Overview
This lecture reviews the mechanisms, clinical uses, dosing, and side effects of ACE inhibitors, angiotensin receptor blockers (ARBs), and renin inhibitors in hypertension and related cardiovascular conditions.
Contributors to Blood Pressure
- Blood pressure is regulated by the autonomic nervous system, hormones, plasma volume, blood vessel anatomy, and the heart.
Renin-Angiotensin-Aldosterone System (RAAS)
- Renin converts angiotensinogen to angiotensin I, which is converted to angiotensin II mainly by ACE.
- Angiotensin II (ATII) acts primarily through the ATII-1 receptor, causing vasoconstriction, increased blood pressure, and aldosterone release.
- Aldosterone increases sodium and water reabsorption at the distal convoluted tubule, raising plasma volume and BP.
- ATII-2 receptor opposes ATII-1 effects, which supports selective AT1 inhibition.
Mechanisms of Drug Classes
- ACE inhibitors block the conversion of angiotensin I to II and prevent bradykinin breakdown, increasing vasodilation.
- ARBs block ATII-1 receptors, preventing vasoconstriction and aldosterone effects.
- Renin inhibitors (e.g., aliskiren) block the conversion of angiotensinogen to angiotensin I.
Clinical Effects
- ACE inhibitors, ARBs, and renin inhibitors all decrease preload and afterload, act as vasodilators, and reduce cardiovascular remodeling.
- These drugs confer renal protection in diabetics by lowering glomerular filtration pressures.
Common Drugs & Dosing
- ACE inhibitors: benazepril, captopril, enalapril, fosinopril, lisinopril, etc.; dosing varies by agent and indication.
- ARBs: azilsartan, candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, etc.; dosing is once or twice daily.
- Renin inhibitor: aliskiren, dosed 150–300 mg QD.
Side Effects & Contraindications
- Angioedema: more common with ACE inhibitors than ARBs.
- Dry cough: seen with ACE inhibitors only.
- Hyperkalemia risk increases, especially with potassium-sparing diuretics or salt substitutes.
- Acute renal failure risk in bilateral renal artery stenosis.
- Contraindicated in pregnancy (Category D, risk of fetal harm).
- NSAIDs can decrease the effectiveness of ACE inhibitors and ARBs.
ARB + Neprilysin Inhibitor (Valsartan + Sacubitril)
- Used in heart failure; reduces CV death and HF hospitalization (PARADIGM-HF trial).
- Side effects: increased creatinine, hypotension, hyperkalemia, dizziness, angioedema.
Key Terms & Definitions
- ACE inhibitor (ACEi) — drug blocking angiotensin-converting enzyme, lowering ATII and increasing bradykinin.
- ARB — angiotensin II receptor blocker, inhibits ATII-1 mediated vasoconstriction and aldosterone release.
- Renin inhibitor — blocks conversion of angiotensinogen to angiotensin I, suppressing the RAAS.
- Preload — the initial stretching of cardiac myocytes prior to contraction.
- Afterload — the pressure the heart must overcome to eject blood.
- Aldosterone — hormone that increases sodium and water reabsorption in the kidney.
- Angioedema — rapid swelling under the skin, a serious ACEi side effect.
Action Items / Next Steps
- Review individual drug dosing and indications.
- Understand contraindications and management of side effects.
- Read up on clinical trial data supporting ACEi/ARB benefits in heart failure.
- Study the RAAS pathway and its pharmacologic modulation.