ACE inhibitor

Angiotensin-converting-enzyme inhibitors, known as ACE inhibitors, are a vital class of medication. They primarily treat high blood pressure, also called hypertension, and heart failure. These drugs are also used for various cardiovascular and kidney diseases. They help manage conditions like acute myocardial infarction, which is a heart attack. They are also helpful for kidney complications caused by diabetes, known as diabetic nephropathy. By lowering blood pressure, they prevent injury to the kidneys.

To understand how these drugs work, we must look at the renin-angiotensin-aldosterone system, or RAAS. This is a major mechanism the body uses to regulate blood pressure. When the body detects low blood pressure or low sodium, the kidneys release an enzyme called renin. Renin acts on a protein from the liver to create angiotensin I. Then, the angiotensin-converting enzyme, or ACE, removes two residues from angiotensin I. This chemical reaction converts it into angiotensin II. Angiotensin II is a potent vasoconstrictor, meaning it causes blood vessels to narrow. This narrowing increases blood pressure and causes the body to retain salt and water.

ACE inhibitors interrupt this specific chemical chain. By blocking the ACE enzyme, these drugs prevent the formation of angiotensin II. This leads to the relaxation of blood vessels, which lowers arteriolar resistance. The drugs also increase the levels of a peptide called bradykinin. Normally, the ACE enzyme breaks down bradykinin. When the enzyme is inhibited, bradykinin levels rise. Bradykinin acts as a vasodilator, which helps blood vessels open wide. This dual action of decreasing a vasoconstrictor and increasing a vasodilator works synergistically to lower blood pressure.

There are several specific types of ACE inhibitors used in medicine. Common examples include captopril, enalapril, lisinopril, and perindopril. Other frequently prescribed versions are benazepril, zofenopril, trandolapril, and ramipril. Doctors often choose these as a first-line treatment, especially for patients with diabetes. In some cases, doctors may prescribe a fixed-dose combination. This might include an ACE inhibitor paired with a thiazide diuretic. These combinations help achieve the desired blood pressure improvements more effectively.

While these medicines are helpful, they can cause various side effects. A very common side effect is a persistent dry cough. This is believed to be linked to the increased levels of bradykinin in the body. Some patients, about 0.7%, may develop angioedema, which is a swelling caused by increased bradykinin. Another serious complication is hyperkalemia, or high potassium levels in the blood. This happens because suppressing angiotensin II also decreases levels of aldosterone. Since aldosterone helps the body excrete potassium, its decrease causes the body to retain it. High potassium can lead to muscle weakness or even cardiac dysfunction.

Medical research has uncovered surprising benefits for these drugs. A 2012 meta-analysis in the BMJ suggested ACE inhibitors might reduce pneumonia risk. For patients who previously had a stroke, the risk reduction was 54%. For those with heart failure, the risk reduction was 37%. In people of Asian descent, the risk reduction was 43% compared to 54% in non-Asian populations. Additionally, enalapril has been shown to help people with schizophrenia. It can decrease excessive water consumption, a condition called psychogenic polydipsia, in 60% of people. They are also used after kidney transplants to manage erythrocytosis, where hematocrit levels stay above 51%.

It is critical to note that ACE inhibitors are dangerous during pregnancy. They are classified as ADEC pregnancy category D. Taking them during the second or third trimester carries a boxed warning in the U.S. because they can cause birth defects. About half of newborns exposed to these drugs are adversely affected. This can include problems like renal dysplasia or pulmonary hypoplasia. Furthermore, patients with certain conditions, such as bilateral renal artery stenosis, should not take them. Doctors must closely monitor kidney function and potassium levels to ensure patient safety.