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Oral hypertensive treatments

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

oral antihypertensive agents

Primary agents

  • thiazide or thiazide-type diuretics
    • e.g - Chlorthalidone, Hydrochlorothiazide, Indapamide, Metolazone
    • Cchlorthalidone preferred based on prolonged half-life and proven trial reduction of CVD
    • monitor for hyponatremia and hypokalemia, uric acid and calcium levels
    • use with caution in patients with history of acute gout unless patient is on uric acid-lowering therapy

  • ACE Inhibitors
    • e.g. ramipril
    • do not use in combination with ARBs or direct renin inhibitor
    • increased risk of hyperkalemia, especially in patients with CKD or in those on K+ supplements or K+-sparing drugs
    • may cause acute renal failure in patients with severe bilateral renal artery stenosis
    • do not use if history of angioedema with ACE inhibitors
    • avoid in pregnancy

  • ARBs
    • e.g. candesartan, losartan
    • do not use in combination with ACE inhibitors or direct renin inhibitor
    • increased risk of hyperkalemia in CKD or in those on K+ supplements or K+-sparing drugs
    • may cause acute renal failure in patients with severe bilateral renal artery stenosis
    • do not use if history of angioedema with ARBs. Patients with a history of angioedema with an ACEI can receive an ARB beginning 6 weeks after ACEI discontinued
    • avoid in pregnancy

  • calcium channel blockers (CCB) - dihydropyridines
    • e.g. - Amlodipine, Felodipine
    • avoid use in patients with , heart failure with reduced ejection fraction (HFrEF); amlodipine or felodipine may be used if required
    • associated with dose-related pedal edema, which is more common in women than men

  • CCB - nondihydropyridines
    • e.g. - Diltiazem, Verapamil
    • avoid routine use with beta blockers due to increased risk of bradycardia and heart block
    • do not use in patients with HFrEF

Secondary agents

  • diuretic-loop
    • e.g. - Bumetanide, Furosemide
    • these are preferred diuretics in patients with symptomatic HF. They are preferred over thiazides in patients with moderate-to-severe CKD (e.g., GFR<30ml/min)
  • diuretic-potassium sparing
    • e.g. - Amiloride
    • these are monotherapy agents and minimally effective antihypertensive agents.
    • combination therapy of potassium-sparing diuretic with a thiazide can be considered in patients with hypokalemia on thiazide monotherapy
    • avoid in patients with significant CKD (e.g., GFR<45ml/min)

  • diuretic- aldosterone antagonists
    • e.g. - Eplerenone, Spironolactone
    • preferred agents in primary aldosteronism and resistant hypertension
    • spironolactone associated with greater risk of gynecomastia and impotence compared to eplerenone
    • 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 blocker- cardioselective
    • e.g. - Atenolol, Bisoprolol
    • 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 blocker- noncardioselective
    • e.g. - Propranolol
    • avoid in patients with reactive airways disease
    • avoid abrupt cessation

  • alpha-1 blockers
    • e.g. - Doxazosin, Prazosin
    • these are associated with orthostatic hypotension, especially in older adults
    • they may be considered as second-line agent in patients with concomitant BPH

  • central alpha2-agonist and other centrally acting drugs
    • e.g. - Clonidine, Methyldopa
    • 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

  • direct vasodilators
    • e.g. - Hydralazine, Minoxidil
    • these are associated with sodium and water retention and reflex tachycardia; use with a diuretic and beta blocker
    • Hydralazine is associated with drug-induced lupus-like syndrome at higher doses
    • Minoxidil is associated with hirsutism and requires a loop diuretic. Minoxidil can induce pericardial effusion.


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