What are ACE inhibitors, and how do they work (mechanism of action)?
Angiotensin II is a very potent chemical produced by the body that primarily circulates in the blood. It causes the muscles surrounding blood vessels to contract, thereby narrowing the vessels. The narrowing of the vessels increases the pressure within the vessels causing increases in blood pressure (hypertension). Angiotensin II is formed from angiotensin I in the blood by the enzyme angiotensin converting enzyme (ACE). (Angiotensin I in the blood is itself formed from angiotensinogen, a protein produced by the liver and released into the blood.) Angiotensin converting enzyme inhibitors (ACE inhibitors) are medications that slow (inhibit) the activity of the enzyme ACE, which decreases the production of angiotensin II. As a result, blood vessels enlarge or dilate, and blood pressure is reduced. This lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. In addition, the progression of kidney disease due to high blood pressure or diabetes is slowed.
Why are ACE inhibitors prescribed (uses)?
- ACE inhibitors are used for:
- Controlling acute and chronic high blood pressure
- Treating left ventricular dysfunction and heart failure
- Preventing strokes
- Preventing and treating kidney disease (nephropathy) in people with hypertension or diabetes
- ACE inhibitors also improve survival after heart attacks. In studies, individuals with hypertension, heart failure, or prior heart attacks who were treated with an ACE inhibitor lived longer than patients who did not take an ACE inhibitor.
- ACE inhibitors are an important group of drugs because they prevent early death resulting from hypertension, heart failure or heart attacks.
- Some individuals with hypertension do not respond sufficiently to ACE inhibitors alone. In these cases, other drugs often are used in combination with ACE inhibitors.
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What are the side effects and adverse event of ACE inhibitors?
ACE inhibitors are well-tolerated by most individuals. Nevertheless, they are not free of side effects, and some patients should not use ACE inhibitors. ACE inhibitors usually are not prescribed for pregnant women because they may cause birth defects. Individuals with bilateral renal artery stenosis (narrowing of the arteries that supply the kidneys) may experience worsening of kidney function, and people who have had a severe reaction to ACE inhibitors probably should avoid them.
The most common side effects are:
- Cough
- Elevated blood potassium levels
- Low blood pressure,
- dizziness
- Headache
- Drowsiness
- Weakness
- Abnormal taste (metallic or salty taste)
- Rash
- Chest pain
- Increased uric acid levels
- Sun sensitivity
- Increased BUN and creatinine levels
It may take up to a month for coughing to subside, and if one ACE inhibitor causes cough it is likely that the others will too.
The most serious, but rare, side effects of ACE inhibitors are:
- Kidney failure
- Allergic reactions
- Pancreatitis
- Liver dysfunction
- A decrease in white blood cells
- Swelling of tissues (angioedema).
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List of examples of brand and generic drug names for ACE inhibitors
The following is a list of the ACE inhibitors that are available in the United States:
- benazepril (Lotensin)
- captopril (Capoten– discontinued brand)
- enalapril (Vasotec, Epaned, [Lexxel- discontinued brand])
- fosinopril (Monopril– Discontinued brand)
- lisinopril (Prinivil, Zestril, Qbrelis)
- moexipril (Univasc– Discontinued brand)
- perindopril (Aceon)
- quinapril (Accupril)
- ramipril (Altace)
- trandolapril (Mavik)
Are there any differences among the different types of ACE inhibitors?
ACE inhibitors are very similar. However, they differ in how they are eliminated from the body and their doses. Some ACE inhibitors remain in the body longer than others, and are given once a day. Some ACE inhibitors need to be converted into an active form in the body before they work. In addition, some ACE inhibitors may work more on ACE that is found in tissues than on ACE that is present in the blood. The importance of this difference or whether one ACE inhibitor is better than another has not been determined.
What drugs or supplements interact with ACE inhibitor drug class?
ACE inhibitors have few interactions with other drugs.
- Since ACE inhibitors may increase blood levels of potassium, the use of potassium supplements, salt substitutes (which often contain potassium), or other drugs that increase the body's potassium may result in excessive blood potassium levels.
- ACE inhibitors also may increase the blood concentration of lithium (Eskalith, Lithobid) and lead to an increase in side effects from lithium.
- There have been reports that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Advil, Children's Advil/Motrin, Medipren, Motrin, Nuprin, PediaCare Fever etc.), indomethacin (Indocin, Indocin-SR), and naproxen (Anaprox, Naprelan, Naprosyn, Aleve) may reduce the blood pressure lowering effects of ACE inhibitors.
- Patients receiving diuretics may experience excessive reduction in blood pressure when ACE inhibitors are started. Stopping the diuretic or increasing salt intake prior to taking the ACE inhibitor may prevent excessive blood pressure reduction. Close supervision for at least two hours after the start of ACE inhibitors and until blood pressure is stable is recommended if the diuretic cannot be stopped.
- ACE inhibitors should not be combined with ARBs because such combinations increase the risk of hypotension, hyperkalemia, and renal impairment.
- Ace inhibitors should not be combined with aliskiren (Tekturna), another class of drugs that is used to treat high blood pressure because such combinations increase the risk of kidney failure, excessive low blood pressure, and hyperkalemia.
- Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and low blood pressure) may occur when injectable (gold sodium aurothiomalate [Myochrysine]), used in the treatment of rheumatoid arthritis, is combined with ACE inhibitors.