13-1

13 CASE SUMMARY

CHAPTER 13
A 64-year-old African American man with HTN, COPD, DM type
2, BPH, chronic kidney disease, and gout presents to his new fam-
HYPERTENSION ily medicine physician for evaluation and follow-up of his medical
problems. His BP is poorly controlled, despite treatment with dox-
Pass the Salt, Please  Level II azosin, hydrochlorothiazide/triamterene, and carvedilol. He states
Julia M. Koehler, PharmD, FCCP he is recovering from a cold, for which he has been taking guaife-
nesin and pseudoephedrine (Mucinex D), and it is possible that
James E. Tisdale, PharmD, BCPS, FCCP the use of this medication has contributed to his poorly controlled

Hypertension
HTN. In addition, the patient takes naproxen for relief of both
headaches and acute gout pain. Because NSAIDs may also exac-
INSTRUCTORS GUIDE TO erbate HTN, consideration of other options for HA and gout pain
CHANGES IN THIS EDITION relief should be explored. The patient admits a lack of adherence
to the low-sodium diet recommended by his former primary care
CASEBOOK physician. Physical examination reveals signs and symptoms consis-
tent with target organ damage. Interventions for this patient should
Objectives
include instruction on lifestyle modification, including appropriate
Revised slightly to reflect the fact that new JNC hypertension diet and exercise, and drug therapy. Selection of an antihypertensive
guidelines are not yet available as of the time of writing of this regimen should include consideration of the degree of this patients
case, but will likely be released around the time that this book HTN as well as patient-specific variables, such as ethnicity and
is published. comorbid conditions. This case points out the need to treat each
patient as an individual and to consider all patient factors when
Patient Presentation selecting drug therapy.
Revisions to patient: 64-year-old (rather than 62 years old),
type 2 diabetes mellitus (DM) (rather than type 1 diabetes),
and new comorbid condition (gout). Patient is now also tak-
ing insulin lispro, carvedilol, fluticasone/salmeterol, naproxen,
QUESTIONS
and allopurinol.
Problem Identification
Clinical Pearl 1.a. Create a list of this patients drug-related problems, includ-
ing any medications that may be contributing to his uncon-
New clinical pearl added highlighting the fact that the majority trolled HTN.
of patients with hypertension require two or more antihyper-
tensive medications to achieve blood pressure goal. HTN inadequately treated with current lifestyle modifica-
tion recommendations and current pharmacotherapy; possi-
bly aggravated by current medication use for cold symptoms,
INSTRUCTORS GUIDE
as well as NSAID use for headaches and episodes of acute
Case Summary goutpain.
Revised to include discussion of NSAIDs as possible contribu- Mucinex D contains pseudoephedrine. Because pseu-
tor to lack of blood pressure control. doephedrine has sympathomimetic activity, it has the
potential to increase BP or worsen BP control. A meta-
Problem Identification analysis analyzing the effects of pseudoephedrine on BP
Revised to include NSAIDs as a possible cause of poor BP illustrated that pseudoephedrine use contributed to a small
control. (~1 mm Hg) and statistically significant increase in both
systolic blood pressure (SBP) and heart rate. While the find-
Added discussion on use of -blockers for hypertension man- ings of this meta-analysis suggest that the increases in BP
agement in patients with COPD. and heart rate observed with pseudoephedrine use may not
be clinically significant, the authors did note that shorter
Therapeutic Alternatives duration of pseudoephedrine use, as well as higher doses
Added discussion of therapeutic alternatives for hypertension and immediate-release preparations, was associated with
in a patient with comorbid gout. greater increases in BP.1 In any case, consideration could be
given to discontinuation of Mucinex D if no longer indi-
cated in this patient, or possible switch to a preparation that
Optimal Plan
contains only guaifenesin.
Added discussion about appropriateness of a nonselective
Because of their potential to promote sodium retention,
-blocker in a hypertensive patient with COPD and lack of
NSAIDs, such as naproxen, may also precipitate increases in
compelling indication for a -blocker in this case.
blood pressure and may compromise the efficacy of blood
pressurelowering medications. Alternatives to NSAIDs for
References headache relief and relief of pain secondary to acute gouty
Revised and updated; two new references added. attacks should be considered for this patient.

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

13-2
Possible doxazosin-induced orthostasis/dizziness. addition, since DM and chronic kidney disease are considered
Possible drugdisease contraindication between carvedilol (a coronary heart disease risk equivalents, the Framingham risk
SECTION 2

nonselective -blocker) and COPD. In the absence of a clear score is not intended for patients with DM and/or chronic kid-
indication for carvedilol in this patient, either an alternative, ney disease; in patients with DM and/or chronic kidney disease,
1-selective -blocker or another class of antihypertensive the 10-year risk for heart disease is >20%. Therefore, it is not
agent should be substituted for carvedilol. necessary to calculate the Framingham risk score in this patient.
Nonadherence to lifestyle modification recommendations. Given the patients comorbid diagnoses of DM and chronic
kidney disease (i.e., CHD risk equivalents), aggressive CV
Chronic kidney disease with evidence of proteinuria.
risk reduction is warranted.
1.b. How would you classify this patients hypertension, accord-
1.d. What evidence of target organ damage or clinical CVD does
Cardiovascular Disorders

ing to current hypertension guidelines?

this patient have?
JNC 7 guidelines (current hypertension guidelines at the time
Evidence of target organ damage or clinical CVD:
of writing of this casebook chapter) recommend the following
classification system for BP2: Eyes: arteriovenous nicking
Kidneys: (+) proteinuria, elevated serum creatinine (SCr)/
chronic kidney disease
Category Systolic BP (mm Hg) Diastolic BP (mm Hg)
Heart: LVH, EF 45%
Normal <120 <80
Prehypertension 120139 8089
Stage 1 HTN 140159 9099 Desired Outcome
Stage 2 HTN 160 100 2. List the goals of treatment for this patient (including his
goalBP).
The goal BP according to JNC 7 guidelines for a patient with
Based on his BP readings of 162/90 and 164/92 mm Hg, this diabetes (or kidney disease) is <130/80 mm Hg. This is also
patient can be classified as having Stage 2 HTN. (When systolic the recommended goal BP according to the National Kidney
and diastolic BPs fall into different categories, the higher of the Foundation and the American Diabetes Association and is con-
two numbers is used to classify the patients stage of HTN.) sistent with the recommendations for a patient with high coro-
In general, there is a strong correlation between BP and CV nary artery disease risk, according tothe2007 American Heart
morbidity and mortality. According to JNC 7 guidelines, a Association scientific statement onthe management of HTN in
patients risk for developing cardiovascular disease (CVD) patients at risk for or with known IHD.4
doubles with each increment of 20/10 mm Hg above a BP of The general goal when treating HTN is to prevent or reduce
115/75 mm Hg. For this reason, JNC 7 guidelines recommend the likelihood of morbidity and/or mortality resulting from
that for patients whose BP falls in the category of Stage 2, more uncontrolled high BP (e.g., retinal damage leading to blind-
than one BP-lowering medication will be necessary in order to ness, renal dysfunction or progression of existing kidney dis-
adequately lower BP and reduce the risk of CVD. ease, stroke, heart failure, acute myocardial infarction). This
1.c. What are the patients known CV risk factors, and what is his should be accomplished while attempting to maximize both
Framingham risk score? pharmacotherapeutic and pharmacoeconomic benefits, while
minimizing the risk for adverse drug events.
According to JNC 7, the risk factors for CVD are HTN, smok-
ing, obesity (BMI >30 kg/m2), physical inactivity, dyslipidemia, Additionally, other modifiable risk factors for coronary artery
DM, microalbuminuria, kidney disease (estimated glomeru- disease should be treated when present.
lar filtration rate <60 mL/min), age (men >55 years or women
>65 years), and family history of premature CVD (men Therapeutic Alternatives
<55years or women <65 years).2 (Note: The American Society 3.a. What lifestyle modifications should be encouraged for this
of Hypertension [ASH] defines a family history of premature patient to achieve and maintain adequate BP reduction?
CVD as age <50 in men, and age <60 in women. Additional
CV risk factors defined by ASH but not specifically defined In order for this patient to receive maximal benefit from the
by JNC 7 include: high heart rate, central obesity [increased drug therapy for his HTN, lifestyle modifications should be
abdominal circumference and/or waist-to-hip ratio], psycho- again encouraged, instituted, and continued indefinitely.
social stressors, and elevated high-sensitivity C-reactive protein Recommended lifestyle modifications should include the fol-
[hs-CRP].)3 lowing:
This patients CV risk factors, as defined by JNC 7, include: Weight reduction: Maintain normal body weight (BMI
18.524.9 kg/m2). A 10-kg weight loss may result in an
HTN approximate 520 mm Hg decrease in SBP.2
Estimated glomerular filtration rate <60 mL/min Sodium restriction: Not more than 2.4 g of sodium or 6 g of
Proteinuria sodium chloride (NaCl) per day. Adequate sodium restric-
DM tion may yield an estimated 28 mm Hg decrease in SBP.
Age (male >55 years) Dietary Approaches to Stop Hypertension (DASH) diet: A
diet that is high in calcium, high in potassium, and low in
Physical inactivity
saturated fat.5 The DASH diet is rich in fruits, vegetables,
Family history cannot necessarily be included as a known CV and low-fat dairy products. It has been demonstrated to be
risk factor for this patient based on the information given. particularly effective in producing BP lowering in African
The Framingham risk score is intended for patients who are American patients.6 The DASH diet may decrease BP by
at risk for, but who do not yet have, coronary heart disease. In 814 mm Hg.

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

 13-3
Moderation of alcohol intake: Not more than 1 oz or 30 mL for the breakdown of bradykinin. (It is believed that accu-
of ethanol per day (e.g., 24 oz of beer, 10 oz of wine, or 3 oz mulation of bradykinin in the lungs is the etiology of ACE

CHAPTER 13
of 80-proof whiskey in men; one drink per day in women inhibitorassociated cough.) Similar to ACE inhibitors,
and lighter-weight persons). ARBs have also been demonstrated to reduce proteinuria
Exercise: 30 minutes per day most days of the week. and delay the progression of kidney disease in patients with
Recommended exercise should include regular aerobic diabetes. Typically, ARBs are reserved for patients who are
activity, such as brisk walking. intolerant of ACE inhibitors due to cough.
Calcium channel blockers impair transport of calcium
Smoking cessation (or encouragement to continue avoiding
through voltage-sensitive calcium channels in vascular
smoking in this patient case).
smooth muscle. Nondihydropyridine calcium channel

Hypertension
3.b. What reasonable pharmacotherapeutic options are available blockers, such as verapamil and diltiazem, work directly on
for controlling this patients BP, and what comorbidities the myocardium, producing both negative inotropic and
and individual patient considerations should be taken into negative chronotropic effects. Dihydropyridine calcium
account when selecting pharmacologic therapy for his HTN? channel blockers, such as amlodipine and nifedipine, yield
How might Mr Franks HTN medications potentially affect peripheral vasodilatory effects and may produce a second-
his other medical problems? ary increase in heart rate, or reflex tachycardia. Although
There are several classes of antihypertensive agents that can be the amount of existing data is small compared to that which
considered in the treatment of HTN. Available classes of anti- exists for ACE inhibitors, nondihydropyridine calcium
hypertensive agents include the following: channel blockers may reduce coronary events, and data
from short-term studies illustrate that nondihydropyridines
Thiazide and thiazidelike diuretics work by blocking sodium reduce proteinuria in patients with diabetes.2,11 Although
reabsorption in the distal tubule. Thiazides have been dem- calcium channel blockers may have greater BP-lowering
onstrated to reduce morbidity and mortality in patients efficacy in African-American patients compared to other
with HTN and are considered the first-line drugs of choice classes of antihypertensives, they are typically not preferred
according to JNC 7 guidelines and the findings of the as first-line treatments either over thiazide diuretics in
Antihypertensive and Lipid-Lowering Treatment to Prevent patients without compelling comorbid indications or over
Heart Attack Trial (ALLHAT).7 Thiazide diuretics, as well other treatments such as ACE inhibitors, in patients with
as calcium channel blockers, may have greater BP-lowering HTN, diabetes, and/or high CHD risk.2
effects in African-American patients compared to other
1-Adrenergic blockers inhibit adrenergic stimulation of
classes of antihypertensives.6
peripheral 1 receptors, resulting in reduced peripheral
-Blockers lower BP by directly blocking adrenergic stimu- resistance and vasodilation. Although these agents are
lation of receptors. They are relatively contraindicated in effective in relieving the symptoms of BPH, they must be
patients with known obstructive lung disease, because of used with caution in elderly patients due to the risk of diz-
their potential to cause bronchospasm. If used in patients ziness, orthostatic hypotension, and resultant potential for
with obstructive lung disease, 1-selective agents, such as syncope. When compared to chlorthalidone as a first-line
metoprolol, are preferred, and nonselective -blockers, antihypertensive agent, doxazosin use was associated with
such as carvedilol or labetalol, should generally be avoided. a higher incidence of congestive heart failure and combined
-Blockers may also mask the signs and symptoms of CVD outcomes in the ALLHAT study.7 The doxazosin arm
hypoglycemia in patients with diabetes. In comparison to of the ALLHAT trial was discontinued early, and current
ACE inhibitors, -blockers were demonstrated to be equally guidelines no longer recommend the use of 1-adrenergic
effective in controlling BP and reducing the complications blockers as monotherapy in the treatment of HTN.2
of diabetes in the UKPDS trial.8 When used as mono-
Central-acting -agonists, such as clonidine, work by
therapy, -blockers may produce less BP-lowering effects in
directly simulating presynaptic 2-receptors in the brain-
African Americans compared to Caucasians.6
stem, thereby reducing sympathetic outflow. This class of
ACE inhibitors inhibit angiotensin-converting enzyme, antihypertensive agents is considered to be equally effective
thereby blocking the conversion of angiotensin I to angio- in lowering BP in all ages and races. This class of medica-
tensin II. ACE inhibitors have been shown to be especially tions carries an extensive side-effect profile, which includes
beneficial in lowering CHD risk in high-risk patients with drowsiness, sedation, fatigue, depression, dry mouth,
and without diabetes.9,10 According to JNC 7 guidelines, orthostasis, bradycardia, and rebound HTN. As such, this
ACE inhibitors are also considered first-line drugs of choice class of medications is poorly tolerated by many patients
in patients with diabetes, as they have been demonstrated and is not recommended by the JNC for first- or second-line
to reduce proteinuria and retard the progression of kidney consideration in the management of HTN.2
disease in such patients.2 As with -blockers, ACE inhibi- Direct vasodilators, such as hydralazine and minoxidil, work
tors, when used as monotherapy, may produce diminished by directly relaxing arterial smooth muscle and reducing
BP-lowering effects in African Americans compared to peripheral vascular resistance. Because these drugs may
Caucasians.6 The BP-lowering effects of ACE inhibitors may produce profound peripheral vasodilation, they often cause
be augmented, however, with concomitant diuretic use. significant side effects, such as peripheral edema and reflex
Compared to Caucasians, African Americans appear to be tachycardia, which warrant additional treatment (i.e., they
at increased risk for experiencing ACE inhibitorinduced typically must be used in combination with a -blocker and
angioedema and ACE inhibitorinduced cough.6 a loop diuretic). These agents are most commonly reserved
Angiotensin II receptor blockers (ARBs) directly antagonize for refractory HTN despite modest doses of three or more
angiotensin II receptors. Although their mechanism is antihypertensive agents.
similar to that of ACE inhibitors, ARBs differ in that they Peripheral adrenergic neuron antagonists, such as reser-
spare angiotensin-converting enzyme and, therefore, allow pine, deplete norepinephrine from peripheral neurons and

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

13-4
inhibit release of norepinephrine in response to sympathetic ACE inhibitors have been shown to delay the progression of
stimulation. Much like central-acting 2-agonists, this class kidney disease in nondiabetic nephropathy.13
SECTION 2

of drugs is associated with significant side effects, such Thiazide diuretics are considered to be ineffective when
as orthostasis, GI disturbances, bradycardia, drowsiness, CrCl is <30 mL/min. Although this patients estimated CrCl
depression, and nightmares, which limit the utility of these is not below 30 mL/min currently, continuous monitoring
agents for most patients. of the progression of this patients kidney disease is impor-
The direct renin inhibitor aliskiren was approved by the tant and could affect the potential efficacy of a thiazide
FDA in 2007. This newer class represents the first new type diuretic in the future.
of antihypertensive available for the treatment of HTN in Potassium-sparing diuretics should be used with caution in
more than a decade. Aliskiren is indicated either alone or patients with mild kidney disease and should be avoided in
Cardiovascular Disorders

in combination with other antihypertensives, such as thiaz- patients with significant kidney disease.
ide diuretics or ARBs. It is administered once daily for the
Gout:
treatment of HTN. Because of the cost of this agent and the
limited data available in treating patients with HTN and In high doses (e.g., 50 mg of hydrochlorothiazide), thiazide
other comorbidities, it is not currently recommended as a diuretics may increase serum uric acid concentrations and
first-line antihypertensive agent. cause other metabolic derangements, such as alterations in
blood glucose and serum lipid concentrations.
Comorbidities that must be specifically taken into account when
Left ventricular hypertrophy:
selecting pharmacologic antihypertensive therapy for this patient
include: ACE inhibitors have been shown to reduce LV mass, as have
most classes of antihypertensive agents, with the exception
DM:
of direct vasodilators.
ACE inhibitors are typically the drugs of choice in patients
African-American race (not a comorbidity but an important
with diabetes, as they have been demonstrated to reduce
consideration):
proteinuria and delay progression of kidney disease. ARBs
have also been demonstrated to have renal protective -Blockers and ACE inhibitors are generally thought to be
effects, particularly in patients with type 2 diabetes and in less effective when used as monotherapy for BP lowering in
those with advanced kidney disease. There is no indication this population of patients. The BP-lowering effect of ACE
in this patient to select an ARB over an ACE inhibitor at inhibitors can be enhanced with the addition of a diuretic.
this time, particularly since it is also important to note Diuretics and calcium channel blockers are considered to
the demonstrated benefit of CV risk reduction with ACE have greater BP-lowering effects than most other antihyper-
inhibitors. tensive classes in African-American patients.
-Blockers have also been shown to control BP and reduce
the complications of diabetes.8 Caution should be used Optimal Plan
when selecting a -blocker for a patient with diabetes, as
-blockers may mask signs and symptoms of hypoglycemia 4.a. Recommend specific lifestyle modifications for this patient.
and may contribute to glucose intolerance. This is not an Nonpharmacologic therapy for this patient should include the
absolute contraindication, however. following:
Thiazides are recommended as first-line antihypertensives Weight reduction. The patients current weight is 95 kg, and
in patients with or without diabetes for control of HTN his BMI is 27 kg/m2. The patients IBW = 82.2 kg. Weight
and reduction of morbidity and mortality.7 It is important reduction by caloric restriction has been shown to reduce
to note, however, that in high doses, thiazides may increase BP, even if IBW is not achieved. A goal for the patient should
blood glucose and cause other metabolic derangements. be to achieve and maintain a BMI of 18.524.9 kg/m2.
Chronic obstructive pulmonary disease: Sodium restriction. The patient has been nonadherent to his
-Blockers are relatively contraindicated in patients with prescribed low-sodium diet. Ideally, he should be restricted
moderate to severe obstructive lung disease. Consideration to not more than 2.4 g of sodium (6 g NaCl) per day. The
must therefore be given to the severity of the disease, patient should be instructed not to add salt to his food. He
risk versus potential benefit, and relative -receptor should also be advised to seek out foods that are low in
selectivity. sodium and/or consult with a dietician to assist with imple-
menting a low-sodium diet.
ACE inhibitors are not contraindicated in patients with
obstructive lung disease. It is important to note, however, DASH diet. The patient should be given information about
that these drugs may cause cough in 1020% of patients, and encouraged to try this diet, which is low in sodium, high
and this is an important monitoring parameter in patients in calcium and potassium, and low in both saturated and
with obstructive lung disease. total fat. This diet has been shown to be particularly effec-
tive in African American hypertensives and may reduce BP
Benign prostatic hyperplasia: better than both weight loss and sodium restriction alone in
1-Blockers are drugs of choice for symptomatic relief. these patients.
These agents should not be used as monotherapy in the Moderation of alcohol intake. The patient should be encour-
treatment of HTN, however, based on the findings of the aged to limit his alcohol intake to not more than 1 oz of
ALLHAT study.12 ethanol, 24 oz of beer, 10 oz of wine, or 3 oz of 80-proof
Chronic kidney disease: whiskey per day.
Both ACE inhibitors and ARBs have been shown to reduce Exercise. The patient should be encouraged to participate
the incidence and severity of proteinuria and delay the in 3045 minutes of aerobic activity most days of the week.
progression of kidney disease in patients with diabetes. Although this can help lower his BP and reduce his overall

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

 13-5
CV risk, this level of activity may not be feasible for this potential for hyperkalemia when combined with an ACE
patient, as he may be limited by the severity of his COPD. inhibitor, particularly in view of the fact that the patient

CHAPTER 13
Continued smoking avoidance. This patient who was a long- has CKD.
time smoker successfully quit smoking 3 years ago. The Doxazosin may be continued in this patient for control of his
patient should be congratulated for his successfully having symptoms of BPH. If continued, consideration should be given
quit smoking, and he should be encouraged to continue to changing the dosing schedule to QHS dosing to reduce possible
to refrain from smoking and to minimize his exposure to doxazosin-induced orthostasis/dizziness. As an alternative, the
second-hand smoke whenever possible. Smoking cessation doxazosin could be changed to tamsulosin, but it should be
results in overall CV risk reduction and may continue to noted that this medication, which is specific for receptors in
positively affect the rate of decline in the patients FEV1 the prostate, will not have an impact on BP lowering.

Hypertension
due to his COPD. If not currently enrolled in a pulmonary There is no reason to select or recommend an ARB over an
rehabilitation program, the patient should receive a referral ACE inhibitor at this time. ARBs are more expensive than
and be given encouragement to participate in the program ACE inhibitors and, although they have been shown to reduce
in order to improve his functional capacity. proteinuria and delay the progression of kidney disease, data
regarding their impact on CV risk reduction are lacking. Thus,
4.b. Outline a specific and appropriate pharmacotherapeutic reg-
an ARB should only be prescribed if the patient develops intol-
imen for this patients uncontrolled HTN, including drug(s),
erance to the ACE inhibitor, such as ACE inhibitorinduced
dose(s), dosage form(s), and schedule(s).
cough.
Drug therapy for HTN must be individualized based on the
Carvedilol should be discontinued in this patient. Nonselective
patients age, race, known pathophysiologic variables, and
-blockers should generally be avoided in this patient with
comorbid conditions. Treatment regimens should be designed
moderate obstructive lung disease, especially since there is no
not only to achieve desired BP goals (<130/80 mm Hg for this
compelling indication to select a -blocker for the patient at
patient), but also to reduce morbidity and mortality associated
this time. If a -blocker is chosen, preference should be given
with HTN.
to a 1-selective agent, such as metoprolol.
Consideration should be given to either discontinuing the
guaifenesin/pseudoephedrine preparation altogether (especially
if no longer needed for the treatment of specific cold symptoms Outcome Evaluation
in this patient) or switching the product to a preparation that 5. Based on your recommendations, what parameters should be
contains guaifenesin without pseudoephedrine. monitored after initiating this regimen and throughout the
Because this patient has Stage 2 HTN and his current BP is treatment course? At what time intervals should these param-
more than 20/10 mm Hg above his goal BP, and because he eters be monitored?
has both DM and chronic kidney disease, a minimum of two Monitor adherence to and accomplishment of lifestyle modi-
antihypertensive medications are indicated for adequate BP fications, including dietary adjustments, exercise, and weight
lowering.2,14 reduction. Because of the close interrelationship of lifestyle
Because this patient has diabetes, chronic kidney disease with modifications with HTN and CV risk, these interventions
proteinuria, LVH, and is considered to be at high risk for should be reinforced at each visit throughout the course of
experiencing a CHD-related event, an ACE inhibitor should be treatment.
added to the patients current antihypertensive regimen. A long- JNC 7 guidelines recommend that BP be monitored at least
acting agent that can be given once daily, such as lisinopril monthly until it is controlled. More frequent monitoring
5mg po once daily or ramipril 2.5 mg po once daily, should should be considered in patients with Stage 2 HTN. In this
be initiated in this patient and titrated upwards as tolerated patient, the BP should be rechecked in 24 weeks.2
in order to achieve the desired BP goal. While ACE inhibitors General laboratory monitoring for this patient should include
can cause cough as an adverse effect, the fact that this patient chemistries (specifically serum sodium, potassium, creatinine,
complains of a cough prior to the initiation of ACE inhibitor and glucose), uric acid, and a fasting lipid profile. Recheck a
therapy is not a reason to withhold ACE inhibitors. In addi- follow-up chemistry in 24 weeks, and if laboratory results are
tion, the fact that this patient has CKD with a SCr concentra- normal, rechecking follow-up chemistry once every 6 months
tion of 2.2mg/dL is also not a reason to withhold therapy with is reasonable.
ACE inhibitors; ACE inhibitors have been shown to prevent
Monitor serum potassium and BUN/SCr closely (e.g.,
the progression of kidney disease in patients with SCr concen-
ideally, approximately 1 week after initiating ACE inhibi-
tration 1.53.0 mg/dL.13
tor therapy). If SCr increases significantly (i.e., by >30%),
Hydrochlorothiazide should be continued in this patient, because discontinue the ACE inhibitor and evaluate the patient for
it is considered an appropriate first-line antihypertensive renal artery stenosis.
according to JNC 7 guidelines and, when given in combina- Monitor for the occurrence of significant adverse effects of
tion with an ACE inhibitor, the two drugs may work synergisti- drug therapy. If an ACE inhibitor and thiazide diuretic combi-
cally to lower BP in this African-American patient. The dose of nation was chosen, these adverse effects would include, but not
hydrochlorothiazide should not be increased, due to the poten- be limited to, orthostasis, headache, dizziness, lightheadedness,
tial for higher doses to cause elevations in blood glucose and sexual dysfunction, glucose intolerance, potassium imbalance,
other metabolic derangements, including possible elevations worsening kidney function, and dry cough. If the patient devel-
in serum uric acid concentration, in this patient with diabetes ops a bothersome dry cough, consider switching to an ARB.
and gout. After initiating an ACE inhibitor in this patient, also monitor
Consideration should be given to changing the triam- closely for the occurrence of angioedema, which occurs most
terene/hydrochlorothiazide combination that the patient commonly in the African-American patient population (esti-
is currently taking to hydrochlorothiazide only, due to the mated at 56% of patients). If angioedema occurs, discontinue

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

13-6
the ACE inhibitor immediately and consider whether or ACE inhibitor (e.g., lisinopril, ramipril):
not a switch to an ARB would be safe for this patient. (In a This medicine lowers BP by relaxing your blood vessels.
SECTION 2

recent meta-analysis, the risk of developing any subsequent

angioedema with ARB use following ACE inhibitorinduced This medication works together with your diuretic, allowing
angioedema was reported as 217%.15) As an alternative, a you to use lower doses of both medications and decrease the
nondihydropyridine calcium channel blocker, such as vera- chance of side effects from either drug.
pamil or diltiazem, could be considered for renal protective This type of medicine can sometimes cause a chronic dry
effect if the patient could not take either an ACE inhibitor or cough. If this occurs, please contact your heath care provider.
an ARB. (Note: In light of this patients already reduced left This is not dangerous, but it can be bothersome.
ventricular ejection fraction [45%], close monitoring for signs If you experience any swelling in your face, lips, or tongue, or
Cardiovascular Disorders

of worsening cardiac function and possible development of have breathing problems, immediately stop taking this medica-
systolic heart failure is warranted. In the event that this patient tion and go to the emergency department for immediate medi-
does eventually develop systolic dysfunction, a nondihydro- cal attention.
pyridine calcium channel blocker would then be contraindi-
If you experience a significant decrease in urinary frequency
cated.) Amlodipine and felodipine are safe for use in patients
while taking this medication, be sure to contact your provider.
with heart failure, but there are few data regarding their effi-
cacy for renal protection. Doxazosin:
This medicine treats the symptoms of BPH, or an enlarged
Patient Education prostate. It may also treat your high blood pressure.
6. Based on your recommendations, provide appropriate educa- This medicine may make you dizzy or drowsy. Avoid driving,
tion to this patient. using machines, or doing anything else that could be dangerous
if you are not alert.
Antihypertensive agents in general:
Because you report symptoms of dizziness currently after tak-
These medicines do not cure high blood pressure. You will ing this medicine in the morning, begin taking this medication
probably need to continue taking these medications on a long- at night, before you go to bed. If you continue to experience
term basis to keep your blood pressure controlled. symptoms of dizziness or lightheadedness, or if you experience
Take these medications exactly as prescribed, do not skip doses, fainting, notify your physician.
and if you do miss a dose, do not double up by taking two Notify your physician if you begin to experience pain on urina-
doses at once. tion, changes in how much or how often you urinate, or red or
Because these drugs lower your blood pressure, you may feel dark brown urine.
dizzy or lightheaded when going from lying down or sitting
to a standing position. Use caution and rise slowly from these
positions until you know how your body reacts. As your body REFERENCES
gets accustomed to these new medicines and your lower blood
pressure, this effect may diminish. 1. Salerno SM, Jackson JL, Berbano EP. Effect of oral pseudoephedrine
If dizziness is extreme or continues beyond a few days, inform on blood pressure and heart rate: a meta-analysis. Arch Intern Med
your health care provider. 2005;165:16861694.
2. Chobanian AV, Bakris GL, Black HR, et al., the National High Blood
These medications can affect different body systems in addition Pressure Education Program Coordinating Committee. Seventh report
to lowering your blood pressure; they may affect your heart rate of the Joint National Committee on Prevention, Detection, Evaluation,
and some of your blood tests. It is extremely important to keep and Treatment of High Blood Pressure. Hypertension 2003;42:
all scheduled appointments with your health care providers to 12061252.
properly monitor your progress. 3. Giles TD, Materson BJ, Cohn JN, Kostis JB. Definition and classifica-
tion of hypertension: an update. J Clin Hypertens 2009;11:611614.
Thiazide diuretic (e.g., chlorthalidone or hydrochlorothi- 4. Rosendorff C, Black HR, Cannon CP, et al. Treatment of hyperten-
azide): sion in the prevention and management of ischemic heart disease:
This medication is used to lower your blood pressure. a scientific statement from the American Heart Association Council
for High Blood Pressure Research and the Councils on Clinical
One of the ways this medicine lowers blood pressure is to cause Cardiology and Epidemiology and Prevention. Circulation 2007;115:
you to lose extra fluid through increased urination. Because of 27612788.
this, you will want to take this medication early in the day, to 5. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pres-
avoid having to get up at night to go to the bathroom. sure of reduced dietary sodium and the Dietary Approaches to Stop
You may take this medication with food, milk, or on an empty Hypertension (DASH) diet. DASH-Sodium Collaborative Research
Group. N Engl J Med 2001;344:310.
stomach.
6. Douglas JG, Bakris GL, Epstein M, et al. Management of high blood pres-
Thiazide diuretics can make you sensitive to sunlight. Be sure sure in African Americans: consensus statement of the Hypertension in
to apply a sunscreen with a sun protection factor (SPF) of at African Americans Working Group of the International Society on
least 15 before any extended exposure to sunlight. Hypertension in Blacks. Arch Intern Med 2003;163:525541.
7. ALLHAT Officers and Coordinators for the ALLHAT Collaborative
Thiazide diuretics may cause you to lose potassium. Your phy-
Research Group. Major outcomes in high-risk hypertensive patients
sician will monitor your potassium balance carefully. If you
randomized to angiotensin-converting enzyme inhibitor or cal-
experience cramping in your feet or lower extremities, this may cium channel blocker vs diuretic: the Antihypertensive and Lipid-
be a sign that your potassium has dropped. If this occurs, notify Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA
your physician. 2002;288:29812997.

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

 13-7
8. UKPDS 39. Efficacy of atenolol and captopril in reducing risk of mac- randomized to doxazosin vs chlorthalidone: the Antihypertensive and
rovascular and microvascular complications in type 2 diabetes: UKPDS Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

CHAPTER 13
39. UK Prospective Diabetes Study Group. BMJ 1998;317:713720. JAMA 2000;283:19671975.
9. Heart Outcomes Prevention Evaluation Study Investigators. Effects of 13. Hou FF, Zhang X, Xie D, et al. Efficacy and safety of benazepril
an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascu- for advanced chronic renal insufficiency. N Engl J Med 2006;354:
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10. Heart Outcomes Prevention Evaluation Study Investigators. Effects of 14. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-
ramipril on cardiovascular and microvascular outcomes in people with pressure lowering and low-dose aspirin in patients with hypertension:
diabetes mellitus: results of the HOPE study and the MICRO-HOPE principal results of the Hypertension Optimal Treatment (HOT) ran-
substudy. Lancet 2000;355:253259. domized trial. HOT Study Group. Lancet 1998;351:17551762.
11. American Diabetes Association. Treatment of hypertension in adults 15. Haymore BR, Yoon J, Mikita CP, Klote MM, DeZee KJ. Risk of angioe-

Hypertension
with diabetes. Diabetes Care 2002;25:S71S73. dema with angiotensin receptor blockers in patients with prior angioe-
12. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative dema associated with angiotensin-converting enzyme inhibitors: a
Research Group. Major cardiovascular events in hypertensive patients meta-analysis. Ann Allergy Asthma Immunol 2008;101:495499.

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.