The renin–angiotensin–aldosterone system (RAAS) raises blood pressure when the kidney senses low perfusion or low sodium.
- The kidney releases renin (also stimulated by beta-1 receptors).
- Renin converts angiotensinogen (from the liver) to angiotensin I.
- Angiotensin-converting enzyme (ACE), mainly in the lungs, converts angiotensin I to angiotensin II. ACE also breaks down bradykinin.
- Angiotensin II acts on AT1 receptors: strong vasoconstriction, aldosterone release (sodium and water retention, potassium loss), thirst, ADH release, and long-term remodeling (fibrosis and hypertrophy of the heart, vessels, and kidney).
Where each drug acts
| Class | Suffix / examples | Action | Result |
|---|
| ACE inhibitors (ACEI) | -pril: lisinopril (prototype), enalapril, captopril, ramipril, benazepril | Block ACE → ↓angiotensin II, ↓aldosterone, ↑bradykinin | Vasodilation, ↓sodium retention, ↑potassium; bradykinin causes cough and angioedema |
| Angiotensin II receptor blockers (ARBs) | -sartan: losartan (prototype), valsartan, irbesartan, candesartan, telmisartan, olmesartan | Block the AT1 receptor | Same benefits; bradykinin not increased → cough is rare |
| ARNI | sacubitril/valsartan | ARB plus neprilysin inhibitor (↑natriuretic peptides) | Preferred RAAS inhibitor in HFrEF |
| Direct renin inhibitor | aliskiren | Blocks renin | Rarely used; never combined with ACEI/ARB in diabetes |
| Mineralocorticoid receptor antagonists (MRAs) | spironolactone, eplerenone, finerenone | Block aldosterone at the kidney and heart | See Diuretics |
Kidney effect: angiotensin II constricts the efferent arteriole to keep glomerular filtration pressure up. Blocking it lowers glomerular pressure — this protects the kidney long term (less proteinuria) but causes a small, expected rise in creatinine at the start, and can cause AKI when kidney perfusion depends on angiotensin II (dehydration, bilateral renal artery stenosis, NSAID use).
| Indication | Key point |
|---|
| Hypertension | ACEI and ARB are two of the four first-line classes (2025 AHA/ACC). Stage 2 hypertension usually starts with two drugs, often an ACEI or ARB plus a thiazide or a dihydropyridine CCB in a single pill |
| HFrEF (LVEF ≤ 40%) | ARNI preferred; ACEI or ARB if ARNI cannot be used — part of the four pillars (see Heart Failure Drugs) |
| After myocardial infarction | Especially with LVEF ≤ 40%, hypertension, diabetes, or CKD — reduces remodeling |
| Diabetes with albuminuria and CKD | Slows kidney disease progression; albuminuria is defined as UACR ≥ 30 mg/g (3 mg/mmol) |
| Stroke prevention, scleroderma renal crisis (captopril) | Specialist indications |
| Drug (generic) | Key point |
|---|
| Lisinopril (prototype ACEI) | Once daily; not a prodrug; excreted by the kidney |
| Enalapril / enalaprilat (IV) | Enalaprilat is the only IV ACEI in the US; enalapril is compatible with breastfeeding |
| Captopril | Short-acting (2–3 doses daily), taken 1 hour before meals; rash, taste loss, and neutropenia are more common |
| Losartan (prototype ARB) | Lowers uric acid slightly; used when ACEI cough occurs |
| Olmesartan | Rare sprue-like enteropathy (severe chronic diarrhea, weight loss) |
| Sacubitril/valsartan | HFrEF; hypotension common; 36-hour washout from an ACEI |
| Aliskiren | Contraindicated with ACEI or ARB in diabetes; avoid combinations when eGFR is below 60 mL/min/1.73 m² |
- Hypotension, especially first-dose hypotension in clients who are volume-depleted, on high-dose diuretics, or have HF
- Hyperkalemia (less aldosterone → potassium retained)
- Rise in creatinine / acute kidney injury — a rise of up to about 30% after starting is expected and not a reason to stop; a larger rise needs review (volume depletion, NSAIDs, renal artery stenosis)
- Dry, persistent, nonproductive cough (ACEI; about 1 in 10 clients) — due to bradykinin; begins days to months after starting and resolves 1–4 weeks after stopping (sometimes longer). Switch to an ARB
- Angioedema — swelling of the lips, tongue, face, larynx, or bowel (abdominal pain); ACEI much more than ARB; more common in Black clients, smokers, and those on sacubitril, mTOR inhibitors (sirolimus, everolimus), or DPP-4 inhibitors. Can occur at any time, even after years. It is bradykinin-mediated, so epinephrine, antihistamines, and corticosteroids work poorly
- Captopril: taste disturbance, rash, rare neutropenia
- Dizziness, headache, fatigue
- Fetal toxicity (boxed warning) — see below
Contraindications
- Pregnancy — boxed warning for all ACEIs, ARBs, ARNI, and aliskiren: drugs acting on the RAAS in the second and third trimesters cause fetal kidney failure, oligohydramnios, skull hypoplasia, and death. Stop as soon as pregnancy is detected; clients who could become pregnant need contraception counseling and a plan before conceiving
- History of angioedema with an ACEI; hereditary or idiopathic angioedema; ARNI is contraindicated with any history of angioedema related to ACEI or ARB
- ARNI with an ACEI — never together; allow 36 hours after the last ACEI dose before starting sacubitril/valsartan
- Aliskiren with ACEI or ARB in diabetes
- Dual RAAS blockade (ACEI + ARB) — not recommended (hyperkalemia, AKI, no benefit)
Cautions: bilateral renal artery stenosis (or stenosis to a single kidney), hyperkalemia, volume depletion, severe aortic stenosis, hepatic impairment, and kidney impairment (dose adjustment).
Lactation: enalapril and captopril are preferred if an ACEI is needed while breastfeeding; limited data for ARBs.
Perioperative: ACEIs and ARBs are often held for 24 hours before surgery in clients with hypertension to reduce intraoperative hypotension; continuation is reasonable in HFrEF — follow the surgical team's instructions.
Major interactions
- Potassium supplements, salt substitutes (potassium chloride), potassium-sparing diuretics and MRAs, trimethoprim, heparin → hyperkalemia
- NSAIDs → reduced BP effect and AKI; NSAID + diuretic + ACEI/ARB is the classic "triple whammy"
- Lithium → raised lithium levels
- Diuretics → first-dose hypotension (the diuretic dose may be reduced or held before the first dose, per order)
- Sacubitril, mTOR inhibitors, DPP-4 inhibitors → higher angioedema risk with ACEI
- Aliskiren or another RAAS blocker → dual blockade harms
Listed in priority order.
- Airway — angioedema
- Assess for swelling of lips, tongue, face, or throat, hoarseness, stridor, or difficulty swallowing at every contact, especially after the first doses
- If it occurs: stop the drug, call for help, protect the airway (sit upright, oxygen, prepare for early advanced airway management), notify the provider. Never rechallenge with an ACEI
- Blood pressure
- BP before each dose and 1–3 hours after the first dose (peak effect); first dose at bedtime or with the client lying down if at risk
- Hold and notify for systolic BP < 90 mmHg or symptomatic hypotension, per order
- Laboratory monitoring
| Test | Normal range | Action |
|---|
| Potassium | 3.5–5.0 mEq/L (mmol/L) | Check at baseline and about 1–2 weeks after starting or increasing the dose; notify for values above 5.0 per protocol; emergency at ≥ 6.5 mEq/L or with ECG changes |
| Creatinine / eGFR | About 0.6–1.2 mg/dL (53–106 µmol/L) | Baseline and 1–2 weeks after changes; report a rise of more than about 30% or falling urine output |
| BUN | About 7–20 mg/dL (urea 2.5–7.1 mmol/L) | Rising with creatinine = kidney hypoperfusion or dehydration |
| CBC | Laboratory reference | Captopril (neutropenia) in clients with kidney or autoimmune disease |
| Pregnancy test | — | Before starting in clients who could become pregnant, per protocol |
- Volume status — intake and output, daily weight in HF, orthostatic BP; hold and notify during vomiting, diarrhea, or poor intake
- Cough — ask about a new dry cough; report rather than treating with cough syrups
- Switching drugs — confirm the 36-hour gap between the last ACEI dose and the first ARNI dose
- Pregnancy: tell your prescriber at once if you might be pregnant or plan to become pregnant — these drugs must be stopped; use effective contraception
- Emergency: swelling of the face, lips, tongue, or throat, or trouble breathing or swallowing — call emergency services. This can happen even after years of use
- A dry, tickly cough is a known side effect of ACE inhibitors; report it — do not stop the drug on your own
- Avoid potassium supplements and salt substitutes unless prescribed; avoid NSAIDs (ibuprofen, naproxen)
- Rise slowly, especially during the first days and after dose increases
- Keep lab appointments for potassium and kidney tests
- Sick-day rule: if you have vomiting, diarrhea, or cannot drink, contact your prescriber — the drug may need to be held for a few days to protect the kidneys
- Take at the same time each day; captopril 1 hour before meals
- Continue taking the drug even when BP is normal — hypertension usually has no symptoms
- Olmesartan: report severe ongoing diarrhea with weight loss
| Problem | Findings | Action |
|---|
| Overdose | Hypotension, dizziness, bradycardia or reflex tachycardia, AKI, hyperkalemia | Supine with legs raised, IV normal saline, vasopressor if needed; some ACEIs (captopril, enalaprilat, lisinopril) are removed by hemodialysis. No specific antidote |
| Angioedema | Lip, tongue, laryngeal swelling; abdominal pain (bowel angioedema) | Stop drug permanently; airway management first — early intubation (often fiberoptic) if the airway is threatened. Epinephrine, antihistamines, and steroids may be tried but are less effective than in allergic angioedema — give epinephrine if anaphylaxis cannot be excluded; bradykinin-directed drugs (e.g., icatibant) or C1 esterase inhibitor are sometimes used, with limited evidence |
| Hyperkalemia | Weakness, paresthesia, peaked T waves, dysrhythmias | Hold the drug; IV calcium, insulin with dextrose, albuterol, potassium binders, dialysis per protocol |
| Acute kidney injury | Rising creatinine, oliguria | Hold drug, correct volume, stop NSAIDs, notify |
- -pril = ACE inhibitor; -sartan = ARB; sacubitril/valsartan = ARNI
- ACEI → dry cough and angioedema (bradykinin); ARB → cough rare — switch to an ARB for cough
- All RAAS inhibitors → hyperkalemia, hypotension, ↑creatinine
- Contraindicated in pregnancy (boxed warning) — stop as soon as pregnancy is detected
- Angioedema = airway emergency; can occur after years; never rechallenge
- 36-hour washout between an ACEI and ARNI; never combine ACEI + ARB
- Avoid potassium supplements, salt substitutes, NSAIDs; lithium levels rise
- Check K⁺ and creatinine at baseline and 1–2 weeks after starting or dose change; a creatinine rise up to about 30% is expected
- First-dose hypotension — higher risk with diuretics and volume depletion
- Renal protection in diabetes with albuminuria; avoid in bilateral renal artery stenosis
Country Notes
United States
- Single-pill combinations (for example, an ACEI or ARB with hydrochlorothiazide or amlodipine) are widely available as generics and are recommended to improve adherence.
- Several ARB products were recalled in 2018–2019 because of nitrosamine impurities; clients who ask should be told not to stop their medicine without speaking to their prescriber or pharmacist.
Philippines
- Losartan is widely used and low-cost; teach that it must be stopped if pregnancy occurs, since many clients of reproductive age take it for hypertension.
- Many "low-sodium" salt products contain potassium chloride; warn clients taking ACEIs, ARBs, or spironolactone to avoid them.