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There are four main classes of antihypertensives, as discussed below. While they are used to control blood pressure, different combinations are preferred in different conditions or diseases.


Combinations of blood pressure control medications is important for many patients to reach optimal pressure control.


The image at left depicts suggested combinations to trial, with blue lines being good combinations and red lines less so.






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Common Medications

  • ACE inhibitors and ARBs
  • beta blockers
  • calcium channel blockers
  • diuretics

ACE Inhibitors and ARBs


ACE inhibitors block the production of ANG II, reducing blood pressure. They also prevent inactivation of bradykinin by kininase, leading to increased vasodilation.

Not best for black people (low renin). Do not use in pregnant women.



  • moderate to severe hypertension
  • reduces proteinuria in diabetes mellitus, especially in combination of ACEi and ARB
  • post-MI, preventing remodeling and hypertrophy
  • heart failure
  • chronic kidney disease, acting to reduce intraglomerular pressure



Absorption Affected by Food

Strengths (mg)

Regular Recommended Starting Dose


Target Dose



2, 4, 8

4 mg once daily

4-8 mg daily



0.5, 1, 2, 4

1 mg once daily

1-2 mg daily



5, 10, 20, 40

10 mg once daily

10-20 mg daily



10, 20

10 mg once daily

20 mg daily



5, 10, 20

10 mg once daily

20 mg daily



12.5, 25, 50, 100

25 mg bid to tid

50 mg b-tid



2.5, 5, 10, 20

5 mg once daily

10-40 mg single or 2 divided doses



1.25, 2.5, 5, 10

2.5 mg once daily

2.5-10 mg daily



1, 2.5, 5

2.5 mg once daily

2.5-5 mg daily



5, 10, 20

20 mg once daily

10-40 mg daily

Table 2. Heart Failure

ACE- Inhibitor

Target Dose


5 mg bid or 10 mg daily


4 mg daily


40 mg daily or 20 mg bid


50 mg tid


2.5 mg daily


10 mg bid


20-35 mg daily

All ACEIs have a duration of action approximately 24 hours except for captopril (6-12 hrs)


Adverse Drug Reactions

It is very important to recheck plasma creatinine and potassium 7-14 days after starting an ACE or ARB. An increase of 20% in sCR, a 20% fall in eGFR, or a rise in potassium above 5.5 mmol/L should prompt change in medication, further investigation, or potassium reduction diet.

  • cough: the most common reason people stop
  • hypotensiondecreased renal perfusion in volume depletion
  • hyperkalemia due to reduced aldosterone production
  • teratogenic


Mechanism of Action

Competitive inhibitor of ACE-I

Indirectly decreases aldosterone

decreases TPR, decreases aldosterone

Increased bradykinin levels

Decreases blood pressure, preload and afterload without changes in HR or norepinephrine rebound.

Can cause a significant regression in LFH

Increase in stroke volume and cardiac index as well as decreases in right atrial pressure, MAP, and systemic vascular resistance in those with CHF.

Increases renal perfusion via dilation of the efferent arteriol and decreases renal vascular resistance

Decreases proteinuria and stabilizes renal function (in chronic renal failure) regardless of the ability to decrease blood pressure.


  • losartan

Adverse Drug Reactions

Decrease in aldosterone causes potassium retention in most patients.

Angioedema has been reported with use of some ACEIs.

Oliguria, azotemia, and renal failure can occur in those with severe HF.

Severe hypotension can occur with those already hypovolemic or treated with other antihypertensives.

Dry cough is a common side effect.

Taste disturbance common with captopril.

Contra-indications and Drug Interactions

Renal arterial stenosis.

Use of ACEIs in pregnancy has been associated with fetal abnormalities.

ACEI + Spironolactone can cause life threatening hyperkalemia and should not be initiated unless under very close observation.

NSAIDS can antagonize the antihypertensive effects of ACEI.

ACEI + Lithium can cause lithium toxicity

Pharmacokinetics, metabolism and excretion

All have active metabolites except for captopril and lisinopril.

Most all ACEIs are excreted solely by the kidney but both renal and fecal elimination is seen with: Benazepril, fosinopril, quinapril, ramipril, and trandolapril.

Advice for Clinical Practice

Adjust dose 2-4 weeks after initiating ACEI if inadequate response and always ask about use of NSAIDS as this can contribute to treatment resistant hypertension.

Advise to discontinue ACEI if swelling of the face or lips occur. If swelling of tongue and/or throat occurs then administration of epinephrine is required.

It is very important to recheck plasma creatinine and potassium 7-14 days after starting an ACE or ARB. An increase of 20% in sCR, a 20% fall in eGFR, or a rise in potassium above 5.5 mmol/L should prompt change in medication, further investigation, or potassium reduction diet.

  • cough: the most common reason people stop

  • hypotension decreased renal perfusion in volume depletion

  • hyperkalemia due to reduced aldosterone production

  • teratogenic

If dry cough occurs and is particularly bothersome then re-challenging with another ACEI is appropriate. Cough usually subsides within 1-3 weeks but may take up to 3 months. Switching to an ARB may be necessary.

ACEI should be a priority for patients with HF or post-MI since they are shown to have a mortality benefit.

When adding an ACEI to a patient already on a diuretic it is suggested to with hold the diuretic 2-3 days prior to initiating the ACEI.

The combination of ACEI + ARB should be avoided unless patients with compelling indications like those with CHF.

ACEI’s should be strongly considered in those with diabetes with or without proteinuria due to their beneficial effects on GFR.

Warn patients that ‘no-salt’ or ‘half-salt’ substitutes might not be appropriate because they’re mostly potassium salts.


Beta Blockers


Do not start in people over 60. Other indications include:

  • moderate to severe hypertension
  • angina
  • congestive heart failure
  • acute coronary syndromes, though no real evidence of improving outcomes
  • (off-label) for stage fright


Drugs that inhibit the sympathetic nervous system are often used in the treatment of cardiovascular disease.


They act by:

  • decrease cardiac output (both HR and contractility)
  • also decrease renin release, leading to lowered Na, water retention and vasodilation
  • competitively inhibits beta1 receptors reducing HR, contractility, BP, and MVO2
  • increases duration of diastole
  • beta blockers work against renin
  • makes exercise difficult
  • propanolol: β1 and β2 antagonist
  • metoprolol: β1 antagonist
  • atenolol
  • acebutamol
  • bisoprolol


Centrally acting

  • act on the BP control centre in the brain
  • thought that they act on α2 receptors to inhibit NE release
  • side effects include sedation
  • methyldopa
  • clonidine



  • block α1 receptors on vascular smooth muscle cells, increasing vasodilation
  • parazosin



Dose and Half Life

oral therapy sufficient in most case of ACS, though IV metoprolol can also be done 5mgx3 over 15 min



Adverse Drug Reactions

increasing doses of beta blockers causes loss of cardioselectivity and

can substantially risk of stroke or diabetes


short term

  • avoid acute adminstration in unstable patients with hypotension or overt HF
  • bradycardia and heart block
  • bronchospasm
  • peripheral vasoconstricion
  • fatigue, lethargy
  • sexual dysfunction

long term

  • depression, vivid dreams, nightmares


Counter-Indications and Drug Interactions


do NOT combine with NDHP CCBs, as this can cause bradycardia

  • absolute: asthma


  • tendency to bronchospasm
  • insulin dependent T2DM
  • conduction system disease
  • peripheral vascular disease


Calcium Channel Blockers

dihydropyridines: nifedipine, amliodipine

non-dihydropyridines: verapamil, diltiazem

type here



good to combine with ACE/ARB

and beta blockers



  • stable angina
  • in ACS, generally only used acutely for ongoing ischemia when beta-blockers are contraindicated


  • blocks Ca2+ influx into VSMCs and cardiomyocytes, leading to vasodilation and decreased contractility
  • causes coronary/peripheral vasodilation, reducing contractility and MVO2

direct effect of reducing contractility may be counteracted by reduction in afterload and activation of



  • verapamil: cardiomyocyte and VSMC
  • diltiazem: similar to verapamil
  • dihydropyridines (ie nifedipine): VSMC


Adverse Drug Reactions

short term

  • avoid short acting dihydropyridines, ie nifedipine, due to its drop in BP
  • non-dihydropyridines (verapamil and diltizaem) are negatively chronotropic and should generally be avoided in patients with poor LV function or HF

can cause headaches, flushing, dizziness

peripheral edema

constipation (verapamil)

bradycardia/heart block (verapamil, diltiaezm)

worsening heart failure




Diuretics act to promote sodium and water loss. They are used to treat hypertension (especially thiazides), heart failure, cirrhosis, nephrotic syndrome, and other causes of edema.



Loop Diuretics

Loop diuretics are powerful drugs that inhibit the Na/K/2Cl triporter in the thick ascending limb, possibly be competing with chloride. This drop in Na and K resorption leads to diuresis and kaluresis.


A loss of renal concentrating and diluting capacity leads to impaired preservation of water and electrolytes during periods of dehydration.


Hypokalemia, hypomagnesemia, and occasionally hyponatremia can be due to loop diuretic use. Furosemide (Lasix) is the most common loop diuretic. Perhaps alkalosis too due to hypokalemia?

Not good for HTN, as it needs to be dosed TID. Good if Cr >130 mmol



Thiazides are key drugs in treating hypertension. They inhibit NaCl transport into the distal convoluted tubule, preserving loop function.

These can also produce hypokalemia.

Hyponatremia is fairly common as volume contraction engages ADH and much free water is reabsorbed. Electrolytes need to be monitored after beginning therapy.



Potassium-Sparing Diuretics

These drugs antagonize the effects of aldosterone at the cortical collecting tubule and late distal tubule.

  • spironolactone inhibits the aldosterone receptor
  • triamterene and amiloride appear to inhibit Na flux through ion channels in the lumenal membrane

Hyperkalemia can result due to decreased K secretion.




Acetazoamide acts on the proximal tubule


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Guidance on Use


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Resources and References


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