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Antihypertensive Drugs

Antihypertensive Drugs

Definition

Antihypertensive drugs are medicines that help lower blood pressure.

Purpose

The overall class of antihypertensive agents lowers blood pressure, although the mechanisms of action vary greatly. In 2003, a Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure report said that recent clinical trials show that antihypertensive treatment can reduce incidence of stroke by 35-40%, heart attack by 20-25%, and onset of new heart failure by 50%. Within this therapeutic class, there are several subgroups of drugs. There are a large number of drugs used to control hypertension, and the drugs listed below are representative, but not the only members of their classes.

Antihypertensive Drugs
Brand Name (Generic
Name)
Possible Common Side Effects Include:
Accupril (quinapril
hydrochloride)
Headache, dizziness
Aldatazide Diarrhea, fever, headache, decreased
coordination
Aldactone
(spironolactone)
Cramps, drowsiness, stomach disorders
Aldomet (methyldopa) Fluid retention, headache, weak feeling
Altace (ramipril) Headache, cough
Calan, Calan SR (vera-
pamil hydrochloride)
Constipation, fatigue, decreased blood
pressure
Capoten (captopril) Decreased sense of taste, decreased blood
pressure tiching, rash
Cardene (nicardipine
Hydrochloride)
Dizziness, headache, indigestion and nausea,
increased heartbeat
Cardizem (diltiazem
hydrochloride)
Dizziness, fluid retention, headache, nausea,
skin rash
Cardura (doxazosin
mesylate)
Dizziness, fatigue, drowsiness, headache
Catapres Dry mouth, drowsiness, dizziness, constipation
Corgard (nadolol) Behaviorial changes, dizziness, decreased
heartbeat, tiredness
Corzide Dizziness, decreased heartbeat, fatigue, cold
hands and feet
Diuril (chlorothiazide) Cramps, constipation or diarrhea, dizziness,
fever, increased glocose level in urine
Dyazide Blurred vision, muscle and abdominal pain,
fatigue
DynaCirc (isradipine) Chest pain, fluid retention, headache, fatigue
HydroDIURIL
(hydrochlorothiazide)
Upset stomach, headache, cramps, loss of
appetite
Hygroton
(chlorthalidone)
Anemia, constipation or diarrhea, cramps,
itching
Hytrin (terazosin
hydrochloride)
Dizziness, labored breathing, nausea, swelling
Inderal (propranolol
hydrochloride)
Constipation or diarrhea, tingling sensation,
nausea and vomiting
Inderide Blurred vision, cramps, fatigue, loss of appetite
Lasix (furosemide) Back and muscle pain, indigestion, nausea
Lopressor (metoprolol
tartrate)
Diarrhea, itching/rash, tiredness
Lotensin (benazepril
hydrochloride)
Nausea, dizziness, fatigue, headache
Alozol (indapamide) Anxiety, headache, loss of energy, muscle
cramps
Maxzide Cramps, labored breathing, drowsiness,
irritated stomach
Minipress (prazosin
hdrochloride)
Headache, nausea, weakness, dizziness
Moduretic Diarrhea, fatigue, itching, loss of appetite
Monopril (fosinopril
sodium)
Nausea and vomiting, headache, cough
Normodyne (labetalol
hydrochloride)
Fatigue, nausea, stuffy nose
Plendil (felodipine) Pain in back, chest, muscles, joints, and
abdomen, itching, dry mouth, respiratory
problems
Procardia, Procardia X
(nifedipine)
Swelling, constipation, decreased blood
pressure, nausea, fatigue
Sectral (acebutolol
hydrochloride)
Constipation or diarrhea, gas, chest and joint
pain
Ser-Ap-Es Blurred vision, cramps, muscle pain, dizziness
Tenex (guanfacine
hydrochloride)
Headache, constipation, dry mouth, weakness
Tenoretic Decreased heartbeat, fatigue, nausea
Tenormin (atenolol) Nausea, fatigue, dizziness
Veseretic Diarrhea, muscle cramps, rash
Antihypertensive Drugs (continued)
Brand Name (Generic
Name)
Possible Common Side Effects Include:
Vasotec (enalapril
maleate)
Chest pain, blurred vision, constipation or diar-
rhea, hives, nausea
Visken (pindolol) Muscle cramps, labored breathing, nausea, fluid
retention
Wytensin (guanabenz
acetate)
Headache, drowsiness, dizziness
Zaroxolyn (metolazone) Constipation or diarrhea, chest pain, spasms,
nausea
Zestoretic (lisinopril)
hydrochlorothiazide)
Fatigue, headache, dizziness
Zestril (lisinopril) Labored breathing, abdominal and chest pain,
nausea, decreased blood pressure

The calcium channel blocking agents, also called slow channel blockers or calcium antagonists, inhibit the movement of ionic calcium across the cell membrane. This reduces the force of contraction of muscles of the heart and arteries. Although the calcium channel blockers are treated as a group, there are four different chemical classes, leading to significant variations in the activity of individual drugs. Nifedipine (Adalat, Procardia) has the greatest effect on the blood vessels, while verapamil (Calan, Isoptin) and diltiazem (Cardizem) have a greater effect on the heart muscle itself.

Peripheral vasodilators such as hydralazine (Apresoline), isoxuprine (Vasodilan), and minoxidil (Loniten) act by relaxing blood vessels.

There are several groups of drugs that act by reducing adrenergic nerve stimulation, the excitatory nerve stimulation that causes contraction of the muscles in the arteries, veins, and heart. These drugs include the beta-adrenergic blockers and alpha/beta adrenergic blockers. There are also non-specific adrenergic blocking agents.

Beta-adrenergic blocking agents include propranolol (Inderal), atenolol (Tenormin), and pindolol (Visken). Propranolol acts on the beta-adrenergic receptors anywhere in the body, and has been used as a treatment for emotional anxiety and rapid heart beat. Atenolol and acebutolol (Sectral) act specifically on the nerves of the heart and circulation.

There are two alpha/beta adrenergic blockers, labetolol (Normodyne, Trandate) and carvedilol (Coreg). These work similarly to the beta blockers.

The ACE II inhibitors, losartan (Cozaar), candesartan (Atacand), irbesartan (Avapro), telmisartan (Micardis), valsartan (Diovan) and eprosartan (Teveten) directly inhibit the effects of ACE II rather than blocking its production. Their actions are similar to the ACE inhibitors, but they appear to have a more favorable side effect and safety profile.

In addition to these drugs, other classes of drugs have been used to lower blood pressure, most notably the thiazide diuretics. There are 12 thiazide diuretics marketed in the United States, including hydrochlorothiazide (Hydrodiuril, Esidrex), indapamide (Lozol), polythiazide (Renese), and hydroflumethiazide (Diucardin). The drugs in this class appear to lower blood pressure through several mechanisms. By promoting sodium loss they lower blood volume. At the same time, the pressure of the walls of blood vessels, the peripheral vascular resistance, is lowered. Thiazide diuretics are commonly used as the first choice for reduction of mild hypertension, and may be used in combination with other antihypertensive drugs.

Debate continued in 2003 as to the best drugs to lower blood pressure. One study seemed to prove that diuretics were the best initial choice, but a study from Australia said that ACE inhibitors were a superior choice. However, many physicians agreed that the best treatment for a particular patient depends on his or her particular age, economic situation, genetic factors and other existing illnesses and conditions.

While designed to lower cholesterol rather than blood pressure, a large clinical trial reported in 2003 that people with high blood pressure may one day benefit from taking them. In the trial, participants with increased risk for heart disease, even if it was not from high cholesterol, benefited from taking statins.

Recommended dosage

Recommended dosage varies with patient, drug, severity of hypertension, and whether the drug is being used alone or in combination with other drugs. Specialized references can be consulted for further information.

Precautions

Because of the large number of classes and individual drugs in this group, specialized references offer more complete information.

Peripheral vasodilators may cause dizziness and orthostatic hypotensiona rapid lowering of blood pressure when the patient stands up in the morning. Patients taking these drugs must be instructed to rise from bed slowly. Pregnancy risk factors for this group are generally category C. Hydralazine has been shown to cause cleft palate in animal studies, but there is no human data available. Breastfeeding is not recommended.

KEY TERMS

Adrenergic Activated by adrenalin (norepinephrine), loosely applied to the sympathetic nervous system responses.

Angioedema An allergic skin disease characterized by patches of confined swelling involving the skin the layers beneath the skin, the mucous membranes, and sometimes the visceracalled also angioneurotic edema, giant urticaria, Quincke's disease, or Quincke's edema.

Arteries Blood vessels that carry blood away from the heart to the cells, tissues, and organs of the body.

Laryngospasm Spasmodic closure of the larynx.

Pregnancy category A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in wellcontrolled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits out-weigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

Sympathetic nervous system The part of the autonomic nervous system that is concerned especially with preparing the body to react to situations of stress or emergency; it contains chiefly adrenergic fibers and tends to depress secretion, decrease the tone and contractility of smooth muscle, and increase heart rate.

ACE inhibitors generally are well tolerated, but rarely may cause dangerous reactions including laryngospasm and angioedema. Persistent cough is a common side effect. ACE inhibitors should not be used in pregnancy. When used in pregnancy during the second and third trimesters, angiotension-converting inhibitors (ACEIs) can cause injury to and even death in the developing fetus. When pregnancy is detected, discontinue the ACE inhibitor as soon as possible. Breastfeeding is not recommended.

ACE II inhibitors are generally well tolerated and do not cause cough. Pregnancy risk factor is category C during the first trimester and category D during the second and third trimesters. Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in patients who were taking ACE inhibitors. When pregnancy is detected, AIIRAs should be discontinued as soon as possible. Breastfeeding is not recommended.

Thiazide diuretics commonly cause potassium depletion. Patients should have potassium supplementation either through diet or potassium supplements. Pregnancy risk factor is category B (chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, metolazone) or category C (bendroflumethiazide, benzthiazide, hydroflumethiazide, methyclothiazide, trichlormethiazide). Routine use during normal pregnancy is inappropriate. Thiazides are found in breast milk. Breastfeeding is not recommended.

Beta blockers may cause a large number of adverse reactions including dangerous heart rate abnormalities. Pregnancy risk factor is category B (acebutolol, pindolol, sotalol) or category C (atenolol, labetalol, esmolol, metoprolol, nadolol, timolol, propranolol, penbutolol, carteolol, bisoprolol). Breastfeeding is not recommended. In 2003, a report announced that adavances in pharmacogenetics mean that in the future, physicians may be able to use a patients genetic information to make certain prescribing decisions for antihypertensives.

Interactions

Specific drug references should be consulted, since interactions vary for antihypertensive drugs.

Resources

PERIODICALS

Belden, Heidi. "Debate Continues Over Best Drug for Hypertension." Drug Topics (April 21, 2003): 32.

Mechcatie, Elizabeth. "Genetics Will Guide Prescribing for Hypertension: Genotype Predicts Response to Drug." Internal Medicine News (July 1, 2003): 48-51.

"New Hypertension Guidelines: JNC-7." Clinical Cardiology Alert (July 2003): 54-63.

"Studies Show ThatáStatins Benefits People With High Blood Pressure." Harvard Health Letter (June 2003).

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Antihypertensive Drugs

Antihypertensive drugs

Definition

Antihypertensive drugs are medicines that help lower blood pressure.


Purpose

All antihypertensive agents lower blood pressure, although the mechanisms of action vary greatly. Within this therapeutic class, there are several subgroups. There are a very large number of drugs used to control hypertension, and the drugs listed below are representatives, but not the only members of their classes.


Description

The calcium channel blocking agents, also called slow channel blockers or calcium antagonists, inhibit the movement of ionic calcium across the cell membrane. This reduces the force of contraction of heart muscles and arteries. Although the calcium channel blockers are treated as a group, there are four different chemical classes, leading to significant variations in the activity of individual drugs. Nifedipine (Adalat, Procardia) has the greatest effect on the blood vessels, while verapamil (Calan, Isoptin) and diltiazem (Cardizem) have a greater effect on the heart muscle itself.

Peripheral vasodilators such as hydralazine (Apresoline), isoxuprine (Vasodilan), and minoxidil (Loniten) act by relaxing blood vessels.

There are several groups of drugs that act by reducing adrenergic nerve stimulation, the excitatory nerve stimulation that causes contraction of the muscles in the arteries, veins, and heart. These drugs include the beta-adrenergic blockers and alpha/beta adrenergic blockers. There are also non-specific adrenergic blocking agents.

Beta-adrenergic blocking agents include propranolol (Inderal), atenolol (Tenormin), and pindolol (Visken). Propranolol acts on the beta-adrenergic receptors anywhere in the body, and has been used as a treatment for emotional anxiety and rapid heart beat. Atenolol and acebutolol (Sectral) act specifically on the nerves of the heart and circulation.

There are two alpha/beta adrenergic blockers, labetolol (Normodyne, Trandate) and carvedilol (Coreg). These work similarly to the beta blockers.

Angiotensin-converting enzyme inhibitors (ACE inhibitors) act by inhibiting the production of angiotensin II, a substance that induces both constriction of blood vessels and retention of sodium, which leads to water retention and increased blood volume. There are 10 ACE inhibitors currently marketed in the United States, including captopril (Capoten), benazepril (Lotensin), enalapril (Vasotec), and quinapril (Acupril). The primary difference between these drugs is their onset and duration of action.

The ACE II inhibitors, losartan (Cozaar), candesartan (Atacand), irbesartan (Avapro), telmisartan (Micardis), valsartan (Diovan), and eprosartan (Teveten) directly inhibit the effects of ACE II rather than blocking its production. Their actions are similar to the ACE inhibitors, but they appear to have a more favorable side effect and safety profile.

In addition to these drugs, other classes of drugs have been used to lower blood pressure, most notably the thiazide diuretics . There are 12 thiazide diuretics marketed in the United States, including hydrochlorothiazide (Hydrodiuril, Esidrex), indapamide (Lozol), polythiazide (Renese), and hydroflumethiazide (Diucardin). The drugs in this class appear to lower blood pressure through several

Antihypertensive Drugs
brand name (generic name) possible common side effects include:
accupril (quinapril hydrochloride) headache, dizziness
aldatazide diarrhea, fever, headache, decreased coordination
aldactone (spironolactone) cramps, drowsiness, stomach disorders
aldomet (methyldopa) fluid retention, headache, weak feeling
altace (ramipril) headache, cough
calan, calan sr (verapamil hydrochloride) constipation, fatigue, decreased blood pressure
capoten (captopril) decreased sense of taste, decreased blood pressure tiching, rash
cardene (nicardipine hydrochloride) dizziness, headache, indigestion and nausea, increased heartbeat
cardizem (diltiazem hydrochloride) dizziness, fluid retention, headache, nausea, skin rash
cardura (doxazosin mesylate) dizziness, fatigue, drowsiness, headache
catapres dry mouth, drowsiness, dizziness, constipation
corgard (nadolol) behaviorial changes, dizziness, decreased heartbeat, tiredness
corzide dizziness, decreased heartbeat, fatigue, cold hands and feet
diuril (chlorothiazide) cramps, constipation or diarrhea, dizziness, fever, increased glocose level in urine
dyazide blurred vision, muscle and abdominal pain, fatigue
dynacirc (isradipine) chest pain, fluid retention, headache, fatigue
hydrodiuril (hydrochlorothiazide) upset stomach, headache, cramps, loss of appetite
hygroton (chlorthalidone) anemia, constipation or diarrhea, cramps, itching
hytrin (terazosin hydrochloride) dizziness, labored breathing, nausea, swelling
inderal (propranolol hydrochloride) constipation or diarrhea, tingling sensation, nausea and vomiting
inderide blurred vision, cramps, fatigue, loss of appetite
lasix (furosemide) back and muscle pain, indigestion, nausea
lopressor (metoprolol tartrate) diarrhea, itching/rash, tiredness
lotensin (benazepril hydrochloride) nausea, dizziness, fatigue, headache
alozol (indapamide) anxiety, headache, loss of energy, muscle cramps
maxzide cramps, labored breathing, drowsiness, irritated stomach
minipress (prazosin hdrochloride) headache, nausea, weakness, dizziness
moduretic diarrhea, fatigue, itching, loss of appetite
monopril (fosinopril sodium) nausea and vomiting, headache, cough
normodyne (labetalol hydrochloride) fatigue, nausea, stuffy nose
plendil (felodipine) pain in back, chest, muscles, joints, and abdomen, itching, dry mouth, respiratory problems
procardia, procardia x (nifedipine) swelling, constipation, decreased blood pressure, nausea, fatigue
sectral (acebutolol hydrochloride) constipation or diarrhea, gas, chest and joint pain
ser-ap-es blurred vision, cramps, muscle pain, dizziness
tenex (guanfacine hydrochloride) headache, constipation, dry mouth, weakness
tenoretic decreased heartbeat, fatigue, nausea
tenormin (atenolol) nausea, fatigue, dizziness
veseretic diarrhea, muscle cramps, rash
vasotec (enalapril maleate) chest pain, blurred vision, constipation or diarrhea, hives, nausea
visken (pindolol) muscle cramps, labored breathing, nausea, fluid retention
wytensin (guanabenz acetate) headache, drowsiness, dizziness
zaroxolyn (metolazone) constipation or diarrhea, chest pain, spasms, nausea
zestoretic (lisinopril hydrochlorothiazide) fatigue, headache, dizziness
zestril (lisinopril) labored breathing, abdominal and chest pain, nausea, decreased blood pressure



mechanisms. By promoting sodium loss they lower blood volume. At the same time, the pressure of the walls of blood vessels, the peripheral vascular resistance, is lowered. Thiazide diuretics are commonly used as the first choice for reduction of mild hypertension, and may be used in combination with other antihypertensive drugs.

Sodium nitroprusside (Nitropress) and diazoxide (Hyperstat) are used for rapid treatment of hypertensive emergencies. They are given by vein, often during surgery, to reduce blood pressure that suddenly becomes elevated.

Many classes of antihypertensive drugs have been used before surgery to maintain a low blood pressure during the procedure. There does not appear to be a significant difference between drugs when they are used for blood pressure reduction during surgery.

Recommended dosage

Recommended dosage varies with patient, drug, severity of hypertension, and whether the drug is being used alone or in combination with other drugs. Patients should consult specialized references or ask a physician for further information.


Precautions

The warnings and precautions given below apply to the use of antihypertensive drugs over a long period of time. These adverse effects are generally not a problem when the drugs are given as a single dose prior to surgery.

Because of the large number of classes and individual drugs in this group, patients should ask their physicians about specific drugs.

Peripheral vasodilators may cause dizziness and orthostatic hypotensiona rapid lowering of blood pressure when the patient stands up in the morning. Patients taking these drugs must be instructed to rise from bed slowly. Pregnancy risk factors for this group are generally category C, meaning they may result in adverse affects on the fetus. Hydralazine has been shown to cause cleft palate in animal studies, but there is no human data available. Breastfeeding is not recommended.

ACE inhibitors are generally well tolerated, but may rarely cause dangerous reactions including laryngospasm and angioedema. Persistent cough is a common side effect. ACE inhibitors should not be used in pregnancy. When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury to and even death in the developing fetus. When pregnancy is detected, discontinue the ACE inhibitor as soon as possible. Breastfeeding is not recommended.

ACE II inhibitors are generally well tolerated and do not cause cough. Pregnancy risk factor is category C during the first trimester and category D (known to cause adverse effects in the fetus) during the second and third trimesters. Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in patients who were taking ACE inhibitors. When pregnancy is detected, discontinue ACE inhibitors as soon as possible. Breast-feeding is not recommended.

Thiazide diuretics commonly cause potassium depletion. Patients should have potassium supplementation either through diet, or potassium supplements. Pregnancy risk factor is category B (chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, metolazone) or category C (bendroflumethiazide, benzthiazide, hydroflumethiazide, methyclothiazide, trichlormethiazide). Routine use during normal pregnancy is inappropriate. Thiazides are found in breast milk. Breastfeeding is not recommended.

Beta blockers may cause a large number of adverse reactions including dangerous heart rate abnormalities. Pregnancy risk factor is category B (acebutolol, pindolol, sotalol) or category C (atenolol, labetalol, esmolol, metoprolol, nadolol, timolol, propranolol, penbutolol, carteolol, bisoprolol). Breastfeeding is not recommended.


Interactions

Patients should ask their doctors and consult specific references for food and drug interactions.

Samuel Uretsky, PharmD

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antihypertensive

antihypertensive (anti-hy-per-ten-siv) adj. describing drugs or other agents used in treating high blood pressure.

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antihypertensive

antihypertensive Drug, diet, or other treatment used to treat hypertension by lowering blood pressure.

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