ACE Inhibitors: What They Are and How They Work

By Gabriel Espinoza, MD

June 21, 2021

ACE Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are a class of medication used to treat high blood pressure, heart failure, and other cardiovascular conditions. ACE inhibitors work by blocking the angiotensin-converting enzymes, leading to less production of angiotensin II. This is a type of hormone that works to constrict blood vessels in the body.

The Food and Drug Administration has approved the use of ACE inhibitors as adjunctive therapy to treat heart failure. It is also approved alone or with another medication in the treatment of high blood pressure. ACE inhibitors provide some protective effects to patients with chronic kidney disease and high blood pressure. ACE inhibitors are also used in people with coronary artery disease and high blood pressure. They have been recommended for chest pain, known as angina, if there is a history of heart failure, type 2 diabetes, or chronic kidney disease. Most importantly, ACE inhibitors have been approved for use during a myocardial infarction—a heart attack—within 24 hours of an event.

This article will review ACE inhibitors’ mechanism of action, adverse effects, common side effects, and associations with COVID-19.

Mechanism of Action

Angiotensin-converting enzyme is involved in an intricate system of hormones that originates in the kidney and controls how tightly blood vessels contract in the body, leading to signs of high blood pressure. This is called the renin-angiotensin-aldosterone system, which stimulates the conversion of angiotensin I, the inactive form, to angiotensin II, the active form of the hormone that works to increase blood pressure by tightly constricting blood vessels in the body. The conversion of angiotensin I to angiotensin II is prevented by ACE inhibitors, leading to a reduction of blood pressure and decreasing the amount of aldosterone, a hormone that helps the body retain salt and in turn, makes the body retain water. This contributes to high blood pressure.

ACE inhibitors are mainly oral medication, but some intravenous forms of the medication are available. Identifying an ACE inhibitor can be simple because the generic form commonly has an “-il” ending, such as:

  • Benazepril
  • Captopril
  • Fosinopril
  • Lisinopril
  • Moexipril
  • Perindopril
  • Quinapril
  • Ramipril
  • Trandolapril

Ace Inhibitors Side Effects

Although ACE inhibitors are beneficial for many cardiovascular conditions, some contraindications to this medication exist. Allergic reactions, such as angioedema, or rapid swelling of the area beneath the skin, can occur when starting this type of medication. This symptom will be noticeable around the face and can be serious and life-threatening because without medical care, angioedema can lead to the closure of your airway due to rapid swelling.

Other contraindications to taking this drug include narrowing of the arteries to your kidneys. Your physician should regularly monitor your kidney function when you are on this medication. ACE inhibitors should not be used in pregnancy.

One of the most common side effects is an ACE inhibitors cough. This side effect can start within one week or up to six months after starting treatment. Discontinuing the medication will usually help the dry cough resolve within 1–4 days, but it can sometimes take up to a month to clear up. The dry cough is likely due to the accumulation of molecules called kinins in the lung, which leads to irritation of the large airways, resulting in coughing. If you develop a cough while on ACE inhibitors, you can change to a different class of medication called angiotensin receptor blockers (ARBs), which have a lower rate of dry cough.

Another side effect of ACE inhibitors includes hyperkalemia, or high potassium levels, due to its mechanism of action. By blocking the development of angiotensin II, ACE inhibitors prevent the release of the hormone aldosterone from the kidneys. This hormone is responsible for the retention of sodium, but it is also responsible for the release of potassium. Therefore, by preventing the release of aldosterone, the body will retain potassium because it is not secreted in the urine.

Although hyperkalemia can be asymptomatic, symptoms can include muscle weakness, numbness, tingling, shortness of breath, chest pain, nausea, or vomiting. If sudden, these can lead to a fatal arrhythmia. Therefore, if you have conditions that lead to hyperkalemia, discuss these with your doctor as ACE inhibitors may not be the best medication for you.

ACE Inhibitors and COVID-19

With the emergence of the COVID-19 pandemic, the use of ACE inhibitors in patients with cardiovascular conditions was questioned because the angiotensin-converting enzyme 2 acts as the binding site of the virus when it enters the airways. In a systemic review conducted by the Journal of the American Medical Association, researchers found patients with COVID-19 on ACE inhibitors or ARBs had a lower risk of mortality and severe adverse events.

In conclusion, starting ACE inhibitors has many benefits if you suffer from cardiovascular diseases such as high blood pressure and heart failure. ACE inhibitors also have huge value in other conditions, such as type I and type II diabetes and nephropathy. Speak with your doctor to see if ACE inhibitors are best for you. Given that most ACE inhibitors can be found in generic form, the ScriptSave® WellRx card will help you save on the price you pay for your prescriptions.

Gabriel Espinoza, MD has experience in caring for patients in both primary care and emergency settings. Some of the topics he has focused on during his medical career include various areas in public health, pediatrics, and wellness. He has co-authored a chapter on the utility of point of care ultrasound in the diagnoses of various eye conditions. The content written by Dr. Espinoza is for information and educational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician with any questions you may have regarding a medical condition.

References:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777978

https://cdn.sanity.io/files/0vv8moc6/ajmc/6310c844dd2adf78bcb5825e8fde6db76117f4d5.pdf

https://www.ncbi.nlm.nih.gov/books/NBK430896/

https://www.kidney.org/atoz/content/what-hyperkalemia

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