ACE Inhibitors & ARBs: Blocking the Pressure Cascade
These two drug families — the '-prils' and the '-sartans' — do far more than lower a number. They protect failing hearts, shield diabetic kidneys, and save lives after a heart attack, all by interrupting the same hormone cascade. They're among the most prescribed drugs on earth. But they hide a lethal danger in pregnancy and a quiet trap for the kidneys, and knowing both is what makes you use them safely.
A man with diabetes has a trace of protein leaking into his urine — the first quiet sign his kidneys are being damaged by years of high sugar and pressure. His doctor starts an ACE inhibitor, not just to lower his blood pressure but specifically to protect those kidneys and slow the leak. Years later, his kidney function is far better preserved than it would have been. That protective power — beyond the blood-pressure number — is what makes these drugs special, and it all comes from blocking the RAAS cascade we mapped earlier.
ACE inhibitors: the '-prils'
ACE inhibitors block angiotensin II from being made. The ACE inhibitors — lisinopril, ramipril, enalapril, captopril — block the angiotensin-converting enzyme, so less angiotensin II forms. The result is relaxed blood vessels (lower resistance), less aldosterone (less salt and water retention), and less of the harmful remodeling of the heart and kidneys. That's why their uses stretch far beyond hypertension: heart failure, after a heart attack, and protecting the kidneys in diabetes and chronic kidney disease. Because ACE also breaks down bradykinin, blocking it lets bradykinin build up — causing the classic dry cough in some patients and, rarely, a dangerous swelling of the lips and throat called angioedema.
ARBs: the '-sartans'
The ARBs — losartan, valsartan, candesartan, irbesartan — reach the same goal from a different angle: instead of stopping angiotensin II from being made, they block its receptor, so the hormone can't act. The blood-pressure and organ-protective benefits are essentially the same as ACE inhibitors. The key difference is that ARBs don't affect bradykinin, so they DON'T cause the cough and rarely cause angioedema — which is exactly why we switch a coughing patient from a '-pril' to a '-sartan.' Otherwise the two families share the same cautions.
- ACE inhibitors (-pril) block angiotensin II formation; ARBs (-sartan) block its receptor.
- Both: hypertension, heart failure, post-MI, and kidney protection in diabetes/CKD.
- ACE inhibitors cause a dry cough & rare angioedema (bradykinin); ARBs largely avoid these.
- Both raise potassium, can cause first-dose hypotension, and are teratogenic.
The dangers: kidneys, potassium, pregnancy
Three cautions apply to both families. First, the kidney: angiotensin II normally tightens the outflow of the kidney's filter to keep filtration up; block it, and filtration can dip — usually a small, safe drop, but in a patient whose kidneys already depend on that mechanism (notably narrowing of both renal arteries), it can cause acute kidney injury. So check kidney function and potassium a week or two after starting. Second, potassium: by lowering aldosterone, these drugs raise blood potassium, which can become dangerous with other potassium-raising drugs. Third, and absolute: they are teratogenic — they harm the developing fetus — so they must never be used in pregnancy. And you should never combine an ACE inhibitor with an ARB, as double blockade multiplies the kidney and potassium risks without added benefit.
A small creatinine rise after starting an ACE inhibitor or ARB is expected and acceptable — up to about a 30% bump usually means the drug is working on the kidney's filter as intended, not harming it. Panicking and stopping the drug over a minor rise deprives the patient of its long-term kidney and heart protection. A LARGE, rapid rise (or a big potassium jump) is the red flag that warrants stopping and looking for renal artery narrowing.
- Using either in pregnancy. They are teratogenic — switch before conception.
- Combining an ACE inhibitor with an ARB. Double RAAS block harms kidneys & raises potassium.
- Starting one in bilateral renal artery stenosis. Can cause acute kidney injury.
- Stopping the drug over a small, expected creatinine rise instead of a large one.
A patient on lisinopril develops a persistent dry cough. The best next step is usually to:
- ACE inhibitors (-pril) block angiotensin II synthesis; ARBs (-sartan) block its receptor.
- Both treat hypertension, heart failure, post-MI, and protect the kidneys.
- ACE-inhibitor cough/angioedema come from bradykinin; switch to an ARB.
- Watch kidneys & potassium; never in pregnancy; don't combine ACE inhibitor + ARB.
- Katzung BG. Basic & Clinical Pharmacology — ACE inhibitors & angiotensin receptor blockers.
- Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics — Renin-angiotensin drugs.
- Rang HP, Dale MM, et al. Rang & Dale's Pharmacology — Drugs affecting the renin-angiotensin system.
- ACC/AHA & ESC guidelines — ACE inhibitors/ARBs in hypertension, heart failure & CKD.
- Whalen K. Lippincott Illustrated Reviews: Pharmacology — ACE inhibitors & ARBs.
