18.2 Angiotensin-Converting Enzyme (ACE) Inhibitors

Renin-Angiotensin-Aldosterone System (RAAS) and ACE Inhibitors

ACE inhibitors lower blood pressure by blocking a key step in the renin-angiotensin-aldosterone system (RAAS). They're among the most commonly prescribed antihypertensives and also play a major role in managing heart failure and protecting the kidneys. Understanding how the RAAS works is essential to understanding why these drugs do what they do.

Blood Pressure Regulation and RAAS

The RAAS is a hormone cascade the body uses to raise blood pressure when it drops too low. Here's how the pathway works step by step:

1. The kidneys detect decreased blood pressure (or decreased sodium delivery to the distal tubule) and release renin into the bloodstream.
2. Renin converts angiotensinogen (a protein made by the liver) into angiotensin I.
3. Angiotensin-converting enzyme (ACE), found primarily in the lungs, converts angiotensin I into angiotensin II.
4. Angiotensin II is a potent vasoconstrictor that directly raises blood pressure. It also stimulates the adrenal cortex to release aldosterone.
5. Aldosterone acts on the kidneys to increase sodium and water reabsorption, which expands blood volume and further raises blood pressure.

This is the system ACE inhibitors interrupt. By blocking step 3, they reduce circulating angiotensin II levels, which means less vasoconstriction and less aldosterone release.

Mechanism of ACE Inhibitors

ACE inhibitors block the enzyme that converts angiotensin I to angiotensin II. With less angiotensin II circulating, two main things happen:

• Vasodilation occurs because angiotensin II is no longer constricting blood vessels. This decreases peripheral vascular resistance and lowers blood pressure.
• Reduced aldosterone secretion means the kidneys excrete more sodium and water, decreasing blood volume and further lowering blood pressure.

There's a third effect that's clinically important: ACE also breaks down bradykinin, a substance that promotes vasodilation. When you block ACE, bradykinin accumulates. This contributes to the blood pressure-lowering effect but is also responsible for the characteristic dry cough that many patients develop.

ACE inhibitors also improve endothelial function over time, which provides additional cardiovascular protection beyond simple blood pressure reduction.

Common ACE Inhibitors and Indications

All ACE inhibitors share the same basic mechanism, but they differ in potency, duration of action, and approved indications. A helpful recognition tip: most generic names end in -pril.

• Captopril (Capoten) — Hypertension, heart failure, post-myocardial infarction (MI). Shortest acting of the group; typically dosed two to three times daily.
• Enalapril (Vasotec) — Hypertension, heart failure. Available in both oral and IV formulations (the IV form is enalaprilat), which is useful for patients who can't take oral medications.
• Lisinopril (Prinivil, Zestril) — Hypertension, heart failure, post-MI. One of the most widely prescribed ACE inhibitors; dosed once daily.
• Ramipril (Altace) — Hypertension, cardiovascular risk reduction (including stroke prevention in high-risk patients).
• Benazepril (Lotensin) — Hypertension. Also used for renal protection in patients with chronic kidney disease (CKD), particularly those with proteinuria.

Adverse Effects of ACE Inhibitors

Common adverse effects:

• Dry, persistent cough — Occurs in up to 10–15% of patients. Caused by bradykinin accumulation in the lungs, not by the blood pressure-lowering effect itself. If the cough is intolerable, the patient is typically switched to an angiotensin II receptor blocker (ARB), which does not affect bradykinin.
• Hypotension — Most likely with the first dose, especially in patients who are volume-depleted (for example, those already taking diuretics). This is sometimes called "first-dose hypotension."
• Hyperkalemia — Because aldosterone normally promotes potassium excretion, reducing aldosterone levels means potassium is retained. Serum potassium must be monitored regularly.
• Renal dysfunction — ACE inhibitors dilate the efferent arteriole of the glomerulus, which reduces filtration pressure. This is usually protective long-term, but it can worsen renal function in patients with bilateral renal artery stenosis or severe pre-existing kidney disease. A mild rise in serum creatinine (up to 30% from baseline) can be expected and is generally acceptable.

Angioedema — Rare but potentially life-threatening. Presents as rapid swelling of the face, lips, tongue, and/or throat, which can compromise the airway. This is more common in African American patients. If angioedema occurs, the ACE inhibitor must be permanently discontinued.

Key drug interactions:

• Potassium supplements and potassium-sparing diuretics (e.g., spironolactone) — Significantly increase the risk of dangerous hyperkalemia when combined with ACE inhibitors.
• NSAIDs (e.g., ibuprofen, naproxen) — Can blunt the antihypertensive effect and increase the risk of renal dysfunction. This combination is common in practice, so it's worth watching for.
• Lithium — ACE inhibitors reduce lithium excretion, raising serum lithium levels and increasing the risk of lithium toxicity. Lithium levels need closer monitoring if both drugs are used together.

Pregnancy contraindication: ACE inhibitors are contraindicated in pregnancy (Category X in the second and third trimesters). They can cause fetal renal damage, oligohydramnios (low amniotic fluid), and fetal death. Women of childbearing age should be counseled about this before starting therapy.

Nursing Considerations for ACE Inhibitors

Before starting therapy:

• Obtain baseline blood pressure, serum creatinine, BUN, and serum potassium.
• Ask about pregnancy status and counsel women of childbearing age about the risks.
• Review the medication list for interacting drugs (potassium supplements, potassium-sparing diuretics, NSAIDs, lithium).

Ongoing monitoring:

• Check blood pressure regularly, especially after the first dose and after dose increases. Hold the medication and notify the provider if blood pressure is below facility parameters.
• Monitor serum potassium and renal function (creatinine, BUN) periodically throughout treatment.
• Watch for signs of angioedema (facial or throat swelling) at every encounter. If it occurs, discontinue the drug immediately and ensure emergency airway management is available.

Patient education:

• Rise slowly from sitting or lying positions to reduce the risk of orthostatic hypotension, especially early in treatment.
• Report a persistent dry cough to the provider. It doesn't mean the drug is harmful, but switching to an ARB can often resolve it.
• Avoid potassium supplements and salt substitutes containing potassium (like KCl-based salt alternatives) unless specifically prescribed.
• Know the signs of hyperkalemia: muscle weakness, fatigue, palpitations, and irregular heartbeat.
• Do not stop the medication abruptly without consulting the provider, even if blood pressure readings seem normal.
• Follow lifestyle modifications that support blood pressure control: a low-sodium diet (the DASH diet is a good framework), regular physical activity, and stress management.
• Keep all follow-up appointments so blood pressure, kidney function, and electrolytes can be tracked over time.