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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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Antihypertensive Drugs

Antihypertensive Drugs

Definition

Antihypertensive drugs are medicines that help lower blood pressure.

Antihypertensive drugs
Brand name (generic name) Possible common side effects include:
Accupril (quinapril hydrochloride)Headache, dizziness
AldactazideDiarrhea, fever, headache, decreased coordination
Aldactone (spironolactone)Cramps, drowsiness, stomach disorders
Aldomet (methylodpa)Fluid retention, headache, weak feeling
Alozol (indapamide)Anxiety, headache, loss of energy, muscle cramps
Altace (ramipril)Headache, cough
Calan, Calan SR (verapamil hydrochloride)Constipation, fatigue, decreased blood pressure
Capoten (captopril)Decreased sense of taste, decreased blood pressure, itching, rash
CapozideDecreasd sense of taste, decreased blood pressure, itching, 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
CatapresDry mouth, drowsiness, dizziness, constipation
Corgard (nadolol)Behavioral changes, dizziness, decreased heartbeat, tiredness
CorzideDizziness, decreased heartbeat, fatigue, cold hands and feet
Diuril (chlorothiazide)Cramps, constipation or diarrhea, dizziness, fever, increased glocose level in urine
DyazideBlurred 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
InderideBlurred 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
MaxzideCramps, labored breathing, drowsiness, irritated stomach
Minipress (prazosin hydrochloride)Headache, nausea, weakness, dizziness
ModureticDiarrhea, fatigue, itching, loss of appetite
Monopril (fosinopril sodium)Nausea and vomiting, headache, cough
Normodyne (labetalol hydrochloride)Fatigue, nausea, stuffy nose
Norvasc (amlodipine besylate)Fluid retention, fatigue, dizziness, headache
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-EsBlurred vision, cramps, muscle pain, dizziness
Tenex (guanfacine hydrocloride)Headache, constipation, dry mouth, weakness
TenoreticDecreased heartbeat, fatigue, nausea
Tenormin (atenolol)Nausea, fatigue, dizziness
VesereticDiarrhea, 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

Purpose

The overall class of antihypertensive agents lowers 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.

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 which 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 both induces 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 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.

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. Consult specialized references for further information.

Precautions

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

Peripheral vasodilators may cause dizziness and orthostatic hypotension—a 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.

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 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. 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.

KEY TERMS

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

Angioedema— An allergic skin disease characterized by patches of circumscribed swelling involving the skin and its subcutaneous layers, the mucous membranes, and sometimes the viscera—called 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 well-controlled 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 outweigh 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.

Interactions

Health care personnel should consult specific references for food and drug interactions.

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Antihypertensive Drugs

Antihypertensive drugs

Definition

Antihypertensive drugs are medications which lower blood pressure .

Description

Hypertension , high blood pressure, is defined as a sustained resting blood pressure with a systolic blood pressure equal to or greater than 140, or a diastolic level equal to or greater than 90, or both. Sometimes, high blood pressure has a recognized cause, such as kidney damage, in which case the condition is termed “secondary” hypertension, but more often, blood pressure is elevated without an obvious reason.

In 2003, the United States National Heart, Lung and Blood Institute convened an expert panel to review diagnosis and treatment of hypertension. Key parts of their report are:

  • In persons older than 50 years, systolic blood pressure, The pressure generated by the heart during its contraction, greater than 140 mmhg is a much more important cardiovascular disease (cvd) risk factor than an elevated diastolic blood pressure, the pressure while the heart is relaxed.
  • The risk of CVD Rises when the blood pressure is consistently greater than 115/75. The risk of developing high blood pressure increases with increasing age.
  • Individuals with a systolic blood pressure of 120–139 mmHg or a diastolic blood pressure of 80–89 mmHg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD.
  • Thiazide-type diuretics, often called water pills, should be used as the first drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. The presence of certain high-risk conditions IS A compelling indication for choosing drugs from other classes rather than diuretics as the first treatment for hypertension. These other classes are angiotensin converting enzyme inhibitors (ACEs), angiotensin receptor blockers (ARBs), beta-blockers, and calcium channel blockers).
  • Most patients with hypertension will require two or more antihypertensive medications to achieve a blood pressure goal (⟨140/90, or ⟨130/80 mmHg for patients with diabetes or chronic kidney disease).

The drugs recommended for first line use are the “thiazide-type” diuretics , a group of drugs that increase the urinary excretion of several electrolytes, particularly potassium and bicarbonate. Although they cause increased urination, which lowers blood volume, and which may be useful in treating swelling and edema , this is not the mechanism by which these drugs lower blood pressure. In time, the increased urination stops, but the benefits to the blood pressure remain. The drugs in this group are bendroflumethiazide, chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, methyclothiazide, metolazone and trichlormethiazide. These drugs are generally similar in activity. The expert panel recommended thiazide-type diuretics for a number of reasons. They are generally well-tolerated, most patients respond to them, and they are low in cost. In studies, the thiazide-type diuretics, which cost only a few cents a day, were as effective as newer, far more costly drugs. Note, however, that because the thiazides deplete potassium, many patients must take potassium supplements in addition to the diuretic. While the potassium supplements are also low in cost, they add another dose to remember for patients who are already on a multi-drug regimen.

Antihypertensive drugs
Brand name Generic name
(Illustration by GGS Information Services. Cengage Learning, Gale)
Accupril, Accuretic (combination drug containing quinapril hydrochloride and hydrochlorothiazide)quinapril
Adalat, Adalat CC, Nifedical XL, Procardia, Procardia XLnifedipine
Aldactazide, Aldoril, Capozide, Dyazide, HydroDIURIL, Inderide, Lopressor HCT, Maxzide, Microzide, Moduretic, Timolidehydrochlorothiazide
Aldactonespironolactone
Altaceramipril
Calan, Calan SR, Covera-HS, Isoptin SR, Verelan, Verelan PMverpamil
Capotencaptopril
Cardene, Cardene SRnicardipine
Cardizem, Cardizem CD, Cardizem Lyo-Ject, Cardizem Monovial, Cardizem SR, Cartia XT, Dilacor XR, Diltia XT, Tiazacdiltiazem
Cardura, Cardura XLdoxazosin
Catapres, Catapres-TTS, Clorpres, Duraclonclonidine
Corgard, Corzide (combination product containing both nadolol and bendroflumethiazide)nadolol
Diuril, Diuril Sodium Intravenouschlorothiazide
DynaCirc, DynaCirc CRisradipine
Hytrinterazosin
Inderal, Inderal LA, Innopran XL, Propranolol Hydrochloride Intensolpropranolol
Lasixfurosemide
Lotensin HCT (combination product)benazepril and hydrochlorothiazide
Minipressprazosin
Monopril, Monopril-HCT (combination product containing fosinopril and hydrochlorothiazide)fosinopril
Mykrox, Zaroxolynmetolazone
Normodyne, Trandatelabetalol
Plendilfelodipine
Prinivil, Zestrillisinopril
Prinzide, Zestoreticlisinopril and hydrochlorothiazide
Sectralacebutolol
Tenexguanfacine
Tenormin, Tenormin I.V., Tenoretic (combination product containing atenolol and chlorthalidone)atenolol
Vasotecenalapril
Viskenpindolol
Wytensinguanabenz

A second widely used class of antihypertensive drugs is the beta adrenergic blocking agents, commonly called “beta blockers.” This is a large group of drugs: atenolol, betaxolol HCl (hydrochloride), penbutolol sulfate, carteolol HCl, pindolol, metoprolol, timolol, acebutolol HCl, nadolol and propanolol HCl. There are two other drugs in the class, esmolol and sotalol but they are not indicated for treatment of high blood pressure. The drugs in this group have many additional uses, including treatment of glaucoma , treating heart arrhythmias , treatment of migraine headaches and stage fright. They are considered appropriate for younger patients, but are also recommended for patients who have had heart attacks since there is evidence that they can extend survival and reduce the risk of a second attack. Because they are useful for migraine headaches, they can be a good choice for patients who also suffer from migraines, and also for patients who have irregular heartbeats.

Two drugs, carvedilol and labetolol are both alpha and the beta blockers ; i.e., they block the proteins on cells called alpha receptors and beta receptors. Although these drugs can be used for treatment of hypertension, they are not frequently used for this, but do have other uses. Carvedilol is commonly used as part of a multidrug regimen for treatment of congestive heart failure , while labetolol, when given by injection, has been useful in treatment of severe and dangerous hypertension in hospitalized patients.

The angiotensin converting enzyme inhibitors (ACE) include captopril, enalapril, lisinopril, benazepril, quinapril, moexipril, perindopril, trandolapril, ramipril, and fosinopril. While there are some differences among them, the ACEs are largely inter-changeable. They are frequently used to treat younger patients, patients with left ventricular failure, patients with type 1 diabetes and diabetic kidney disease, and patients with other kidney disorders. These drugs can be less effective for people of african descent.

There is a second group of drugs, the Angiotensin receptor blockers: losartan, valsartan, irbesartan, candesartan, telmisartan, eprosartan and olmesartan. These drugs are appropriate for patients who would be candidates for the ACE inhibitors, but cannot take them because of side effects.

The calcium channel blocking agents, which are sometimes called the “slow channel blockers” are amlodipine, diltiazem, nicardipine, nifedipine, nisoldipine, nimodipine, isradipine and verapamil. These drugs control the flow of calcium in the heart. These drugs are often preferred for elderly patients, people of African ancestry, patients who experience angina , and those with heart beat irregularities. With the exception of nifedipine, these drugs can be preferred for patients with a high risk of coronary artery disease.

There are a few older drugs used to treat hypertension, guanethidine, hydralazine, methyldopa and reserpine, but they have largely been supplanted by the newer agents. There is also a large number of combination drugs, which contain two drugs that are commonly used together. In most cases, these contain a thiazide diuretic with an ACE inhibitor or calcium channel blocker. These combinations offer some degree of convenience.

Precautions

All drugs in this group are generally well tolerated when used to treat uncomplicated hypertension in otherwise healthy individuals. However, when these drugs are used in patients with significant problems such as coronary artery disease or angina, those who are recovering from a heart attack , or simply the elderly, the potential for adverse reactions is greatly increased. Consult product specific literature for the warnings and precautions that apply to a patient's specific condition.

Thiazides: Hypokalemia, a low blood potassium level, can develop, with consequent weakness, cramps, and heart rhythm abnormalities. Hypokalemia can be seen during the simultaneous use of steroids, when diuresis or water loss is particularly rapid, with severe liver disease or cirrhosis , vomiting or diarrhea , or after prolonged therapy. Hypokalemia can cause cardiac arrhythmias and sensitize or exaggerate the heart's response to the toxic effects of digitalis.

ACE I inhibitors: Angiotensin-converting enzyme inhibitors (ACEs) can cause a profound fall in blood pressure, hypotension, following the first dose. Excessive hypotension is rare in uncomplicated hypertensive patients, but is possible with ACE use in people who are slat or water depleted, such as those treated vigorously with diuretics or patients on dialysis. Patients at risk for excessive hypotension include those with the following conditions or characteristics: heart failure, hyponatremia (a low blood sodium level), high-dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, dialysis, or severe volume and/or salt depletion.

Side effects

These drugs have a large number of side effects reported. These side effects may vary with the patient's specific condition. See drug specific references.

Interactions

See drug specific references

Caregiver concerns

Be alert for significant adverse effects. Note particularly the symptoms of hypokalemia in patients taking thiazides.

Be sure the patient is taking medication as prescribed. Antihypertensive drugs must be taken regularly. If adherence to the medication regimen is a problem, discuss the selection of drugs with the prescriber.

  • Is there a less costly, formulary drug or drugs available?
  • If I am taking one of the thiazides, should I supplement my potassium intake with certain foods or a supplement?
  • What are the potential interactions with my other medications?

KEY TERMS

Congestive heart failure —heart failure in which the heart is unable to maintain adequate circulation of blood in the tissues of the body.

CVD —Cardiovascular disease, includes heart attack, stroke, heart failure and rheumatic heart disease.

Diastolic —The relaxation period of heart cycle during which the chambers fill with blood.

Glaucoma —A disease of the eye marked by increased pressure within the eyeball that can result in damage to the optic disk and gradual loss of vision

Hypertension —High blood pressure

Hypokalemia —Low serum potassium

Migraine —A condition that is marked by recurrent usually one-sided severe headache often accompanied by nausea and vomiting and followed by sleep

Systolic —The contraction period of the heart cycle during which blood is pumped to the body.

Resources

BOOKS

Higgins, B (ch) Hypertension: Management in Adults in Primary Care: Pharmacological Update Royal College of Physicians, London 2006

Fennell, J, Baker AH Hypertension: Methods and Protocols Humana, Totowa NJ 2005

Zanchetti, A, Hansen, L Hypertension McGraw-Hill, New York 2001

PERIODICALS

Duprez DA Systolic hypertension in the elderly: addressing an unmet need Am J Med. 2008 Mar;121(3):179-184.e3.

Aronow WS. Optimal medical therapy after MI in the elderly. Geriatrics. 2008 Jan;63(1):24-30

Neutel JM, Gilderman LI. Hypertension control in the elderly. J Clin Hypertens (Greenwich). 2008 Jan; 10(1 Suppl 1):33-9.

Veronesi M, Cicero AF, Prandin MG, et al A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice. Vasc Health Risk Manag. 2007;3(6):999-1005

Schneider PJ, Murphy JE, Pedersen CA. Impact of medication packaging on adherence and treatment outcomes in older ambulatory patients. J Am Pharm Assoc (2003). 2008 Jan-Feb;48(1):58-63

Saunders E, Cable G, Neutel J. Predictors of blood pressure response to angiotensin receptor blocker/diuretic combination therapy: a secondary analysis of the irbesartan/hydrochlorothiazide blood pressure reductions in diverse patient populations (INCLUSIVE) study. J Clin Hypertens (Greenwich). 2008 Jan;10(1):27–33.

Wright JT Jr, Harris-Haywood S, Pressel S, et al Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2008 Jan 28; 168(2):207-17.

Tay EL, Chan M, Tan V, et al Impact of combination evidence-based medical therapy on mortality following myocardial infarction in elderly patients. Am J Geriatr Cardiol. 2008 Jan-Feb;17(1):21-6.

Shimosawa T, Gohchi K, Yatomi Y, et al Effectiveness of add-on low-dose diuretics in combination therapy for hypertension: losartan/hydrochlorothiazide vs. candesartan/amlodipine. Hypertens Res. 2007 Sep;30(9):831-7.

Weir MR, Levy D, Crikelair N, et al Time to achieve bloodpressure goal: influence of dose of valsartan monotherapy and valsartan and hydrochlorothiazide combination therapy. Am J Hypertens. 2007 Jul; 20(7):807-15.

Spencer CG, Felmeden DC, Blann AD, et al Effects of “newer” and “older” antihypertensive drugs on hemorrheological, platelet, and endothelial factors. A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial. 1: Am J Hypertens. 2007 Jun;20(6):699–704

Poldermans D, Glazes R, Kargiannis S et al Tolerability and blood pressure-lowering efficacy of the combination of amlodipine plus valsartan compared with lisinopril plus hydrochlorothiazide in adult patients with stage 2 hypertension. 1: Clin Ther. 2007 Feb;29 (2):279-89.

OTHER

http://www.nhlbi.nih.gov/guidelines/hypertension/jncintro.htm

http://online.factsandcomparisons.com/

http://www.merck.com/mmpe/index.html

http://www.nlm.nih.gov/medlineplus/highbloodpressure.html

http://www.nlm.nih.gov/medlineplus/ency/article/000153.htm

http://health.nih.gov/result.asp/329/10

http://www.americanheart.org/presenter.jhtml?identifier=2114

http://www.nhlbi.nih.gov/hbp/http://www.mayoclinic.com/health/high-blood-pressure/DS00100

http://www.drugbank.ca/

ORGANIZATIONS

American Heart Association, 7272 Greenville Avenue, Dallas, Texas, 75231, 1-800-242-8721, http://www.americanheart.org.

World Hypertension League, 100-1260 Hamilton Street, Suite 52, Vancouver, BC, Canada, V6B 2S8, +1-604-268-7176, +1-604-291-5927, [email protected], http://www.worldhypertensionleague.org/.

Sam Uretsky PharmD

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"Antihypertensive Drugs." The Gale Encyclopedia of Senior Health: A Guide for Seniors and Their Caregivers. . Retrieved September 23, 2018 from Encyclopedia.com: http://www.encyclopedia.com/caregiving/encyclopedias-almanacs-transcripts-and-maps/antihypertensive-drugs

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Antihypertensive Drugs

Antihypertensive Drugs

Definition
Purpose
Description
Recommended dosage
Precautions
Interactions

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

KEY TERMS

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

Angioedema— An allergic skin disease characterized by patches of circumscribed swelling involving the skin and its subcutaneous layers, the mucous membranes, and sometimes the viscera—also called 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 well-controlled 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 outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

Sympathetic nervous system The part of the autonomic nervous system that is concerned 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.

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, labetalol (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 I, a substance that induces both constriction of blood vessels and retention of sodium, which leads to water retention and increased blood volume. As of the early 2000s, there are 10 ACE inhibitors marketed in the United States, including captopril (Capoten), benazepril (Lotensin), enalapril (Vasotec), lisinopril (Prinivil, Zestril), 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 a number of thiazide diuretics marketed in the United States, including hydrochlorothiazide (Hydrodiuril, Esidrex), indapamide (Lozol), polythiazide (Renese), and hydroflume-thiazide (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. These drugs cause a constant loss of potassium from the body; patients should check with their physicians about augmenting their potassium intake.

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 hypotension—a 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. Breast-feeding 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. Breast-feeding 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. Breast-feeding 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). Breast-feeding is not recommended.

Interactions

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

Sam Uretsky, Pharm.D.

Fran Hodgkins

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