Spironolactone is associated with greater risk of gynecomastia and impotence as compared with eplerenone. This is common add-on therapy in resistant hypertension. Avoid use with K+ supplements, other K+ -sparing diuretics, or significant renal dysfunction. Eplerenone often requires twice-daily dosing for adequate BP lowering. Beta blockers cardioselective Atenolol 25 100 2 Beta blockers are not recommended as first-line agents unless the patient has IHD or HF. These are preferred in patients with bronchospastic airway disease requiring a beta blocker. Bisoprolol and metoprolol succinate are preferred in patients with HFrEF. Avoid abrupt cessation. Beta blockers cardioselective and vasodilatory Nebivolol 5 40 1 Nebivolol induces nitric oxide induced vasodilation. Avoid abrupt cessation. Beta blockers noncardioselective Nadolol 40 120 1 Avoid in patients with reactive airways disease. Avoid abrupt cessation. Beta blockers intrinsic sympathomimetic activity Acebutolol 200 800 2 Generally avoid, especially in patients with IHD or HF. Avoid abrupt cessation. Beta blockers combined alpha- and beta-receptor Carvedilol 12.5 50 2 Carvedilol is preferred in patients with HFrEF. Avoid abrupt cessation. Direct renin inhibitor Aliskiren 150 300 1 Do not use in combination with ACE inhibitors or ARBs. Aliskiren is very long acting. There is an increased risk of hyperkalemia in CKD or in those on K+ supplements or K+ -sparing drugs. Aliskiren may cause acute renal failure in patients with severe bilateral renal artery stenosis. Avoid in pregnancy. Alpha-1 blockers Doxazosin 1 16 1 These are associated with orthostatic hypotension, especially in older adults. They may be considered as second-line agent in patients with concomitant BPH. - agonist and other centrally acting drugs Clonidine oral 0.1 0.8 2 These are generally reserved as last-line because of significant CNS adverse effects, especially in older adults. Avoid abrupt discontinuation of clonidine, which may induce hypertensive crisis; clonidine must be tapered to avoid rebound hypertension. 