Essential Hypertension

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Elevation in blood pressure beyond normal parameters

  • Essential (Primary) - No identifiable cause


  • Secondary (~5-10%) - Identifiable underlying cause



Diagnosis of hypertension in adults and recommendations for follow-up


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Primary (essential hypertension)

  • No identifiable cause



  • Endocrine (e.g. hyperaldosteronism, thyroid, parathyroid, pheochromocytoma)
  • Renal disorders (e.g. glomerulonephritis)
  • Obstructive sleep apnea
  • Metabolic syndrome
  • Coarctation of aorta
  • Drug induced
  • Genetic (rare)
  • Lifestyle
  • Others


Risk factors

  • Cigarette smoking
  • Age (men >55, women >65)
  • Obesity (body mass index ≥30 kg/m2)
  • Dyslipidemia
  • Diabetes mellitus and metabolic syndrome
  • Physical inactivity
  • Diet-high sodium intake
  • Family history of premature vascular disease


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  • Third leading cause of death world wide
  • Increases with age
  • Affects 22% of Canadians between the ages of 18-70 years
  • Affects 50% of Canadians over the age of 65 years
  • Affects 65 million Americans
  • Typical onset between 25 and 55


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Though still poorly understood, various factors have been suggested including enhanced beta adrenergic response, increased angiotensin II activity, and excess mineralocorticoids, which ultimately lead to:

  • Increased peripheral vascular resistance
  • Increased cardiac output
  • Increased blood volume

Genetic factors account for 30% cases (patients with family history of one or both parents).


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Clinical Presentation:

1) Mild to moderate cases:

  • Often asymptomatic
  • May present with early morning pulsating headaches, which subsides during the day


2) Chronic cases:

- Usually asymptomatic

- May present with


Symptoms of target organ damage (TOD) including


  • Chronic kidney disease (CKD)
    • Fatigue
    • Anemia
    • Signs and symptoms of uremia
    • Labs: Proteinuria, reduced GFR
  • Retinopathy
    • Blurred vision
    • Floating spots
    • Loss of vision


Macrovascular damage:

  • Cardiac manifestations
    • Chest pain
    • Edema
    • Dyspnea/ CHF
  • Cerebral manifestations
    • Headache
    • visual disturbance
    • Stroke
    • Confusion/ encephalopathy
  • Peripheral arterial damage
    • Claudication
    • Skin changes, dryness, scaling, hair loss
    • Cold extremities
    • Reduced peripheral pulses
    • Ulceration, gangrene


- Associated with underlying cause include

  • Edema due to chronic kidney disease
  • Hormonal symptoms such as weight changes, sweating, tachycardia, anxiety


3) Hypertensive Emergency and Urgency:


Characterized by a severe elevation in blood pressure with evidence of target organ damage (TOD). CHEP 2012 guidelines suggest a DBP of ≥130 with TOD, while JNC VII suggests BP of >180/120 mmHg complicated by evidence of impending or progressive target organ dysfunction.

  • Hypertensive encephalopathy: Accelerated hypertension associated with somnolence, confusion, visual disturbances, nausea and vomiting


  • Intracranial hemorrhage: Sudden severe headache followed by altered mentation, paralysis, stupor and coma


  • Acute aortic dissection or MI: Sudden severe pain in the chest


  • Acute left ventricular failure or acute pulmonary edema: Dyspnea, edema


  • Acute renal failure: Oliguria, anuria, altered mentation



Characterized by severe elevation in BP (>180 systolic ± >120 diastolic) without any progressive target organ damage (can have symptoms but no TOD)

  • Blurred vision, headache, dizziness, edema, nausea
  • Peripheral swelling


4) Pheochromocytoma:

Episodic hypertension mostly accompanied with anxiety attacks due to catecholamine release

  • Palpitation
  • Perspiration
  • Pallor
  • Tremor
  • Vomiting
  • Angina
  • Orthostatic hypotension


5) White coat hypertension, WCH (doctors office


  • Is suspected when there is a significant increase in BP values within medical environment compared to with outside usual activities (usually diagnosed with an ambulatory blood pressure monitor)
  • Once diagnosed, accurate home BP values may be the best guide for therapy


6) Uncontrolled hypertension:

Failure to achieve targeted pressure despite ≥3 antihypertensive drugs (whereby patient is adherent) may suggest an identifiable or secondary cause, such as obesity, renovascular hypertension (renal stenosis) or primary hyperaldosteronism.


7) Pregnancy:

A systolic BP ≥169 mmHg or a diastolic BP ≥109 mmHg is often a part of following hypertensive emergency presentation:

  • Eclampsia: Ictric, pruritus, headaches, seizures
  • Hypertensive encephalopathy: Restlessness, irritability, headaches, seizure and coma


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Investigation and Workup:


Evaluation of patients with documented hypertension has three objectives:

  • To exclude secondary causes of hypertension
  • To ascertain the presence or absence of target organ damage
  • To assess lifestyle and identify other cardiovascular risk factors or concomitant disorders that affect risk factors, prognosis and treatment

Ambulatory monitoring and blood pressure self-measurement are helpful in patients with:

  • Apparent drug resistance
  • Episodic hypertension or autonomic dysfunction
  • Patients with hypotensive symptoms who take antihypertensive medications



  • Episodes of headache, sweating, palpitations, weakness, muscle cramp, and vision disturbances
  • Previous episodes of high blood pressure
  • History of diabetes, CAD, peripheral artery disease and renal disease
  • History of coexisting diseases such as migraine, gout, asthma, heart failure and BPH
  • Inquire about sedentary life style, dietary habits, salt intake, cigarette smoking and alcohol consumption
  • Family history of hypertension, diabetes, CAD, peripheral artery disease and renal disease
  • Medication history
    • Oral contraceptives
    • NSAIDs
    • Antidepressants
    • Nasal decongestants



Look for evidence of target organ damage and clues to secondary causes of hypertension.

- Vitals:

  • Confirm BP and consider an automated BP cuff e.g. The BP Tru™

- General appearance:

  • Example, cushinoid

- Weight:

  • Assess for obesity, metabolic syndrome

- Fundoscopy:

  • Papilledema
  • Hypertensive retinopathy

- Neck exam:

  • Carotid bruits
  • Distended veins
  • Enlarged thyroid gland

- Chest auscultation for

  • Abnormal heart sound
  • Pulmonary edema

- Abdominal exam:

  • Renal bruits
  • Palpable kidney
  • Masses
  • Abnormal aortic pulsations

- Examination of the extremities:

  • Diminished/ absent peripheral arterial pulsations
  • Bruits
  • Edema



  • Complete blood count (CBC)
  • Serum electrolytes
  • Uric acid
  • Blood sugar
  • Creatinine and eGFR
  • Lipid profile
  • Urine analysis and albumiuria assessment with urine albumin/creatinine ratio (ACR)
  • Electrocardiogram (ECG)


Additional investigations for secondary causess:

  • Plasma renin level (renovascular hypertension)
  • Serum aldosterone or 24-hour urine aldosterone
  • 24-hour urinary free cortisol level
  • Thyroid-stimulating hormone (TSH) level
  • Urinary catecholamines and fractionated metanephrines



  • Chest X-ray
  • Renal ultrasound
  • Renal angiogram (usually with CT/CTA or MRI/MRA)
  • CT scan of abdomen
  • ECHO cardiography


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Treatment Goals:
  • Goal is to control and achieve target blood pressure (mmHg)

1-Image-HTN-GOT-Pharma-Goal To control

  • Decrease the risk of morbid hypertensive complications, e.g.
    • Cerebrovascular
    • Cardiac
    • Renal
    • Retinal
  • Lowest possible effective dosage should be used
  • In the absence of hypertensive crisis, control the BP gradually to avoid end-organ ischemia


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Therapeutic Choices:


- Weight:

Aim for an ideal Body Mass Index, decrease as little as 4.5 kg in weight significantly reduces BP.


Target: BMI = 18.5 to 24.9 kg/m2 in non-hypertensive individuals


Formula: BMI = weight in kilograms / height in meter 2


- Waist circumference:

1-b-Image-HTN-Treatment-Waist circumference


- Salt intake:

2-b-1-IMAGE- NURSING-Treatment- Low Sodium Age Recommended

1,500 mg sodium (Na) = 65 mmol sodium (Na) = 3.75 g of salt (NaCl) = 1/2 level teaspoon of table salt


- Alcohol: Restrict intake to a maximum of

  • Two standard drinks per day or 14 drinks per week for men
  • One standard drink per day or 9 drinks per week for women

One standard drink is equivalent to:

  • 5 oz./142 ml of wine (12% alcohol)
  • 1.5 oz./43 ml of spirits (40% alcohol)
  • 12 oz./341 ml regular strength beer (5% alcohol)


- Exercise:

Moderate intensity dynamic exercise, such as brisk walking for 30-60 minutes every day, or at least 5 times a week


- Diet:

A diet rich in fruits, vegetables and dairy products with reduced saturated and total fat can substantially lower BP - consider the DASH diet.


- Smoking:

Cessation of smoking and smoke-free environment is important to reduce hypertension, stroke and cardiovascular risk.

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  • BP 160/100 without TOD or risk factors [2013 CHEP guidelines]
  • Patients with target organ damage e.g. left ventricular hypertrophy (140-159/90-99 mmHg)
  • Diabetes or chronic kidney disease with BP ≥130/80
  • Chronic kidney disease with BP ≥140/90
  • Presence of other risk factors (over 90% of Canadians with hypertension have other risk factors)
  • BP 140-159/90-99 despite lifestyle modification


Treatment Gap Alert: Many younger hypertensive Canadians with multiple cardiovascular risks are currently not treated with pharmacotherapy. Health care professionals need to be aware of this important care gap and recommend pharmacotherapy.


Considerations in selection of therapy:

  • Race: Diuretics preferred over renin angiotensin system (RAS) inhibitors for African-Americans
  • Age
  • Coexisting diseases and therapies
  • Quality of life (QOL)
  • Economic consideration
  • Dose per day (compliance factor)


- Diuretics:

  • Thiazides are used as 1st line agents because of effectiveness, compliance and cost
  • Loop diuretics should be used in patients with decreased renal function, defined as CrCl <20-30 mL/min
  • Aldosterone antagonists: Prescribed in patients with primary hyperaldosteronism or those with resistant hypertension


- Βeta blockers:

  • May be used 1st line for patients with ischemic heart disease, CHF, migraine
  • Not indicated 1st line in patients over the age of 60 years


- ACE inhibitors:

  • Should be considered in patients with diabetes, chronic kidney disease, atrial fibrillation, CAD or CHF
  • Contraindicated in pregnancy


- Angiotensin receptor blocking agents:

  • Considered in patients with diabetes, renal insufficiency, chronic kidney disease, or CHF (when ACE intolerant)
  • Contraindicated in pregnancy


- Dihydropyridine calcium channel blockers:

  • Considered in patients with isolated systolic hypertension, angina, and those at high CV risk
  • Shown to be safe in pregnancy


- Non-dihydropyridine calcium channel blockers:

  • Considered in patients with atrial arrhythmia, tachycardia, stable angina, migraine


- Alpha-adrenoceptor antagonists:

  • Non-selective antagonists are usually reserved for use in hypertensive emergencies caused by a pheochromocytoma or as 4th line agents
  • Consider in hypertensive males with BPH


- Direct renin inhibitors:

  • Indicated for the treatment of mild to moderate essential hypertension and reduction of proteinuria in addition to ACEIs or ARBs
  • Contraindicated in pregnancy

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- Drugs with central sympatholytic action (alpha

agonists, central):

  • Effective in hypertensive patients with renal disease because they do not compromise renal function; considered as 4th line agents
  • Methyldopa is traditionally considered as a first line therapy in pregnancy


- Vasodilators:

  • Usually prescribed as adjunct therapy with other BP drugs and rarely are used alone
  • Hydralazine also may be used to control high BP in pregnant women
  • Nitroglycerin/ nitroprusside can be used in hypertensive emergencies


- Combination drugs:

May be used to:

  • Simplify regimen and improve adherence
  • Avoid side effects that may occur from high doses of a single agent
  • If the BP is >20 mmHg systolic ± >10 mmHg diastolic above target - consideration should be given initially to start with 2 drugs from different classes, preferably as a combination product


Note: Beta-blockers and non-DHP CCBs should not be used routinely in combination. ACEIs and ARBs are also not recommended to be used in combination; as the combination has not shown to reduce CV events; when compared with ACEI alone


If hypertension is NOT adequately controlled with single agent, patient should follow up monthly or more frequently if severe hypertension. Also consider


  • Patient non-adherence: Cost and adverse effects/allergy should be considered
  • Suboptimal dose: Increase dose if patient is considered adherent, however combination therapy is usually preferred to maximal doses of single agents
  • Add in a second drug from another class; to improve control, and minimize adverse effects caused by the maximum dose of single agents
  • If no change in BP, and patient is adherent, 1st choice option may be ineffective and a new agent should be substituted


Specific Paradigms for Treatment of Hypertension:

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  • Initially reduce mean arterial BP by no more than 25% within minutes to an hour, once stable, further stabilization to 160/100-110 mmHg within the next 2-6 hours to avoid further organ damage



  • Avoid precipitous drop in BP. Aggressive dosing with intravenous drugs or even oral agents, to rapidly lower BP is not without risk
  • Patients with stage II hypertension with associated symptoms such as severe headache, shortness of breath, epistaxis, or severe anxiety, should have their BP lowered upto 20% over several hours
  • Some hypertensive urgencies may benefit from treatment with oral, short-acting agents. Most importantly, patients should not leave the ER without a confirmed follow-up appointment within few days



  • Monitor for end organ injury:
    • Abnormal neurologic signs (stroke, seizures)
    • Severe headache
    • Pulmonary edema
    • Chest pain (MI, aortic dissection)
    • Vision difficulty (retinal edema, hemorrhage)
  • Hospitalization, IV treatment and ICU monitoring usually required for hypertension emergency/urgency
  • Parenteral antihypertensive agents may include:
    • Vasodilators: e.g. Sodium nitroprusside, nitroglycerin, hydralazine
    • Adrenergic inhibitors: e.g. Labetalol, methyldopa, phentolamine
    • ACEIs: e.g. Enalaprilat
  • Diuretics may be used to induce diuresis if required
  • Ionotropic pressure support may be required for precipitous drop in BP


Special Considerations:

Hypertension and stroke

  • Avoid overzealous BP lowering in acute stroke. Treat extreme BP elevation (systolic >220 mmHg, diastolic >120 mmHg) by 15-25% over the first 24 hour with gradual reduction thereafter
  • If eligible for thrombolytic therapy in acute stroke, treat very high BP (>185/110 mmHg)
  • In secondary prevention, the benefits of BP lowering is seen in both normotensive and hypertensive patients
  • ACEI plus diuretic or ARB - based treatment should be considered


Aortic dissection

  • Emergent cases, often requiring surgical management, especially in ascending aortic dissection
  • Do not use sodium nitroprusside without beta blockers, (increases the chances of aortic rupture)



  • Alpha and beta adrenergic receptors are stimulated by excess catecholamine in pheochromocytoma
  • Preferred treatment is surgical resection of tumor, following α-adrenergic blockade to avoid catecholamine surge
  • β-Adrenergic blockade alone may result in more severe hypertension owing to the unopposed α-adrenergic stimulation


Elderly hypertensive patient (age >60 years)

  • May also have coexisting medical conditions
  • Dosage should be increased gradually
  • Diuretics, CCBs and ACE inhibitors/ARBs are good choices
  • Avoid excess BP lowering especially if postural hypotension


Hypertension in patients of African descent

  • Beta blockers and ACE inhibitors are less effective
  • Calcium channel blockers, diuretics and possibly ARBs are good choice


Obese hypertensive patient

  • Weight reduction is mainstay of non-pharmacological therapy
  • Treatment is similar to isolated hypertension. However, there may be associated risk of left ventricular hypertrophy, endothelial dysfunction, renal hyperfiltration, microalbuminuria, hence ACEI or ARB may be reasonable option

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The diabetic patient

  • Usually require combination therapy to achieve desired levels ≤130/80 mmHg
  • Should start with ACE inhibitors (or ARBs) and consider combination therapy if BP is >20 mmHg systolic ± >10 mmHg diastolic above target
  • Caution with blockers because of their masking hypoglycemic symptoms


Patient with chronic kidney disease

  • Most patients with hypertension require combination therapy to achieve optimal BP goals <130/80 mmHg
  • Initially start with diuretics (especially loop diuretics if Clcr <20-30 mL/min) and ACEI or ARBs


Patient with left ventricular hypertrophy (LVH)

  • May start with ACEI or ARBs. Long acting CCB or thiazide diuretics are other options


Patients with coronary artery disease (CAD)

  • Increased risk of unstable angina (UA) and myocardial infarction (MI)
  • May start with beta adrenergic antagonist, long-acting CCB or ACE inhibitors
  • Cautiously use non-dihyidropyridine calcium channel blockers in MI and cardiac conduction system disease


Patients with heart failure (HF)

  • ACEI and Beta blocker (ARB if ACEI intolerant)
  • Titrate doses of beta-blockers and ACEI/ ARB to those used in clinical trials
  • Avoid calcium channel blockers because of negative inotropic effects
  • Add aldosterone antagonist in class 2, 3 or 4 HF


Pregnancy and hypertension

  • Treatment should start if diastolic BP >100 mmHg
  • Avoid non-pharmacologic therapy such as:
    • Weight reduction
    • Exercise
  • Alpha-methyldopa has the largest amount of safety data and is still preferred
  • Hydralazine, labetalol, diuretics are considered safe during pregnancy and are reasonable alternatives. In late pregnancy beta blockers (not atenolol) and calcium channel blockers are additional safe choices
  • ACEIs, ARBs and nitroprusside are contraindicated in the pregnancy


Surgical/ Interventional

Treatment of renovascular hypertension

  • Percutaneous transluminal angioplasty
  • Stent placement (for fibromuscular hyperplasia and for discrete stenotic arteriosclerotic lesions not involving the renal artery ostium)
  • Rarely bypass graft


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  • ➣ Thiazide diuretics
  • ➣ Loop diuretics
  • ➣ Aldosterone receptor blockers
  • ➣ Inhibitors of renal epithelial Na+ channels


Thiazide diuretics



  • Block Na/Cl transport in proximal part of renal distal convoluted tubules




  • Initial 12.5 mg PO daily. Usual dose 25 mg PO daily; minimal benefit for lowering BP beyond 25 mg, however, side effects (such as hypokalemia and hyponatremia) increase



  • Initial 12.5 mg PO daily, increase to 25 mg/day if needed. Maximum dose is 50 mg/day, although there is minimal additional BP lowering effect beyond 25 mg/day



  • Initial 1.25 mg PO daily; usual 2.5 mg/day, can be used when renal function <30 mL/min


  • Titration: Increase by 1.25 mg PO every 4 weeks, according to blood pressure response; Max. 2.5 mg daily


Loop diuretics



  • Loop Diuretics → Block Na/K/Cl transporter in renal loop of Henle




  • Initial 20 mg PO BID, it can be given 40 mg PO BID and then adjusted according to the response


Note: Will only consider if eGFR <30 mL/minute


Aldosterone receptor blockers



  • Blocks aldosterone receptors in renal collecting tubule → results in increased excretion of sodium and water and decreased excretion of potassium




  • Initial 25-100 mg PO in single or divided doses, should be continued for 2 weeks then adjustments should be made according to the response



  • Initial 50 mg PO Daily for should be continued for 4 weeks, can go up to 50 mg PO BID. No therapeutic benefits observed with >100 mg/day


Inhibitors of renal Epithelial Na+ Channels



  • Disrupts sodium ↔ potassium exchange in the distal convoluted tubule and collecting ducts of the nephron
  • Inhibits Sodium-Potassium-ATPase
  • Decreases calcium excretion
  • Increases magnesium loss




  • Initial 5 mg PO daily, usual 5-10 mg PO daily; Max. 20 mg/day (usually used in combination with other antihypertensive)



  • Initial 50 mg PO daily; usual 50-100 mg PO daily (usually used in combination with thiazide diuretic)

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Beta-adrenergic blocking agents



  • ➣ Acebutolol
  • ➣ Atenolol
  • ➣ Bisoprolol
  • ➣ Metoprolol


Non- Cardioselective:

  • ➣ Carvedilol
  • ➣ Nadolol
  • ➣ Propranolol
  • ➣ Timolol
  • ➣ Pindolol
  • ➣ Labetalol



  • Block beta receptors
  • Decrease heart rate and cardiac output
  • Decrease renin release





  • Mild to moderate hypertension 200-400 mg PO daily in 2 divided doses
  • Patient with severe hypertension may respond to higher doses



  • Initial 25-50 mg PO daily, doses >100 mg/day show no additional benefit



  • In some case initial 2.5 mg PO daily is preferable (especially in renal and hepatic impairment), usual 5 mg PO daily; may increase up to 20 mg/day if required



Conventional tablets:

  • Initial 25-50 mg/day PO BID; usual 100-200 mg/day in divided doses; Max. 400 mg/day in 2 divided doses

Extended-release tablets:

  • Initial 25-100 mg PO daily; usual 100-200 mg PO daily

IV Metoprolol:

May be used to control hypertension/ventricular rate control in patients NPO or nonfunctioning GI tract.

  • Initial low dose of 1.25-5 mg IV every 6-12 hrs


Non- Cardioselective:


Extended-release capsules:

  • Initial 10 mg PO daily; Max. 80 mg/day

Immediate-release tablets (not indicated in Canada for HTN):

  • Initial 6.25 mg PO BID; usual 12.5-25 mg PO BID; Max. 25 mg PO BID



  • Initial 100 mg PO BID; usual 200-400 mg PO BID
  • In severe hypertension maximum dose 1200 mg/day


  • Titration: Increase dosage by 100 mg PO BID every 2-3 days


Hypertensive emergency

  • IV: Initial 10-20 mg IV over 2 min x 1
    • Additional doses of up to 40-80 mg at 10-minute intervals may be required to achieve desired BP. Total cumulative dose of 300 mg; Max. 300 mg/day IV
  • IV infusion: Initial 0.5-2 mg/minute continuous IV infusion (discontinue after 2.5 hrs of infusion)
  • Oral dose following IV: Initial 100 mg PO daily; maintenance dose 200-400 mg PO in 2 divided doses



  • Initial 40 mg PO daily; usual 40-80 mg PO daily; Max. 320 mg/day


  • Titration: Gradually increase by 40-80 mg/day every 3-7 days


  • In renal impairment depending on the CrCl dose interval is increased and doses are reduced



Conventional tablets:

  • Not indicated for hypertension

Long acting (extended- release) capsules:

  • Initial 80 mg PO; usual 160-320 mg PO daily; Max. 320 mg/day


  • Titration: Increase dose 120-160 mg/day every 3-7days



  • Initial 10 mg PO BID; usual 20-40 mg/day in 2 divided doses; Max. 60 mg/day


  • Titration: May increase dose gradually at 5 mg BID intervals every 14 days



  • Initial 5 mg PO twice daily; usual dose is 10-40 mg PO BID; Max. 60 mg/day


  • Titration: Increase gradually by 10 mg/day every 3-4wks

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ACE (angiotensin-converting enzyme) inhibitors

  • ➣ Captopril
  • ➣ Enalapril
  • ➣ Lisinopril
  • ➣ Perindopril
  • ➣ Ramipril
  • ➣ Trandolapril



  • Inhibition of the renin-angiotensin aldosterone system
  • Inhibit bradykinin degradation
  • Stimulate vasodilating prostaglandin synthesis
  • Reduce sympathetic nervous system activity


Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.




  • Initial 12.5-25 mg PO BID or TID; usual 50 mg PO BID or TID; Max. 450 mg/day


  • Titration: Increase by 12.5-25 mg/dose every 1-2 week; up to 50 mg 3 times/day


  • Usually after 50 mg PO TID, consider adding a diuretic (thiazide)



  • Initial 2.5-5 mg PO daily; usual 2.5-40 mg/day in 1-2 divided doses; Max: 40 mg/day


Enalaprilat IV

  • Initial 1.25 mg IV over 5 minutes every 6hrs; usual 0.625-1.25 mg IV over 5 minutes given every 6 hrs, up to 36 hrs
  • If concomitant diuretic use - begin with 0.625 mg IV over 5 minutes



  • Start 10 mg PO daily; usual 10-40 mg PO daily; Max. 80 mg/day


  • If concomitant diuretic - use cautiously, begin with 5 mg PO daily


  • Moderate renal failure (CrCl 10-30): Begin with 5 mg PO daily; only if the decline/failure is not secondary to bilateral renal stenosis


  • Dialysis patients: Begin with 2.5 mg once daily (adjust according to BP response)



  • Initial 2-4 mg PO daily; usual 4-8 mg PO daily; Max. 16 mg/day



  • Initial 2.5 mg PO daily (Max. 20 mg/day). Adjust at 1-2 week intervals by doubling dose, or 5 mg increments



  • Initial 1 mg PO daily or 2 mg PO daily in black patients; usual 2-4 mg PO daily. Adjust dosage at weekly intervals

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Angiotensin receptor blocking agents

  • ➣ Candesartan
  • ➣ Eprosartan
  • ➣ Telmisartan
  • ➣ Irbesartan
  • ➣ Losartan
  • ➣ Valsartan



  • Block AT1 angiotensin receptors
  • Blocks the vasoconstrictor and aldosterone secreting effects of angiotensin II
  • Reduce vasoconstriction


Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.




  • Initial 8-16 mg PO daily; Max. 32 mg/day



  • Initial 400-600 mg PO daily. Total daily dose 400-800 mg/day in 1-2 divided doses; Max 800 mg daily



  • Initial 150 mg PO daily; usual 150-300 mg PO daily; Max. 300 mg/day


Note: Starting dose in volume-depleted patients should be 75 mg.



  • Initial 50 mg PO daily; usual 25-100 mg PO daily in 2 divided doses; Max. 100 mg



  • Initial 40 mg PO daily; usual 20-80 mg PO daily; Max. 80 mg/day



  • Initial 80-160 mg PO daily, in non-volume depleted patients; Max dose is 320 mg PO daily


Direct renin inhibitor

  • ➣ Aliskiren



Decrease plasma renin activity → inhibits conversion of angiotensinogen to angiotensin I → results in decreased the formation of angiotensin II

Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.




  • Initial 150 mg PO daily; Max. 300 mg/day

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Calcium channel blocking agents (CCBs)


Non- Dihydropyridines:

  • ➣ Diltiazem
  • ➣ Verapamil



  • ➣ Amlodipine
  • ➣ Felodipine
  • ➣ Nifedipine



  • Blocks the inward movement of calcium by binding to the L-type calcium channels in the heart and in smooth muscle of the peripheral vasculature
  • This decreases intracellular calcium leading to a reduction in muscle contraction
  • Significant reduction in afterload but not preload



Non- Dihydropyridines:


  • Initial 120-240 mg Po daily, usual 180-360 mg PO in 2 divided doses, Max. 360 mg/day


  • Titration: Over 7-14 days


Canadian extended-release formulations

  • XC or CD: Initial 120-240 mg PO daily; usual 240-360 mg PO daily


USA extended-release formulations-XR form and LA

  • XR: Initial 180-240 mg PO daily; usual 180-480 mg PO daily
  • LA: Initial 180-240 mg PO daily; usual 120-540 mg PO daily



Immediate-release form:

  • Initial 80 mg TID or, usual 80 mg PO TID; Max. 480 mg/day; Elderly: Initial 40 mg PO TID

Verapamil (SR):

  • Initial 180 mg every morning, usual 120-480 mg/day; Max. 480 mg/day; Elderly: Initial 120 mg every morning

Extended-release form (PM):

  • Initial 200 mg at night, usual 200 mg at bed time; Max. 400 mg/day; Elderly: Initial 100 mg at bed time

Verapamil (HS):

  • Initial 180 mg PO at bed time; usual 240-480 mg PO at bed time; Max. 480 mg PO at bed time




  • Initial 5 mg PO daily or 2.5 mg PO daily in elderly; usual 5-10 mg PO once daily; Max. 10 mg/day


  • Titration: Increase 2.5 mg over 1-2 wk (up to a maximum dose)



  • Initial 2.5-5 mg PO daily; usual 5-10 mg PO daily; Max. 20 mg/day


Nifedipine - DO NOT USE immediate release formulation


  • Initial 30-60 mg PO daily; usual 30-90 mg PO daily; Max. 120 mg/day


  • Titration: Increase dose by every 7-14 days



  • Oral: Initial 20 mg PO TID; usual 20-40 mg PO TID; Max. 120 mg/day


- Other Dihydropyridine NOT available in Canada:

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Alpha-adrenoceptor antagonists


Selective alpha-adrenoceptor antagonists

  • ➣ Prazosin
  • ➣ Terazosin
  • ➣ Doxazosin


Non-selective alpha-adrenoceptor antagonists

  • ➣ Phentolamine



  • Block postsynaptic alpha receptors
  • Relax smooth muscle
  • Lowers peripheral vascular resistance




  • Initial 2-3 mg PO TID daily; maintenance 2-20 mg in 2-3 divided doses; Max. 20 mg/day



  • Initial 1 mg PO daily at bed time; usual 1-10 mg daily at bed time; Max. 20 mg/day



  • Initial 1 mg PO daily daily at bed time; may increase dose to 2 mg daily, make subsequent adjustments by doubling dose at intervals of 2-4 weeks until desired effect is achieved; Max. 16 mg/day


  • Note: Substantial risk of syncope/postural effects with dosages >4 mg/daily.



Hypertensive crisis (especially secondary to catecholamine excess)

  • IV: Initial 5-15 mg bolus


Agents with central sympatholytic action (alpha agonists, central)


  • ➣ Clonidine
  • ➣ Methyldopa



  • Stimulates alpha-adrenergic receptors in the central nervous system → reduces efferent peripheral sympathetic outflow





  • Initial 0.05 mg PO BID. Usual 0.1 mg/day PO daily


  • Titration: May increase by 0.1 mg/day every week until desire response achieved, then taper dose gradually over 2-4 days


Transdermal (available in the US):

  • Initial 0.1 mg/week; usual 0.1-0.3 mg/week


  • Titration: May increase by 0.1 mg 1-2 week interval




  • Initial 250 mg BID or TID; usual 250 mg to 1 g daily in 2-3 divided doses. Max. 3 g/day (divided) in adults; 1 g/day in elderly


  • Titration: Adjust dosage every 2 days until an adequate response is achieved


Intravenous (IV):

  • 250 mg to 1 g every 6-8h, maximum: 1 g every 6 hrs



  • ➣ Hydralazine
  • ➣ Minoxidil
  • ➣ Nitroglycerin
  • ➣ Nitroprusside



  • Relax vascular smooth muscle
  • Produce peripheral vasodilatation
  • Decrease pre and after-load
  • Reduces myocardial oxygen demand
  • Nitroglycerin dilates coronary arteries





  • Initial 10 mg/day every 6 hrs for 2-4 days; usual 25 mg/day QID; Max. 300 mg/day


  • Titration: Dosage may increase by 10-25 mg/dose every2-5 days; up to a maximum dosage


Intravenous (maximum rate: 5 mg/minute):

  • 10-20 mg every 4-6 hr


  • Titration: May increase to 40 mg/dose


Intramuscular (IM):

  • 10-50 mg every 4-6 hr


  • Titration: May increase to 40 mg/dose



  • Oral: Initial 5-10 mg PO daily; usual 10-40 mg/day in 1-2 divided doses; Max. 100 mg/day



In hypertensive emergency

  • IV: 5 mcg/min; usual range 5-100 mcg/min; Max. 200 mcg/min


  • Titration: Increase 5 mcg/minute every 3-5 min to 20 mcg/minute, if no response; increase 10-20 mcg/min every 3-5 min up to maximum dosage



In hypertensive emergency

  • IV: Initial 0.25-0.3 mcg/kg/min; usual 3-4 mcg/kg/min; Max. 10 mcg/kg/min for 10 min


  • Titration: Increase 0.5 mcg/kg/minute to maximum dosage till desired effect achieved or adverse effect appears

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Examples of some commonly used agents

Diuretic combinations:

Hydrochlorothiazide 25 mg/Spironolactone 25 mg

  • Dosage: Initial 1/2 tab/day; Max. 4 tab/day


Hydrochlorothiazide 25 mg/Triamterene 37.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Hydrochlorothiazide 50 mg/Amiloride 5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Ace inhibitors and Diuretics

Benazepril 10 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Captopril 25 mg/Hydrochlorothiazide 15 mg

  • Dosage: Initial 1 tab/day; Max. 2 tabs/day


Lisinopril 10 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tabs/day


Enalapril 5 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Angiotensin receptor blockers and Diuretics

Losartan 50 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Candesartan 16 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Irbesartan 150 mg/ Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Valsartan 80 mg/Hydrochlorothiazide 12.5 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Beta adrenergic blockers and Diuretics

Atenolol 50 mg/Chlorthialidone 25 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Pindolol 10 mg/Hydrochlorothiazide 25 mg

  • Dosage: Initial 1 tab/day; Max. 2 tab/day


Metoprolol 50 mg/Hydrochlorothiazide 25 mg

  • Dosage: 1 tab once or twice daily; Max. 2 tab


Propranolol 40 mg/Hydrochlorothiazide 25 mg

  • Dosage: 2 tab BID; Max. 3 tab


Central alpha/Adrenergic agonist and Diuretics

Methyldopa 250 mg/Hydrochlorothiazide 15 mg

  • Dosage: Initial 1 tab PO BID; Max. 4 tab


Calcium channel blockers and Ace inhibitors

Amlodipine 2.5 mg/Benazepril 10 mg

  • Dosage: Initial 1 cap daily; Max. 4 cap/day


Felodipine 5 mg/Enalapril 5 mg

  • Dosage: Initial 1 tab daily; Max. 3 tab/day


Verapamil extended-release 180 mg/Trandolapril 2 mg

  • Dosage: Initial 1 tabs daily; Max. 3 tab/day


Calcium channel blockers and Angiotensin II receptor blocker

Amlodipine (mg)/Telmisartan (mg)

  • Dosage: 40/5, 40/10, 80/5 and 80/10 are all available


Direct renin inhibitor and Diuretics

Aliskiren 150/Hydrochlorothiazide 12.5

  • Dosage: Initial 1 tab daily; Max. 2 tab/day


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Clinical Trials:
  • LIFE Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against Atenolol


  • ACCOMPLISH Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension


  • HYVET Hypertension in the very elderly


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Pipeline Agents:
  • APOLLO: A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People


  • ALTITUDE: Studying aliskiren on top of ACE-inhibitor or angiotensin-receptor-blocker (ARB) therapy in patients with type 2 diabetes and renal impairment compared with a placebo add-on


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Pharmacist Resources:

1. Tips for Patient Care


  • Patient to establish a daily routine for pill-taking
  • To stop smoking and reduce alcohol consumption
  • To do regular exercise
  • Educate and advise self-measurement of blood pressure
  • Self-monitoring of adherence: Advise pill counts and tracking on a calendar



  • If possible - simplifying medication regimens
  • Many drugs that are ineffective as monotherapy for hypertension may be effective components in a rational combination regimen
  • Appreciate lower starting dose of antihypertensive drugs in elderly patients
  • Evaluate cost and affordability and insurance coverage for patients
  • Consider concurrent risk factors and comorbid states with the prescribed therapy
    • Heart failure: Avoid Nondihydropyridine CCB
    • Angina: Avoid short-acting nifedipine
    • Left ventricular hypertrophy: Avoid hydralazine and minoxidil
    • Renovascular disease: Avoid ACE inhibitors or ARBs in patients with bilateral renal artery stenosis or unilateral disease with a solitary kidney
    • Peripheral arterial disease: Avoid beta-blockers in patients with severe disease
    • Pheochromocytoma: Use of beta-blockers should be avoided adequate untill alpha blockade has been achieved


Unlabeled/ Alternate uses:

Includes but not limited to:

  • Thiazide diuretics
    • Diabetes insipidus
    • Chlorthalidone: Pediatric hypertension
  • Loop diuretics
    • Bumetanide: Hypertension
  • Aldosterone receptor blockers
    • Spironolactone: Acne (adjunctive therapy); hirsutism; hypertension (pediatric); diuretic (pediatric)
  • Inhibitors of renal epithelial Na+ Channels
    • Amiloride (investigational): Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
  • Beta 1-adrenergic blocking agents
    • Acebutolol: Treatment of chronic stable angina
    • Atenolol: Acute ethanol withdrawal, supraventricular and ventricular arrhythmias, and migraine headache prophylaxis
  • Bisoprolol
    • Chronic stable angina, supraventricular arrhythmias, heart failure (HF)



  • Ensure patient is well informed about hypertension and its treatment, both non-pharmacological and pharmacological
  • Include family or social support in lifestyle modification
  • Consider informing patients of their global risk to improve the effectiveness of risk factor modification



  • Uncontrolled hypertension despite ≥3 antihypertensive drugs (whereby patient is adherent) may suggest an identifiable or secondary cause, such as obesity, renovascular hypertension (renal stenosis) or primary hyperaldosteronism
  • Drugs and other exogenous factors that can induce or aggravate hypertension
    • NSAIDs including coxibs
    • Corticosteroids and anabolic steroids
    • Oral contraceptives and sex hormones
    • Vasoconstrictive sympathomimetic decongestants
    • Calcineurin inhibitors e.g. cyclosporine, tacrolimus
    • Erythropoietin and analogues
    • Monoamine oxidase inhibitors
  • Other factors
    • Licorice root
    • Stimulants, including cocaine
    • Salt
    • Excessive alcohol use
    • Sleep apnea



  • Adherence should be assessed at each visit
  • Women on HRT should have their BP monitored every six months


Expected outcome

  • Optimal blood pressure control prevents and/or decreases the end organ damage complication due to hypertension


2. Scales and Table



  • BMI calculation:

3-LightBox-HTN-Resources-BMI Calculation

  • Waist circumference (recommended):
    • <102 cm (40 in.) for men
    • <88 cm (35 in.) for women


Specific Paradigms for Treatment of Hypertension:


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Core Resources:

  • Canadian Hypertension Education Program 2013 guidelines;
  • Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist association. Toronto: Webcom Inc. 2012
  • Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth's Textbook of Canadian Medical-Surgical Nursing. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
  • Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
  • Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6th ed. Toronto: Webcom Inc. 2011
  • Grundy SM, Cleeman JI, Bairey Merz CN, et al, for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110:227-239
  • Hurst's the Heart Manual of Cardiology, 12th Edition
  • Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill; 2009
  • Leiter LA, Fitchett DH, Gilbert RE, Gupta M, et al. Cardiometabolic Risk in Canada: A Detailed Analysis and Position Paper. Canadian Journal of Cardiology 27 (2011) e1-e33
  • Longo D, Fauci A, Kasper D, et al (eds). Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2011
  • McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49th ed. New York: McGraw-Hill; 2010
  • Pagana KD, Pagana TJ eds. Mosby's Diagnostic and Laboratory Test Reference. 9th ed. St. Louis: Elsevier-Mosby; 2009
  • Skidmore-Roth L. ed. Mosby's drug guide for nurses. 9th ed. St. Louis: Elsevier-Mosby; 2011
  • Skidmore-Roth L, ed. Mosby's nursing drug reference. 24th ed. St. Louis: Elsevier-Mosby; 2011


Online Pharmacological Resources:

  • e-Therapeutics
  • Lexicomp
  • RxList
  • Epocrates


Journals/Clinical Trials:

  • Al-Balas M, Bozzo P, Einarson A. Use of diuretics during pregnancy Can Fam Physician. 2009; 55(1): 44-45
  • Beckett NS et al. Treatment of hypertension in patients 80 years of age or older (HYVET) NEJM 2008; 358:1887-98
  • 2012 CHEP Recommendations for the Management of Hypertension
  • Canadian Hypertension Education Program, 2013,
  • Canadian Hypertension Education Program. 2011 guideline details: assessment of overall cardiovascular risk. Available at: Accessed October 17, 2011
  • Cushman WC, Evans GW, Byington RP et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus.N Engl J Med 2010; 362:1575-1585
  • Dahlof B, Devereux RB, Kjeldsen SE et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against Atenolol. Lancet. 2002;359:995-1003
  • Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult - 2009 recommendations. Can J Cardiol 2009; 25;567-579
  • The 7th Report of the Joint National Committee (JNC-7) on Prevention, detection, evaluation and treatment of high blood pressure. JAMA 2003: 289; 2560-71
  • Kenneth J, et al. Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) N Engl J Med 2008; 359:2417-2428
  • Okin PM, Wachtell K, Kjeldsen SE, et al. Incidence of atrial fibrillation in relation to changing heart rate over time in hypertensive patients: the LIFE study. Circ Arrhythm Electrophysiol. 2008 ;1:337-43
  • Olsen MH, Wachtell K, Beevers G, et al. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens. 2009; 27:567-74
  • Olsen MH, Wachtell K, Beevers G, et al. Prognostic importance of hemoglobin in hypertensive patients with electrocardiographic left ventricular hypertrophy: the Losartan Intervention For End point reduction in hypertension (LIFE) study. Am Heart J. 2009; 157:177-84
  • Sharma AM. Is There a Rationale for Angiotensin Blockade in the Management of Obesity Hypertension? Hypertension. 2004; 44: 12-19
  • The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. NIH Publication No. 04-5230; August 2004


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Andrew Steele , MD, FRCPC , Medical Director and Chief of Nephrology, Lakeridge Health, Associate Professor of Medicine (Adjunct) Queens University, ON Canada
.......................................... PHARMACY REVIEWER:
Ann Thompson, BSc. (Pharm), ACPR, Pharm.D., Director, Experiential Education, Faculty of Pharmacy and Pharmaceutical Sciences, University Of Alberta, Canada

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