ANGIOTENSIN II RECEPTOR BLOCKERS

The ARBs are a class of competitive and noncompetitive antagonists of the AT1 angiotensin receptor. These agents are very similar to ACE inhibitors, but they do differ in several important respects. First, because they do not interfere with bradykinin metabolism, these agents are associated with a much smaller risk of cough and angioedema. Second, ARBs are theoretically more potent than ACE inhibitors because they can inhibit the small amount of AII produced through ACE independent mechanisms. Third, ARBs block AT1 receptors but not AT2 receptors, although the significance of this difference is unclear.

The indications for ARBs are essentially the same as those for ACE inhibitors. In many instances, patients are started on ARBs if they are unable to tolerate the coughing associated with ACE inhibitors. The major adverse effects of ARBs include angioedema (although to a lesser extent than with ACE inhibitors), hyperkalemia, and acute kidney injury, all of which occur through the same mechanisms as with ACE inhibitors.

DIRECT RENIN INHIBITORS

The direct renin inhibitors (DRIs) block the conversion of angiotensinogen, renin’s only known substrate, to angiotensin I. Thus, unlike ACE inhibitors, these agents can effectively block the non-ACE conversion of angiotensin I to angiotensin II, and they do not interfere with bradykinin metabolism. Unlike ARBs, they also prevent AT2 receptor-mediated signaling. These drugs have been associated with a reduction of proteinuria in combination with ACE inhibitors and ARBs. Their adverse effect profile appears to be similar to that of ARBs.