oral hypertensive treatments

Last edited 12/2018

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.

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.