Oral hypertensive treatments

Oral antihypertensive agents

Primary agents

• thiazide or thiazide-type diuretics
  • e.g. - Chlorthalidone, Hydrochlorothiazide, Indapamide, Metolazone
  • Chlorthalidone 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 hyperkalaemia, 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 hyperkalaemia 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 oedema, which is more common in women than men
    
    
• CCB - non-dihydropyridines
  • 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 hypokalaemia 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- non-cardioselective
  • 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.

Reference:

1. Whelton PK et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138(17):e426-e483.