Angiotensin-converting enzyme inhibitors

Definition

Angiotensin-converting enzyme inhibitors (also called ACE inhibitors) are medicines that block the conversion of the chemical angiotensin I to a substance that increases salt and water retention in the body.

Description

ACE inhibitors are used in the treatment of high blood pressure. They may be used alone or in combination with other medicines for high blood pressure. They work by preventing a chemical in the blood, angiotensin I, from being converted into a substance that increases salt and water retention in the body. Increased salt and water retention lead to high blood pressure. ACE inhibitors also make blood vessels relax, which helps lower blood pressure and allows more oxygen-rich blood to reach the heart.

Treating high blood pressure is important because the condition puts a burden on the heart and the arteries, which can lead to permanent damage over time. If untreated, high blood pressure increases the risk of heart attacks, heart failure, stroke , or kidney failure.

ACE inhibitors may also be prescribed for other conditions. For example, captopril (Capoten) is used to treat kidney problems in people who take insulin to control diabetes. Captopril and lisinopril are also given to some patients after a heart attack . Heart attacks damage and weaken the heart muscle, and the damage continues even after a person recovers from the attack. This medicine helps slow down further damage to the heart. ACE inhibitors also may be used to treat congestive heart failure .

ACE inhibitors are available only with a physician 's prescription and come in tablet, capsule, and injectable forms. Some commonly used ACE inhibitors are benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace) and trandolapril (Mavik).

Recommended dosage

The recommended dosage depends on the type of ACE inhibitor and the medical condition for which it is being taken. Check with the physician who prescribed the drug or the pharmacist who filled the prescription for the correct dosage.

This medicine may take weeks to noticeably lower blood pressure. Take it exactly as directed.

Do not stop taking this medicine without checking with the physician who prescribed it.

Precautions

A person taking an ACE inhibitor should see a physician regularly. The physician will check the blood pressure to make sure the medicine is working as it should and will note any unwanted side effects. People who have high blood pressure often feel perfectly fine. However, they should continue to see their physicians even when they feel well so that the physician can keep a close watch on their condition. It is also important for patients to keep taking their medicine even when they feel fine.

ACE inhibitors will not cure high blood pressure, but will help control the condition. To avoid the serious health problems that high blood pressure can cause, patients may have to take medicine for the rest of their lives. Furthermore, medicine alone may not be enough. Patients with high blood pressure may also need to avoid certain foods, such as salty snacks, and keep their weight under control. The health care professional who is treating the condition can offer advice on what measures may be necessary. Patients being treated for high blood pressure should not change their diets without consulting their physicians.

Anyone taking this medicine for high blood pressure should not take any other prescription or over-the-counter (OTC) medicine without first checking with his or her physician. Some medicines, such as certain cold remedies, may increase blood pressure.

Some people feel dizzy or lightheaded after taking the first dose of an ACE inhibitor, especially if they have been taking a water pill (diuretic). Anyone who takes these drugs should not drive, use machines or do anything else that might be dangerous until they have found out how the drugs affect them. Such symptoms should be reported to the physician or pharmacist if they do not subside within a day or so. For the first one or two days of taking an ACE inhibitor, patients may become lightheaded when arising from bed in the morning. Patienst should rise slowly to a sitting position before standing up.

While a goal of treatment with an ACE inhibitor is to lower the blood pressure, patients must be careful not to let their blood pressure get too low. Low blood pressure can lead to dizziness , lightheadedness and fainting . To prevent the blood pressure from getting too low, observe these precautions:

• Do not drink alcohol without checking with the physician who prescribed this medicine.
• Captopril and moexipril should be taken one hour before meals. Other ACE inhinbitors may be taken with or without meals.
• Avoid overheating when exercising or in hot weather. The loss of water from the body through heavy sweating can cause low blood pressure.
• Check with a physician right away if illness occurs while taking an ACE inhibitor. This is especially true if the illness involves severe nausea, vomiting, or diarrhea. Vomiting and diarrhea can cause the loss of too much water from the body, which can lead to low blood pressure.

Anyone who is taking ACE inhibitors should be sure to tell the health care professional in charge before having any surgical or dental procedures or receiving emergency treatment.

Some ACE inhibitors may change the results of certain medical tests, such as blood or urine tests. Before having medical tests, anyone taking this medicine should alert the health care professional in charge.

Do not use a potassium supplement or a salt substitute that contains potassium without first checking with the physician who prescribed the ACE inhibitor.

Special conditions

People with certain medical conditions or who are taking certain other medicines can have problems if they take ACE inhibitors. Before taking these drugs, be sure to let the physician know about any of these conditions.

ALLERGIES Anyone who has had unusual reactions to an ACE inhibitor in the past should let his or her physician know before taking this type of medicine again. The physician should also be told about any allergies to foods, dyes, preservatives, or other substances.

OTHER MEDICAL CONDITIONS Before using ACE inhibitors, people with any of these medical problems should make sure their physicians are aware of their conditions:

• diabetes
• heart or blood vessel disease
• recent heart attack or stroke
• liver disease
• kidney disease
• kidney transplant
• scleroderma
• systemic lupus erythematosus (SLE)

USE OF CERTAIN MEDICINES Taking ACE inhibitors with certain other drugs may affect the way the drugs work or may increase the chance of side effects.

Side effects

The most common side effect is a dry, continuing cough. This usually does not subside unless the medication is stopped. Ask the physician if the cough can be treated. Less common side effects, such as headache, loss of taste, unusual tiredness, and nausea or diarrhea also may occur and do not need medical attention unless they are severe or they interfere with normal activities.

More serious side effects are rare, but may occur. If any of the following side effects occur, check with a physician immediately:

• swelling of the face, lips, tongue, throat, arms, legs, hands, or feet
• itchy skin
• sudden breathing or swallowing problems
• chest pain
• hoarseness
• sore throat
• fever and chills
• stomach pain
• yellow eyes or skin

In addition, anyone who has any of the following symptoms while taking an ACE inhibitor should check with his or her physician as soon as possible:

• dizziness, lightheadedness, fainting
• confusion
• nervousness
• fever
• joint pain
• numbness or tingling in hands, feet, or lips
• weak or heavy feeling in the legs
• skin rash
• irregular heartbeat
• shortness of breath or other breathing problems

Other side effects may occur. Anyone who has unusual symptoms after taking an ACE inhibitor should get in touch with his or her physician.

Interactions

ACE inhibitors may interact with certain foods and other medicines. For example, captopril (Capoten) interacts with food and should be taken one hour before meals. Anyone who takes ACE inhibitors should let the physician know all other medicines he or she is taking and should ask about foods that should be avoided. Among the foods and drugs that may interact with ACE inhibitors are:

• water pills (diuretics)
• lithium, used to treat bipolar disorder
• tetracycline, an antibiotic
• medicines or supplements that contain potassium
• salt substitutes that contain potassium

The list above may not include everything that interacts with ACE inhibitors. Be sure to check with a physician or pharmacist before combining ACE inhibitors with any other prescription or nonprescription (over-the-counter) medicine.

Interactions

Diuretics and other drugs which lower blood pressure—these will cause an additive effect which may result in dizziness. The extent of the effects varies between drugs. This interaction is commonly used therapeutically, so that ACEIs are administered with diuretics, but even so a careful dose adjustment is essential.

Fosinopril and trandolapril should not be taken with antacids , since this will lower the blood veles (?) of thr ACE inhibitors. If the two classes of drugs are required, they should be dosed at intervals of not less than 2 hours.

Non-steroidal anti-inflammatory drugs (NSAIDs), particularly indomethicin, may reduce the effectiveness of ACEIs.

Lithium levels will be increased if taken with an ACEI.

Patients who are being treated with bee or wasp venom to prevent allergic reactions to stings may have a severe allergic reaction to certain ACE inhibitors.

Other drug interactions have been reported. Review the interactions specific for the drug being administered.

Caregiver concerns

Adverse effects may be most common during the first two weeks of treatment. Patients should be observed closely during this period.

Extremely low blood pressure may be observed as postural hypotension-a sudden drop in blood pressure when rising from as prone or supine position. While this can be dealt with my having the patient rise slowly to a standing position, observe patient for signs of dizziness on arising.

QUESTIONS TO ASK YOUR PHARMACIST

• Are there any drug interactions specific to the drug prescribed to me?
• Is there a less expensive formulary drug available?

KEY TERMS

Class effect —A property or therapeutic rersult seen with all members of a chemicaslly related group of drugs.

Enzyme —A protein molecule, produced by an organism, which acts as a catalyst to a chemical reaction within the organism and is neither destroyed nor changed as a result of the reaction.

Essential —In the context of hypertension: without specific or established cause.

Hepatic —Pertaining to the liver.

Hypertension —High blood pressure.

Preload —Relating to the heart: the amount of pressure placed on the heart just before the muscle walls contract.

Renal —Relating to the kidneys.

Renin —An enzyme, produced by the kidneys that acts as a catalyst, causing separation of the leucine-leucine bond in angiotensin to produce angiotensin.

Thiazide —A group of drugs used as oral diuretics especially in the control of high blood pressure.

Vasoconstrictor —An agent that causes blood vessels to contract.

Vasodilator —Anb agent that causes blood vessels to relax.

Resources

BOOKS

Reynild J (ed) Martindale the Extra Pharmacopoeia 30th ed. London: The Pharmaceutical Press, 1993.

Opie LH Angiotensin-Converting Enzyme Inhibitors: Scientific Basis for Clinical Use. New York: John Wiley and Sons, 1994.

National Institutes of Health The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. NIH Publication No. 98-4080, November 1997.

PERIODICALS

Blicklé JF, Doucet J, Krummel T. “Diabetic nephropathy in the elderly.” Diabetes Metab. (April 2007) 33 Suppl 1: S40–55.

Aronow WS, Frishman WH, Cheng-Lai A. “Cardiovascular drug therapy in the elderly.” Cardiol Rev. (Jul-Aug 2007) 15(4): 195–215.

Iannello S, Milazzo P, Bordonaro F, Belfiore F. “Low-dose enalapril in the treatment of surgical cutaneous hypertrophic scar and keloid—two case reports and literature review.” MedGenMed. (Dec 20) 2006 8(4):60.

Andraws R, Brown DL. “Effect of inhibition of the reninangiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials).” Am J Cardiol. (April 1) 2007 99(7): 1006–12.

Nash DT. “Systolic hypertension.” Geriatrics. (December 2006) 61(12): 22–8.

Grady KL. “Management of heart failure in older adults.” J Cardiovasc Nurs. (Sep-Oct 2006) 21(5 Suppl 1): S10–4.

Dagenais GR, Pogue J, Fox K, et al. “Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials.” Lancet. (August 12, 2006) 368(9535): 581–8.

Aronow WS. “Heart failure update: treatment of heart failure with a normal left ventricular ejection fraction in the elderly.” Geriatrics. (August 2006) 61(8): 16–20.

Gold LD, Krumholz HM. “Gender differences in treatment of heart failure and acute myocardial infarction: a question of quality or epidemiology?” Cardiol Rev. Jul-(August 2006) 14(4): 180–6

Mangoni AA, Jackson SH. “The implications of a growing evidence base for drug use in elderly patients Part 2. ACE inhibitors and angiotensin receptor blockers in heart failure and high cardiovascular risk patients.” Br J Clin Pharmacol. (May 2006) 61(5): 502–12

Sleight P, Pouleur H, Zannad F. “Benefits, challenges, and registerability of the polypill.” Eur Heart J. (July 2006) 27(14): 1651–6

Blicklé JF. “Management of hypertension in elderly diabetic patients.” Diabetes Metab. (December 31, 2005) Spec No 2: 5S82–5S91.

ORGANIZATIONS

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

Sam Uretsky PharmD