# ACE Inhibitors, ARBs and ARNI Pharmacology

> ACE inhibitor, ARB and ARNI pharmacology for NEET-PG Medicine, covering mechanisms, cough and angioedema, hyperkalaemia, contraindications and neprilysin.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/ace-inhibitors-arbs-and-arni-pharmacology
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: KD Tripathi's Essentials of Medical Pharmacology; Goodman and Gilman's The Pharmacological Basis of Therapeutics; Harrison's Principles of Internal Medicine
- How to cite: "ACE Inhibitors, ARBs and ARNI Pharmacology", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/ace-inhibitors-arbs-and-arni-pharmacology

## Direct answer

ACE inhibitors, angiotensin receptor blockers (ARBs) and the sacubitril-valsartan combination (ARNI) all act on the renin-angiotensin system, reducing angiotensin II effects on vessels and the kidney. ACE inhibitors also raise bradykinin, which causes dry cough and, rarely, angioedema, while ARBs rarely cause cough. Sacubitril-valsartan adds neprilysin inhibition to raise natriuretic peptides, and all three raise potassium and are contraindicated in pregnancy.

## What you must remember

- **ACE inhibitors:** enalapril, ramipril, lisinopril and perindopril block conversion of angiotensin I to II and the breakdown of bradykinin, causing dry cough in a notable minority.
- **Angioedema:** bradykinin-mediated and potentially fatal if the airway is involved; it is more common with ACE inhibitors and needs the drug stopped permanently.
- **ARBs:** losartan, telmisartan and valsartan block the AT1 receptor without raising bradykinin, so cough is uncommon.
- **ARNI:** sacubitril-valsartan combines a neprilysin inhibitor with AT1 blockade, and is indicated in heart failure with reduced ejection fraction.
- **Washout:** an ACE inhibitor must be stopped at least 36 hours before starting sacubitril-valsartan, because combined use raises angioedema risk.
- **Hyperkalaemia:** all three raise potassium and can reduce glomerular filtration, so potassium and creatinine are checked within one to two weeks.
- **Contraindications:** pregnancy, bilateral renal artery stenosis and previous angioedema; ACE inhibitor with ARB dual blockade is avoided.

## Comparing the classes

A 56-year-old man on enalapril develops a persistent dry cough, and his physician must decide whether to switch class. The table compares the three classes by site of action, adverse effect and typical use.

| Class | Site of action | Signature adverse effect | Typical use |
|---|---|---|---|
| ACE inhibitor (enalapril, ramipril) | Blocks ACE, reducing angiotensin II and raising bradykinin | Dry cough, angioedema | Hypertension, heart failure, diabetic nephropathy |
| ARB (losartan, telmisartan) | Blocks the AT1 receptor directly | Hyperkalaemia, dizziness | Hypertension after ACE inhibitor cough, nephropathy |
| ARNI (sacubitril-valsartan) | Neprilysin inhibition plus AT1 blockade | Hypotension, hyperkalaemia, angioedema | Heart failure with reduced ejection fraction |
| Aliskiren | Direct renin inhibition | Diarrhoea, hyperkalaemia | Limited use; avoided with ACE inhibitor in diabetes |
| Common to all | Contraindicated in pregnancy and after prior angioedema; bilateral renal artery stenosis | Hyperkalaemia, fall in glomerular filtration | Check potassium and creatinine; 36-hour ACE inhibitor washout before ARNI |

Cough points to bradykinin accumulation and usually prompts a switch to an ARB, which keeps the renal and cardiac protection without that side effect. Sacubitril-valsartan is reserved for symptomatic heart failure with reduced ejection fraction, after a 36-hour ACE inhibitor washout. Potassium and creatinine are checked after every switch.

## Where the exam tries to catch you

Most wrong answers come from mixing up the mechanism of cough with that of the drug class.

- **Trap:** switching an ACE inhibitor to sacubitril-valsartan on the same day — **Correct:** a 36-hour washout is needed, because the combination raises the risk of angioedema.
- **Trap:** blaming an ARB for a dry cough — **Correct:** cough is a bradykinin effect of ACE inhibitors, and ARBs rarely cause it.
- **Trap:** adding an ARB to an ACE inhibitor for extra proteinuria control — **Correct:** dual blockade raises hyperkalaemia and renal injury without a mortality benefit, as the ONTARGET trial showed.

## Frequently asked questions

### Why do ACE inhibitors cause cough but ARBs usually do not?

ACE inhibitors cause cough because ACE also breaks down bradykinin, and bradykinin accumulates when ACE is blocked. ARBs block the angiotensin II receptor directly and do not affect bradykinin, so cough is uncommon with them. Cough usually resolves after the ACE inhibitor is stopped.

### What is the washout period before switching to sacubitril-valsartan?

An ACE inhibitor must be stopped at least 36 hours before starting sacubitril-valsartan. Combined use raises the risk of angioedema, because both drugs affect bradykinin pathways. The washout is essential and is not shortened for convenience.

### Which drugs acting on the renin-angiotensin system are contraindicated in pregnancy?

ACE inhibitors, ARBs, sacubitril-valsartan and aliskiren are contraindicated in pregnancy because of fetotoxicity in the second and third trimesters. They are switched to safer agents before conception. If pregnancy is discovered during treatment, the drug is stopped promptly and the patient is reviewed.

### Why is potassium checked after starting an ACE inhibitor or ARB?

Potassium is checked because ACE inhibitors and ARBs reduce aldosterone effects, which impairs renal potassium excretion. Hyperkalaemia is a common and dangerous effect, especially in chronic kidney disease or with potassium-sparing diuretics and supplements. Creatinine is checked at the same time to detect a fall in glomerular filtration.