MEDICINES FOR HYPERTENSION

 

 

 

Which medicines are used to treat hypertension?

• ACE inhibitors stop the production of a hormone called angiotensin II that makes the blood vessels narrow. As a result, the vessels expand, improving blood flow. Tension in the circulation is also lowered by the kidneys filtering more fluid from the blood vessels into urine. This also helps reduce blood pressure. If your blood pressure is not easily controlled on simple medication, your doctor will probably use a medicine of this type.

What are ACE inhibitors, and how do they work?

Angiotensin II is a very potent chemical that causes the muscles surrounding blood vessels to contract, thereby narrowing the vessels. The narrowing of the vessels increases the pressure within the vessels causing high blood pressure (hypertension). Angiotensin II is formed from angiotensin I in the blood by the enzyme angiotensin converting enzyme (ACE). ACE inhibitors are medications that slow (inhibit) the activity of the enzyme ACE, which decreases the production of angiotensin II. As a result, the blood vessels enlarge or dilate, and blood pressure is reduced. This lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. In addition, the progression of kidney disease due to high blood pressure or diabetes is slowed.

For what conditions are ACE inhibitors used?

ACE inhibitors are used for controlling blood pressure, treating heart failure, preventing strokes, and preventing kidney damage in people with hypertension or diabetes. They also improve survival after heart attacks. In studies, individuals with hypertension, heart failure, or prior heart attacks who were treated with an ACE inhibitor lived longer than patients who did not take an ACE inhibitor. Because they prevent early death resulting from hypertension, heart failure or heart attacks, ACE inhibitors are one of the most important group of drugs. Some individuals with hypertension do not respond sufficiently to ACE inhibitors alone. In these cases, other drugs are used in combination with ACE inhibitors.

Are there any differences among the different types of ACE inhibitors?

ACE inhibitors are very similar. However, they differ in how they are eliminated from the body and their doses. Some ACE inhibitors need to be converted into an active form in the body before they work. In addition, some ACE inhibitors may work more on ACE that is found in tissues than on ACE that is present in the blood. The importance of this difference or whether one ACE inhibitor is better than another has not been determined.

What are the side effects of ACE inhibitors?

ACE inhibitors are well-tolerated by most individuals. Nevertheless, they are not free of side effects, and some patients should not use ACE inhibitors.
ACE inhibitors usually are not prescribed for pregnant patients because they may cause birth defects.
Individuals with bilateral renal artery stenosis (narrowing) may experience worsening of kidney function, and people who have had a severe reaction to ACE inhibitors probably should avoid them.
The most common side effects are:

• cough,
• elevated blood potassium levels,
• low blood pressure, dizziness,
• headache,
• drowsiness,
• weakness,
• abnormal taste (metallic or salty taste), and
• rash.

It may take up to a month for coughing to subside, and if one ACE inhibitor causes cough it is likely that the others will too. The most serious, but rare, side effects of ACE inhibitors are kidney failure, allergic reactions, a decrease in white blood cells, and swelling of tissues (angioedema).

With which drugs do ACE inhibitors interact?

ACE inhibitors have few interactions with other drugs. Since ACE inhibitors may increase blood levels of potassium, the use of potassium supplements, salt substitutes (which often contain potassium), or other drugs that increase the body's potassium may result in excessive blood potassium levels. ACE inhibitors also may increase the blood concentration of lithium (Eskalith) and lead to an increase in side effects from lithium. There have been reports that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Advil, Children's Advil/Motrin, Medipren, Motrin, Nuprin, PediaCare Fever etc.), indomethacin (Indocin, Indocin-SR), and naproxen (Anaprox, Naprelan, Naprosyn, Aleve) may reduce the effects of ACE inhibitors.

What are some examples of ACE inhibitors

The following is a list of the ACE inhibitors that are available in the United States:

• benazepril (Lotensin),
• captopril (Capoten),
• enalapril (Vasotec),
• fosinopril (Monopril),
• lisinopril (Prinivil, Zestril)
• moexipril (Univasc), and
• perindopril(Aceon),
• quinapril (Accupril),
• ramipril (Altace),
• trandolapril (Mavik).

• Angiotensin-II receptor antagonists work in a similar way to ACE inhibitors. But instead of stopping the production of angiotensin II, they block its action. This allows the blood vessels to expand, improving blood flow and reducing blood pressure. Angiotensin II is a very potent chemical that causes muscles surrounding blood vessels to contract, thereby narrowing blood vessels. This narrowing increases the pressure within the vessels and can cause high blood pressure (hypertension). Angiotensin II receptor blockers (ARBs) are medications that block the action of angiotensin II by preventing angiotensin II from binding to angiotensin II receptors on blood vessels. As a result, blood vessels enlarge (dilate) and blood pressure is reduced. Reduced blood pressure makes it easier for the heart to pump blood and can improve heart failure. In addition, the progression of kidney disease due to high blood pressure or diabetes is slowed. ARBs have effects that are similar to angiotensin converting enzyme (ACE) inhibitors, but ACE inhibitors act by preventing the formation of angiotensin II rather than by blocking the binding of angiotensin II to muscles on blood vessels.
  

  For what conditions are ARBs used?

  
  ARBs are used for controlling high blood pressure, treating heart failure, and preventing kidney failure in people with diabetes or high blood pressure. They may also prevent diabetes and reduce the risk of stroke in patients with high blood pressure and an enlarged heart. ARBs may also prevent the recurrence of atrial fibrillation. Since these medications have effects that are similar to those of ACE inhibitors, they often are used when ACE inhibitors are not tolerated by patients (for example, due to excessive coughing).
  
  

  Are there any differences among the different types of ARBs?

  
  ARBs are similar in actions and side effects. They differ in how they are eliminated from the body and the extent to which they are distributed throughout the body. Some ARBs need to be converted to an active form in the body before they can lower blood pressure. In addition, some ARBs are better at lowering blood pressure. In some studies, irbesartan (Avapro) and candesartan (Atacand) reduced blood pressure better than losartan (Cozaar).
  
  

  What are the side effects of ARBs?

  
  ARBs are well tolerated by most individuals. The most common side effects are cough, elevated potassium levels in the blood (hyperkalemia), low blood pressure, dizziness, headache, drowsiness, diarrhea, abnormal taste sensation (metallic or salty taste), and rash. Compared to ACE inhibitors, cough occurs less often with ARBs. The most serious, but rare, side effects are kidney failure, liver failure, allergic reactions, a decrease in white blood cells, and swelling of tissues (angioedema). ARBs usually are not prescribed for pregnant patients because they may cause birth defects. Individuals who have narrowing of both kidney arteries or have had a severe reaction to ARBs should avoid them. Like other antihypertensives, ARBs have been associated with sexual dysfunction.
  

  With which drugs do ARBs interact?

  
  ARBs have few interactions with other drugs. Since ARBs may increase blood levels of potassium, the use of potassium supplements, salt substitutes (which often contain potassium), or other drugs that increase potassium may result in excessive blood potassium levels and cardiac arrhythmias. ARBs may also increase the blood concentration of lithium (Eskalith) and lead to an increase in side effects from lithium. Rifampin (Rifadin) reduces the blood levels of losartan, and fluconazole (Diflucan) reduces the conversion of losartan to its active form. These effects could decrease the effects of losartan.
  
  

  What are the available ARBs?

  
  The following is a list of currently available ARBs:
  
  • candesartan (Atacand),
  • eprosartan (Teveten),
  • irbesartan (Avapro),
  • telmisartan (Micardis),
  • valsartan (Diovan),
  • losartan (Cozaar), and
  • olmesartan (Benicar).

• Beta-blockers block the effect of the hormone adrenaline and the sympathetic nervous system on the body. This relaxes the heart so that it beats more slowly, lowering the blood pressure.

Beta blockers, also known as beta-adrenergic blocking agents, are drugs that block norepinephrine and epinephrine (adrenaline) from binding to beta receptors on nerves. There are three types of beta receptors and they control several functions based on their location in the body.

• Beta-1 (β1) receptors are located in the heart, eye, and kidneys;
• beta (β2) receptors are found in the lungs, gastrointestinal tract, liver, uterus, blood vessels, and skeletal muscle; and
• beta (β3) receptors are located in fat cells.

Beta blockers primarily block β1 and β2 receptors. By blocking the effect of norepinephrine and epinephrine, beta blockers reduce heart rate; reduce blood pressure by dilating blood vessels; and may constrict air passages by stimulating the muscles that surround the air passages to contract.

For what conditions are beta blockers used?

Beta blockers are used for treating:

• abnormal heart rhythm,
• high blood pressure,
• heart failure,
• angina (chest pain),
• tremor,
• pheochromocytoma, and
• prevention of migraines.

They also have been found to prevent further heart attacks and death after a heart attack. Other uses include the treatment of hyperthyroidism, akathisia (restlessness or inability to sit still), and anxiety. Some beta blockers reduce the production of aqueous humor in the eye and therefore are used for reducing pressure in the eye caused by glaucoma.

Are there any differences between beta blockers?

Beta blockers differ in the type of beta receptors they block and, therefore, their effects.

• Non-selective beta blockers, for example, propranolol (Inderal), block β1 and β2 receptors and, therefore, affect the heart, blood vessels, and air passages.
• Selective beta blockers, for example, metoprolol (Lopressor, Toprol XL) primarily block β1 receptors and, therefore, mostly affect the heart and do not affect air passages.
• Some beta blockers, for example, pindolol (Visken) have intrinsic sympathomimetic activity (ISA), which means they mimic the effects of epinephrine and norepinephrine and can cause an increase in blood pressure and heart rate. Beta blockers with ISA have smaller effects on heart rate than agents that do not have ISA.
• Labetalol (Normodyne, Trandate) and carvedilol (Coreg) block beta and alpha-1 receptors. Blocking alpha receptors adds to the blood vessel dilating effect of labetalol (Normodyne, Trandate) and carvedilol (Coreg).

What are the side effects of beta blockers?

• Beta blockers may cause:
  
  
  • diarrhea,
  • stomach cramps,
  • nausea, and
  • vomiting.
• Rash, blurred vision, muscle cramps, and fatigue may also occur.
• As an extension of their beneficial effect, they slow heart rate, reduce blood pressure, and may cause heart failure or heart block in patients with heart problems.
• Beta blockers should not be withdrawn suddenly because sudden withdrawal may worsen angina (chest pain) and cause heart attacks or sudden death.
• Central nervous system effects of beta blockers include:
  
  
  • headache,
  • depression,
  • confusion,
  • dizziness,
  • nightmares, and
  • hallucinations.
• Beta blockers that block β2 receptors may cause shortness of breath in asthmatics.
• As with other drugs used for treating high blood pressure, sexual dysfunction may occur.
• Beta blockers may cause low or high blood glucose and mask the symptoms of low blood glucose (hypoglycemia) in diabetic patients.

With which drugs do beta blockers interact?

• Combining propranolol (Inderal) or pindolol (Visken) with thioridazine (Mellaril) or chlorpromazine (Thorazine) may result in low blood pressure (hypotension) and abnormal heart rhythms because the drugs interfere with each others' elimination and result in increased levels of the drugs.
• Dangerous elevations in blood pressure may occur when clonidine (Catapres) is combined with a beta blocker, or when clonidine (Catapres) or beta blocker is discontinued after their concurrent use. Blood pressure should be closely monitored after initiation or discontinuation of clonidine (Catapres) or a beta blocker when they have been used together.
• Phenobarbital and similar agents may increase the breakdown and reduce blood levels of propanolol (Inderal) or metoprolol (Lopressor, Toprol XL). This may reduce effectiveness of the beta blocker.
• Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) (for example, ibuprofen) may counteract the blood pressure reducing effects of beta blockers because they reduce the effect of prostaglandins. Prostaglandins play a role in control of blood pressure.

What are some examples of beta blockers?

• acebutolol (Sectral)
• atenolol (Tenormin)
• betaxolol (Kerlone)
• betaxolol (Betoptic, Betoptic S)
• bisoprolol fumarate (Zebeta)
• carteolol (Cartrol)
• carvedilol (Coreg)
• esmolol (Brevibloc)
• labetalol (Trandate, Normodyne)
• metoprolol (Lopressor, Toprol XL)
• nadolol (Corgard)
• nebivolol (Bystolic)
• penbutolol (Levatol)
• pindolol (Visken)
• propranolol (Inderal, InnoPran)
• sotalol (Betapace)
• timolol (Blocadren)
• timolol ophthalmic solution (Timoptic)

• Alpha-blockers cause the blood vessels to relax and widen. Combining them with beta-blockers has a greater effect on the resistance in the circulation.

Alpha blockers are a type of medicine sometimes used to treat high blood pressure. They are not usually used alone, and many patients are more familiar with alpha blockers because they are used to treat other illnesses, including:

• Enlarged Prostate (benign prostatic hypertrophy)
• Pheochromocytoma (a type of hormone-secreting tumor)
• Peripheral artery disease (poor circulation, usually in the legs)

While other medicines are usually tried before considering alpha blockers, for some patients they represent an important treatment option.

How Alpha Blockers Work:

Alpha blockers, also called alpha adrenergic blocking agents, work by interferring with the transfer of messages to specific parts of the body. Like other "blocker" medications, alpha blockers attach themselves to molecules in the body that serve as receptors for certain chemical messages. Because the chemical message is then prevented from reaching its target, it is said to be blocked.
Alpha blockers block targets called alpha receptors, which are found on blood vessels, in the prostate, and in special blood pressure sensors called baroreceptors.
Patients are usually told to take alpha blockers before bed.

Names of Common Alpha Blockers:

Many different alpha blockers are available. Some commonly prescribed alpha blockers include:

• Doxazosin (Cardura)
• Phentolamine
• Tamsulosin (Flomax)
• Terazosin

Other alpha blockers are availabe, both within the U.S. and around the world. However, the vast majority of prescriptions in the U.S. are for the drugs listed above. Other types of alpha blockers are used mainly in special circumstances or controlled hospital settings.

Side Effects of Alpha Blockers:

Alpha blockers tend to be well tolerated, but have some important side effects. These include:

• Dizziness
• Fainting
• Low blood pressure
• Sudden blood pressure changes when standing after sitting

In addition to these side effects, an important research  found that long-term use of alpha blockers seems to increase the risk of heart failure. While this risk is real, it is small, and the main reason that alpha blockers are not used as "first choice" drugs is that, unlike other high blood pressure medicines, they have not been shown to reduce the risk of stroke and heart attack.

Notes:

Only you and your doctor can decide on a proper medication for treatment of high blood pressure. Be sure to notify your doctor if you are pregant or breastfeeding, and to supply the names of any other medicines and/or suppliments you are taking. Remember to include over-the-counter medicines like aspirin or Advil and herbal/natural suppliments.

• Calcium-channel blockers reduce muscle tension in the arteries, expanding them and creating more room for the blood flow. In addition, they slightly relax the heart muscle so it beats more slowly, reducing blood pressure. In order to pump blood, the heart needs oxygen. The harder the heart works, the more oxygen it requires. Angina (heart pain) occurs when the supply of oxygen to the heart is inadequate for the amount of work the heart must do. By dilating the arteries, CCBs reduce the pressure in the arteries. This makes it easier for the heart to pump blood, and, as a result, the heart needs less oxygen. By reducing the heart's need for oxygen, CCBs relieve or prevent angina. CCBs also are used for treating high blood pressure because of their blood pressure-lowering effects. CCBs also slow the rate at which the heart beats and are therefore used for treating certain types of abnormally rapid heart rhythms.
  
  

  For what conditions are calcium channel blockers used?

  CCBs are used for treating high blood pressure, angina, and abnormal heart rhythms (for example, atrial fibrillation, paroxysmal supraventricular tachycardia).
  They also may be used after a heart attack, particularly among patients who cannot tolerate beta-blocking drugs, have atrial fibrillation, or require treatment for their angina.
  Unlike beta blockers, CCBs have not been shown to reduce mortality or additional heart attacks after a heart attack.
  CCBs are as effective as ACE inhibitors in reducing blood pressure, but they may not be as effective as ACE inhibitors in preventing the kidney failure caused by high blood pressure or diabetes.
  They also are used for treating:
  
  • pulmonary hypertension,
  • Raynaud's syndrome,
  • cardiomyopathy, and
  • subarachnoid hemorrhage.
  CCBs are also used in the prevention of migraine headaches.
  
  

  Are there any differences among calcium channel blockers?

  CCBs differ in their duration of action, the process by which they are eliminated from the body, and, most importantly, in their ability to affect heart rate and contraction. Some CCBs [for example, amlodipine (Norvasc)] have very little effect on heart rate and contraction so they are safer to use in individuals who have heart failure or bradycardia (a slow heart rate). Verapamil (Calan, Isoptin) and diltiazem (Cardizem) have the greatest effects on the heart and reduce the strength and rate of contraction. Therefore, they are used in reducing heart rate when the heart is beating too fast.
  

  What are the side effects of calcium channel blockers?

  • The most common side effects of CCBs are constipation, nausea, headache, rash, edema (swelling of the legs with fluid), low blood pressure, drowsiness, and dizziness.
  • Liver dysfunction and over growth of gums may also occur. When diltiazem (Cardizem) or verapamil (Calan, Isoptin) are given to individuals with heart failure, symptoms of heart failure may worsen because these drugs reduce the ability of the heart to pump blood.
  • Like other blood pressure medications, CCBs are associated with sexual dysfunction.
  
  

  With which drugs do calcium channel blockers interact?

  Most of the interactions of CCBs occur with verapamil (Calan, Isoptin) or diltiazem (Cardizem). The interaction occurs because verapamil and diltiazem decrease the elimination of a number of drugs by the liver. Through this mechanism, verapamil and diltiazem may reduce the elimination and increase the blood levels of carbamazepine (Tegretol), simvastatin (Zocor), atorvastatin (Lipitor), and lovastatin (Mevacor). This can lead to toxicity from these drugs.
  
  Grapefruit juice (approximately 200 ml) may elevate serum concentrations of felodipine (Plendil), verapamil (Calan, Isoptin), nisoldipine (Sular), nifedipine (Adalat, Procardia), nicardipine (Cardene), and possibly amlodipine (Norvasc). Grapefruit juice should not be consumed within 2 hours before or 4 hours after administration of affected CCBs.
  
  

  What calcium channel blockers are available?

  The CCBS that have been approved  include:
  
  • amlodipine (Norvasc)
  • clevidipine (Cleviprex)
  • diltiazem (Cardizem),
  • felodipine (Plendil),
  • isradipine (Dynacirc),
  • nifedipine (Adalat, Procardia),
  • nicardipine (Cardene),
  • nimodipine (Nimotop),
  • nisoldipine (Sular), and
  • verapamil (Calan, Isoptin).

• Diuretics help the body get rid of excess salt and fluids via the kidneys. In certain cases, they relax blood vessels, reducing the strain on your circulation. For high blood pressure, diuretics, commonly known as "water pills," help your body get rid of unneeded water and salt through the urine. Getting rid of excess salt and fluid helps lower blood pressure and can make it easier for your heart to pump. Diuretics may be used to treat a number of heart-related conditions, including high blood pressure, heart failure, kidney and liver problems, and glaucoma.
  While diuretics are used to remove fluid, only thiazide diuretics, such as Esidrix or Zaroxolyn, are used to lower blood pressure.
  Loop diuretics (Lasix, Bumex) are more powerful and are often used when people have congestive heart failure symptoms and are especially useful in emergencies but do not significantly lower blood pressure.
  Potassium-sparing diuretics (like Aldactone) help your body retain potassium and are used more often in congestive heart failure patients. They are often prescribed in conjunction with the other two types of diuretics, but also do not significantly lower blood pressure.
  
  

  What Are the Side Effects of Diuretics?

  Like any drug, diuretics come with potential side effects. They include:
  
  • Frequent urination. This may last for several hours after a dose.
  • Arrhythmia (abnormal heart rhythm)
  • Electrolyte abnormalities -- Blood test monitoring of electrolytes is important before and during drug use.
  • Extreme tiredness or weakness. These effects should decrease as your body adjusts to the medication. Call your doctor if these symptoms persist.
  • Muscle cramps or weakness. Be sure that you are taking your potassium supplement correctly, if prescribed. Contact your doctor if these symptoms persist.
  • Dizziness, lightheadedness. Try rising more slowly when getting up from a lying or sitting position.
  • Blurred vision, confusion, headache, increased perspiration (sweating), and restlessness. If these effects are persistent or severe, contact your doctor.
  • Dehydration. Signs include dizziness, extreme thirst, excessive dryness of the mouth, decreased urine output, dark-colored urine, or constipation. If these symptoms occur, don't assume you need more fluids, call your doctor.
  • Fever, sore throat, cough, ringing in the ears, unusual bleeding or bruising, rapid and excessive weight loss. Contact your doctor right away.
  • Skin rash. Stop taking the medication and contact your doctor right away.
  • Loss of appetite, nausea, vomiting, or muscle cramps. Be sure that you are taking your potassium supplement correctly, if prescribed.
  Rarely, potassium-sparing diuretics like Aldactone can cause breast enlargement in men and women, deepening of the voice, increased hair growth and irregular menstrual cycles.
  In addition, most diuretics are sulfa drugs.If you are allergic to sulfa drugs, tell your doctor.
  Contact your doctor if you have any other symptoms that cause concern.
  

  Guidelines for Taking Diuretics

  Here are some general guidelines if you're taking a diuretic:
  
  • Before a diuretic is prescribed, tell your doctor if you are taking any other medications that may have been prescribed by another physician or any over-the-counter or herbal remedies. Also, tell your doctor if you have any other medical problems.
  • Follow your doctors instructions on how often you should take the diuretic. If you are taking a single dose a day, it might be better to take it in the morning instead of at night, so that you will not have your sleep interrupted by frequent trips to the bathroom. (This is more pertinent for patients with congestive heart failure or patients with cirrhosis and portal hypertension.)
  • While taking a diuretic, have your blood pressure and kidney function tested regularly, as advised by your doctor.
  • Keep all appointments with your doctor and the laboratory so that your response to this drug can be monitored.

The following medicines are used less frequently.

• Indapamide (eg Natrilix) is a mildly diuretic preparation that also relaxes the peripheral arteries.
• Hydralazine (eg Apresoline) relaxes the vascular walls in the peripheral arteries thereby reducing the blood pressure.
• Methyldopa (eg Aldomet) stimulates the alpha receptors in the brain that relax the blood vessels, causing the blood pressure to drop.
• Moxonidine (eg Physiotens) is another medicine that acts on receptors in the involuntary part of the brain, causing blood pressure to decrease.
• Minoxidil (Loniten) relaxes the small arteries so that blood pressure drops. It must be used in combination with other hypertension medicines