Understanding ACE Inhibitors and Their Function
Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat high blood pressure (hypertension), heart failure, and to improve survival after a heart attack [1.4.1, 1.11.2]. They work by blocking the action of the angiotensin-converting enzyme, which is part of the renin-angiotensin-aldosterone system (RAAS) [1.4.2]. This enzyme converts angiotensin I to angiotensin II, a potent substance that constricts blood vessels and stimulates the release of aldosterone, a hormone that causes sodium and water retention [1.4.1]. By inhibiting this process, ACE inhibitors cause blood vessels to relax and widen (vasodilation), which lowers blood pressure and decreases the workload on the heart [1.4.2, 1.4.5]. Common examples of these medications, which often have names ending in "-pril," include lisinopril, enalapril, and ramipril [1.4.1].
Major Side Effect 1: Persistent Dry Cough
One of the most frequently reported side effects of ACE inhibitors is a chronic, dry, hacking cough [1.2.2]. This side effect is estimated to affect between 5% and 35% of patients taking these drugs [1.5.5]. The cough is thought to be caused by the accumulation of bradykinin and substance P in the respiratory tract [1.3.2, 1.5.5]. Normally, the ACE enzyme helps break down these substances, but when the enzyme is inhibited, their levels increase, which can irritate the airways and trigger the cough reflex [1.3.2, 1.4.1]. The onset of the cough can range from a few hours after the first dose to several months into therapy [1.5.5]. It is not harmful but can be bothersome enough for patients to discontinue the medication [1.2.2]. The only consistently effective treatment for ACE inhibitor-induced cough is to stop taking the medication, with resolution typically occurring within one to four weeks [1.5.5].
Major Side Effect 2: Angioedema
A less common but more serious side effect is angioedema, which is a rapid swelling of the deep layers of the skin and mucous membranes [1.2.3, 1.3.3]. It is reported to affect 0.1% to 0.7% of individuals taking an ACE inhibitor [1.3.3]. Like the cough, angioedema is also linked to the accumulation of bradykinin, which increases vascular permeability, leading to fluid leakage into the tissues [1.4.1]. Symptoms include swelling of the lips, tongue, face, and throat [1.2.1, 1.3.3]. Swelling of the throat can be life-threatening as it can obstruct the airway, making breathing difficult or impossible [1.2.5, 1.9.1]. Angioedema requires immediate medical attention [1.2.3]. Discontinuing the ACE inhibitor is the essential long-term management strategy [1.3.3].
Other Significant Side Effects: Hyperkalemia and Hypotension
Beyond cough and angioedema, two other clinically important side effects are hyperkalemia (high potassium levels) and hypotension (low blood pressure).
- Hyperkalemia: By reducing aldosterone levels, ACE inhibitors decrease the excretion of potassium from the body, which can lead to elevated potassium levels in the blood [1.6.2, 1.6.5]. The risk is higher in patients with chronic kidney disease, diabetes, or those taking other medications that increase potassium, such as potassium-sparing diuretics [1.6.1, 1.6.2].
- Hypotension: Because ACE inhibitors lower blood pressure, some patients may experience dizziness, lightheadedness, or fainting, particularly with the first few doses or if they become dehydrated [1.2.1, 1.6.4]. It's often advised to stand up slowly to mitigate this effect [1.2.3].
Comparison of Common Medication Side Effects
| Medication Class | Common Side Effects | Severe/Major Risks |
|---|---|---|
| ACE Inhibitors | Dry cough (5-35%), dizziness, headache, fatigue [1.2.3, 1.5.5] | Angioedema (0.1-0.7%), hyperkalemia, hypotension [1.3.3, 1.6.5] |
| ARBs | Dizziness, headache, hyperkalemia [1.6.5] | Angioedema (much rarer than with ACE inhibitors) [1.9.1, 1.10.3] |
| Beta-Blockers | Fatigue, cold hands/feet, bradycardia (slow heart rate) | Worsening heart failure symptoms, severe bradycardia |
| Calcium Channel Blockers | Swelling in ankles/legs, headache, dizziness, flushing | Tachycardia (fast heart rate) or bradycardia, hypotension |
| Diuretics (Thiazide) | Increased urination, dizziness, hypokalemia (low potassium) | Dehydration, electrolyte imbalances, gout attacks |
Managing Side Effects and Alternatives
If a patient experiences intolerable side effects from an ACE inhibitor, healthcare providers have several alternatives. For patients who develop a cough, the most common switch is to an Angiotensin II Receptor Blocker (ARB) [1.10.1, 1.10.3]. ARBs, such as losartan or valsartan, work similarly to ACE inhibitors by blocking the RAAS system but do not affect bradykinin levels, and thus have a much lower incidence of cough and angioedema [1.6.5, 1.10.3]. Other alternatives, depending on the patient's specific condition (e.g., hypertension, heart failure), include calcium channel blockers, thiazide diuretics, or beta-blockers [1.10.4]. The management of angioedema is an emergency that involves securing the airway and discontinuing the drug immediately [1.5.1, 1.5.3].
Conclusion
ACE inhibitors are a cornerstone of therapy for hypertension and heart failure, effectively reducing blood pressure and improving cardiovascular outcomes. However, they are associated with two well-known major side effects: a persistent dry cough and, more rarely, potentially life-threatening angioedema. Both are primarily caused by the drug's mechanism leading to an increase in bradykinin [1.4.1]. Other notable side effects include hyperkalemia and hypotension. Fortunately, for patients who cannot tolerate these effects, effective alternatives like ARBs are available, allowing for continued management of their cardiovascular conditions [1.10.4]. Patient education and monitoring are key to safely using these important medications.
For more information, you can visit the National Kidney Foundation's page on ACE Inhibitors and ARBs. [1.9.1]
