💊 ACE Inhibitors for Hypertension: How They Work, List of Drugs, and Side Effects

ACE inhibitors are among the most widely prescribed and extensively studied medications for high blood pressure. They are a cornerstone of treatment, particularly for people with diabetes, kidney disease, or heart failure. Dr. Ravi Sishir Reddy explains exactly what ACE inhibitors are, how they lower blood pressure, what to expect when taking them, and why they have a special role in protecting vital organs.

1. What Are ACE Inhibitors?

ACE stands for Angiotensin‑Converting Enzyme. This enzyme is responsible for converting angiotensin I into angiotensin II — a powerful hormone that narrows blood vessels and raises blood pressure. ACE inhibitors block this enzyme, reducing the production of angiotensin II. With less angiotensin II circulating, blood vessels relax and widen, and the kidneys excrete more sodium and water. The overall effect is a drop in blood pressure, along with a reduction in the workload on the heart.

Commonly prescribed ACE inhibitors include:

• Lisinopril (Prinivil, Zestril) — once‑daily dosing, widely used.
• Ramipril (Altace) — proven to reduce cardiovascular events in high‑risk patients.
• Enalapril (Vasotec) — available as an intravenous form for emergencies.
• Captopril — short‑acting, now less commonly used for long‑term BP control.
• Perindopril, Quinapril, Benazepril, Trandolapril — other options with similar profiles.

2. How Do They Lower Blood Pressure?

The renin‑angiotensin‑aldosterone system (RAAS) is a hormone chain that regulates blood pressure. When the kidneys sense low blood flow, they release renin, which leads to the formation of angiotensin II. Angiotensin II does three things:

1. Constricts blood vessels — raising pressure.
2. Stimulates aldosterone release — causing salt and water retention.
3. Thickens and stiffens the heart and blood vessel walls over time.

ACE inhibitors block the enzyme that produces angiotensin II, thereby interrupting this chain. Blood vessels relax, blood flows more easily, and the heart doesn’t have to pump as hard. Additionally, ACE inhibitors reduce the breakdown of bradykinin, a substance that promotes vasodilation — contributing further to the pressure‑lowering effect (though this also contributes to the famous side effect of cough).

3. Why Are ACE Inhibitors So Widely Used?

ACE inhibitors are more than just blood pressure pills. They have proven organ‑protective benefits:

• Kidney protection: They reduce pressure inside the kidney’s filtering units (intraglomerular pressure), slowing the progression of kidney disease, especially in people with diabetes or protein in the urine (proteinuria).
• Heart protection: They reverse left ventricular hypertrophy (thickening of the heart muscle) and improve survival after a heart attack and in heart failure.
• Stroke reduction: By lowering blood pressure and stabilising the inner lining of blood vessels (endothelium), ACE inhibitors reduce stroke risk.

For these reasons, ACE inhibitors are often the first choice in patients with diabetes, chronic kidney disease, coronary artery disease, or heart failure — not just those with simple hypertension.

4. Side Effects and What to Expect

ACE inhibitors are generally well tolerated, but some side effects are common:

• Dry cough: The most well‑known side effect, occurring in about 10‑20% of patients. It is a dry, tickly cough that can develop weeks to months after starting the drug. It is not dangerous but can be annoying enough to require switching to an ARB (angiotensin receptor blocker), which does not cause cough.
• Elevated potassium (hyperkalemia): Because they reduce aldosterone, which normally helps the body excrete potassium, ACE inhibitors can cause potassium levels to rise. Mild elevations are common; dangerously high levels are rare but require monitoring, especially if you have kidney disease or are also taking potassium supplements or certain diuretics (spironolactone).
• Dizziness or lightheadedness: Particularly after the first dose or when the dose is increased. Taking the medication at bedtime can minimise this. Usually, tolerance develops.
• Angioedema: A rare but serious side effect — swelling of the lips, tongue, throat, or face. This is a medical emergency that can block the airway. It occurs in fewer than 1 in 1,000 patients but is more common in people of African descent. Anyone who experiences angioedema on an ACE inhibitor must stop the drug immediately and never take it again.
• Taste disturbances and rash: Less common.

5. Contraindications: Who Should Avoid ACE Inhibitors?

ACE inhibitors are contraindicated (not to be used) in:

• Pregnancy: They can cause fetal kidney damage, low amniotic fluid, and skull defects. Women of childbearing age should use reliable contraception while on an ACE inhibitor, and the drug must be stopped immediately if pregnancy is suspected.
• History of angioedema: As mentioned, a previous episode of ACE‑inhibitor‑induced angioedema is an absolute contraindication.
• Bilateral renal artery stenosis: Narrowing of both renal arteries can cause a sudden drop in kidney function when ACE inhibitors are started. This is a rare situation but is screened for if kidney function declines acutely after starting the drug.
• Severe hyperkalemia: If potassium is already very high, ACE inhibitors should be avoided or used with extreme caution.

Caution is also required in patients with pre‑existing kidney impairment and those taking NSAIDs (painkillers like ibuprofen), which can blunt the BP‑lowering effect and increase the risk of kidney injury.

6. Practical Tips When Taking an ACE Inhibitor

• Take it regularly: Most ACE inhibitors are taken once daily. Do not skip doses, even if you feel fine.
• Monitor potassium and kidney function: Your doctor will check blood tests (potassium, creatinine) within 1‑2 weeks of starting or changing the dose, and periodically thereafter.
• Stand up slowly: Because these drugs reduce pressure, orthostatic hypotension (a drop in BP when standing) can occur, especially early in treatment.
• Avoid salt substitutes containing potassium chloride unless approved by your doctor.
• Stay hydrated: Dehydration can increase the risk of kidney stress when on an ACE inhibitor.
• Report a persistent cough to your doctor: There is an alternative class (ARBs) that works similarly without causing cough.

7. ACE Inhibitors vs. ARBs

ACE inhibitors and ARBs (angiotensin receptor blockers) both target the RAAS but at different points. ACE inhibitors block the formation of angiotensin II; ARBs block the receptor that angiotensin II binds to. Clinically, they are very similar in effectiveness. The main practical difference is that ARBs do not cause the dry cough. For this reason, if a patient cannot tolerate an ACE inhibitor due to cough, switching to an ARB is standard practice. However, ACE inhibitors are still favoured by many guidelines as first‑line due to the very large body of evidence behind them.

👉 Read more: ARBs for Hypertension →