ACE Inhibitors

High-yield Verified · Jul 2026

Prototype: lisinopril

Angiotensin-converting enzyme inhibitors. Recognizable by the generic stem -pril.

How it works in the body

The system involved, what goes wrong, and how the drug and body interact.

01 The renin-angiotensin-aldosterone system (RAAS)

The RAAS is the body’s master control for blood pressure and fluid balance — a hormone cascade, not a single switch. When the kidney senses low blood pressure, low sodium, or sympathetic drive, it releases the enzyme renin.

Renin cleaves angiotensinogen (made by the liver) into angiotensin I. As blood passes through the lungs, angiotensin-converting enzyme (ACE) snips angiotensin I into angiotensin II — the powerful hormone that actually raises pressure.

Angiotensin II does three things: it constricts blood vessels (raising resistance), it triggers the adrenal glands to release aldosterone (which makes the kidney retain sodium and water, expanding blood volume), and it boosts ADH and sympathetic tone. The net result is higher blood pressure and more fluid — helpful in a crisis, harmful when switched on chronically.

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The RAAS cascade: renin → angiotensin I → (ACE) → angiotensin II → higher blood pressure and volume.

02 Why chronic RAAS activation harms the heart and kidneys

In hypertension and heart failure, the RAAS is switched on all the time. Persistent vasoconstriction keeps the heart pumping against high resistance (afterload), while aldosterone-driven fluid retention overloads an already-struggling pump. Angiotensin II also directly remodels the heart and blood-vessel walls, thickening and stiffening them.

In the kidney, angiotensin II preferentially tightens the *efferent* (outflow) arteriole of each glomerulus, driving up the pressure inside the filter. Over years — especially in diabetes — that high intraglomerular pressure damages the kidney. This is the specific problem ACE inhibitors are designed to relieve.

03 How ACE inhibitors intervene

ACE inhibitors block the converting enzyme, so far less angiotensin II is made. Vessels relax (lowering blood pressure and afterload), and aldosterone falls (so the body sheds sodium and water). By dilating the efferent arteriole, they lower the pressure inside the glomerulus and protect the kidney — the reason they are first-line in diabetic kidney disease.

There is a second consequence. ACE normally also breaks down bradykinin, a vasodilator. Block ACE and bradykinin accumulates — adding helpful vasodilation, but also causing the two signature side effects: a dry cough and, rarely, angioedema.

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Blocking ACE lowers angiotensin II (↓ BP, renal protection) but lets bradykinin build up (cough, angioedema).

04 How the body reacts — and why the side effects appear

Because aldosterone normally tells the kidney to excrete potassium, lowering aldosterone causes potassium to rise — real hyperkalemia risk, especially with potassium supplements, salt substitutes, or kidney disease. Dropping the intraglomerular pressure also nudges serum creatinine up by a small amount; a *mild* rise is expected and acceptable, but a large jump signals the kidney was depending on angiotensin II (as in bilateral renal artery stenosis) and is now under-perfused.

In pregnancy, blocking the fetal RAAS impairs fetal kidney development and urine production — causing oligohydramnios, renal failure, and death. This is the basis of the boxed warning: stop the drug the moment pregnancy is detected.

Drug names

Generic Brand

lisinopril Prinivil, Zestril

enalapril Vasotec

ramipril Altace

Indications

Hypertension
Heart failure & post-MI (cardioprotective)
Diabetic nephropathy / chronic kidney disease (renal protection)

Mechanism of action

Inhibit the angiotensin-converting enzyme, blocking conversion of angiotensin I to angiotensin II — reducing vasoconstriction and aldosterone-driven sodium/water retention. Reduced breakdown of bradykinin contributes to vasodilation (and the dry cough).

In plain terms

They relax blood vessels and let the body shed extra fluid, so blood pressure drops and the heart has an easier job.

Therapeutic effects — what you'll see working

Every therapeutic effect flows from one action — less angiotensin II. Judge the blood-pressure response over 1–2 weeks, and remember that in heart failure and diabetic kidney disease the benefit is *protective*, not just a number on the monitor.

↓ Blood pressure ↓ Afterload Renal protection

↓ Blood pressure: Less angiotensin II means less vasoconstriction and, via lower aldosterone, less fluid retention — so both resistance and volume fall. The effect builds gradually as the body offloads sodium and water.
↓ Afterload: By relaxing arteries, ACE inhibitors reduce the resistance the heart pumps against. A failing heart ejects blood more easily, which is why they improve survival in heart failure with reduced EF.
Renal protection: Dilating the glomerular efferent arteriole lowers the damaging pressure inside the kidney’s filter — slowing the progression of diabetic and chronic kidney disease. (The trade-off is a small, expected rise in creatinine.)

Adverse effects

The side effects split cleanly into two mechanisms: too little angiotensin II / aldosterone (hyperkalemia, first-dose hypotension, rising creatinine) and too much bradykinin (dry cough, angioedema).

Common Hold & notify

Persistent dry cough, first-dose hypotension, hyperkalemia, dizziness, mildly rising serum creatinine.

The dry, hacking cough (up to ~10% of patients) comes from bradykinin accumulating in the airways — it is harmless but often intolerable, and reverses when the drug is stopped. Hyperkalemia arises because low aldosterone means the kidney holds onto potassium. A small creatinine rise reflects the intended drop in glomerular pressure and is acceptable within limits.

Serious Report immediately

Angioedema (may compromise the airway — a medical emergency), acute kidney injury, severe hyperkalemia.

Angioedema — bradykinin-mediated swelling of the lips, tongue, or throat — can obstruct the airway and is a reason to stop the drug permanently. Acute kidney injury occurs when the kidney was relying on angiotensin II to maintain filtration, as in bilateral renal artery stenosis; removing it drops the glomerular pressure too far.

■ Boxed warning · fetal toxicity

Can cause injury and death to the developing fetus — discontinue as soon as pregnancy is detected.

In the 2nd and 3rd trimesters, blocking the fetal RAAS impairs fetal kidney development and urine output, causing oligohydramnios, skull and lung underdevelopment, renal failure, and death. Any patient of childbearing age must understand this before starting.

Interactions

K-sparing diuretics, potassium supplements, salt substitutes drug

Additive potassium retention → potentially fatal hyperkalemia.

NSAIDs drug

Blunt the antihypertensive effect and add renal risk (↓ effect / renal impairment).

Lithium drug

Reduced lithium clearance → ↑ lithium levels and toxicity.

Contraindications

The contraindications track the same two mechanisms — situations where removing angiotensin II is dangerous, and where extra bradykinin is deadly.

Prior angioedema (from any ACE inhibitor, hereditary, or idiopathic)

Re-exposure can trigger recurrent, potentially fatal airway swelling driven by bradykinin.

Pregnancy

Fetal renal toxicity, oligohydramnios, and death (the boxed warning). Stop immediately if pregnancy occurs.

Within 36 hours of a neprilysin inhibitor (sacubitril / ARNI)

Both raise bradykinin; overlapping them sharply increases the risk of angioedema.

Bilateral renal artery stenosis

These kidneys depend on angiotensin II to maintain filtration pressure — blocking it precipitates acute kidney injury.

Hyperkalemia use caution

ACE inhibitors raise potassium; starting one with an already-high level risks dangerous arrhythmias.

When to hold

Assess before giving — these findings mean hold the dose and act.

Pregnancy (boxed warning — teratogen)

Stop the drug immediately — fetal renal toxicity, oligohydramnios, and death.

First-dose hypotension (volume-depleted or on a diuretic)

Check BP; anticipate a first-dose drop — consider a bedtime first dose and monitor closely.

Nursing considerations

The RN-specific layer — each action paired with the reason it matters.

Monitoring

Check potassium and creatinine at baseline and after every dose change.

Why: Falling aldosterone raises potassium, and lower glomerular pressure raises creatinine; a mild creatinine bump is expected, but a large rise or hyperkalemia signals kidney compromise.

Watch for angioedema — facial, tongue, or throat swelling is an emergency; hold the drug and call the provider immediately.

Why: Bradykinin-mediated airway swelling can be rapid and life-threatening; it warrants permanent discontinuation.

Anticipate first-dose hypotension — consider a bedtime first dose and monitor BP, especially in volume-depleted or diuretic-treated patients.

Why: Abruptly removing angiotensin II support can drop BP sharply the first time, causing dizziness or falls.

Patient teaching

A dry, tickling cough is common and reversible — report it if intolerable; the provider may switch to an ARB.

Why: ARBs block the angiotensin receptor without affecting bradykinin, so they don’t cause the cough.

Avoid potassium-based salt substitutes and potassium supplements unless told otherwise; report swelling of the face or lips.

Why: These add to the drug’s potassium-raising effect and can push potassium into a dangerous range.

Do not use if pregnant or planning pregnancy; use reliable contraception.

Why: Fetal toxicity is the boxed warning — the risk is greatest in the 2nd and 3rd trimesters.

Sources

Educational summary for nursing students. Always verify against current prescribing information and your institution's protocols before administering. Not medical advice.