with high blood pressure and diabetes.

Adverse effects of ACE inhibitors

Like any drug, ACE inhibitors can also have side effects. The most common side effect of these drugs is a dry cough, but it is not permanent. This cough, as well as occasional spasms of lung airways and an allergic skin reaction called angioedema, has been attributed partly to the activation of bradykinin that happens when ACE is blocked.

Other reported side effects of ACE inhibitors include:

• Headache
• Dizziness
• Fatigue
• High potassium levels
• Rarely, a reduction in the number of white blood cells
• 10 percent of people treated with one type of ACE inhibitor, captopril, experienced a skin rash that was not permanent

Although ACE inhibitors can help individuals with some types of kidney disease, they should not be used in those with bilateral renal artery stenosis (narrowing of the arteries that supply blood to both kidneys).

Vasodilators

Vasodilators widen arteries and veins, making it easier for the blood to pass through them. Your doctor may prescribe a vasodilator in combination with a diuretic or a beta-blocker. These drugs generally should not be used in people who have angina or who have had a heart attack.

How vasodilators work

Two of the most commonly prescribed vasodilators are prazosin hydrochloride and terazosin. Both of these medications work by dilating both arteries and veins. Prazosin is often used along with a diuretic or beta-blocker, but can also be used alone. Terazosin needs to be taken less frequently than prazosin, since its effects last for a longer time.

Prazosin works by binding to receptors than control blood vessel constriction, called alpha 1 receptors. The chemicals that would normally cause blood vessels to constrict can no longer bind to these sites, and both arteries and veins dilate.

Adverse effects of vasodilators

Vasodilators can have some side effects including:

• Headache
• Drowsiness
• Palpitations (the sensation of the heart beating rapidly, slowly, irregularly, or forcefully).

  For further information about palpitations, see Palpitations.

• Dizziness and/or occasional fainting upon standing, due to change in blood pressure

Examples Of Antihypertensive Agents*

*Representative examples from each class but not all-inclusive listing. (G) = available in generic form.