Which feature best distinguishes ACE inhibitors from angiotensin II receptor blockers (ARBs) in terms of their mechanism and adverse effect profile?

## Mechanism-Based Distinction Between ACE Inhibitors and ARBs ### Key Structural Difference **Key Point:** ACE inhibitors and ARBs differ fundamentally in their site of action within the renin-angiotensin-aldosterone system (RAAS). | Feature | ACE Inhibitors | ARBs | |---------|----------------|------| | **Site of Action** | Inhibit ACE enzyme | Block AT1 angiotensin II receptors | | **Effect on Angiotensin II** | Prevent formation (↓ Ang II) | Allow formation but block action (↑ Ang II, blocked effect) | | **Bradykinin Metabolism** | Inhibited (ACE breaks down bradykinin) | Normal | | **Dry Cough** | Common (15–20% incidence) | Rare (< 2%) | | **Hyperkalemia Risk** | Moderate to high | Moderate to high | | **Angioedema** | Yes (bradykinin-mediated) | Rare | ### Why the Correct Answer is Correct **High-Yield:** ARBs selectively block AT1 receptors, preventing angiotensin II from exerting its vasoconstrictive and aldosterone-stimulating effects. ACE inhibitors, by contrast, block the enzyme that *converts* angiotensin I to angiotensin II, preventing formation of the hormone itself. This mechanistic difference explains the divergent adverse effect profile. ### Clinical Pearl: The Cough Mechanism ACE inhibitors cause a dry cough in 10–20% of patients because ACE also metabolizes bradykinin. Inhibition of ACE leads to bradykinin accumulation in the lungs, triggering cough. ARBs do not affect bradykinin metabolism, so cough is rare. ### Angioedema Risk Angioedema (especially involving the face, lips, and airways) occurs in 0.1–0.2% of ACE inhibitor users, again due to bradykinin accumulation. ARBs carry a much lower risk (< 0.1%). **Warning:** Do not confuse "both increase bradykinin" with "both cause cough equally." Only ACE inhibitors accumulate bradykinin; ARBs do not affect its metabolism. [cite:KD Tripathi 8e Ch 21]