antihypertensive

What is antihypertensive

Antihypertensives are medications commonly used to treat high blood pressure or hypertension. If your blood pressure is high, it doesn’t necessarily mean you’ll need to take antihypertensive meds. However, your risk of developing cardiovascular disease — such as stroke and heart attack — increases with high blood pressure. In deciding whether you need antihypertensive medicines, your doctor will check your overall risk of developing heart disease in the next 5 years or so.

Hypertension affects at least 50% of persons over the age of 60 and is an important cause of morbidity and mortality from cardiovascular and cerebrovascular disease.

More than 200 medications are used in the therapy of hypertension. The drugs can be categorized into seven major classes:

  1. Diuretics,
  2. Sympatholytic drugs (alpha blockers and beta blockers),
  3. Calcium channel blockers,
  4. Angiotensin converting enzyme (ACE) inhibitors,
  5. Angiotensin 2 receptor antagonists/blockers (ARBs),
  6. Direct renin antagonists (Aliskiren), and
  7. Various vasodilators.

Table 1. Common blood pressure medications

Drug typeExamplesHow they workBest used in people with
ACE inhibitorscaptopril (Capoten)

lisinopril (Prinivil)

ramipril (Altace)

Help the body produce less angiotensin, a hormone that narrows blood vesselsDiabetes or heart failure
Angiotensin 2 receptor blockers (ARBs)irbesartan (Avapro)

losartan (Cozaar)

valsartan (Diovan)

Block the effect of angiotensin, a hormone that narrows blood vesselsDiabetes or heart failure
Beta blockersatenolol (Tenormin)

metoprolol (Lopressor)

nebivolol (Bystolic)

Help reduce heart rateHeart palpitations, angina (chest pain), irregular heartbeat
Calcium-channel blockersamlodipine (Norvasc)

diltiazem (Cardizem)

felodipine (Plendil)

nifedipine (Procardia)

verapamil (Calan)

Help prevent calcium from entering the heart and blood vessel walls and causing harder heart contractionsAngina (chest pain), irregular heartbeat
Diureticschlorthalidone (Hygroton)

furosemide (Lasix)

hydrochlorothiazide (Esidrix, HydroDiuril, Microzide)

spironolactone (Aldactone)

Help reduce or prevent
salt retention and reduce fluid volume in the body
Heart failure, peripheral edema (fluid accumulation that causes swelling, usually in the lower limbs)

Diuretics

Diuretics constitute a large family of medications that increase urine flow and induce urinary sodium loss and are widely used for therapy of hypertension, congestive heart failure, and edematous states.

Diuretics are typically classified as thiazide diuretics (bendroflumethiazide, chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, metolazone and polythiazide), loop diuretics (bumetanide, ethacrynic acid, furosemide, and torsemide), and potassium-sparing agents (amiloride, eplerenone, spironolactone, and triamterene). The carbonic anhydrase blockers acetazolamide and methazolamide are also diuretics, but are more commonly used for the therapy of glaucoma.

Diuretics are some of the most frequently used medications in medicine and are usually well tolerated.

Diuretics common side effects are those that are caused by the diuresis and mineral loss such as weakness, dizziness, electrolyte imbalance, low sodium and potassium. Most information on hepatotoxicity is available on the commonly used diuretics which include (and the number of prescriptions filled in 2007 for each): hydrochlorothiazide (45 million), furosemide (37 million), triamterene (21 million), spironolactone (8 million), and metolazone, bumetanide, indapamide and torsemide (1 to 2 million each). Diuretics implicated in rare cases of drug induced liver injury include hydrochlorothiazide, acetazolamide, amiloride, spironolactone and triamterene.

Diuretics in current use in the United States include:

  1. Carbonic Anhydrase Inhibitors
    • Acetazolamide
    • Methazolamide
  2. Loop Diuretics
    • Bumetanide
    • Ethacrynic Acid
    • Furosemide
    • Torsemide
  3. Potassium-Sparing Diuretics
    • Amiloride
    • Eplerenone
    • Spironolactone
    • Triamterene
  4. Thiazide Diuretics
    • Bendroflumethiazide
    • Chlorothiazide
    • Chlorthalidone
    • Hydrochlorothiazide
    • Indapamide
    • Metolazone
    • Polythiazide
  5. Vasopressin Antagonists
    • Tolvaptan

Alpha blockers

Alpha-blockers also called alpha-1 adrenergic receptor antagonists treat conditions such as high blood pressure and benign prostatic hyperplasia (BPH).

Alpha blockers relax certain muscles and help small blood vessels remain open. They work by keeping the hormone norepinephrine (noradrenaline) from tightening the muscles in the walls of smaller arteries and veins, which causes the vessels to remain open and relaxed. This improves blood flow and lowers blood pressure.

Because alpha blockers also relax other muscles throughout the body, these medications can help improve urine flow in older men with prostate problems.

Several alpha blockers are available, in either short-acting or long-acting forms. Short-acting medications work quickly, but their effects last only a few hours. Long-acting medications take longer to work, but their effects last longer. Which alpha blocker is best for you depends on your health and the condition being treated.

Alpha blockers are also called alpha-adrenergic blocking agents, alpha-adrenergic antagonists, adrenergic blocking agents and alpha-blocking agents.

Examples of alpha blockers used to treat high blood pressure include:

  • Doxazosin (Cardura)
  • Prazosin (Minipress)
  • Terazosin

Uses for alpha blockers

Doctors prescribe alpha blockers to prevent, treat or improve symptoms mainly in these conditions:

  • High blood pressure
  • Enlarged prostate (benign prostatic hyperplasia [BPH])

Though alpha blockers are commonly used to treat high blood pressure, they’re typically not the first treatment option. Instead, they’re used in combination with other drugs, such as diuretics, when your high blood pressure is difficult to control.

Alpha blockers side effects and cautions

Some alpha blockers might have what’s called a “first-dose effect.” When you start taking an alpha blocker, you might develop pronounced low blood pressure and dizziness, which can make you faint when you rise from a sitting or lying position. As a result, the first dose is often taken at bedtime.

Other side effects might include:

  • Headache
  • Pounding heartbeat
  • Weakness
  • Dizziness
  • Weight gain

On the positive side, alpha blockers might decrease low-density lipoprotein (LDL) cholesterol (the “bad” cholesterol).

Alpha blockers can increase or decrease the effects of other medications you take. Before taking an alpha blocker, be sure your doctor knows about other medications you take, such as beta blockers, calcium channel blockers or medications for erectile dysfunction.

Some research has found that long-term use of some alpha blockers can increase the risk of heart failure. More research is needed to confirm this finding.

Beta blockers

Beta blockers, also called beta-adrenergic blocking agents, treat a variety of conditions, such as high blood pressure and migraines.

Beta blockers work by blocking the effects of the hormone epinephrine, also known as adrenaline.

When you take beta blockers, your heart beats more slowly and with less force, thereby reducing blood pressure. Beta blockers also help blood vessels open up to improve blood flow.

Some beta blockers mainly affect your heart, while others affect both your heart and your blood vessels. Which one is best for you depends on your health and the condition being treated.

Examples of oral beta blockers include:

  • Acebutolol (Sectral)
  • Atenolol (Tenormin)
  • Bisoprolol (Zebeta)
  • Metoprolol (Lopressor, Toprol-XL)
  • Nadolol (Corgard)
  • Nebivolol (Bystolic)
  • Propranolol (Inderal LA, InnoPran XL)

Uses for beta blockers

Doctors prescribe beta blockers to prevent, treat or improve symptoms in a variety of conditions, such as:

  • High blood pressure
  • Irregular heart rhythm (arrhythmia)
  • Heart failure
  • Chest pain (angina)
  • Heart attacks
  • Migraine
  • Certain types of tremors

Beta blockers aren’t usually prescribed for blood pressure until other medications, such as diuretics, haven’t worked effectively. Your doctor may prescribe beta blockers as one of several medications to lower your blood pressure, including angiotensin-converting enzyme (ACE) inhibitors, diuretics or calcium channel blockers.

Beta blockers may not work as effectively for people of African heritage and older people, especially when taken without other blood pressure medications.

Beta blockers side effects and cautions

Side effects may occur in people taking beta blockers. However, many people who take beta blockers won’t have any side effects.

Common side effects of beta blockers include:

  • Fatigue
  • Cold hands or feet
  • Weight gain

Less common side effects include:

  • Shortness of breath
  • Trouble sleeping
  • Depression

Beta blockers generally aren’t used in people with asthma because of concerns that the medication may trigger severe asthma attacks. In people who have diabetes, beta blockers may block signs of low blood sugar, such as rapid heartbeat. It’s important to monitor your blood sugar regularly.

Beta blockers can also affect your cholesterol and triglyceride levels, causing a slight increase in triglycerides and a modest decrease in high-density lipoprotein, the “good” cholesterol. These changes often are temporary. You shouldn’t abruptly stop taking a beta blocker because doing so could increase your risk of a heart attack or other heart problems.

Calcium channel blockers

Calcium channel blockers or calcium antagonists, treat a variety of conditions, such as high blood pressure, chest pain and Raynaud’s disease.

Calcium channel blockers prevent calcium from entering cells of the heart and blood vessel walls, resulting in lower blood pressure. Calcium channel blockers, also called calcium antagonists, relax and widen blood vessels by affecting the muscle cells in the arterial walls.

Some calcium channel blockers have the added benefit of slowing your heart rate, which can further reduce blood pressure, relieve chest pain (angina) and control an irregular heartbeat.

Some calcium channel blockers are available in short-acting and long-acting forms. Short-acting medications work quickly, but their effects last only a few hours. Long-acting medications are slowly released to provide a longer lasting effect.

Several calcium channel blockers are available. Which one is best for you depends on your health and the condition being treated.

Examples of calcium channel blockers include:

  • Amlodipine (Norvasc)
  • Diltiazem (Cardizem, Tiazac, others)
  • Felodipine
  • Isradipine
  • Nicardipine
  • Nifedipine (Adalat CC, Afeditab CR, Procardia)
  • Nisoldipine (Sular)
  • Verapamil (Calan, Verelan)

In some cases, your doctor might prescribe a calcium channel blocker with other high blood pressure medications or with cholesterol-lowering drugs such as statins.

Uses for calcium channel blockers

Doctors prescribe calcium channel blockers to prevent, treat or improve symptoms in a variety of conditions, such as:

  • High blood pressure
  • Coronary artery disease
  • Chest pain (angina)
  • Irregular heartbeats (arrhythmia)
  • Some circulatory conditions, such as Raynaud’s disease

For people of African heritage and older people, calcium channel blockers might be more effective than other blood pressure medications, such as beta blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers.

Calcium channel blockers side effects and cautions

Side effects of calcium channel blockers may include:

  • Constipation
  • Headache
  • Palpitations
  • Dizziness
  • Rash
  • Drowsiness
  • Flushing
  • Nausea
  • Swelling in the feet and lower legs

Certain calcium channel blockers interact with grapefruit products.

Angiotensin-converting enzyme (ACE) inhibitors

ACE inhibitors treat a variety of conditions, such as high blood pressure, scleroderma and migraines.

Angiotensin-converting enzyme (ACE) inhibitors help relax blood vessels. ACE inhibitors prevent an enzyme in your body from producing angiotensin II, a substance in your body that narrows your blood vessels and releases hormones that can raise your blood pressure. This narrowing can cause high blood pressure and force your heart to work harder.

Many ACE inhibitors are available. Which one is best for you depends on your health and the condition being treated. People with chronic kidney disease may benefit from having an ACE inhibitor as one of their medications. People of African heritage and older people respond less well to ACE inhibitors than do white and younger people.

Examples of ACE inhibitors include:

  • Benazepril (Lotensin)
  • Captopril
  • Enalapril (Vasotec)
  • Fosinopril
  • Lisinopril (Prinivil, Zestril)
  • Moexipril
  • Perindopril (Aceon)
  • Quinapril (Accupril)
  • Ramipril (Altace)
  • Trandolapril (Mavik)

Uses for ACE inhibitors

Doctors prescribe ACE inhibitors to prevent, treat or improve symptoms in conditions such as:

  • High blood pressure
  • Coronary artery disease
  • Heart failure
  • Diabetes
  • Certain chronic kidney diseases
  • Heart attacks
  • Scleroderma
  • Migraines

Your doctor may prescribe other medications in addition to an ACE inhibitor, such as a diuretic or calcium channel blocker, as part of your high blood pressure treatment. ACE inhibitors are usually taken once daily.

ACE inhibitors side effects and cautions

Doctors commonly prescribe ACE inhibitors because they don’t often cause side effects.

Possible ACE inhibitor side effects include:

  • Dry cough
  • Increased blood-potassium level (hyperkalemia)
  • Fatigue
  • Dizziness
  • Headaches
  • Loss of taste

In rare cases — but more commonly in people of African heritage and in smokers — ACE inhibitors can cause some areas of your tissues to swell (angioedema). If it occurs in the throat, the swelling can be life-threatening.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve), decrease the effectiveness of ACE inhibitors. Taking an occasional dose of these medications shouldn’t change the effectiveness of your ACE inhibitor, but talk to your doctor if you regularly take NSAIDs.

Because ACE inhibitors can cause birth defects, talk to your doctor about other options to treat your blood pressure if you’re pregnant or you plan to become pregnant.

Angiotensin II receptor blockers (ARBs)

Angiotensin II receptor blockers (ARBs) also called angiotensin II receptor antagonists, are used to treat conditions such as high blood pressure and heart failure. Angiotensin 2 receptor blockers (ARBs) help relax your blood vessels, which lowers your blood pressure and makes it easier for your heart to pump blood.

Angiotensin is a chemical in your body that affects your cardiovascular system in various ways, including narrowing your blood vessels. This narrowing can increase your blood pressure and force your heart to work harder.

Angiotensin II receptor blockers block the action of angiotensin II, allowing blood vessels to widen (dilate).

Several angiotensin II receptor blockers are available. Which one is best for you depends on your health and the condition being treated.

Examples of angiotensin 2 receptor blockers include:

  • Azilsartan (Edarbi)
  • Candesartan (Atacand)
  • Eprosartan
  • Irbesartan (Avapro)
  • Losartan (Cozaar)
  • Olmesartan (Benicar)
  • Telmisartan (Micardis)
  • Valsartan (Diovan)

Uses for angiotensin 2 receptor blockers

Doctors prescribe these drugs to prevent, treat or improve symptoms in various conditions, such as:

  • High blood pressure
  • Heart failure
  • Kidney failure in diabetes
  • Chronic kidney diseases

Angiotensin II receptor blockers side effects and cautions

Few people have side effects when taking angiotensin II receptor blockers. Possible side effects include:

  • Dizziness
  • Elevated blood potassium level (hyperkalemia)
  • Localized swelling of tissues (angioedema)

There have been some reports of intestinal problems in those taking olmesartan. Talk to your doctor if you develop severe diarrhea or lose a lot of weight while taking olmesartan.

Because angiotensin II receptor blockers can injure a developing fetus, don’t take them if you are pregnant or plan to become pregnant.

First line antihypertensive

The ACE inhibitors are considered first line drugs for the therapy of hypertension and are considered particularly helpful in preventing the renal complications of diabetes and high blood pressure. ACE inhibitors are sometimes used even in patients with relatively normal blood pressure for treatment of heart failure and prevention of diabetic neuropathy. Other most common blood pressure medicines are calcium channel blockers, angiotensin II receptor blockers (ARBs), beta blockers, and diuretics. Many people need more than one medicine to bring their high blood pressure under control.

The safety and effectiveness of a particular drug can be affected by other health problems. In many cases, it’s a balancing act. For example:

  • Taking a diuretic can help if you have heart failure. This is because diuretics reduce fluid levels in the body, and people with heart failure often experience fluid buildup because their hearts aren’t pumping blood effectively. However, if you have high cholesterol or high triglycerides, diuretics may increase those levels.
  • If you have gout, diuretics may trigger an attack. In those cases an ACE inhibitor or an angiotensin II receptor blocker (ARB) may be a better choice.
  • For active people, ACE inhibitors or angiotensin II receptor blockers (ARBs) may also be better options, as opposed to diuretics or beta blockers, because the latter can impair physical activity. However, beta blockers are a good choice if you have palpitations or abnormal heart rhythms (arrhythmias).

If you’re having trouble reaching your blood pressure goal with combinations of the above medications, your doctor may prescribe:

  • Alpha blockers. These medications reduce nerve impulses to blood vessels, reducing the effects of natural chemicals that narrow blood vessels. Alpha blockers include doxazosin (Cardura), prazosin (Minipress) and others.
  • Alpha-beta blockers. In addition to reducing nerve impulses to blood vessels, alpha-beta blockers slow the heartbeat to reduce the amount of blood that must be pumped through the vessels. Alpha-beta blockers include carvedilol (Coreg) and labetalol (Trandate).
  • Beta blockers. These medications reduce the workload on your heart and open your blood vessels, causing your heart to beat slower and with less force. Beta blockers include acebutolol (Sectral), atenolol (Tenormin) and others. Beta blockers aren’t usually recommended as the only medication you’re prescribed, but they may be effective when combined with other blood pressure medications.
  • Aldosterone antagonists. Examples are spironolactone (Aldactone) and eplerenone (Inspra). These drugs block the effect of a natural chemical that can lead to salt and fluid retention, which can contribute to high blood pressure.
  • Renin inhibitors. Aliskiren (Tekturna) slows down the production of renin, an enzyme produced by your kidneys that starts a chain of chemical steps that increases blood pressure. Aliskiren works by reducing the ability of renin to begin this process. Due to a risk of serious complications, including stroke, you shouldn’t take aliskiren with ACE inhibitors or ARBs.
  • Vasodilators. These medications, including hydralazine and minoxidil, work directly on the muscles in the walls of your arteries, preventing the muscles from tightening and your arteries from narrowing.
  • Central-acting agents. These medications prevent your brain from signaling your nervous system to increase your heart rate and narrow your blood vessels. Examples include clonidine (Catapres, Kapvay), guanfacine (Intuniv, Tenex) and methyldopa.

To reduce the number of daily medication doses you need, your doctor may prescribe a combination of low-dose medications rather than larger doses of one single drug. In fact, two or more blood pressure drugs often are more effective than one. Sometimes finding the most effective medication or combination of drugs is a matter of trial and error.

Resistant hypertension: When your blood pressure is difficult to control

If your blood pressure remains stubbornly high despite taking at least three different types of high blood pressure drugs, one of which usually should be a diuretic, you may have resistant hypertension.

People who have controlled high blood pressure but are taking four different types of medications at the same time to achieve that control also are considered to have resistant hypertension. The possibility of a secondary cause of the high blood pressure generally should be reconsidered.

Having resistant hypertension doesn’t mean your blood pressure will never get lower. In fact, if you and your doctor can identify what’s behind your persistently high blood pressure, there’s a good chance you can meet your goal with the help of treatment that’s more effective.

Your doctor or hypertension specialist may:

  • Evaluate potential causes of your condition and determine if those can be treated
  • Review medications you’re taking for other conditions and recommend you not take any that worsen your blood pressure
  • Recommend that you monitor your blood pressure at home to see if you may have higher blood pressure in the doctor’s office (white coat hypertension)
  • Suggest healthy lifestyle changes, such as eating a healthy diet with less salt, maintaining a healthy weight and limiting how much alcohol you drink
  • Make changes to your high blood pressure medications to come up with the most effective combination and doses
  • Consider adding an aldosterone antagonist such as spironolactone (Aldactone), which may lead to control of resistant hypertension

Some experimental therapies such as catheter-based radiofrequency ablation of renal sympathetic nerves (renal denervation) and electrical stimulation of carotid sinus baroreceptors are being studied.

If you don’t take your high blood pressure medications exactly as directed, your blood pressure can pay the price. If you skip doses because you can’t afford the medications, because you have side effects or because you simply forget to take your medications, talk to your doctor about solutions. Don’t change your treatment without your doctor’s guidance.

Lifestyle changes to treat high blood pressure

You may be able to reduce your blood pressure and reduce your risk of heart disease in other ways. Some people are able to reduce their blood pressure without taking blood pressure medicines. It helps to:

  • Eat healthy foods. Eat a heart-healthy diet. Try the Dietary Approaches to Stop Hypertension (DASH) diet, which emphasizes fruits, vegetables, whole grains, poultry, fish and low-fat dairy foods. Get plenty of potassium, which can help prevent and control high blood pressure. Eat less saturated fat and trans fat.
  • Decrease the salt in your diet. Aim to limit sodium to less than 2,300 milligrams (mg) a day or less. However, a lower sodium intake — 1,500 mg a day or less — is ideal for most adults. While you can reduce the amount of salt you eat by putting down the saltshaker, you generally should also pay attention to the amount of salt that’s in the processed foods you eat, such as canned soups or frozen dinners.
  • Maintain a healthy weight. Keeping a healthy weight, or losing weight if you’re overweight or obese, can help you control your high blood pressure and lower your risk of related health problems. In general, you may reduce your blood pressure by about 1 mm Hg with each kilogram (about 2.2 pounds) of weight you lose.
  • Increase physical activity. Regular physical activity can help lower your blood pressure, manage stress, reduce your risk of several health problems and keep your weight under control. Aim for at least 150 minutes a week of moderate aerobic activity or 75 minutes a week of vigorous aerobic activity, or a combination of moderate and vigorous activity. For example, try brisk walking for about 30 minutes most days of the week. Or try interval training, in which you alternate short bursts of intense activity with short recovery periods of lighter activity. Aim to do muscle-strengthening exercises at least two days a week.
  • Limit alcohol. Even if you’re healthy, alcohol can raise your blood pressure. If you choose to drink alcohol, do so in moderation. For healthy adults, that means up to one drink a day for women, and up to two drinks a day for men. One drink equals 12 ounces of beer, 5 ounces of wine or 1.5 ounces of 80-proof liquor.
  • Don’t smoke. Tobacco can injure blood vessel walls and speed up the process of buildup of plaque in the arteries. If you smoke, ask your doctor to help you quit.
  • Manage stress. Reduce stress as much as possible. Practice healthy coping techniques, such as muscle relaxation, deep breathing or meditation. Getting regular physical activity and plenty of sleep can help, too.
  • Monitor your blood pressure at home. Home blood pressure monitoring can help you keep closer tabs on your blood pressure, show if medication is working, and even alert you and your doctor to potential complications. Home blood pressure monitoring isn’t a substitute for visits to your doctor, and home blood pressure monitors may have some limitations. Even if you get normal readings, don’t stop or change your medications or alter your diet without talking to your doctor first. If your blood pressure is under control, check with your doctor about how often you need to check it.
  • Practice relaxation or slow, deep breathing. Practice taking deep, slow breaths to help relax. There are some devices available that promote slow, deep breathing. According to the American Heart Association, device-guided breathing may be a reasonable nondrug option for lowering blood pressure, especially when anxiety accompanies high blood pressure or standard treatments aren’t well-tolerated.
  • Control blood pressure during pregnancy. If you’re a woman with high blood pressure, discuss with your doctor how to control your blood pressure during pregnancy.

Your doctor can give you more specific guidance to suit your needs.

Many people with high blood pressure don’t have any symptoms. It is important for all adults to get their blood pressure checked at least every 2 years.

Antihypertensive medication list

Diuretics

Diuretics are also known as fluid tablets. They work by making you urinate more to get rid of any excess water in your body. When the excess fluid is reduced, the pressure in your blood vessels and heart also lowers.

The diuretics can be categorized into four groups: thiazides, loop diuretics, potassium-sparing diuretics, and carbonic anhydrase inhibitors.

  1. Carbonic Anhydrase Inhibitors
    • Acetazolamide
    • Methazolamide
  2. Loop Diuretics
    • Bumetanide
    • Ethacrynic Acid
    • Furosemide
    • Torsemide
  3. Potassium-Sparing Diuretics
    • Amiloride
    • Eplerenone
    • Spironolactone
    • Triamterene
  4. Thiazide Diuretics
    • Bendroflumethiazide
    • Chlorothiazide
    • Chlorthalidone
    • Hydrochlorothiazide
    • Indapamide
    • Metolazone
    • Polythiazide
  5. Vasopressin Antagonists
    • Tolvaptan

Carbonic Anhydrase Inhibitors

Acetazolamide and methazolamide are carbonic anhydrase inhibitors ( an enzyme that converts carbon dioxide and water to carbonic acid) used as diuretics and in the therapy of glaucoma.

Acetazolamide and methazolamide are inhibitors of carbonic anhydrase, an enzyme that converts carbon dioxide and water to carbonic acid. Inhibition of this enzyme in the kidney causes an alkalization of the urine and diuresis. In the eye, inhibition of carbonic anhydrase causes a decrease in intraocular pressure making these agents valuable in the treatment of glaucoma. The effects of acetazolamide on acid-base status (causing a mild metabolic acidosis) are also of potential value in managing other conditions including epilepsy, sleep apnea, and acute mountain sickness.

Acetazolamide was approved for use in the United States in 1986 for treatment of glaucoma and as a diuretic. Acetazolamide is available in 125 and 250 mg tablets in generic forms and under the brand name of Diamox. Acetazolamide is also available in extended release forms (capsules of 500 mg) and as powder for injection. The recommended dose and regimen of acetazolamide varies by indication, but for chronic use in adults the typical dose is 250 to 1,000 mg daily in divided doses.

Methazolamide was approved for use in the United States in 1959 for the treatment of glaucoma. Methazolamide is available as tablets of 25 and 50 mg in generic forms and under the trade name Neptazane. Typical doses of methazolamide in adults with glaucoma are 50 to 100 mg two to three times daily.

The common side effects of acetazolamide and methazolamide are change in taste, numbness and tingling in fingers and toes, blurred vision, tinnitus, dizziness, decrease in hearing, polyuria, nausea, diarrhea, fatigue, and headache. Methazolamide and acetazolamide have similar chemical structures and are related to the sulfonamides and can cause allergic reactions including anaphylaxis, rash, erythema multiforme, and Stevens Johnson Syndrome.

Loop Diuretics

The loop diuretics are potent and widely used agents in the therapy of edematous states and congestive heart failure and less commonly for hypertension.

The loop diuretics act by inhibition of the sodium-potassium-chloride symporter present in the thick ascending limb of the loop of Henle causing an inhibition of sodium reuptake. The increase in delivery of sodium to the distal convoluted loop overwhelms its capacity for sodium reabsorption and a brisk sodium diuresis ensues. The loop diuretics are grouped together because of shared mechanism of action, but they have distinct chemical structures. The loop diuretics are more potent than the typical thiazide diuretics and usually have a shorter duration of action. As a result, the loop diuretics are used more for the therapy of edema than long term therapy of hypertension. Common and shared side effects of the loop diuretics include dizziness, headache, gastrointestinal upset, hypernatremia, hypokalemia and dehydration.

  • Furosemide was the first loop diuretic to be approved in the United States (1966) and is still widely used with more than 37 million prescriptions filled yearly. Furosemide is available in tablets of 20, 40 and 80 mg in generic forms and under the brand name Lasix. Furosemide is also available as an oral solution and as a liquid solution for injection. The usual adult dose of furosemide is 20 to 320 mg daily, given in one to three divided doses.
  • Ethacrynic acid was the second loop diuretic to be approved for use in the United States (1967), but is now rarely used; it remains available in 25 mg tablets and a solution for intravenous use generically and under the brand name Edecrin. The usual oral adult dose is 25 to 100 mg in one to three divided doses daily.
  • Bumetanide is a potent loop diuretic that was approved for use in the United States in 1983 and continues to be used for the treatment of edema. Bumetanide is available as tablets of 0.5, 1 and 2 mg in generic forms and under the trade name of Bumex. The usual oral adult dose is 0.5 to 2 mg in two or three divided doses daily.
  • Torsemide was approved for use in edema in the United States in 1993 and is still in common use used for both edema and hypertension. Torsemide is available in tablets of 5, 10, 20 and 100 mg in generic forms and under the brand name of Demadex. Solutions are available for intravenous use as well. The usual oral adult dose is 5 to 100 mg daily in one or two divided doses.

Potassium-Sparing Diuretics

Amiloride

Amiloride is a potassium-sparing diuretic used in the therapy of edema often in combination with thiazide diuretics. Amiloride is similar in action to triamterene, but differs in chemical structure. Amiloride was approved for use in the United States in 1986, but is not widely used.

Amiloride is a pyrazinoylguanidine derivative that acts on the sodium channels of renal epithelial cells causing an increase in sodium excretion with little or no effect on potassium excretion, thus accounting for its potassium-sparing characteristics.

Amiloride is available in 5 mg tablets in generic forms and under the brand name of Midamor. The typical dose of amiloride is 5 to 20 mg in one or two doses daily. Amiloride causes only a modest diuresis and it is often used in combination with a thiazide diuretic (such as hydrochlorothiazide: Moduretic), which takes advantage of it potassium-sparing characteristics to offset the potassium-wasting characteristics of the thiazides.

The major side effects of amiloride include hyperkalemia, headache, dizziness, gastrointestinal upset and rash.

Eplerenone

Eplerenone is an aldosterone receptor antagonist and potassium-sparing diuretic used in the therapy of hypertension. Eplerenone was approved for use in the United States in 2002 for treatment of hypertension and later for improving survival of stable patients with heart failure after myocardial infarction.

Eplerenone is a competitive antagonist of aldosterone at the mineralocorticoid receptor. The aldosterone receptor in the late distal tubules and collecting ducts of the kidneys induces sodium reabsorption and potassium excretion in the distal tubule. Inhibition of this receptor promotes a sodium diuresis, but maintains body potassium levels. Eplerenone has a higher affinity for the aldosterone receptor than spironolactone and is claimed to have fewer anti-androgenic effects (gynecomastia, hair loss). However, the two molecules are structurally quite similar.

Eplerenone is available in 25 and 50 mg tablets generically and under the brand name of Inspra. The typical dose of eplerenone is 25 or 50 mg once daily initially, with modification of the dose based upon blood pressure response and tolerance, maintenance doses ranging from 25 to 100 mg daily in one or two divided doses.

Eplerenone is well tolerated and the most common side effects are hyperkalemia and increases in serum creatinine.

Spironolactone

Spironolactone is an aldosterone receptor antagonist and potassium-sparing diuretic widely used in the therapy of edema, particularly in patients with cirrhosis in which hyperaldosteronism appears to play a major role. Spironolactone is particularly helpful in edematous states caused or exacerbated by hyperaldosteronism, which is typical of the edema and ascites caused by cirrhosis. Because of its potassium-sparing actions, spironolactone is also used in combination with thiazide or loop diuretics in an attempt to prevent hypokalemia. Chronic low dose therapy with spironolactone has also been reported to improve survival in patients with heart failure after myocardial infarction.

Spironolactone was approved for use in the United States in 1960 and continues to be widely used.

Spironolactone is a competitive inhibitor of the mineralocorticoid receptor in the late distal tubule and collecting duct of the kidneys, which causes a decrease in sodium reabsorption and potassium excretion in the distal tubule. As a result, spironolactone promotes a sodium diuresis, but maintains body potassium levels.

Spironolactone is available in 25, 50, 75 and 100 mg tablets generically and under the brand name of Aldactone. Fixed combinations of spironolactone and hydrochlorothiazide are also available under the brand name Aldactizide. The typical dose of spironolactone is 25 mg one to three times daily initially, with modification of the dose based upon clinical efficacy and tolerance to maintenance doses of 75 to 450 mg daily.

The major side effects of spironolactone are due to its antiandrogen-like effects and include hair growth and gynecomastia.

Triamterene

Triamterene is a potassium-sparing diuretic widely used in the therapy of edema. Triamterene is used largely in therapy of edema and can be safely used in patients with cirrhosis. Because of its potassium-sparing actions, triamterene is also used in combination with thiazide or loop diuretics in an attempt to prevent hypokalemia.

Triamterene was approved for use in the United States in 1964 and continues to be widely used with more than 20 million prescriptions filled yearly.

Triamterene is an inhibitor of renal epithelial sodium channels in the late distal tubule and collecting ducts of the kidney. As a result, triamterene promotes a mild sodium diuresis, but maintains body potassium levels. Triamterene is available in tablets and capsules of 50 and 100 mg in generic forms and under the brand name of Dyrenium. The typical dose of triamterene is 50 to 200 mg daily in one or two divided doses. Triamterene is also available in fixed dose combinations with hydrochlorothiazide (Maxide, Dyazide and generically).

The major side effects of triamterene are dizziness, fatigue, headache, dry mouth, hyperkalemia and dehydration.

Thiazide Diuretics

The thiazides are the most commonly used oral diuretics and are widely used in the therapy of hypertension and congestive heart failure, as well as the treatment of edema due to local, renal and hepatic causes. The general indications for the thiazide diuretics are treatment of hypertension and edema.

The benzothiazide diuretics are structurally related drugs that act by inhibition of sodium (and chloride) transport in the distal convoluted tubule by binding to and inhibiting the Na+-Cl- symporter. As a result, there is increased excretion of sodium and water and an associated loss of potassium. Chronic therapy may also result in increase calcium and magnesium loss. The thiazide diuretics are grouped together based upon shared chemical, sulfonamide-like, structure. More recently non-benzothiazide drugs with a similar mechanism of action have been developed (metolazone, indapamide), which are referred to as thiazide-like diuretics. The thiazide and thiazide-like diuretics are all available generically and differ largely in their pharmacokinetic properties of oral availability, relative potency, serum and effective half-life and route of elimination.

Thiazide diuretics are available in multiple forms and all are available generically. Many of the thiazide diuretics are also available in fixed dose combination with other antihypertensive medications or with potassium-sparing diuretics.

  • Bendroflumethiazide is available in tablets of 2.5 mg in generic forms; recommended oral doses in adults are 2.5 to 10 mg in two divided doses. It is also available in a fixed dose with nadolol generically and under the brand name Corzide.
  • Chlorothiazide is available in tablets of 250 and 500 mg generically and under the trade name of Diuril; recommended oral doses in adults are 500 to 1000 mg once or twice daily.
  • Chlorthalidone is available in tablets of 25 and 50 mg generically and under the brand name of Thalitone; recommended oral doses in adults are 25 to 100 mg once daily or 100 mg every other day.
  • Hydrochlorothiazide is available in tablets of 25 and 50 mg and as capsules of 12.5 mg generically and under the trade names of Hydrodiuril, Microzide and Esidrix; recommended oral doses in adults are 12.5 to 50 mg daily given in one or two divided doses.
  • Methyclothiazide is available in tablets of 2.5 and 5 mg generically and under the trade name of Enduron; recommended oral doses in adults are 2.5 to 5 mg once daily.
  • Polythiazide is available in tablets of 1, 2 and 4 mg generically and under the trade name of Renese; typical oral doses in adults are 2 to 4 mg in one or two divided doses daily.
  • Metolazone is a thiazide-like diuretic that is available as tablets of 2.5 and 5 mg generically and under the trade name of Zaroxolyn; recommended oral doses in adults are 2.5 to 20 mg once daily.
  • Indapamide is a thiazide-like diuretic that is available as tablets of 1.25 and 2.5 mg generically and under the trade name of Lozol; recommended oral doses in adults are 1.25 to 5 mg once daily.

Thiazide diuretics common side effects of the thiazide and thiazide-like diuretics include nausea, dizziness, headache, polyuria, dehydration, hyponatremia, hypokalemia and hypomagnesia. Chronic therapy may be associated with hyperuricemia and gout, and possibly an increased risk of cholecystitis.

Vasopressin Antagonists

Tolvaptan is a vasopressin 2 receptor antagonist which is used for short term treatment of severe hyponatremia in patients with heart failure, cirrhosis or syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Tolvaptan has also been used experimentally to prevent progression of disease in patients with autosomal dominant polycystic kidney disease (ADPKD), but has not been approved for this use in the United States.

Inappropriate secretion of vasopressin (as occurs in some paraneoplastic syndromes) is associated with retention of water and dilutional hyponatremia that can be symptomatic and even fatal. In controlled clinical trials, tolvaptan given for 28 days resulted in an increase in serum sodium and diuresis in patients with hypervolemic hyponatremia, in patients with cirrhosis and heart failure, and euvolemic hyponatremia in patients with SIADH. Tolvaptan was approved for use in the United States in 2009 and current indications are for short term therapy of patients with hypervolemic or euvolemic hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH), congestive heart failure or cirrhosis.

Tolvaptan is a vasopressin 2 receptor antagonist (vaptan) that is used for treatment of hyponatremia caused by elevated levels of arginine vasopressin (also known as antidiuretic hormone: ADH), commonly found in patients with inappropriate ADH syndrome (SIADH) or with fluid overload from heart failure or cirrhosis. Vasopressin acts on type 2 receptors in the distal renal tubules causing reabsorption of free water, without electrolytes.

Tolvaptan is available in tablets of 15 and 30 mg under the brand name Samsca. The recommended dose is 15 mg initially, titrating up to a maximum of 60 mg once daily, but limiting therapy to 30 days.

Tolvaptan common side effects include excessive thirst, dry mouth and urinary frequency. Rare, but more serious side effects include hypernatremia and osmotic demyelination injury.

Sympatholytic drugs (alpha blockers and beta blockers)

Sympatholytic drugs include alpha- and beta-adrenergic receptor antagonists (alpha blockers and beta blockers) as well as centrally acting agents such as clonidine, guanabenz, methyldopa, minoxidil, and reserpine. Beta blockers work by reducing nerve signals to the heart and blood vessels. This reduces your blood pressure and the amount of work your heart needs to do.

  • Alpha Adrenergic Receptor Antagonists (alpha blockers)
  • Beta Adrenergic Receptor Antagonists (beta blockers)
  • Clonidine
  • Methyldopa
  • Reserpine

Alpha blockers

Alpha-blockers also called alpha-1 adrenergic receptor antagonists are a family of agents that bind to and inhibit type 1 alpha-adrenergic receptors and thus inhibit smooth muscle contraction. Their major uses are for hypertension and for symptomatic benign prostatic hypertrophy (BPH). Alpha-blockers use in therapy of hypertension is based on the inhibition of vascular resistance in arterioles from alpha-adrenergic blockade, which results in an increase in venous capacitance and lowering of blood pressure. At present, however, the alpha-1 adrenergic antagonists are recommended only as adjunctive therapy of hypertension and not as monotherapy. Postural hypotension is particularly common after the initial dose of the alpha-1 adrenergic antagonist. Also, long term therapy has not been associated with improvement in survival; indeed at least one study has shown an increase in heart failure, stroke and cardiovascular disease with long term therapy with alpha-blockers. Because the nonselective alpha-1 adrenergic antagonists cause a relaxation of smooth muscle both in arterioles (alpha-1b receptors) and in the bladder neck and prostate (alpha-1a receptors), they are also useful in the therapy of symptoms of urinary obstruction due to benign prostatic hypertrophy. Recently, selective alpha-1a adrenergic receptors blockers have been developed for use in benign prostatic hypertrophy that are claimed to have less effect on blood pressure. Thus, only the nonselective agents are used for treatment of hypertension, whereas both selective and nonselective agents have been used for the symptomatic relief of prostatic hypertrophy.

The nonselective alpha-1 adrenergic antagonists in clinical use for hypertension in the United States include three agents of similar chemical structure (piperazinyl quinazolines) and activity, but somewhat different potencies and pharmacokinetics: prazosin (Minipress), terazosin (Hytrin), and doxazosin (Cardura).

Alpha-blockers used to treat hypertension include:

  • Doxazosin (Cardura)
  • Prazosin (Minipress)
  • Terazosin

Doxazosin

Doxazosin is a nonselective alpha-1 adrenergic antagonist (alpha-blocker) used in the therapy of hypertension and benign prostatic hypertrophy (BPH). The inhibition of alpha-adrenergic tone in blood vessels causes relaxation of arteriolar resistance and lowering of the blood pressure. The effects of the agent on smooth muscle of the bladder and prostate causes improvement in urine flow in men with partial obstruction due to benign prostatic hypertrophy. Doxazosin was approved for use in the United States in 1990, and currently more than 5 million prescriptions are filled yearly. Doxazosin is still used for treatment of hypertension, although rarely as a first line agent and usually in combination with other antihypertensive drugs.

Doxazosin was the third alpha-1 adrenergic antagonist to be approved for use in the United States and is still widely used for therapy of hypertension and benign prostatic hypertrophy. Doxazosin inhibits alpha-adrenergic receptors present on smooth muscle in arterioles (so-called alpha-1b adrenergic receptors) as well as in those in the bladder neck and prostate (alpha-1a adrenergic receptors).

Doxazosin is available in tablets of 1, 2, 4 and 8 mg generically and under the trade name Cardura. Doxazosin is usually started at a dose of 1 mg once daily, with increase in the dose based upon tolerance and clinical response to an average of 4 to 8 mg in one daily dose. Higher doses can be used in treating hypertension. An extended release formulation of doxazosin is also available in doses of 4 and 8 mg (Cardura XL).

Doxazosin side effects include dizziness and syncope (particularly with the initial dose), fatigue, headache, palpitations, impotence, incontinence and gastrointestinal upset. Rare, but potentially severe adverse reactions include severe postural hypotension, floppy iris syndrome and priapism.

Prazosin

Prazosin is a nonselective alpha-adrenergic antagonist (alpha-blocker) used in the therapy of high blood pressure (hypertension). Prazosin was the first alpha-adrenergic antagonist to be approved for use in the United States and is still widely used for therapy of hypertension. Prazosin was approved for use in the United States in 1976 and is still used for treatment of hypertension, although rarely as a first line agent and usually in combination with other antihypertensives.

Prazosin inhibits alpha-adrenergic receptors present on smooth muscle in arterioles (so-called alpha-1b adrenergic receptors) as well as in those in the bladder neck and prostate (alpha-1a adrenergic receptors). The inhibition of alpha-adrenergic tone in blood vessels causes relaxation of arteriolar resistance and lowering of the blood pressure.

Prazosin is available in capsules of 1, 2 and 5 mg generically and under the trade name Minipress. Prazosin is usually started at a dose of 1 mg two or three times daily, with increase in the dose based upon tolerance and clinical response to an average of 5 to 20 mg daily in divided doses. Prazosin is also available in a fixed combination with polythiazide (Minizide).

Prazosin side effects include dizziness and syncope (particularly with the initial dose), fatigue, headache, palpitations, impotence, incontinence and gastrointestinal upset. Rare, but potentially severe side effects include severe postural hypotension and priapism.

Terazosin

Terazosin is a nonselective alpha-1 adrenergic antagonist used in the therapy of hypertension and benign prostatic hypertrophy. Terazosin was the second alpha-1 adrenergic antagonist to be approved for use in the United States and is still widely used for therapy of hypertension and benign prostatic hypertrophy. Terazosin was approved for use in the United States in 1987 and is still used for treatment of hypertension, although rarely as a first line agent and usually in combination with other antihypertensive drugs. Terazosin is also approved for alleviation of the symptoms of urinary obstruction due to benign prostatic hypertrophy. More than 4 million prescriptions for terazosin are filled yearly.

Terazosin inhibits alpha-adrenergic receptors present on smooth muscle in arterioles (so-called alpha-1b adrenergic receptors) as well as in those in the bladder neck and prostate (alpha-1a adrenergic receptors). The inhibition of alpha-adrenergic tone in blood vessels causes relaxation of arteriolar resistance and lowering of the blood pressure.

Terazosin is available in tablets or capsules of 1, 2, 5 and 10 mg generically and under the trade name Hytrin. Terazosin is usually started at a dose of 1 mg daily at bedtime with increase in the dose based upon tolerance and clinical response to an average of 5 to 10 mg daily in one dose daily, usually at bedtime.

Terazosin side effects include dizziness and syncope (particularly with the initial dose), fatigue, headache, palpitations, impotence, incontinence and gastrointestinal upset. Rare, but potentially severe adverse events include postural hypotension and priapism.

Beta blockers

Beta blockers also called beta-adrenergic receptor antagonists are a family of agents that are widely used to treat high blood pressure (hypertension), angina pectoris and cardiac arrhythmias. Beta blockers are usually not prescribed to treat high blood pressure in the first instance. This is because other medicines with fewer health risks are available. Yet, beta blockers can be useful for some people with high blood pressure and other conditions, including ischemic heart disease. Beta-blockers are also used for migraine prophylaxis, to treat anxiety, to prevent essential tremor, and to block the side effects of hyperthyroidism. Nonspecific beta-blockers are also recommended for treatment of portal hypertension in patients with cirrhosis. The beta-blockers act by competing with beta-adrenergic agonists (such as epinephrine and norepinephrine) for beta-receptor sites.

Beta-blockers are often categorized as “selective” or “non-selective” based upon whether they block both beta-1 receptors that are predominantly present in cardiac muscle and beta-2 receptors found in bronchial and smooth muscles. Beta-1 selective blockers work by blocking the effects of the hormone adrenaline, are preferred for therapy of heart disease, whereas the nonselective beta-blockers are preferred as therapy to prevent recurrent variceal hemorrhage in patients with cirrhosis and portal hypertension. Beta-1 selective blockers make your heart beat slower and relax the blood vessels, which, in turn, reduces blood pressure. Beta-1 selective blockers also help the heart to beat more regularly. Nonselective beta-blockers (common brand name and the year of their approval for use in the United States) include propranolol (Inderal, 1967), nadolol (CorGard, 1979), pindolol (Visken, 1982), labetalol (Normodyne, Trandate, 1984), penbutolol (Levatol, 1987), sotalol (Betapace, 1992), carvedilol (Coreg, 1995), and timolol (Biocarden, 1995). Beta-1 selective blockers include metoprolol (Lopressor, Toprol, 1978), atenolol (Temormin, 1981), acebutolol (Sectral, 1984), betaxolol (Kerlone, 1985), esmolol (Brevibloc, 1986), bisoprolol (Zebeta, 1992) and nebivolol (Bystolic, 2008).

Beta-blockers drugs list:

  • Acebutolol (Sectral)
  • Atenolol (Tenormin)
  • Betaxolol
  • Bisoprolol (Zebeta)
  • Carvedilol
  • Esmolol
  • Labetalol
  • Metoprolol (Lopressor, Toprol-XL)
  • Nadolol (Corgard)
  • Nebivolol (Bystolic)
  • Penbutolol
  • Pindolol
  • Propranolol (Inderal LA, InnoPran XL)
  • Sotalol
  • Timolol

Beta blockers risks

Beta-blockers are some of the most frequently used medications in medicine and are usually well tolerated. Common side effects are those that are caused by the beta-adrenergic blockade and include bradycardia, fatigue, dizziness, depression, memory loss, insomnia, impotence, cold limbs and, less commonly, severe hypotension, heart failure and acute bronchospasm.

Beta blockers are not suitable for people with asthma or chronic obstructive pulmonary disease (COPD). They can also cause low mood and can sometimes mask the signs of low glucose in people with diabetes. They are not suitable as the first choice of medication for people with high blood pressure that’s not complicated by other conditions.

Still, beta blockers can be very useful when combined with other high blood pressure medications, especially if other heart conditions are present, such as:

  • angina — pain in the chest caused by too little blood and oxygen getting to the heart
  • arrhythmia — irregular or fast heart beat or rhythm
  • after a heart attack

Calcium channel blockers

The calcium channel blockers act by blocking the influx of calcium ions into vascular smooth muscle and cardiac muscle cells during membrane depolarization. Because muscle contraction is largely dependent upon influx of calcium, its inhibition causes relaxation, particularly in arterial beds. Thus, the major effects of the calcium channel blockers are relaxation of vascular and arterial smooth muscle cells resulting in arterial vasodilation. The major use of the calcium channel blockers is for hypertension and angina pectoris (variant, exertional, and unstable). Some calcium channel blockers are also used for supraventricular arrhythmias and heart failure. Off label uses include migraine headaches. The major calcium channel blockers used in the United States include amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, and verapamil. While all affect the L type voltage gated calcium channel, the structure and site of interaction within the channel varies among the agents. Verapamil blocks the phenylalkylamine site and diltiazem the benzothiazepine site, while the remaining agents (exemplified by amlopidine and nifedipine) bind to the 1,4 dihydropyridine site. These agents are also commonly referred to as being first generation (verapamil, diltiazem, nifedipine) or second generation (amlopine, felodipine, isradipine, nicardipine, nimodipine and others) calcium channel blockers. Several of the calcium channel blockers are now available in generic forms and some are available as combinations with diuretics and lipid lowering agents.

Examples of calcium channel blockers include:

  • Amlodipine (Norvasc)
  • Diltiazem (Cardizem, Tiazac, others)
  • Felodipine
  • Isradipine
  • Nicardipine
  • Nifedipine (Adalat CC, Afeditab CR, Procardia)
  • Nisoldipine (Sular)
  • Verapamil (Calan, Verelan)

Angiotensin-Converting Enzyme (ACE) Inhibitors

The angiotensin-converting enzyme (ACE) inhibitors are a widely used class of antihypertensive medications that act by blocking the conversion of angiotensin I to angiotensin II, thus inhibiting an intermediate step in the renin-angiotensin pathway. The ACE inhibitors are considered first line drugs for the therapy of hypertension and are considered particularly helpful in preventing the renal complications of diabetes and high blood pressure. ACE inhibitors are sometimes used even in patients with relatively normal blood pressure for treatment of heart failure and prevention of diabetic neuropathy.

The ACE inhibitors act by blocking the conversion of angiotensin 1 to angiotensin 2, the active peptide that causes the vasoconstriction and sodium retention induced by activation of the renin-angiotensin pathway.

Currently, there are 10 ACE inhibitors approved for use in the United States: captopril (Capoten: 1981), enalapril (Vasotec: 1985), lisinopril (Prinivil, Zestril: 1987), benazepril (Lotensin: 1991), fosinopril (Monopril: 1991), quinapril (Accupril: 1991), ramipril (Altase: 1991), perindopril (Aceon: 1993), moexipril (Univasc: 1995), and trandolapril (Mavik: 1996).

Examples of ACE inhibitors include:

  • Benazepril (Lotensin)
  • Captopril
  • Enalapril (Vasotec)
  • Fosinopril
  • Lisinopril (Prinivil, Zestril)
  • Moexipril
  • Perindopril (Aceon)
  • Quinapril (Accupril)
  • Ramipril (Altace)
  • Trandolapril (Mavik)

Angiotensin 2 Receptor Antagonists

The angiotensin II receptor antagonists, also known as angiotensin II receptor blockers (ARBs), are a family of agents that bind to and inhibit the angiotensin II type 1 receptor (AT1) and thus inhibit the renin-angiotensin system and its cascade of effects in causing arteriolar contraction and sodium retention. While angiotensin converting enzyme (ACE) inhibitors block the cleavage of angiotensin I to angiotensin II, the active peptide that causes a pressor response, the angiotensin II receptor blockers inhibit its peripheral action. The angiotensin II receptor blockers reduce blood pressure in animal models as well as in humans. Since their introduction in 1995, these agents have been used widely in the therapy of hypertension and to reduce the complications of hypertensive cardiovascular disease and diabetic nephropathy.

The angiotensin II receptor blockers in clinical use in the United States include eight agents of similar chemical structure and activity, but somewhat different pharmacokinetics: losartan (Cozaar: 1995), valsartan (Diovan: 1996), irbesartan (Avapro: 1997), eprosartan (Teveten: 1997), candesartan (Atacand: 1998), telmisartan (Micardis: 1998), olmesartan (Benicar: 2002) and azilsartan (Edarbi: 2011).

Examples of angiotensin 2 receptor blockers include:

  • Azilsartan (Edarbi)
  • Candesartan (Atacand)
  • Eprosartan
  • Irbesartan (Avapro)
  • Losartan (Cozaar)
  • Olmesartan (Benicar)
  • Telmisartan (Micardis)
  • Valsartan (Diovan)

Vasodilators

Various arterial and venous vasodilators are useful for managing hypertension in special situations.

  • Hydralazine
  • Minoxidil
  • Sodium Nitroprusside

Hydralazine

Hydralazine is a commonly used oral antihypertensive agent that acts by inducing peripheral vasodilation. Hydralazine was one of the first oral antihypertensive medications introduced into clinical medicine and was first used in the late 1950s, but was officially approved for use in the United States in 1984. The vasodilation caused by hydralazine is followed by reflex sympathetic response that may partially reverse its antihypertensive effects. Nevertheless, when combined with other antihypertensive medications, hydralazine is effective in lowering blood pressure and it is still widely used, with more than 2 million prescriptions for hydralazine being filled yearly in the United States.

Hydralazine is a phthalazine derivative and antihypertensive agent which acts by direct relaxation of arteriolar smooth muscle, probably by alteration in intracellular calcium signaling.

Hydralazine is available in generic forms and under the brand name of Apresoline in tablets of 10, 25, 50 and 100 mg as well as in parenteral forms. The typical dose is 10 mg four times daily initially, with subsequent increases to a maximum of 200 mg daily.

Hydralazine common side effects include dizziness, headache, tachycardia, orthostatic hypotension, flushing, nausea and gastrointestinal upset.

Minoxidil

Minoxidil is an antihypertensive agent that is used largely for patients with severe and refractory hypertension not responding to conventional therapies. Minoxidil is also used topically to treat male pattern baldness. Minoxidil was approved for use in the United States in 1979 and continues to be used for treatment of severe and refractory hypertension, usually in combination with beta blockers and diuretics.

Minoxidil is one of the first antihypertensive agents developed for use in humans. Minoxidil is activated in the liver and acts to relax vascular smooth muscle by opening cell surface potassium channels causing an efflux of potassium, hyperpolarization and relaxation of smooth muscle cells. The increased vasodilation caused by minoxidil can result in a reflex increase in cardiac output and sodium retention for which reasons it is not recommended as monotherapy or as a first line agent for hypertension.

Minoxidil is available in tablets of 2.5 and 10 mg in generic forms and under the brand name Loniten. The usual initial dose in adults is 2.5 to 5 mg once daily, with subsequent adjustment based upon tolerance and clinical effect to a typical maintenance dose is 10 to 40 mg daily.

Minoxidil has many side effects including sodium retention, edema, headache, nausea, breast tenderness, gynecomastia, hypertrichosis and rash. The effect on hair growth has led to the use of topical minoxidil to treat male pattern baldness.

Nitroprusside

Sodium nitroprusside is a nitrovasodilator that is used intravenously for therapy of severe hypertension, hypertensive emergencies and heart failure. Nitroprusside was approved for use in the United States in 1981 and continues to be used in critical or emergency situations.

Sodium nitroprusside is a nonselective vasodilator that acts through release of nitric oxide to cause relaxation of smooth muscle cells of arterioles and venules. Nitroprusside is used predominantly to treat hypertensive emergencies, such as to lower blood pressure during acute aortic dissection or to improve cardiac output in severe congestive heart failure. Nitroprusside is unstable and must be administered intravenously with careful monitoring. It is rarely used for more than a few hours or days.

Sodium nitroprusside is available in solution for injection in 2 or 5 mL vials of 50 mg generically and under the brand name of Nitropress. The usual initial dose is 0.25 to 0.30 mcg/kg/minute by intravenous infusion with subsequent increase based upon clinical effect and blood pressure. The rate of infusion should be carefully managed; the average effective dose in children and adults is 3 mcg/kg/minute and the maximum recommended dose is 10 mcg/kg/minute.

Nitroprusside has many side effects including hypotension, dizziness, headache, drowsiness, stupor, bradycardia, palpitations, flushing, nausea, metabolic acidosis and rash.

Aliskiren

Aliskiren is a unique antihypertensive agent that acts by direct inhibition of renin and has only recently been introduced into clinical practice. Aliskiren is effective in lowering blood pressure and can be used alone or in combination with other antihypertensive medications, including other inhibitors of the renin-angiotensin system such as the angiotensin converting enzyme (ACE) inhibitors and the angiotensin receptor blockers (ARBs). In 2007, aliskiren became the first in the class of direct renin inhibitors to be approved for use in the United States.

Aliskiren is a direct inhibitor of renin and acts to inhibit its ability to convert angiotensinogen to angiotensin 1, an early step in the renin-angiotensin system pathway. By inhibiting renin and the subsequent production of angiotensin II and aldosterone release, aliskiren results in a decrease in peripheral vasoconstriction and increase in sodium excretion.

Aliskiren is available in under the brand name of Tekturna in tablets of 150 and 300 mg. Fixed combinations of aliskiren with hydrochlorthiazide (Tekturna HCT), valasartan (Valturna) and amlodipine (Amturnide) are also available. The typical initial dose of aliskiren in adults is 150 daily, which can be increased to 300 mg daily based upon effects and tolerance.

Aliskiren side effects are uncommon and usually mild; they include diarrhea, headaches, fatigue, dizziness and nasopharyngitis.

Clonidine

Clonidine is a centrally active alpha-adrenergic agonist used predominantly as an antihypertensive agent, usually in combination with other agents. Clonidine is effective in lowering blood pressure and can be used alone or in combination with other antihypertensive medications. Clonidine is also used in several other conditions in which central nervous system sympathetic activity is believed to contribute including neuropathy, smoking and alcohol cessation, attention deficit disorder, vascular headache, menopausal symptoms, diabetic diarrhea, and restless leg syndrome. Current approved indications are for treatment of hypertension, but some preparations are also approved for cancer pain management and treatment of attention deficit disorder. Off label uses include treatment of Tourette syndrome, migraine headahces, stress and sleep disorders, and to alleviate symptoms of alcohol, nicotine or narcotic withdrawal.

Clonidine was approved for use in the United States in 1974 and continues to be widely used with more than 11 million prescriptions being filled yearly.

Clonidine is an antihypertensive agent which acts by stimulation of the alpha 2A subtype of alpha adrenergic receptors in the brainstem, causing a reduction in the sympathic outflow of the central nervous system. Decreases in plasma levels of norepinephrine correlate closely with its antihypertensive effects.

Clonidine is available in tablets of 0.1, 0.2 and 0.3 mg generically and under the brand name of Catapres. Clonidine is also available in fixed combination with diuretics, as a solution for injection and in a transdermal formulation for application once weekly. The typical maintenance dose of clonidine in adults is 0.1 to 0.6 mg daily in 2 to 3 divided doses.

Clonidine side effects

Clonidine side effects are usually mild and include sedation, fatigue, bradycardia, dry mouth, headaches, dizziness, postural hypotension, male impotence and gastrointestinal upset. Sudden withdrawal can cause rebound hypertension.

Methyldopa

Methyldopa (alpha-methyldopa or α-methyldopa) is a centrally active sympatholytic agent that has been used for more than 50 years for the treatment of hypertension. Introduced in 1960, methyldopa rapidly became a leading antihypertensive agent, but in the last two decades its use has decreased markedly, replaced by better tolerated and more effective antihypertensive medications. Currently, the major use of methyldopa is treatment of hypertension during pregnancy, a use based upon its established record of safety during pregnancy and breast feeding.

Methyldopa is a centrally active sympatholytic agent that reduces sympathic drive to the heart and peripheral circulation, leading to decreased cardiac output and lowered peripheral arterial resistance.

Methyldopa is available generically and under the trade name Aldomet as 125, 250 and 500 mg tablets. Fixed combinations with hydrochlorothiazide are also available (Aldoril). The recommended maintenance dose in adults is 500 mg to 2 g daily in 2-4 divided doses.

Methyldopa common side effects

Methyldopa common side effects include nausea, diarrhea, headache, dizziness, sedation, dry mouth and rash. Rare but potentially severe adverse effects include hemolytic anemia (Coombs positive), lupus-like syndrome, mycocarditis, pancreatitis and hepatotoxicity.

Reserpine

Reserpine is an oral antihypertensive medication that acts through inhibitor of alpha-adrenergic transmission and was one of the first antihypertensive agents introduced into clinical practice. The antihypertensive effect of reserpine correlates with the depletion of sympathetic amines in both the central nervous system and periphery. Reserpine is effective in lowering blood pressure and can be used alone or in combination with other antihypertensive medications. Reserpine was approved for use in the United States in 1955 but is currently rarely used, largely because of its central nervous system effects and the availability of many better tolerated and more potent antihypertensive medications.

Reserpine was one of the first antihypertensive agents developed for use in humans. It is an alkaloid extract of the Rauwolifia serpentine (thus its name) which is a climbing shrub found in India. Reserpine is thought to act by binding to adrenergic storage vesicles in neurons, inhibiting their capacity to concentrate and store norepinephrine and dopamine.

Reserpine continues to be available in generic forms as tablets of 0.1 and 0.25 mg. The typical maintenance dose in adults is 0.05 to 0.25 mg once daily.

Reserpine side effects

Side effects are common and include sedation, difficulty concentrating, fatigue, depression, dry mouth, headaches, dizziness, postural hypotension, male impotence and gastrointestinal upset.

Antihypertensive drugs side effects

Antihypertensive drugs side effects depend on the type of antihypertensive medications used. See above for individual side effects and cautions.