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Hypertension
Goals of Therapy
Blood Pressure Targets in Treated Patients
Investigations
Drugs and Other Exogenous Factors That Can Induce or Aggravate Hypertension
Hypertensive Patients Requiring Additional Laboratory Testing
Therapeutic Choices
Nonpharmacologic Choices
Effect of Lifestyle Changes on Blood Pressure in Adults with Hypertension
Pharmacologic Choices
Diuretics
Beta 1 -Adrenergic Antagonists
Drugs that Act via the Renin Angiotensin Aldosterone System
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II Receptor Blockers
Direct Renin Inhibitors
Long-Acting Calcium Channel Blockers
Other Antihypertensive Drugs
Combination Therapy
Adherence
Resistant Hypertension
Hypertensive Emergencies
Individualization of Antihypertensive Therapy
Choices during Pregnancy and Breastfeeding
Hypertension and Pregnancy
Management
Hypertension and Breastfeeding
Therapeutic Tips
Algorithm
Diagnosis of Hypertension
Drug Table
Drugs Used for Hypertension
Suggested Readings
References
All Tables
All Figures
Hypertension
Goals of Therapy
Investigations
Therapeutic Choices
Therapeutic Tips
Algorithms
Drug Table
Suggested Readings
References
All Tables
All Figures
Hypertension
Raj Padwal, MD, FRCPC
Paul Gibson, MD, FRCPC
Ross T. Tsuyuki, PharmD, MSc, FCSHP, FACC
Date of Revision: September 2017
Peer Review Date: May 2016
CPhA acknowledges the contribution of Norm R.C. Campbell as a previous author of this chapter.
Goals of Therapy
Reduce the risk of premature cardiac, cerebrovascular, renal and other vascular morbidity and mortality.
Achieve blood pressure targets in treated patients. The targets presented in Table 1 are maximums; thus, the
desired systolic blood pressure (SBP) and diastolic blood pressure (DBP) values are below these thresholds.
1
PrintTable 1: Blood Pressure Targets in Treated Patients
Setting Target SBP/DBP (mm Hg)
Homea <135/85
Office
general patient population <140/90
isolated systolic hypertension SBP <140
Diabetes mellitus <130/80
High risk of cardiovascular eventsb SBP <120
aMeasured by a validated home blood pressure monitor.

b High risk includes: ≥75 years of age, presence of clinical or subclinical cardiovascular disease, chronic kidney
disease, or estimated 10-year Framingham risk score >15%.
Abbreviations:
DBP
diastolic blood pressure
SBP
systolic blood pressure
Investigations
History:
duration of hypertension, usual level of blood pressure, any sudden change in severity of hypertension,
prior hospitalization or emergency department visit for hypertensive urgency or emergency
history of antihypertensive drug use, reason for changing therapy, effectiveness, side effects and
intolerance
drugs that may cause hypertension (see Table 2)
drugs that may interact with antihypertensive drugs (those that induce or inhibit metabolism)
adherence with lifestyle recommendations and drug therapy
family history of hypertension, cardiovascular risk factors and premature cardiovascular disease
personal history of cigarette and alcohol use, usual physical activity, usual diet and sodium intake,
current weight and recent weight change, waist circumference, diabetes and dyslipidemia
cerebrovascular, cardiac and peripheral vascular symptoms to assess for target organ damage
symptoms of secondary hypertension, which include, for example, pheochromocytoma

(hyperadrenergic symptoms), hyper- and hypothyroidism, Cushing syndrome, renal/urinary symptoms
or past history of renal disease
1
PrintTable 2: Drugs and Other Exogenous Factors That Can Induce or Aggravate Hypertension
Alcohol (excessive use) NSAIDs including COX-2 inhibitors
Calcineurin inhibitors, e.g., cyclosporine, tacrolimus Oral contraceptive and sex hormones
Corticosteroids and anabolic steroids Salt (sodium—high intake)
Erythropoietin and analogues Selective serotonin reuptake inhibitors (SSRIs)
Licorice root Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Midodrine Stimulants, including cocaine
MAOIs Vasoconstricting, sympathomimetic decongestants
Diagnosis:1
The diagnosis of hypertension is immediate in the case of hypertensive emergencies and urgencies. This
includes patients with hypertension that is compromising vital organ function (encephalopathy, cardiac
or rapidly decreasing renal function), hypertension and a major artery dissection, or those with DBP
≥130 mm Hg.
The diagnostic process in nonurgent cases is summarized in Figure 1. Mandatory elements for accurate
diagnosis include strictly following recommended techniques, using the mean of multiple readings for
clinical decision making, and using out-of-office measurement to rule in or rule out the diagnosis.
Measurements using a validated electronic device are preferred to auscultation. Automated office
measurement is the preferred method of measuring blood pressure in the office or pharmacy setting. An
automated office device automatically performs serial measurements (usually 3–6 depending on the
device) and calculates the mean. Ensuring that the patient is unattended during automated measurement
is critical to minimizing white-coat effect.
Hypertension may be diagnosed if the mean blood pressure at the initial office visit is
≥180/110 mm Hg. If the BP is less elevated at the initial office visit (see Figure 1 for threshold values),
out-of-office measurement should be performed.
Diagnosis of hypertension through out-of-office measurement can be done by performing a 24-hour

ambulatory blood pressure monitoring study or a home blood pressure series. Ambulatory (continuous)
monitoring is preferred and is considered the gold-standard method of blood pressure measurement. The
home blood pressure series comprises 2 readings taken each morning and evening for 7 days; discard
the first-day readings and take the mean of the remaining 24 readings.
Out-of-office measurement of blood pressure can identify white-coat and masked hypertension. Regular
home blood pressure measurement can improve blood pressure control and improve medication
adherence in poorly adherent patients.
Physical exam:
fundi for hypertensive retinopathy
bruits and peripheral pulses for vascular disease and renovascular hypertension
edema and lung fields for signs of heart failure
heart sounds (4th heart sound), sustained and displaced apex for left ventricular hypertrophy
abdominal mass for polycystic kidneys and aortic aneurysm
neurologic exam for cerebrovascular disease
Initial laboratory testing:
serum potassium, sodium and creatinine
urinalysis
urinary albumin and/or albumin-creatinine ratio in patients with diabetes
fasting glucose and/or HbA 1c
total cholesterol, HDL-C, LDL-C, triglycerides (lipids may be measured in the fasting or nonfasting
state)
standard 12-lead ECG
select patients should have additional testing (see Table 3)

1
PrintTable 3: Hypertensive Patients Requiring Additional Laboratory Testing
If these characteristics are present: Check for:

• High serum creatinine (high normal in the elderly) Renal disease
If these characteristics are present: Check for:
• Urinary albumin or protein Diabetes, renal disease
• Paroxysmal and/or severe sustained hypertension refractory to usual Pheochromocytoma

antihypertensive therapy
• Hypertension and symptoms suggestive of catecholamine excess (2 or more of

headaches, palpitations, sweating, etc.)
• Hypertension triggered by beta-blockers, monoamine oxidase inhibitors, micturition

or changes in abdominal pressure
• Incidentally discovered adrenal adenoma
• MEN 2A or 2B; von Recklinghausen neurofibromatosis or von Hippel-Lindau

disease
• Spontaneous hypokalemia Hyperaldosteronism
• Profound diuretic-induced hypokalemia (K + <3 mmol/L)
• Hypertension refractory to treatment with ≥3 drugs
• Incidental adrenal adenoma
Two or more of: Renovascular disease
• Sudden onset or worsening of hypertension in patients >55 y or <30 y
• Abdominal bruit
• Uncontrolled hypertension despite use of ≥3 drugs
• Decreased renal function associated with use of an ACE inhibitor or ARB
• Overt atherosclerotic vascular disease
• Recurrent episodes of hypertension and flash pulmonary edema
Abbreviations:
ACE
angiotensin-converting enzyme
ARB
angiotensin receptor blocker
MEN
multiple endocrine neoplasia
Therapeutic Choices
Nonpharmacologic Choices
All individuals should be advised about a healthy lifestyle to prevent or control hypertension and cardiovascular
disease (see Table 4).
Weight loss of 4 kg or more if overweight (target body mass index: 18.5–24.9 kg/m2 ; waist circumference
<102 cm in men and <88 cm in women).
Healthy diet—high in fresh fruits, vegetables, soluble fibre and low-fat dairy products, low in saturated fats
and sodium, e.g., DASH eating plan available at
www.nhlbi.nih.gov/health/public/heart/hbp/dash/new_dash.pdf.
Sodium intake target of <2000 mg (88 mmol) per day.
Increase dietary potassium intake (e.g., fruit and vegetable component of DASH eating plan) if the patient is
not at risk of hyperkalemia. Risk factors include renin-angiotensin inhibitors or other agents that can increase
potassium, chronic kidney disease and serum potassium >4.5 mmol/L.
Regular, moderate intensity cardiorespiratory physical activity for 30–60 minutes on most days.
Low-risk alcohol consumption (0–2 drinks/day or ≤10 drinks/week for women; 0–3 drinks/day or ≤15
drinks/week for men).
Smoke-free environment.
PrintTable 4: Effect of Lifestyle Changes on Blood Pressure in Adults with Hypertension
Intervention Recommendation Change in Blood Pressure

(systolic/diastolic) mm Hg
Reduction in sodium intake Reduce by 1800 mg (78 mmol) per −5.8/−2.5

day
Weight loss Reduce by 4.5 kg −7.2/−5.9
Reduction in alcohol intake Reduce by 2.7 drinks/day −4.6/−2.3
Exercise 30–45 min, 3 times/week −10.3/−7.5
Dietary modification DASH eating plan a −11.4/−5.5
a Available from: www.nhlbi.nih.gov/health/public/heart/hbp/dash/new_dash.pdf.
Adapted with permission from Campbell N. Canadian Hypertension Education Program. Brief overview of 2004
recommendations. Can Fam Physician 2004;50:1411-5.
Pharmacologic Choices
In patients with baseline SBP of ≥130 mm Hg who are at high cardiovascular risk, intensive systolic blood pressure
reduction to around 120 mm Hg should be considered. [Evidence: SORT B] This is based primarily on the results of
the Systolic Blood Pressure Intervention Trial (SPRINT).2 High risk is defined as ≥75 years of age, clinical or
subclinical cardiovascular disease, chronic kidney disease (eGFR 20–59 mL/min/1.73m2 ) or estimated 10-year
Framingham risk score ≥15%. Excluded from SPRINT were patients with diabetes, prior stroke and a prior history
of heart failure; exercise caution when generalizing the results to these individuals.
Useful Info?
Follow these important therapeutic principles when attempting intensive blood pressure reduction:
The patient should agree to intensive management and be a willing, active participant, particularly with
respect to medication adherence.
Blood pressure measurements should be carefully performed according to recommended techniques (see
Investigations, Diagnosis).1
If the average SBP/DBP is ≥160/100 mm Hg, pharmacologic treatment is recommended in addition to

nonpharmacologic measures.
If the average SBP/DBP is 140–159/90–99 mm Hg, pharmacologic treatment is recommended in the presence of
either:
hypertensive target organ damage or
other independent risk factors for cardiovascular disease, e.g., cigarette smoking, dyslipidemia, strong family
history of premature cardiovascular disease, truncal obesity, sedentary lifestyle, males older than 55 years of
age, females older than 60 years of age. 1 More than 90% of patients with hypertension have other
cardiovascular risks or overt cardiovascular disease, so pharmacologic therapy is almost always
recommended.3
If the average SBP/DBP is 140–159/90–99 mm Hg and the individual does not have additional risk factors, the
short-term benefits of pharmacotherapy are small; discuss the risks and benefits of therapy with the patient. Initiate
health behaviour modification. Monitor blood pressure and other risk factors, regardless of whether such a patient
chooses to begin drug therapy, as generally the risks accumulate and blood pressure increases over time.
Consider low-dose ASA in patients over 50 years of age once blood pressure is controlled (see Primary Prevention
of Vascular Disease). Consider therapy for dyslipidemia if the patient meets the current Canadian criteria (see
Dyslipidemias).
In general, the reduction in cardiovascular risk depends more on the extent of the reduction in blood pressure than on
the specific blood pressure medication. Pharmacologic therapy should usually be started with a low dose of the
initial drug. Consider concurrent risk factors and disease states when selecting initial therapy (see Table 5). Dose
titration to achieve goal blood pressure should be done every 4–8 weeks for all but those with severe hypertension or
target organ damage or high cardiovascular risk, for whom closer follow-up and more frequent dosage titration is
required. Lack of control over blood pressure is in most cases due to a failure to titrate therapy (adding drugs and/or
increasing doses) in response to high office readings. Greater confidence in office readings can result from
supplementing with home blood pressure measurements or ambulatory 24-hour monitors. Generally, high office
readings should trigger a dosage increase, addition of another medication, investigations to identify the cause of the
high readings or a follow-up appointment within 2–8 weeks to reassess blood pressure. Medications that can be
considered are shown in Table 6.
Diuretics
Extensive evidence supports low-dose thiazide or related diuretics (e.g., indapamide) as first-line therapy for
uncomplicated hypertension. They should generally be selected unless there are specific indications for other drugs
(see Table 5). They have proven antihypertensive effectiveness in patients with isolated systolic hypertension, the
elderly and black patients. Trial data for cardiovascular benefit are more consistent for chlorthalidone and
indapamide than for hydrochlorothiazide, but head-to-head comparisons among these agents are unavailable. 4
Diuretics can cause hypokalemia that may be associated with adverse cardiovascular outcomes. Consider alternative
first-line agents in those with or strongly predisposed to a serious arrhythmia, for example, prolonged QT syndrome.
Consider using a combination product to minimize the risk of hypokalemia (hydrochlorothiazide plus a potassium-
sparing diuretic—spironolactone, amiloride or triamterene). Reserve the use of high doses (e.g., >25 mg/day of
hydrochlorothiazide) for patients with resistant hypertension unresponsive to treatment with multiple drugs or
secondary to renal impairment. Consider using a loop diuretic in patients with renal impairment. Diuretics may
worsen dysglycemia, although cardiovascular outcomes in patients with diabetes who are treated with diuretics are
similar to those treated with ACE inhibitors.5
Beta1-Adrenergic Antagonists
Beta1 -adrenergic antagonists (beta-blockers) are first-line therapy in patients who are younger than 60 years of age,
or who have stable angina, heart failure or a history of MI. Beta-blockers are also useful in patients who have
migraine headaches, tachycardia or essential tremor. However, beta-blockers are not as effective as ARBs, CCBs or
diuretics, as initial therapy for primary prevention of cardiovascular events in patients over 60 years of age.
Drugs that Act via the Renin Angiotensin Aldosterone System

The renin angiotensin aldosterone system (RAAS) plays a crucial role in modulating blood pressure, kidney
function, electrolyte balance and vascular and cardiac structure. Drugs that act directly on this system include ACE
inhibitors, angiotensin receptor antagonists, direct renin inhibitors and spironolactone. Antihypertensive drugs that
stimulate the RAAS axis (e.g., diuretics) are as effective as those that block this system in preventing cardiovascular
events in patients with hypertension. However, some inhibitors of the RAAS do provide additional benefits in
certain patients, including those with heart failure, diabetes and/or chronic kidney disease. ACE inhibitors, ARBs
and direct renin inhibitors are contraindicated in pregnant women.6,7,8 Drugs from these classes should not be
prescribed in women of childbearing potential unless the risks are carefully weighed and adequate measures are
taken to prevent pregnancy (see Choices during Pregnancy and Breastfeeding).
Angiotensin-Converting Enzyme Inhibitors

ACE inhibitors are first-line agents for non-black patients with uncomplicated hypertension and for patients with
diabetes, ischemic heart disease, recent MI, heart failure or chronic kidney disease.
Angiotensin II Receptor Blockers

ARBs are first-line agents for patients with uncomplicated hypertension, for patients with diabetes or ischemic heart
disease. They are good alternatives when ACE inhibitors are specifically indicated but not tolerated.
Direct Renin Inhibitors
Aliskiren, a direct renin inhibitor, prevents renin from converting angiotensinogen to angiotensin I. The drug has a
long duration of action and lowers blood pressure to the same extent as drugs from other antihypertensive classes.
Aliskiren should be used as an add-on agent after all first-line therapies have been tried.
Long-Acting Calcium Channel Blockers

Long-acting dihydropyridine CCBs can be used as first-line agents. Short-acting formulations of these agents have
caused an increase in cardiovascular events in randomized controlled trials and should not be used. Elderly patients
with isolated systolic hypertension and black patients are particularly responsive to CCBs.
Other Antihypertensive Drugs

In general, other classes of antihypertensive drugs should not be prescribed unless there are specific indications (see
Table 5), contraindications or intolerance to first-line therapy, or a requirement for additional blood pressure
lowering in combination with first-line antihypertensive drugs.
Combination Therapy
About 50% of patients will require more than 1 antihypertensive agent to achieve blood pressure targets. If the goal
blood pressure is not achieved with moderate doses of a suitable first-line drug, add, rather than substitute, a second
drug. Combining 2 drugs from different classes yields a 5 times greater incremental reduction in blood pressure than
doubling the dose of 1 drug.9
In high-risk patients (hypertension with diabetes or known cardiovascular disease), an ACE inhibitor (benazepril)
with amlodipine was superior to an ACE inhibitor with a diuretic at preventing cardiovascular events. The Canadian
Hypertension Education Program (CHEP) recommends consideration of an ACE inhibitor with amlodipine in high-
risk patients whose blood pressure requires 2 or more medications for control.10 CHEP recommends initiating
therapy with a combination of 2 first-line agents if a patient’s SBP is ≥20 or DBP is ≥10 mm Hg above the
recommended target.1 A synergistic effect is often seen when ACE inhibitors or ARBs are combined with
thiazide/thiazide-like diuretics and when ACE inhibitors or ARBs are combined with CCBs. In contrast, any
combination of a beta-blocker, ACE inhibitor and/or an ARB has less than additive antihypertensive effects when
combined in a 2-drug regimen. These combinations should be avoided unless there is a specific indication, for
example, use of an ACE inhibitor and a beta-blocker in post-MI patients or in those with heart failure (see Table 5).
All possible combinations of first-line agents are rational choices to lower blood pressure when 3 or 4 drugs are
required, with the exception of the simultaneous prescription of ACE inhibitors and ARBs. A combination of an
ACE inhibitor plus an ARB may further lower blood pressure but is associated with more adverse effects (e.g.,
hyperkalemia, renal impairment) and no clear benefit in terms of cardiovascular events.11 This combination is
generally not recommended for the treatment of hypertension, though it may be appropriate in some medical
circumstances such as refractory heart failure.
Adherence
Medication adherence should be assessed at each visit. Poor adherence to therapy is a major cause of poor blood
pressure control. Patients may admit to poor adherence when questioned in a nonthreatening manner, or it may be
indicated by:
Failure to keep scheduled appointments
Poor blood pressure control
Lack of secondary physiologic effects, e.g., decreased heart rate on beta-blocker
Failure to renew prescriptions on time
Lack of awareness of usual pill-taking routine and prescriptions
Poor adherence can be prevented. Routine care should include the following:
Ensure patients are well informed about hypertension and its treatment, preferably verbally and with patient
information pamphlets (available at www.hypertension.ca in the Public section)
Include family or social support in lifestyle modification
Use a simplified regimen of long-acting, once-daily drugs, and prescribe formulations that contain 2 drugs in
combination when appropriate
Ensure patients can afford the prescribed drugs
Advise patients to establish a daily routine for pill-taking, e.g., putting their pills by their toothbrush and
taking them every morning prior to brushing
Treat poor adherence:
Determine the reason for poor adherence and tailor advice or interventions to the cause
Increase the frequency of office visits
Advise use of adherence-enhancing medication dispensers, e.g., dosette box
Advise self-measurement of blood pressure
Consider assessing adherence with an electronic pill dispenser
Advise home-monitoring of adherence with pill counts and marking on a calendar when the prescription needs
renewing
Consider regular telephone contact with patients, if feasible
Resistant Hypertension
Resistant hypertension is defined as a blood pressure that is above target despite treatment with 3 drugs, optimally
dosed, one of which is a diuretic. Resistant hypertension has been estimated to affect about 10% of hypertensive
patients, but the true prevalence is likely much lower because many patients have either white-coat effect or are not
adherent.12 Other potential causes that should be looked for are secondary hypertension, renal dysfunction, and in
those with a poor response to an adequate combination of medications, consider the possibility of an “interfering
lifestyle.” Refer (to a hypertension specialist, nephrologist or internist) those who do not achieve blood pressure
targets with medication regimens you feel comfortable prescribing.
Hypertensive Emergencies
It is uncommon for elevated blood pressure alone, without new or progressive target organ damage, to require
emergency therapy. Refer true hypertensive emergencies to experienced centres with facilities to continuously
monitor blood pressure. In stabilizing patients for transfer, the use of intermediate-acting drugs (e.g., felodipine)
with close blood pressure monitoring is generally safer than using short-acting drugs that can rapidly produce
hypotension with complications.
1
PrintTable 5: Individualization of Antihypertensive Therapy
Category (BP
Targets) Risk Factor/Disease Initial Therapy Second-Line Therapy Notes/Cautions
Hypertension Diastolic ± systolic Thiazide diuretic, Combinations of first- Beta-blockers are not
without other hypertension beta-blocker, ACE line drugs recommended as initial
compelling inhibitor, ARB or therapy in patients over 60
indications long-acting CCB years of age.
Consider ASA and Avoid hypokalemia in those

statins in select who are prescribed diuretics
patients as monotherapy by using K+-
sparing agents.
Consider initiating
therapy with a ACE inhibitors are not
combination of first- recommended as initial
line drugs if SBP is therapy in black patients.
≥20 mm Hg or DBP
is ≥10 mm Hg above ACE inhibitors, ARBs and
target direct renin inhibitors are
teratogenic. Marked caution
is required if prescribing to
women of childbearing
potential.
Combination of an ACE
inhibitor with an ARB is not
recommended.
Isolated systolic Thiazide diuretic, Combinations of first- See diastolic ± systolic

hypertension without ARB or long-acting line drugs hypertension above.
other compelling dihydropyridine
indications CCB
Diabetes Diabetes mellitus ACE inhibitor or Addition of a A loop diuretic could be
Category
mellitus (BP with albuminuria, ARB dihydropyridine CCB is considered in hypertensive
Targets) Risk
renal Factor/Disease
disease, CVD Initial Therapy Second-Line
preferred overTherapy
thiazide Notes/Cautions
CKD patients with
or additional diuretics extracellular fluid volume
cardiovascular risk overload.
factors
Diabetes mellitus not ACE inhibitor, ARB, Combinations of first- Albuminuria is defined as an
included in the long-acting line drugs albumin to creatinine ratio
above category dihydropyridine (ACR) >2 mg/mmol.
CCB or thiazide If combination with ACE
diuretic inhibitor is being Combination of an ACE
considered, a inhibitor with an ARB is
dihydropyridine CCB is specifically not
preferable to thiazide recommended.
diuretics
Cardiovascular Coronary artery ACE inhibitor or Long-acting CCB Avoid short-acting

and disease ARB (except in low- nifedipine.
cerebrovascular risk patients); beta- When combination
diseases blocker or CCB for therapy is being used for Combination of an ACE
patients with stable high-risk patients, an inhibitor with an ARB is
angina ACE specifically not
inhibitor/dihydropyridine recommended.
CCB is preferred
Recent MI Beta-blocker and Long-acting CCB Non-dihydropyridine CCBs

ACE inhibitor should not be used in the
presence of concomitant
(ARB if ACE heart failure.
inhibitor not
tolerated)
Heart failure ACE inhibitor and ARB added to ACE Titrate doses of ACE
beta-blocker inhibitor inhibitors and ARBs to those
used in clinical trials.
(ARB if ACE Hydralazine/isosorbide
inhibitor not dinitrate combined if Monitor serum K+ and SCr
tolerated) black, or if ACE with the combination of
inhibitor and ARB ACE inhibitor, ARB or
Aldosterone contraindicated or not aldosterone antagonist.
antagonist in patients tolerated
with a recent
cardiovascular Thiazide or loop diuretic
hospitalization, acute as additive therapy
MI, elevated BNP,
elevated NT- Dihydropyridine CCB
proBNP, or NYHA (except nifedipine)
class II to IV
symptoms
Left ventricular ACE inhibitor, ARB, Combinations of Hydralazine and minoxidil

hypertrophy long-acting CCB or additional agents should not be used.
thiazide diuretic
Past stroke or TIA ACE Combinations of Hypertension should not be
Category (BP inhibitor/diuretic additional agents treated in acute stroke unless
Targets) Risk Factor/Disease Initial Therapy
combination Second-Line Therapy Notes/Cautions
BP extremely elevated.
inhibitor with an ARB is
specifically not
recommended.
Nondiabetic Nondiabetic chronic ACE inhibitor (ARB Combinations of Carefully monitor serum K+
chronic kidney kidney disease with if ACE inhibitor not additional agents and SCr in patients on an
disease proteinuria tolerated) diuretics ACE inhibitor or an ARB.
as additive therapy
inhibitor with an ARB is
specifically not
recommended in patients
with chronic kidney disease
without proteinuria.
Renovascular Does not affect Combinations of Avoid ACE inhibitors or

disease initial treatment additional agents ARBs in patients with
recommendations bilateral renal artery stenosis
or unilateral disease with a
solitary kidney.
Other conditions Peripheral arterial Does not affect Combinations of Avoid beta-blockers in
disease initial treatment additional agents patients with severe disease.
recommendations
Dyslipidemia Does not affect Combinations of

initial treatment additional agents
recommendations
Overall vascular Statin therapy for

protection patients with
hypertension and 3
or more
cardiovascular risk
factors or with
atherosclerotic
disease
Low-dose ASA in Exercise caution if blood

patients over 50 y pressure is not controlled.
with controlled
blood pressure
Adapted with permission from Canadian Hypertension Education Program.
Abbreviations:
ACE
ARB
angiotensin II receptor blocker
ASA
acetylsalicylic acid
BNP
brain natriuretic peptide
CCB
calcium channel blocker
CKD
chronic kidney disease
CVD
cardiovascular disease
DBP
MI
myocardial infarction
NT-proBNP
N-terminal-proBNP
NYHA
New York Heart Association
SBP
SCr
serum creatinine
TIA
transient ischemic attack
Hypertension and Pregnancy

Inform women with pre-existing hypertension who are of childbearing potential, particularly those who are
considering pregnancy, that they are at an increased risk of adverse pregnancy outcomes including intrauterine
growth restriction; placental abruption; preterm delivery and the attendant neonatal risks of prematurity; and
particularly a heightened risk of preeclampsia, with a crude risk of about 20–25% (varying with the severity and
duration of the pre-existing hypertension). Enhanced surveillance is required during pregnancy to monitor for these
complications. Prior to conception, or immediately upon recognition of an unplanned pregnancy, review the choice
of antihypertensive medication. Women thought to be at high risk of preeclampsia (this includes all women with
chronic hypertension) should be offered ASA 81 mg daily13,14 and should be receiving at least 1 g daily of calcium
supplementation irrespective of dietary intake.13,15
Management
While there remains a dearth of high-quality data on the effects of many common antihypertensive medications on
the developing fetus, international guidelines13,16,17 have reached some consensus regarding a list of “preferred”
medications for use in pregnancy, as well as a few “avoid” and “must avoid” drugs. Medications widely considered
first-line for the management of hypertension that is not considered severe include: methyldopa (250 mg BID to
1000 mg TID), labetalol (100 mg BID to 800 mg TID) and nifedipine XL (30 mg daily to 60 mg BID). These
medications are preferred as they have evidence and/or a strong clinical record of safe and effective use in
pregnancy,18,19 as well as an absence of demonstrated adverse effects on subsequent neonatal and childhood
development. For the acute management of severe hypertension in pregnancy (SBP ≥160 mm Hg and/or DBP ≥110
mm Hg), rapid lowering of blood pressure is recommended with either immediate-release oral nifedipine (5–10 mg
every 30 minutes as required), parenteral labetalol (20 mg IV; repeat 20–80 mg IV every 30 minutes as required) or
parenteral hydralazine (5 mg IV; repeat 5–10 mg IV every 30 minutes as required).13 Other antihypertensive
medications considered appropriate for use in pregnancy include clonidine and other beta-blockers (oxprenolol,
pindolol, propranolol, metoprolol). The data regarding the use of nondihydropyridine calcium channel
blockers20,21 and alpha-blockers in pregnancy is very limited, so these agents are typically deferred or exchanged
for other preferred agents.
Avoid atenolol, as its use for the treatment of hypertension in pregnancy has been associated with fetal intrauterine
growth restriction (IUGR).22 The other beta-blockers, in contrast, are only weakly associated with IUGR and have
been used widely in pregnancy for various indications. Thiazides and loop diuretics are other classes of
medications that most experts caution to avoid during pregnancy. These medications may prevent the physiologic
volume expansion seen in normal pregnancy, and thereby impair uteroplacental perfusion and fetal growth.21
Available data do not support an adverse effect on perinatal outcome,16 however, and these medications may
therefore be considered or continued in women felt to have volume-dependent hypertension (renal impairment).
They should be avoided in settings in which uteroplacental perfusion is already reduced (preeclampsia or IUGR).
Spironolactone should not be used at all in pregnancy, due to its anti-androgenic effects.23
ACE inhibitors have been clearly shown to be fetotoxic when taken during the 2nd and 3rd trimesters,24 leading to
oligohydramnios, IUGR, fetal/neonatal renal failure and other growth effects. First-trimester exposure has also been
shown to lead to teratogenic effects, mainly to the fetal cardiovascular and central nervous system.25 Discontinue
these drugs prior to conception, or immediately upon discovery of an unplanned pregnancy. The data regarding the
risk of fetal harm from ARBs26 and direct renin inhibitors27 are less robust (mainly animal data), but they appear to
have similar harmful effects and should be avoided just as strictly as ACE inhibitors during pregnancy.
Most women with pre-existing hypertension, particularly those with long-standing, difficult-to-control hypertension
or end-organ damage, should be followed throughout pregnancy by a specialist in obstetrics and gynecology. These
clinicians are skilled at ongoing maternal management as well as appropriate monitoring of fetal growth and well-
being. Women with difficult-to-control hypertension or other medical issues benefit from assessment and follow-up
with a hypertension specialist or obstetric medicine physician during their pregnancy.
Hypertension and Breastfeeding

Following the completion of a pregnancy, many women require ongoing antihypertensive therapy. The choice of
antihypertensive agent may be influenced by whether or not the woman is breastfeeding, as all oral medications
appear in breast milk to some degree.28 Breastfeeding women may safely continue treatment with any “pregnancy-
preferred” drug. Most other antihypertensive medications may also be safely utilized, but a few choices to avoid in
these women include diuretics (which may suppress lactation), atenolol and other beta-blockers with low serum
protein-binding (which concentrate in breast milk), as well as long-acting ACE inhibitors and those for which there
is little or no lactation data (ramipril, lisinopril, cilazapril and perindopril).
A discussion of general principles on the use of medications in these special populations can be found in Drug Use
during Pregnancy and Drug Use during Breastfeeding. Other specialized reference sources are also provided in these
appendices.
Therapeutic Tips
Prescribe a lower starting dose of antihypertensive drugs in elderly patients.
Recent onset of hypertension or change in blood pressure control suggests an identifiable or secondary cause,
such as drugs known to exacerbate hypertension or new onset of significant renal artery stenosis.
Many drugs ineffective as monotherapy for hypertension are effective components in a rational combination
regimen.
Consider concurrent cardiovascular risk factors and disease states when prescribing therapy (see Table 5).
Cardiovascular risk can vary 10-fold in persons with the same blood pressure. Assess global cardiovascular
risk in all hypertensive patients using a risk form, chart or computer program (see Dyslipidemias, Figure 1 as
an example).
Blood pressure readings provided in a pharmacy or taken at home should be considered only if taken correctly
using a validated and Hypertension Canada–approved instrument. Blood pressure measurements taken at
home correlate better with cardiovascular outcomes than office-based measurements.29,30 A home blood
pressure series is the recommended method of taking home blood pressure. Four readings per day (2 in the
morning and 2 in the evening) are taken for 7 days. First-day readings are discarded and the mean of the latter
readings (24 in total) is used for clinical management. Recommend monitors endorsed by the Canadian
Hypertension Society and train patients to use the proper technique. To allay anxiety, caution patients that
some variation throughout the day is normal. Patient instructions for selecting and using home blood pressure
monitors can be found in the Public section of www.hypertension.ca.
Pharmacists and nurses can play an important role in hypertension screening, medication selection, patient
education, follow-up and adherence monitoring. Dietitians can assist patients in managing their sodium and
caloric intake.
A team approach to hypertension management is more effective than usual care. In patients with hypertension
and diabetes, joint care by a family physician, community pharmacist and nurse resulted in an approximately
6 mm Hg greater reduction in SBP over 6 months, compared with usual physician-based care.31
Algorithms
PrintFigure 1: Diagnosis of Hypertension
a If AOBP is used, use the mean calculated and displayed by the device. If non-AOBP is used, take at least 3
readings, discard the 1st and calculate the mean of the remaining measurements. A history and physical exam should
be performed and diagnostic tests ordered.
b AOBP is performed with the patient unattended in a private area. Non-AOBP is performed using an electronic
upper arm device with the provider in the room.
c Diagnostic thresholds for AOBP, ABPM and home BP in patients with diabetes have yet to be established (and
may be lower than 130/80 mmHg).
d Serial office measurements over 3–5 visits can be used if ABPM or home measurement not available.
e Home BP series–2 readings taken each morning and evening for 7 days (28 total). Discard 1st-day readings and
average the last 6 days.
f Annual BP measurement is recommended to detect progression to hypertension.
Abbreviations:
ABPM
ambulatory blood pressure measurement

AOBP
automated office blood pressure
BP
blood pressure
non-AOBP
non-automated measurement
Adapted with permission from Leung AA, Nerenberg K, Daskalopoulou SS et al. for the Canadian Hypertension
Education Program. Hypertension Canada’s 2016 Canadian Hypertension Education Program guidelines for blood
pressure measurement, diagnosis, assessment of risk, prevention and treatment of hypertension. Can J Cardiol
2016;32(5):569-88.
Drug Table
PrintTable 6: Drugs Used for Hypertension
Drug/Costa Dosage Adverse Effects Drug Interactions Comments
Drug Class: ACE Inhibitors
benazepril Dry cough, Marked increase in
Lotensin, generics Initial: 10 hyperkalemia, serum K+ in patients Contraindicated in
mg/day angioedema pregnancy—
receiving K+
$$ (unusual). caution when
Usual: 20 supplements and/or
prescribing to
mg/day potassium-sparing
Can precipitate women of
diuretics.
renal failure in childbearing
Maximum: 40 renovascular
Reduced hypotensive potential.6,7 Use
mg/day disease, volume effect with NSAIDs lower (50%) initial
depletion or and increased risk of doses if on diuretics
Once daily or
those receiving renal dysfunction. (increased risk of
divided BID po
NSAIDs. hypotension with
Elevated Li+ levels hypovolemia).
(potential toxicity).
Hyperkalemia
usually occurs only
in those on K+
supplements or
drugs that cause K +
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
captopril Dry cough, Marked increase in

generics Initial: 25 hyperkalemia, serum K+ in patients Contraindicated in
receiving K+
prescribing to
diuretics.
Drug/Costa Maximum:
Dosage renovascular
Adverse Effects Reduced potential.6,7 Use
hypotensive Comments
Drug Interactions
150 mg/day disease, volume effect with NSAIDs lower (50%) initial
Divided BID or those receiving renal dysfunction. (increased risk of
TID po NSAIDs. hypotension with
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
cilazapril Dry cough, Marked increase in
Inhibace, generics Initial: 2.5 hyperkalemia, serum K+ in patients Contraindicated in
receiving K+
$ (unusual). caution when
Usual: 2.5–5 supplements and/or
prescribing to
diuretics.
Once daily or
divided BID po
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
enalapril Dry cough, Marked increase in

Vasotec, Enalapril, other Initial: 5 mg/day hyperkalemia, serum K+ in patients Contraindicated in
generics angioedema pregnancy—
Usual: 10–40 receiving K+
(unusual). caution when
$ mg/day supplements and/or
prescribing to
potassium-sparing
Maximum: 40 renal failure in diuretics.
childbearing
mg/day renovascular Reduced hypotensive potential.6,7 Use
Drug/Costa Once
Dosagedaily or disease,
Adversevolume
Effects effect with NSAIDs Comments
Drug Interactions lower (50%) initial
divided BID po depletion or and increased risk of doses if on diuretics
+
Elevated Li levels hypovolemia).
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
fosinopril Dry cough, Marked increase in
generics Initial: 10 hyperkalemia, serum K+ in patients Contraindicated in
$ receiving K+
prescribing to
diuretics.
Once daily or
divided BID po
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
lisinopril Dry cough, Marked increase in

Prinivil, Zestril, Lisinopril, Initial: 10 hyperkalemia, serum K+ in patients Contraindicated in
other generics mg/day angioedema pregnancy—
receiving K+
$ prescribing to
diuretics.
Maximum: 40 renovascular Reduced hypotensive potential.6,7 Use
Drug/Costa Once daily po
Dosage depletion or
Adverse Effects and
Drugincreased risk of Comments
Interactions doses if on diuretics
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
perindopril Dry cough, Marked increase in
Coversyl, generics Initial: 4 mg/day hyperkalemia, serum K+ in patients Contraindicated in
angioedema pregnancy—
Maximum: 8 receiving K+
mg/day supplements and/or
prescribing to
potassium-sparing
Once daily or diuretics.
divided BID po renovascular
disease, volume effect with NSAIDs lower (50%) initial
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
quinapril Dry cough, Marked increase in

Accupril, generics Initial: 10 hyperkalemia, serum K+ in patients Contraindicated in
$ receiving K+
Maximum: 40 supplements and/or
prescribing to
diuretics.
Once daily or renovascular potential.6,7 Use
divided BID po disease, volume Reduced hypotensive
effect with NSAIDs lower (50%) initial
those receiving
Drug/Costa Dosage NSAIDs.
Adverse Effects renal
Drug dysfunction.
Interactions (increased risk of
Comments
hypotension with
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
ramipril Dry cough, Marked increase in
Altace, Ramipril, Ramipril - Initial: 2.5 hyperkalemia, serum K+ in patients Contraindicated in
2.5/5/10, other generics mg/day angioedema pregnancy—
receiving K+
$ prescribing to
diuretics.
Once daily or
divided BID po
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
trandolapril Dry cough, Marked increase in

Mavik Initial: 1 mg/day hyperkalemia, serum K+ in patients Contraindicated in
angioedema pregnancy—
$$ Maximum: 4 receiving K+
mg/day supplements and/or
prescribing to
potassium-sparing
Once daily po renal failure in diuretics.
childbearing
renovascular Reduced hypotensive potential.6,7 Use
Drug/Costa Dosage NSAIDs.
Adverse Effects Elevated Li+ levels
Drug Interactions hypotension with
Comments
(potential toxicity). hypovolemia).
Hyperkalemia
usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
Drug Class: Alpha1 -Adrenergic Antagonists
doxazosin Orthostatic Caution when
Cardura, generics Initial: 1 mg/day hypotension, adding other Not for initial
headache, hypotensive drugs, therapy.
$ Usual: 1–8 drowsiness, may cause syncope.
mg/day palpitations,
nasal congestion.
Maximum: 16
mg/day Syncope usually
occurs at the
Once daily po
start of therapy,
with rapid dose
titration or on
addition of other
agents. Titrate
slowly. If
interrupted for
several days,
restart at initial
dose.
prazosin Orthostatic Caution when

generics Initial: 0.5 mg hypotension, adding other Not for initial
with p.m. meal headache, hypotensive drugs, therapy.
$-$$ (day 1), then 0.5 drowsiness, may cause syncope.
mg BID–TID po palpitations,
× 3 days and nasal congestion.
gradually
increase as Syncope usually
required occurs at the
start of therapy,
Maximum: with rapid dose
20 mg/day titration or on
addition of other
agents. Titrate
slowly. If
interrupted for
several days,
restart at initial
dose.
terazosin
Drug/Costa Initial:
Dosage1 mg Orthostatic
Adverse Effects Caution when
Drug Interactions Not for initial
Comments
generics QHS po hypotension, adding other therapy.
headache, hypotensive drugs,
$ Usual: drowsiness, may cause syncope.
1–5 mg/day palpitations,
nasal congestion. Verapamil increases
Maximum: 20 serum concentrations
mg/day Syncope usually of terazosin.
occurs at the
Once daily or start of therapy,
divided BID po with rapid dose
titration or on
addition of other
agents. Titrate
slowly. If
interrupted for
several days,
restart at initial
dose.
Drug Class: Angiotensin Receptor Blockers (ARBs)

azilsartan Hyperkalemia. Marked increase in
Edarbi Initial: 40 serum K+ in patients Contraindicated in
mg/day Can precipitate pregnancy—
$$ receiving K+
renal failure in caution when
Maximum: 80 susceptible supplements and/or
prescribing to
patients women of
diuretics.
(bilateral childbearing
Once daily po renovascular
May elevate Li+ potential.8
disease, those
with volume levels (monitor Li+ Use lower initial
depletion or with levels, adjust dose). doses in patients
concurrent who are volume
NSAID use). depleted or on
diuretics (increased
Angioedema has risk of hypotension
been reported, in hypovolemia).
but a causal
association has Hyperkalemia
not been usually occurs only
established. in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
candesartan Hyperkalemia. Marked increase in

Atacand, Candesartan, other Initial: 8 mg/day serum K+ in patients Contraindicated in
generics Can precipitate pregnancy—
Usual: 8–16 receiving K+
$ mg/day supplements and/or
susceptible prescribing to
potassium-sparing
patients women of
Dosage (bilateral
Adverse Effects diuretics.
Drug Interactions childbearing
Comments
renovascular potential.8
disease, those May elevate Li+
but a causal
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
eprosartan Hyperkalemia. Marked increase in

Teveten Initial: serum K+ in patients Contraindicated in
600 mg/day Can precipitate pregnancy—
$$ receiving K+
Maximum: supplements and/or
800 mg/day potassium-sparing
patients women of
diuretics.
Once daily or renovascular
divided BID po disease, those
but a causal
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
irbesartan Hyperkalemia. Marked increase in

Avapro, Irbesartan,
Drug/Cost a other Initial:
Dosage150 Can precipitate
Adverse Effects K+ in patients Comments
Drug Interactions
serum Contraindicated in
generics mg/day renal failure in receiving K+ pregnancy—
susceptible supplements and/or caution when
$ Usual: 150–300 patients prescribing to
potassium-sparing
mg/day (bilateral women of
diuretics.
renovascular childbearing
Once daily po disease, those
May elevate Li + potential.8
with volume
levels (monitor Li+
depletion or with Use lower initial
levels, adjust dose).
concurrent doses in patients
NSAID use). who are volume
depleted or on
Angioedema has diuretics (increased
been reported, risk of hypotension
but a causal in hypovolemia).
association has
not been Hyperkalemia
established. usually occurs only
in those on K+
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
losartan Hyperkalemia. Marked increase in

Cozaar, Losartan, other generics Initial: 50 serum K+ in patients Contraindicated in
$ receiving K+
Usual: supplements and/or
25–100 mg/day potassium-sparing
patients women of
diuretics.
Maximum: renovascular
100 mg/day disease, those
Once daily or
divided BID po
but a causal
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Drug/Costa Dosage Adverse Effects Drug Interactions Assess SCr and K+
Comments
after a few days,
then regularly.
olmesartan Hyperkalemia. Marked increase in
Olmetec, generics Initial: 20 serum K+ in patients Contraindicated in
$$ receiving K+
Maximum: 40 supplements and/or
patients women of
diuretics.
disease, those
but a causal
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
telmisartan Hyperkalemia. Marked increase in

Micardis, Telmisartan, other Initial: 80 serum K+ in patients Contraindicated in
generics mg/day Can precipitate pregnancy—
receiving K+
$ Usual: 80 supplements and/or
patients women of
diuretics.
disease, those
but a causal
supplements or
Drug/Costa Dosage Adverse Effects Drug Interactions retention, those
Comments
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
valsartan Hyperkalemia. Marked increase in
Diovan, Valsartan, other Initial: 80 serum K+ in patients Contraindicated in
generics mg/day Can precipitate pregnancy—
receiving K+
Usual: 80–320 supplements and/or
$ susceptible prescribing to
patients women of
diuretics.
disease, those
but a causal
supplements or
retention, those
with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
Drug Class: Beta1 -Adrenergic Antagonists, nonselective

nadolol Fatigue, Bradycardia with
generics Initial: 20 bradycardia, digoxin or Beta-blockers
mg/day decreased nondihydropyridine should not be used
$$ exercise CCBs. as initial therapy in
Usual: 160 capacity, patients >60 y of
mg/day headache, Cardiodepressant age unless
impotence, vivid effects with specifically
Maximum: 320 nondihydropyridine indicated.
dreams.
mg/day CCBs and
Less common: amiodarone. Avoid in patients
Once daily po
hyperglycemia, with asthma.32
depression, heart
failure, heart Avoid abrupt
block. withdrawal (may
precipitate rebound
hypertension and
ischemia). Taper
Drug/Costa Dosage Adverse Effects Drug Interactions the dose before
Comments
discontinuation.
Avoid in patients
with severe PAD.
Contraindicated in
patients with 2nd or
3rd degree heart
block in the
absence of a
pacemaker.
propranolol, controlled-release Fatigue, Bradycardia with
Inderal-LA Initial: 80 bradycardia, digoxin or Beta-blockers
$$$$ exercise CCBs. as initial therapy in
Maximum: nondihydropyridine indicated.
dreams.
480 mg/day CCBs and
SR (once daily
po) formulation
depression, heart CYP2D6 inhibitors
recommended increase levels of Avoid abrupt
failure, heart
block. propranolol. withdrawal (may
precipitate rebound
Propranolol hypertension and
increases serum ischemia). Taper
levels of rizatriptan. the dose before
discontinuation.
Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
Propranolol is more
likely to cause CNS
side effects
(insomnia,
depression, vivid
dreams) than other
agents because of
greater lipid
solubility.
timolol Fatigue, Bradycardia with

generics Initial: 5 mg bradycardia, digoxin or Beta-blockers
BID decreased nondihydropyridine should not be used
Usual: 20 mg capacity, patients >60 y of
BID headache, Cardiodepressant age unless
Drug/Costa Maximum:
Dosage 30 impotence, vivid effects
Adverse Effects with
Drug Interactions specifically
Comments
mg BID po dreams. nondihydropyridine indicated.
CCBs and
depression, heart
precipitate rebound
hypertension and
ischemia). Taper
the dose before
discontinuation.
Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
Drug Class: Beta1 -Adrenergic Antagonists, β1 -selective
atenolol Fatigue, Bradycardia with
Tenormin, Atenolol, other Initial: 25 bradycardia, digoxin or Beta-blockers
generics mg/day decreased nondihydropyridine should not be used
exercise CCBs. as initial therapy in
$ Usual: 50 capacity, patients >60 y of
dreams.
100 mg/day CCBs and
Once daily or
divided BID po
depression, heart
precipitate rebound
Fewer hypertension and
noncardiac ischemia). Taper
effects due to the dose before
cardioselectivity. discontinuation.
Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
bisoprolol Fatigue, Bradycardia with

Bisoprolol, other generics Initial: 5 mg/day bradycardia, digoxin or Beta-blockers
decreased nondihydropyridine should not be used
Usual: 10
Drug/Costa mg/day
Dosage exercise
Adverse Effects CCBs.
Drug Interactions as initial therapy in
Comments
$ capacity, patients >60 y of
Maximum: 20 headache, Cardiodepressant age unless
mg/day impotence, vivid effects with specifically
dreams. nondihydropyridine indicated.
Once daily po CCBs and
depression, heart
precipitate rebound
Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
metoprolol Fatigue, Bradycardia with
Lopresor, Metoprolol-L, other Initial: 50 bradycardia, digoxin or Beta-blockers
generics mg/day decreased nondihydropyridine should not be used
exercise CCBs. as initial therapy in
$ Usual: capacity, patients >60 y of
100–200 mg/day headache, Cardiodepressant age unless
dreams.
400 mg/day CCBs and
Give regular
formulations
BID po; SR increase levels of Avoid abrupt
failure, heart
formulations metoprolol. withdrawal (may
block.
once daily po precipitate rebound
Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
nebivolol Fatigue, Bradycardia with

Bystolic Initial: 5 mg/day bradycardia, digoxin or Beta-blockers
Drug/
$$ Costa Usual:
Dosage10 decreased
Adverse Effects nondihydropyridine should not be used
Drug Interactions Comments
mg/day exercise CCBs. as initial therapy in
capacity, patients >60 y of
Maximum: 20 headache, Cardiodepressant age unless
mg/day impotence, vivid effects with specifically
Once daily po CCBs and
failure, heart increase levels of Avoid abrupt
block. nebivolol. withdrawal (may
precipitate rebound
Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
Drug Class: Beta1 -Adrenergic Antagonists, nonselective with intrinsic sympathomimetic activity (ISA)
pindolol Fatigue, Bradycardia with
Visken, generics Initial: 5 mg bradycardia, digoxin or Beta-blockers
BID po decreased nondihydropyridine should not be used
BID po headache, Cardiodepressant age unless
dreams.
mg/day CCBs and
depression, heart
precipitate rebound
hypertension and
ischemia). Taper
the dose before
discontinuation.
Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
Drug/Costa Dosage Adverse Effects Drug Interactions Agents with ISA
Comments
have less effect on
resting heart rate
than those without
ISA.
Drug Class: Beta1 -Adrenergic Antagonists, β1 -selective with ISA
acebutolol Fatigue, Bradycardia with
Sectral, generics Initial: 100 bradycardia, digoxin or Beta-blockers
$ exercise CCBs. as initial therapy in
dreams.
800 mg/day CCBs and
Once daily or
divided BID po
depression, heart
precipitate rebound
Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
Agents with ISA

have less effect on
resting heart rate
than those without
ISA.
Drug Class: Beta1 -Adrenergic Antagonists with alpha1 -blocking activity

labetalol Fatigue, Bradycardia with
Trandate, generics Initial: 50 mgbradycardia, digoxin or Beta-blockers
BID po decreased nondihydropyridine should not be used
BID po headache, Cardiodepressant age unless
dreams.
mg/day CCBs and
depression, heart
Drug/Costa Dosage Edema,
Adverse Effects Drug Interactions precipitate rebound
Comments
dizziness, nasal hypertension and
congestion and ischemia). Taper
postural the dose before
hypotension due discontinuation.
to alpha1
antagonism. Avoid in patients
with severe PAD.
Contraindicated in
3rd degree heart
block in the
absence of a
pacemaker.
Drug Class: Calcium Channel Blockers, dihydropyridine
amlodipine Ankle edema, CYP3A4 substrate
Norvasc, Amlodipine, other Initial: 2.5 flushing, (many potential
generics mg/day headache and interactions).
palpitations.
$ Maximum: 10 Strong inhibitors
mg/day include azole
antifungals, protease
Once daily po inhibitors,
macrolides and
quinidine.
Grapefruit juice may

increase serum
concentrations.
felodipine, extended-release Ankle edema, CYP3A4 substrate

Plendil, generics Initial: 2.5 flushing, (many potential Grapefruit juice
mg/day headache and interactions). causes marked
$ palpitations. elevations in
Usual: 10 Strong inhibitors felodipine serum
mg/day include azole levels and adverse
antifungals, protease events.
Maximum: 20 inhibitors,
mg/day macrolides and
quinidine.
Once daily po
increase serum
concentrations.
nifedipine, extended-release Ankle edema, CYP3A4 substrate

Adalat XL, Nifedipine ER, Initial: 30 flushing, (many potential Do not use short-
other generics mg/day headache and interactions). acting nifedipine
palpitations. formulations for
$ Usual: 60 Strong inhibitors treatment of
mg/day include azole essential
antifungals, protease hypertension.
Maximum: 120 inhibitors,
mg/day macrolides and
quinidine.
Once daily po
Drug/Costa Dosage Adverse Effects increase serum
concentrations.
Drug Class: Calcium Channel Blockers, nondihydropyridine
diltiazem Headache, CYP3A4 substrate
Tiazac, Tiazac XC, Diltiazem Initial: 120 dizziness, (many potential Caution in patients
CD, other generics mg/day bradycardia, interactions). with heart failure,
heart block, new or 2nd or 3rd degree
$ Usual: onset or Strong inhibitors heart block without
240–360 mg/day worsening of include azole a functioning
heart failure. antifungals, protease pacemaker.
Maximum: inhibitors,
360 mg/day macrolides and
quinidine.
Give CD or XC
formulation Grapefruit juice may
once daily po, increase serum
SR formulation concentrations.
divided BID po
Nondihydropyridines
inhibit the
metabolism of
carbamazepine,
cyclosporine,
lovastatin,
simvastatin.
Rifampin induces
metabolism of
nondihydropyridines.
Additive negative
chronotropic effects
with amiodarone,
beta-blockers and
digoxin.
verapamil Headache, CYP3A4 substrate

Isoptin SR, generics Initial: 80 mg dizziness, (many potential Caution in patients
TID po bradycardia, interactions). with heart failure,
$-$$ heart block, new or 2nd or 3rd degree
Maximum:160 onset or Strong inhibitors heart block without
mg TID po worsening of include azole a functioning
heart failure. antifungals, protease pacemaker.
SR (once daily inhibitors,
Constipation.
or divided BID macrolides and
po): Initial: 180 quinidine.
mg/day; Usual:
180–480 Grapefruit juice may
mg/day; increase serum
Maximum: 480 concentrations.
mg/day
Nondihydropyridines
inhibit the
metabolism of
carbamazepine,
cyclosporine,
lovastatin,
simvastatin.
Drug/Costa Dosage Adverse Effects Rifampin induces
metabolism of
nondihydropyridines.
Additive negative
chronotropic effects
with amiodarone,
beta-blockers and
digoxin.
Verapamil increases
digoxin levels by
50–75% within 1 wk
(monitor levels).
Drug Class: Centrally Acting Antihypertensive Agents
methyldopa Drowsiness, dry Iron salts reduce
generics Initial: 500 mouth, nasal absorption (separate Positive Coombs
mg/day congestion, administration). test is common, but
$$ depression, usually
Usual: 2000 orthostatic Additive unimportant;
mg/day hypotension, hypotension with hemolytic anemia is
palpitations, levodopa. rare.
Maximum:
sexual
3000 mg/day May exacerbate Li+ Drug fever with or
dysfunction,
adverse events without an
Divided BID or sodium and influenza-like
water retention. without increasing
TID po illness; hepatic
Li+ levels.
disorders have
occurred.
Drug Class: Direct Renin Inhibitors

aliskiren Diarrhea. The Avoid combining
Rasilez Initial: 150 incidence of dry with an ACE Avoid use in
mg/day cough and inhibitor or ARB in pregnancy.
$$ hyperkalemia is patients with
Maximum: 300 low compared significant renal May take 4 wk to
mg/day with ACE impairment. realize maximum
inhibitors. antihypertensive
Once daily po Grapefruit juice may effect.
reduce serum
concentrations. Effect on
cardiovascular
outcomes not yet
established.
Limited data in
patients with
greater than
moderate renal
dysfunction.
Drug Class: Diuretics

hydrochlorothiazide Hypotension, Li+ excretion
generics Initial: 12.5 weakness, Particularly
reduced (monitor Li+
mg/day muscle cramps, levels, adjust dose). effective in ISH,
$ impotence. the elderly and
Usual: 25 black patients.
NSAIDs reduce
mg/day Hypokalemia, hypotensive efficacy.
Dosage hyponatremia,
Adverse Effects Diuretic-induced Monitor SCr and
hyperuricemia, hypokalemia K +.
hyperglycemia, increases the risk of
hyperlipidemia. digoxin toxicity. Consider
alternatives in
Azotemia (rare), Reduced efficacy of patients with or
blood dyscrasias antihyperglycemic predisposed to
(rare), allergic agents. arrhythmias.
reactions
(potential cross Can exacerbate
sensitivity with gout and diabetes
other (biochemical
sulfonamide abnormalities are
derivatives less frequent at low
[rare]), fatigue doses).
(rare),
photosensitivity Ineffective in
(rare). patients with ClCr
<30–40 mL/min.
chlorthalidone Hypotension, Li+ excretion
generics Initial: 12.5 weakness, Lowest available
mg/day muscle cramps, levels, adjust dose). tablet strength is 50
$ impotence. mg. Tablet (or
Usual: 12.5–25 “pill”) splitters,
NSAIDs reduce
mg/day Hypokalemia, hypotensive efficacy. widely available in
hyponatremia, pharmacies, can be
Once daily po hyperuricemia, used to derive a
Diuretic-induced
hyperglycemia, hypokalemia dose of 12.5 mg
hyperlipidemia. increases the risk of (one-quarter tablet)
digoxin toxicity. with reasonable
Azotemia (rare), accuracy.
blood dyscrasias Reduced efficacy of
(rare), allergic antihyperglycemic Particularly
reactions agents. effective in ISH,
(potential cross the elderly and
sensitivity with black patients.
other
sulfonamide Monitor SCr and
derivatives K +.
[rare]), fatigue
(rare), Consider
photosensitivity alternatives in
(rare). patients with or
predisposed to
arrhythmias.
Can exacerbate
gout and diabetes
(biochemical
abnormalities are
less frequent at low
doses).
Ineffective in
patients with ClCr
<30–40 mL/min.
indapamide Hypotension, Li+ excretion

Lozide, generics Initial: 1.25 weakness, Particularly
Drug/
$ Costa mg/day
Dosage muscle
Adversecramps,
Effects reduced (monitor Li+ Comments
Drug Interactions effective in ISH,
impotence. levels, adjust dose). the elderly and
Usual: 2.5 black patients.
mg/day Hypokalemia, NSAIDs reduce
hyponatremia, hypotensive efficacy. Monitor SCr and
Once daily po hyperuricemia, K +.
hyperglycemia, Diuretic-induced
hyperlipidemia. hypokalemia Consider
increases the risk of alternatives in
Azotemia (rare), digoxin toxicity. patients with or
blood dyscrasias predisposed to
(rare), allergic Reduced efficacy of arrhythmias.
reactions antihyperglycemic
(potential cross agents. Can exacerbate
other (biochemical
(rare),
photosensitivity
(rare).
metolazone Hypotension, Li+ excretion

Zaroxolyn Initial: 2.5 weakness, Particularly
mg/day muscle cramps, levels, adjust dose). effective in ISH,
$ impotence. the elderly and
Usual: 5 mg/day black patients.
NSAIDs reduce
Hypokalemia, hypotensive efficacy.
Maximum: 10 hyponatremia, Monitor SCr and
mg/day hyperuricemia, Diuretic-induced K +.
hyperglycemia, hypokalemia
Once daily po Consider
hyperlipidemia. increases the risk of
digoxin toxicity. alternatives in
Azotemia (rare), patients with or
blood dyscrasias Reduced efficacy of predisposed to
(rare), allergic antihyperglycemic arrhythmias.
reactions agents.
other (biochemical
(rare),
photosensitivity Metolazone is
(rare). effective in patients
with moderate to
severe renal
dysfunction.
Drug Class: ACE Inhibitor/Calcium Channel Blocker Combinations

perindopril /amlodipineb Dry cough, Marked increase in
Viacoram Initial: 3.5/2.5 hyperkalemia, serum K+ in patients Contraindicated in
mg angioedema pregnancy—
receiving K+
$$ Usual: 7/5 mg (unusual). caution when
supplements and/or
Maximum: prescribing to
potassium-sparing
14/10 mg Can precipitate women of
diuretics.
Once daily po renal failure in childbearing
Drug/Costa Dosage renovascular
Adverse Effects Reduced
Drug Interactions potential.6,7 Use
hypotensive Comments
Ankle edema, (potential toxicity).
flushing, Hyperkalemia
headache and CYP3A4 substrate usually occurs only
palpitations. (many potential in those on K+
interactions). supplements or
Strong inhibitors drugs that cause K +
include azole retention, those
antifungals, protease with renal
inhibitors, impairment or
macrolides and diabetics with high
quinidine. serum K+ levels.
Assess SCr and K+
Grapefruit juice may after a few days,
increase serum then regularly.
concentrations.
trandolapril /verapamilb Dry cough, Marked increase in

Tarka Trandolapril 1–4 hyperkalemia, serum K+ in patients Contraindicated in
mg/day plus angioedema pregnancy—
receiving K+
$$$ verapamil 180– (unusual). caution when
supplements and/or
480 mg/day. prescribing to
potassium-sparing
Once daily or Can precipitate women of
diuretics.
divided BID po renal failure in childbearing
renovascular Reduced hypotensive potential.6,7 Use
Headache,
dizziness, Hyperkalemia
bradycardia, CYP3A4 substrate usually occurs only
heart block, new (many potential in those on K+
onset or interactions). supplements or
worsening of
heart failure. Strong inhibitors retention, those
include azole with renal
Constipation. antifungals, protease impairment or
inhibitors, diabetics with high
macrolides and
serum K+ levels.
quinidine.
Assess SCr and K+
Grapefruit juice may after a few days,
increase serum then regularly.
concentrations.
Caution in patients
Inhibits metabolism with heart failure,
of carbamazepine, or 2nd or 3rd degree
cyclosporine, heart block without
lovastatin, a functioning
simvastatin. pacemaker.
Rifampin increases
Drug/Costa Dosage Adverse Effects metabolism of
verapamil.
Additive negative
inotropic effects with
amiodarone, beta-
blockers, digoxin.
Verapamil increases
digoxin levels by
50–75% within 1 wk
(monitor levels).
Drug Class: ACE Inhibitor/Diuretic Combinations

cilazapril /hydrochlorothiazide b Combination of Monitor serum K+ in
5/12.5 mg once ACE inhibitor Contraindicated in
Inhibace Plus, generics patients receiving K+
daily po and diuretic pregnancy.
supplements and/or
$ adverse effects potassium-sparing
possible, e.g., Can exacerbate
diuretics. gout and diabetes
dry cough,
electrolyte (biochemical
Reduced hypotensive
disturbances, abnormalities are
effect with NSAIDs
hypotension and less frequent at low
and increased risk of
renal failure. diuretic doses).
renal dysfunction.
Monitor SCr and
Li+ excretion may be
K +.
altered (monitor Li+
levels, adjust dose). Ineffective in
patients with ClCr
Reduced efficacy of <30–40 mL/min.
antihyperglycemic
agents.
enalapril /hydrochlorothiazide b Combination of Monitor serum K+ in

5/12.5 mg or ACE inhibitor Contraindicated in
Vaseretic, generics patients receiving K+
10/25 mg once and diuretic pregnancy.
supplements and/or
$$ daily po adverse effects potassium-sparing Can exacerbate
possible, e.g., diuretics.
dry cough, gout and diabetes
Reduced hypotensive
effect with NSAIDs
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
antihyperglycemic
agents.
lisinopril /hydrochlorothiazide b Combination of Monitor serum K+ in

10/12.5 mg, ACE inhibitor Contraindicated in
Zestoretic, generics patients receiving K+
20/12.5 mg or and diuretic pregnancy.
supplements and/or
$-$$ 20/25 once daily adverse effects potassium-sparing Can exacerbate
po possible, e.g., diuretics.
Drug/Costa Dosage dry cough,
Adverse Effects Reduced hypotensive Comments
Drug Interactions gout and diabetes
electrolyte effect with NSAIDs (biochemical
disturbances, and increased risk of abnormalities are
hypotension and renal dysfunction. less frequent at low
altered (monitor Li+ Monitor SCr and
levels, adjust dose). K +.
Reduced efficacy of Ineffective in

antihyperglycemic patients with ClCr
agents. <30–40 mL/min.
perindopril /indapamide b Combination of Monitor serum K+ in

Coversyl Plus, Coversyl Plus patients receiving K+
LD, Coversyl Plus HD 4/1.25 mg or and diuretic pregnancy.
supplements and/or
8/2.5 mg once adverse effects potassium-sparing Can exacerbate
$$ daily po possible, e.g., diuretics. gout and diabetes
dry cough,
Reduced hypotensive
effect with NSAIDs
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
antihyperglycemic
agents.
quinapril /hydrochlorothiazide b Combination of Monitor serum K+ in

Accuretic, generics patients receiving K+
20/12.5 mg or and diuretic pregnancy.
supplements and/or
$-$$ 20/25 mg once adverse effects potassium-sparing Can exacerbate
daily po possible, e.g., diuretics. gout and diabetes
dry cough,
Reduced hypotensive
effect with NSAIDs
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
antihyperglycemic
agents.
ramipril /hydrochlorothiazide b Combination of Monitor serum K+ in

2.5/12.5 mg, ACE inhibitor Contraindicated in
Altace HCT, generics patients receiving K+
5/12.5 mg, and diuretic pregnancy.
supplements and/or
$ 10/12.5 mg, 5/25 adverse effects
potassium-sparing Can exacerbate
mg or 10/25 mg possible, e.g.,
once daily po dry cough,
Drug/Costa Dosage electrolyte
Drug Interactions (biochemical
disturbances, effect with NSAIDs abnormalities are
hypotension and and increased risk of less frequent at low
renal failure. renal dysfunction. diuretic doses).
Li+ excretion may be Monitor SCr and

altered (monitor Li+ K +.
Ineffective in
Reduced efficacy of patients with ClCr
antihyperglycemic <30–40 mL/min.
agents.
Drug Class: ARB/Diuretic Combinations

azilsartan/chlorthalidone b Combination of Monitor serum K+ in
40/12.5 mg, ARB and Contraindicated in
Edarbyclor patients receiving K+
40/25 mg or diuretic adverse pregnancy.
supplements and/or
$$ 80/12.5 mg once effects possible potassium-sparing Can exacerbate
daily po e.g., electrolyte diuretics. gout and diabetes
disturbances,
hyperuricemia, (biochemical
Reduced hypotensive
hypotension and abnormalities are
effect with NSAIDs
renal failure. less frequent at low
diuretic doses).
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
Reduced efficacy of to <30–40 mL/min.
antihyperglycemic
agents.
candesartan/hydrochlorothiazide Combination of Monitor serum K+ in

b 16/12.5 mg once ARB and Contraindicated in
patients receiving K+
Atacand Plus, Candesartan daily po diuretic adverse pregnancy.
supplements and/or
HCT, other generics effects possible potassium-sparing
e.g., electrolyte Can exacerbate
$ disturbances,
Reduced hypotensive
effect with NSAIDs
diuretic doses).
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
antihyperglycemic
agents.
eprosartan/hydrochlorothiazide Combination of Monitor serum K+ in

b 600/12.5 mg ARB and Contraindicated in
Teveten Plus once daily po diuretic adverse pregnancy.
supplements and/or
effects possible potassium-sparing
$$ e.g., electrolyte Can exacerbate
diuretics.
Drug/Costa Dosage disturbances,
Drug Interactions gout and diabetes
hyperuricemia, effect with NSAIDs (biochemical
hypotension and and increased risk of abnormalities are
renal failure. renal dysfunction. less frequent at low
diuretic doses).
altered (monitor Li+ Monitor SCr and
levels, adjust dose). K +.
Reduced efficacy of Ineffective in

antihyperglycemic patients with ClCr
agents. to <30–40 mL/min.
irbesartan/hydrochlorothiazide b Combination of Monitor serum K+ in

Avalide, Irbesartan HCT, other 150/12.5 mg or ARB and patients receiving K+
Contraindicated in
generics 300/12.5 mg diuretic adverse pregnancy.
supplements and/or
once daily po effects possible potassium-sparing Can exacerbate
$ e.g., electrolyte diuretics.
disturbances, gout and diabetes
Reduced hypotensive
effect with NSAIDs
diuretic doses).
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
antihyperglycemic
agents.
losartan/hydrochlorothiazide b Combination of Monitor serum K+ in

50/12.5 mg or ARB and Contraindicated in
Hyzaar, Hyzaar DS, Losartan patients receiving K+
HCT, other generics 100/25 mg once diuretic adverse pregnancy.
supplements and/or
daily po effects possible potassium-sparing
$ e.g., electrolyte diuretics. Can exacerbate
disturbances, gout and diabetes
hyperuricemia, Reduced hypotensive (biochemical
hypotension and effect with NSAIDs abnormalities are
diuretic doses).
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
antihyperglycemic
agents.
olmesartan/hydrochlorothiazide Combination of Monitor serum K+ in

b 20/12.5 mg, ARB and Contraindicated in
Olmetec Plus, generics 40/12.5 mg or diuretic adverse pregnancy.
supplements and/or
40/25 mg once effects possible potassium-sparing Can exacerbate
$$ daily po e.g., electrolyte diuretics. gout and diabetes
Drug/Costa Dosage disturbances,
Drug Interactions (biochemical
hyperuricemia, effect with NSAIDs abnormalities are
hypotension and and increased risk of less frequent at low
renal failure. renal dysfunction. diuretic doses).
Li+ excretion may be Monitor SCr and

altered (monitor Li+ K +.
Ineffective in
Reduced efficacy of patients with ClCr
antihyperglycemic to <30–40 mL/min.
agents.
telmisartan/hydrochlorothiazide Combination of Monitor serum K+ in

b 80/12.5 mg or ARB and Contraindicated in
Micardis Plus, Telmisartan 80/25 mg once diuretic adverse pregnancy.
supplements and/or
HCT, other generics daily po effects possible potassium-sparing Can exacerbate
e.g., electrolyte diuretics.
$ disturbances, gout and diabetes
Reduced hypotensive
effect with NSAIDs
diuretic doses).
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
antihyperglycemic
agents.
valsartan/hydrochlorothiazide b Combination of Monitor serum K+ in

Diovan-HCT, Valsartan HCT, 80/12.5 mg, ARB and patients receiving K+
Contraindicated in
other generics 160/12.5 mg or diuretic adverse pregnancy.
supplements and/or
160/25 mg once effects possible potassium-sparing Can exacerbate
$ daily po e.g., electrolyte diuretics. gout and diabetes
disturbances,
Reduced hypotensive
effect with NSAIDs
diuretic doses).
renal dysfunction.
Monitor SCr and
K +.
patients with ClCr
antihyperglycemic
agents.
Drug Class: Beta1 -adrenergic Antagonist/Diuretic Combinations

atenolol/chlorthalidone b Fatigue, Bradycardia with
Tenoretic, generics 50/25 mg, or bradycardia, digoxin or Beta-blockers
100/25 mg once decreased nondihydropyridine should not be used
$ daily po exercise CCBs. as initial therapy in
Drug/Costa Dosage headache,
Adverse Effects Cardiodepressant age unless
CCBs and
+
depression, heart Li excretion
failure, heart reduced (monitor Li+ Avoid abrupt
block. levels, adjust dose). withdrawal (may
precipitate rebound
Hypotension, NSAIDs reduce hypertension and
weakness, hypotensive efficacy. ischemia). Taper
muscle cramps, the dose before
impotence. Diuretic-induced discontinuation.
hypokalemia
Hypokalemia, increases the risk of Avoid in patients
hyponatremia, digoxin toxicity. with severe PAD.
hyperuricemia,
hyperglycemia, Reduced efficacy of Contraindicated in
hyperlipidemia. antihyperglycemic patients with 2nd or
agents. 3rd degree heart
Azotemia (rare),
block in the
blood dyscrasias
absence of a
(rare), allergic
pacemaker.
reactions
(potential cross Particularly
sensitivity with effective in ISH,
other the elderly and
sulfonamide black patients.
derivatives
[rare]), fatigue Monitor SCr and
(rare), K +.
photosensitivity
(rare). Consider
alternatives in
patients with or
predisposed to
arrhythmias.
Can exacerbate
gout and diabetes
(biochemical
abnormalities are
doses).
pindolol/hydrochlorothiazide b Fatigue, Bradycardia with
Viskazide 10/25 mg or bradycardia, digoxin or Beta-blockers
10/50 mg once decreased nondihydropyridine should not be used
$$ daily po exercise CCBs. as initial therapy in
headache, Cardiodepressant age unless
CCBs and
depression, heart Li+ excretion
failure, heart reduced (monitor Li+ Avoid abrupt
Drug/Costa Dosage Hypotension,
Adverse Effects levels, adjust dose). Comments
Drug Interactions precipitate rebound
weakness, hypertension and
muscle cramps, NSAIDs reduce ischemia). Taper
impotence. hypotensive efficacy. the dose before
discontinuation.
Hypokalemia, Diuretic-induced
hyponatremia, hypokalemia Avoid in patients
hyperuricemia, increases the risk of with severe PAD.
hyperglycemia, digoxin toxicity.
hyperlipidemia. Contraindicated in
Reduced efficacy of patients with 2nd or
Azotemia (rare), antihyperglycemic
3rd degree heart
blood dyscrasias agents.
block in the
(rare), allergic absence of a
reactions pacemaker.
(potential cross
sensitivity with Particularly
other effective in ISH,
sulfonamide the elderly and
derivatives black patients.
[rare]), fatigue
(rare), Monitor SCr and
photosensitivity K +.
(rare).
Consider
alternatives in
patients with or
predisposed to
arrhythmias.
Can exacerbate
gout and diabetes
(biochemical
abnormalities are
doses).
Drug Class: Calcium Channel Blocker/ARB Combinations

amlodipine/telmisartanb Ankle edema, CYP3A4 substrate
Twynsta 5/40 mg, 5/80 flushing, (many potential Contraindicated in
mg, 10/40 mg or headache and interactions). pregnancy—
$$ 10/80 mg once palpitations. caution when
daily po Hyperkalemia. Strong inhibitors prescribing to
include azole women of
Can precipitate antifungals, protease childbearing
renal failure in inhibitors, potential.8
susceptible macrolides and
patients quinidine. Use lower initial
(bilateral doses in patients
renovascular Grapefruit juice may who are volume
disease, those increase serum depleted or on
with volume concentrations. diuretics (increased
depletion or with risk of hypotension
concurrent Marked increase in in hypovolemia).
NSAID use). serum K+ in patients
receiving K+ Hyperkalemia
Angioedema has supplements and/or usually occurs only
been reported, potassium-sparing in those on K+
but a causal diuretics. supplements or
Drug/Costa Dosage association has May
Adverse Effects Drugelevate Li+
Interactions drugs that cause K +
Comments
not been levels (monitor Li+ retention, those
established. levels, adjust dose). with renal
impairment or
diabetics with high
serum K+ levels.
Assess SCr and K+
after a few days,
then regularly.
Drug Class: Calcium Channel Blocker/HMG-CoA Reductase Inhibitor Combinations

amlodipine/atorvastatin Ankle edema, CYP3A4 substrate
Caduet, generics Amlodipine 5 or flushing, (many potential For patients with
10 mg plus headache and interactions). hypertension and an
$-$$ atorvastatin 10, palpitations. indication for an
20, 40 or 80 mg Strong inhibitors HMG-CoA
once daily po Adverse effects include azole inhibitor.
of atorvastatin antifungals, protease
include inhibitors,
constipation, macrolides and
flatulence, quinidine.
dyspepsia,
abdominal pain Grapefruit juice may
and myalgia. increase serum
concentrations.
Amlodipine and
atorvastatin are both
substrates of
CYP3A4.
Drug Class: Direct Renin Inhibitor/Diuretic Combinations

aliskiren/hydrochlorothiazide Diarrhea. The Avoid combining
Rasilez HCT 150/12.5 mg, incidence of dry with an ACE Avoid use in
cough and inhibitor or ARB in pregnancy.
$$ 150/25 mg, hyperkalemia is patients with
300/12.5 mg low compared significant renal May take 4 wk to
with ACE impairment. realize maximum
or 300/25 mg antihypertensive
inhibitors.
Hypotension, Grapefruit juice may effect.
once daily po
weakness, reduce serum
concentrations. Effect on
muscle cramps,
cardiovascular
impotence.
Li+ excretion outcomes not yet
established.
Hypokalemia, reduced (monitor Li+
hyponatremia, levels, adjust dose). Limited data in
hyperuricemia,
patients with
hyperglycemia, NSAIDs reduce
greater than
hyperlipidemia. hypotensive efficacy.
moderate renal
Azotemia (rare), Diuretic-induced dysfunction.
blood dyscrasias hypokalemia
Particularly
(rare), allergic increases the risk of
effective in ISH,
reactions digoxin toxicity.
the elderly and
(potential cross
Reduced efficacy of black patients.
sensitivity with
other antihyperglycemic
Monitor SCr and
sulfonamide agents.
K +.
Drug/Costa Dosage derivatives
Adverse Effects Drug Interactions Consider
Comments
[rare]), fatigue alternatives in
(rare), patients with or
photosensitivity predisposed to
(rare). arrhythmias.
Can exacerbate
gout and diabetes
(biochemical
abnormalities are
doses).
Drug Class: Diuretic Combinations

hydrochlorothiazide /amiloride Hypotension, Li+ excretion
(50/5) One-half tablet weakness, Particularly
generics once daily po muscle cramps, effective in ISH,
impotence. the elderly and
$ NSAIDs reduce black patients.
hyponatremia, Monitor SCr and
hyperuricemia, Diuretic-induced K +.
hyperlipidemia. increases the risk of Consider
reactions agents.
sensitivity with May exacerbate ACE gout and diabetes
other inhibitor–induced (biochemical
sulfonamide hyperkalemia. abnormalities are
(rare),
photosensitivity Lower incidence of
(rare). hypokalemia than
with
hydrochlorothiazide
alone.

/triamterene (25/50) Initial: One-half weakness, Particularly
generics tablet muscle cramps, levels, adjust dose). effective in ISH,
$ Usual: 1 tablet black patients.
NSAIDs reduce
Once daily po hyponatremia, Monitor SCr and
reactions agents.
Drug/Costa Dosage sensitivity with
Adverse Effects May
Drugexacerbate ACE Comments
Interactions gout and diabetes
other inhibitor–induced (biochemical
(rare),
with
hydrochlorothiazide
alone.
/spironolactone (25/25) Initial: One-half weakness, Particularly
Aldactazide, generics tablet muscle cramps, effective in ISH,
$ Usual: 1 tablet black patients.
NSAIDs reduce
Once daily po hyponatremia, Monitor SCr and
reactions agents.
sensitivity with May exacerbate ACE gout and diabetes
other inhibitor-induced (biochemical
(rare),
with
Gynecomastia in hydrochlorothiazide
men and breast alone.
tenderness in
women.
aCost of 30-day supply of usual dose of drug; includes drug cost only.
bThe Canadian Hypertension Education Program recommends initiating therapy with a combination of 2 first-line
agents if a patient's SBP is ≥20 or DBP is ≥10 mm Hg above the recommended target.
Dosage adjustment may be required in renal impairment; see Dosage Adjustment in Renal Impairment.
Abbreviations:
ACE
CCB
calcium channel blocker
CV
cardiovascular
DBP
IR
immediate-release
ISA
intrinsic sympathomimetic activity
ISH
isolated systolic hypertension
NSAID
nonsteroidal anti-inflammatory drug
PAD
peripheral arterial disease
SBP
SCr
serum creatinine
SR
sustained-release
TCA
tricyclic antidepressant
Legend:
$
<$20
$-$$
<$20–40
$$
$20–40
$$$
$40–60
$$$$
$60–80
Suggested Readings
Adrogue HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med
2007;356(19):1966-78.
Canadian recommendations on the management of hypertension are updated annually. A summary of the important
and new recommendations can be found at www.hypertension.ca/ in the Professional section and is also broadly
published in multidisciplinary journals annually.
References
1. Leung AA, Daskalopoulou SS, Dasgupta K et al. Hypertension Canada’s 2017 guidelines for diagnosis, risk
assessment, prevention and treatment of hypertension. Can J Cardiol 2017;33(5):557–76.
2. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard
blood-pressure control. N Engl J Med 2015;373(22):2103-16.
3. Khan N, Chockalingam A, Campbell NR. Lack of control of high blood pressure and treatment
recommendations in Canada. Can J Cardiol 2002;18(6):657-61.
4. Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing
cardiovascular events: systematic review and network meta-analyses. Hypertension 2012;59(6):1110-7.
5. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive
and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive
patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA
2002;288(23):2981-97.
6. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimester
exposure to ACE inhibitors. N Engl J Med 2006;354(23):2443-51.
7. Friedman JM. ACE inhibitors and congenital anomalies. N Engl J Med 2006;354(23):2498-500.
8. Alwan S, Polifka JE, Friedman JM. Angiotensin II receptor antagonist treatment during pregnancy. Birth
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RxTx, Compendium of Therapeutic Choices © Canadian Pharmacists Association, 2018. All rights reserved

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Raj Padwal, MD, FRCPC

Paul Gibson, MD, FRCPC

Ross T. Tsuyuki, PharmD, MSc, FCSHP, FACC

Date of Revision: September 2017

Peer Review Date: May 2016

Setting Target SBP/DBP (mm Hg)

general patient population <140/90

isolated systolic hypertension SBP <140

Diabetes mellitus <130/80

High risk of cardiovascular eventsb SBP <120

aMeasured by a validated home blood pressure monitor.

systolic blood pressure

drugs that may cause hypertension (see Table 2)

adherence with lifestyle recommendations and drug therapy

symptoms of secondary hypertension, which include, for example, pheochromocytoma

Alcohol (excessive use) NSAIDs including COX-2 inhibitors

Corticosteroids and anabolic steroids Salt (sodium—high intake)

Erythropoietin and analogues Selective serotonin reuptake inhibitors (SSRIs)

Licorice root Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Midodrine Stimulants, including cocaine

MAOIs Vasoconstricting, sympathomimetic decongestants

Diagnosis of hypertension through out-of-office measurement can be done by performing a 24-hour

fundi for hypertensive retinopathy

edema and lung fields for signs of heart failure

abdominal mass for polycystic kidneys and aortic aneurysm

neurologic exam for cerebrovascular disease

Initial laboratory testing:

serum potassium, sodium and creatinine

urinary albumin and/or albumin-creatinine ratio in patients with diabetes

fasting glucose and/or HbA 1c

standard 12-lead ECG

select patients should have additional testing (see Table 3)

If these characteristics are present: Check for:

• Urinary albumin or protein Diabetes, renal disease

• Paroxysmal and/or severe sustained hypertension refractory to usual Pheochromocytoma

• Hypertension and symptoms suggestive of catecholamine excess (2 or more of

• Hypertension triggered by beta-blockers, monoamine oxidase inhibitors, micturition

• Incidentally discovered adrenal adenoma

• MEN 2A or 2B; von Recklinghausen neurofibromatosis or von Hippel-Lindau

• Spontaneous hypokalemia Hyperaldosteronism

• Profound diuretic-induced hypokalemia (K + <3 mmol/L)

• Hypertension refractory to treatment with ≥3 drugs

• Incidental adrenal adenoma

Two or more of: Renovascular disease

• Sudden onset or worsening of hypertension in patients >55 y or <30 y

• Uncontrolled hypertension despite use of ≥3 drugs

• Decreased renal function associated with use of an ACE inhibitor or ARB

• Overt atherosclerotic vascular disease

• Recurrent episodes of hypertension and flash pulmonary edema

angiotensin receptor blocker

multiple endocrine neoplasia

Sodium intake target of <2000 mg (88 mmol) per day.

PrintTable 4: Effect of Lifestyle Changes on Blood Pressure in Adults with Hypertension

Intervention Recommendation Change in Blood Pressure

Reduction in sodium intake Reduce by 1800 mg (78 mmol) per −5.8/−2.5

Weight loss Reduce by 4.5 kg −7.2/−5.9

Reduction in alcohol intake Reduce by 2.7 drinks/day −4.6/−2.3

Exercise 30–45 min, 3 times/week −10.3/−7.5

Dietary modification DASH eating plan a −11.4/−5.5

a Available from: www.nhlbi.nih.gov/health/public/heart/hbp/dash/new_dash.pdf.

If the average SBP/DBP is ≥160/100 mm Hg, pharmacologic treatment is recommended in addition to

hypertensive target organ damage or

Drugs that Act via the Renin Angiotensin Aldosterone System

trandolapril /verapamilb Dry cough, Marked increase in

enalapril /hydrochlorothiazide b Combination of Monitor serum K+ in