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8 - Respiratory Disorders |
217
C 2: C O P
D
Setting:
Assisted living facility.
Subjective:
SM is a 69-year-old male who is a long-time resident of the assisted living facility. Recently, he
has been more short of breath. The staff reports that he is having trouble using his inhalers.
Past Medical History:
Parkinson disease ×10 years, COPD, and osteoarthritis.
Medications:
Carbidopa/levodopa 25/250 four times a day, tiotropium inhaler daily, albuterol inhaler four
times a day.
Allergies:
NKDA.
Social History:
Denies use of tobacco or illicit drug use; drinks alcohol on special occasions.
Family History:
Lives in assisted living facility, widowed ×5 years.
Objective:
BP 128/78, P 88 BPM, RR 20, Ht 70˝, Wt 205 lb
Physical Examination:
Well-nourished male who is slightly short of breath. Parkinsonian tremor and rigidity noted to
both upper extremities R>L.
Assessment:
SM is experiencing shortness of breath that is exacerbated by poor inhaler technique.
Plan:
1.
Stop the albuterol and tiotropium inhalers.
2. Start albuterol and ipratropium inhalation solution via nebulizer four times a day.
3. Have staff assist with daily cleaning of the nebulizer
Rationale:
It is likely that his Parkinson disease is interfering with his hand-breath coordination, resulting
in less-than-optimal delivery of his bronchodilators. Nebulizers are not dependent on hand-
breath coordination and are a better option for this patient.
Case Summary:
It is important for the clinician to determine the best device for administration of respiratory
medications. A complete assessment of the physical and mental status of the patient is
essential at baseline and periodically thereafter.
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| Fundamentals of Geriatric Pharmacotherapy
C S
Respiratory disorders have a significant impact
on the quality of life of older adults. Whether it
is a chronic condition such as asthma or COPD
or an episode of TB, the central issues remain:
accurate diagnosis, appropriate therapy, and
adequate monitoring. The diagnosis of respi-
ratory disorders in older adults is sometimes
challenging due to differences in disease
presentation, such as pneumonia and TB.
Under-diagnosis is also common in asthma.
Regardless of the condition, data evaluating
the treatment options for respiratory disorders
in older adults are sparse, particularly the frail
elderly. In a majority of the cases, the application
and adaptation of standard adult treatment will
be appropriate. However, the clinician needs to
anticipate the various problems that may occur in
older adults, including the potential for medica-
tion adverse effects, especially in those patients
with multiple medical comorbidities; drug inter-
actions in patients receiving polypharmacy; and
issues of effective medication delivery, particu-
larly inhaled medications. With appropriate
assessment, monitoring, and follow-up, respi-
ratory disorders can be effectively managed in
older adults.
S-A Q
1. How well are older adults with asthma and
COPD represented in the medical literature?
What age groups are represented? What
medical comorbidities do they have?
2.
How can mental status influence the use of
inhaled medications?
3.
What are the pros and cons of inhalers and
nebulizers?
4.
What classes of medications should be
avoided in older adults with COPD?
5.
What is the two-step tuberculin skin test,
and why is it useful in older adults?
6. What potential medication-related problems
are anticipated with the use of antitubercu-
lous drugs?
7. What parameters should be monitored with
antituberculous drugs to determine efficacy
and safety?
Clinical Pearls
• Atypical disease presentation can make it difficult for the clinician to differentiate signs
of respiratory conditions such as COPD from other conditions, such as heart failure.
Older patients may be vulnerable to receiving medications directed at symptoms without
a clear diagnosis of the underlying cause. When a drug regimen review reveals the
use of breathing treatments such as albuterol or ipratropium nebulizers for shortness
of breath in combination with medications such as furosemide for edema, a diagnostic
evaluation to confirm the root cause and initiate the appropriate evidence-based therapy
is necessary.
•
Obtaining a patient’s smoking history at any transition of care is important. The smoking
history allows the clinician to determine how ready a current smoker is for smoking ces-
sation. The history helps determine the severity of respiratory diseases and the potential
for drug/smoking interactions (e.g., theophylline).
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8 - Respiratory Disorders |
219
14. National Institute for Clinical Excellence (NICE).
National clinical guidelines for management of
chronic obstructive airway disease in primary and
secondary care. Managing stable COPD. orax.
2004;59(S1):39–130.
15.
Allen SC. Competence thresholds for use of inhalers
in people with dementia. Age Aging. 1997;26:83–6.
16.
Connolly M. Inhaler technique of elderly patients:
Comparison of metered dose inhalers and large
volume spacers. Age Aging. 1995;24(3);190–192.
17.
Jarvis S, Ind PW, Shiner RJ. Inhaled therapy in elderly
COPD patients; time for re-evaluation? Age Aging.
2007;36:213–218.
18.
Pederson S, Steense G. Fenoterol powder inhalation
technique in children; inuence of inspiratory ow
rate and breath holding. Eur Respir J. 1986;68:207–
211.
19. Allen SC, Ragab S. Ability to learn inhaler technique
in relation to cognitive scores and tests of praxis in old
age. Postgrad Med J. 2002;78:37–39.
20. Allen SC, Jain M , Regab S, et al. Acquisition and
short-term retention of inhaler techniques require
intact executive function in elderly subjects. Age Aging.
2003;32:299–302.
21. Jones V, Fernandez C, Diggory P. A comparison of
large volume spacers, breath-activated, and dry powder
inhalers in older people. Age Aging. 1999;28:418–484.
22. Dolovich M, Aherns RC, Hess DR, et al. Device
selection and outcomes with aerosol therapy: evidence-
based guidelines. Chest. 2005;127:335–371.
23. Fink JB, Rubin BK. Problems with inhaler use; a call
for improved clinician and patient education. Resp
Care. 2005;50:1360–1374.
24.
Corden ZM, Bosley CM, Ress PJ, et al. Home
nebulized therapy for patients with COPD: patient
compliance with treatment and its relation to quality
of life. Chest. 1997;112:1278–1282.
25. Vozoris NT, Fischer HD, Wang X, et al. Benzodiaz-
epine use among older adults with chronic obstructive
pulmonary disease: a population-based cohort study.
Drugs Aging. 2013;30:183-192.
26. Braman SS. Drug treatment of asthma in the elderly.
Drugs. 1996;51:415–423.
27.
Braman SS. Asthma in the elderly. Clin Geriatr Med.
2003;19:57–75.
28. Barua P, O’Mahony MS. Overcoming gaps in the
management of asthma in older patients: new insights.
Drugs Aging. 2005;22:1029–1059.
29. Restrepo RD. Use of inhaled anticholinergic agents in
obstructive airway disease. Respir Care. 2007;52:833–
851.
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1. Mannino DM, Homa DM, Akinbami LJ, et al.
Chronic obstructive pulmonary disease surveillance,
United States, 1971–2000. MMWR Surveill Summ.
2002;51:1–16.
2.
Global Initiative for Chronic Obstructive Lung
Disease. Global strategy for the diagnosis, manage-
ment and prevention of chronic obstructive pulmonary
disease. NHLBI/WHO Workshop report. http://
www.goldcopd.com/. Bethesda, MD: National Heart
Lung and Blood Institute; updated 2014.
3.
Zeleznik J. Normative aging and the respiratory
system. Clin Geriatr Med. 2003;19:1–18.
4.
Gupta P, O’Mahony MS. Potential adverse eects of
bronchodilators in the treatment of airways obstruc-
tion in older people: recommendations for prescribing.
Drugs Aging. 2008;25:415–433.
5.
Diette G, Krishnan J, Dominici F, et al. Asthma in
older patients; factors associated with hospitalization.
Arch Intern Med. 2002;162:1123–1132.
6.
Salpeter SR, Ormiston TM, Salpeter EE. Cardiovas-
cular eects of beta-agonist in patients with asthma
and COPD: a meta-analysis. Chest. 2004;125:2309–
2321.
7. Ebell M. Beta agonists may slightly increase risk
of adverse cardiac events. http://www.aafp.org/
afp/20041015/tips/1.html. Accessed February 10,
2014.
8. Calverley PMA, Anderson JA, Celli B, et al. e
TORCH investigators: salmeterol and uticasone
propionate and survival in chronic obstructive pulmo-
nary disease. N Engl J Med. 2007;356:775–789.
9. Salpeter SR, Aaron SD. Should we avoid beta-agonists
for moderate and sever chronic obstructive pulmonary
disease? Can Fam Physician. 2007;53:1290–1293.
10. Gartlehner G, Hansen RA, Carson SS, et al. Ecacy
and safety of inhaled corticosteroids in patients with
COPD; a systematic review and meta-analysis of
health outcomes. Ann Fam Med. 2006;4:253–262.
11.
Jones A, Fay JK, Burr M, et al. Inhaled corticoste-
roid eects on bone metabolism in asthma and mild
chronic obstructive pulmonary disease. Cochrane
Database of Systematic Rev. 2002;(1):CD003537.
12.
Suissa S, McGhan R, Niewoehner D, et al. Inhaled
corticosteroids in chronic obstructive pulmonary
disease. Proc Am orac Sco. 2007;4:535–542.
13. Leone FT, Fish JE, Szefer SJ, et al. Systematic review
of the evidence regarding the potential complica-
tions of inhaled corticosteroid use in asthma. Chest.
2003;124:2329–2340.
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30. Run RE, Wol RK, Dolovich MB, et al. Aerosol
therapy with Sch 1000: short-term mucociliary clear-
ance in normal subjects. Chest. 1988;93:739–741.
31.
Singh S, Loke YK, Furberg CD. Inhaled anticho-
linergic and risk of major cardiovascular events in
patients with chronic obstructive pulmonary disease.
JAMA. 2008;300:1439–1450.
32.
NAEPP Working Group Report. Considerations
for diagnosing and managing asthma in the elderly.
National Heart, Lung, and Blood Institute, NIH
publication no. 96–3662; 1996.
33.
Zevallos M, Justman JE. Tuberculosis in the elderly.
Clin Geriatr Med. 2003;121–138.
34.
Rajagopalan S, Yoshikawa TT. Tuberculosis in long-
term-care facilities. Infect Control Hosp Epidemiol.
2000;21:611–615.
35.
rupp L, Bradley S, Smith P, et al. Tuberculosis
prevention and control in long-term-care facili-
ties for older adults. Infect Control Hosp Epidemiol.
2004;25(12):1097–1108.
36. American oracic Society. American oracic Society/
Centers for Disease Control and Prevention/Infectious
Diseases Society of America: treatment of tuberculosis.
Am J Resp Crit Care Med. 2003;167:603–662.
37. Van den Brande P. Revised guidelines for the diagnosis
and control of tuberculosis impact on management in
the elderly. Drugs Aging. 2005;22(8):663–689.
38.
Gomez-Reino JJ, Carmona L, Rodriquez V, et
al. Treatment of rheumatoid arthritis with tumor
necrosis factors inhibitors may predispose to signi-
cant increase in tuberculosis risk. Arthritis Rheum.
2003;48(8):2122–2127.
39.
Keane J, Gershon S, Wise RP, et al. Tuberculosis
associated with iniximab, a tumor necrosis factor
α-neutralizing agent. N Engl J Med. 2001;345:1098–
1104.
40.
Gardam MA, Keystone EC, Menzies R, et al. Anti-
tumour necrosis factor agents and tuberculosis risk:
mechanisms of action and clinical management. Lancet
Infect Dis. 2003;3:148–155.
41.
Keane J, Gershon SK, Braun MM. Tuberculosis
and treatment with iniximab. N Engl J Med.
2002;346:625–626.
42.
Ormerod LP, Milburn HJ, Gillespie S, et al. BTS
recommendations for assessing risk and for managing
Mycobacterium tuberculosis infection and disease in
patients due to start anti-TNF-α treatment. orax.
2005;60:800–805.
43. Kopano DE, Snider DE, Caras GJ. Isoniazid-related
hepatitis: a U.S. Public Health Service cooperative
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1001.
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9
R U
D
ERICA L. ESTUS, NICOLE J. ASAL, and
NORMA J. OWENS
L O
1. Evaluate the changes in renal function that occur with age and determine how these changes result in an
increased risk for older patients with chronic illnesses.
2.
In a patient with chronic kidney disease (CKD) and diabetes, develop a treatment plan to help preserve renal
function.
3.
Assess a pharmacotherapy regimen for recent onset drug-induced incontinence in an older person.
4. Distinguish between older men with benign prostatic hyperplasia (BPH) who would benefit from single-agent
versus combined therapy with alpha reductase inhibition and alpha blockade.
K T D
ARGININE VASOPRESSIN (AVP): A hormone secreted from the posterior pituitary gland that helps to retain
water by increasing water absorption in the collecting ducts of the nephron. Vasopressin is also frequently
referred to as anti-diuretic hormone (ADH).
DETRUSOR MUSCLE: The muscular coat of the urinary bladder that contracts to empty urine.
KEGEL EXERCISES: Pelvic muscle exercises intended to strengthen the muscles of the pelvic floor to improve
urethral and rectal sphincter function.
MICTURITION: Urination or voiding.
NEUROGENIC BLADDER: Dysfunction of the bladder caused by neurologic damage. Potential causes include
brain or spinal cord injuries, diabetes, acute infection, or genetic nerve complications.
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| Fundamentals of Geriatric Pharmacotherapy
R D
Changes in the Kidney with Age
T
he aging kidney gradually develops
anatomic and physiologic changes that
are usually not perceptible until an illness alters
the body’s compensatory balance. The vascular
system changes in the aging kidney, leading to
hypertrophy of arteries, with the most significant
impact occurring in the cortex of the kidney.
1
Most of the size changes in the aging kidney
occur in the cortex with a loss of about 35% of the
number of glomeruli as well as a decrease in the
surface area and a thickening of the basement
membrane of the glomeruli. Glomerular atrophy
in the aging kidney results in a decrease of the
glomerular filtration rate (GFR) of about 0.75–1.0
mL/min/1.73 m
2
each year beginning by about
40 years of age.
2
These changes in the structure
and function of the kidney in an older person
also affect his or her ability to maintain a normal
fluid and electrolyte balance, especially when
challenged with drugs and illness. Older people
experience a delay in compensation to a very low
sodium diet as well as an exaggerated increase
in blood pressure in response to an increase
in sodium intake. Older people also have a
decreased response to the diuretic and natriuretic
effects of loop diuretics. The regulation of water
balance changes with age due to the decreased
ability of the aging kidney to concentrate, as well
as a decreased ability to excrete a water load.
Older people increase their body proportion of fat
and lose a similar proportion of water, which leads
to greater changes in solutes (such as sodium)
and in the clinical consequence of dehydration or
fluid overload. These changes in kidney size and
physiology result in significant alterations to kidney
function with age, resulting in a decrease in GFR
and a decreased ability to respond to changes in
fluid and electrolyte balance.
1,2
Epidemiology and Risk Factors of
Chronic Kidney Disease
CKD is a common and important disorder in
older persons and is associated with serious
adverse outcomes such as kidney failure, cardio-
vascular disease, anemia, functional decline,
and death. In 2002, The National Kidney Foun-
dation defined CKD as the presence of protein
(albumin) in the urine for at least 3 months, or an
estimated glomerular filtration rate (GFR) of <60
mL/min/1.73 m
2
. This group also created a five-
stage system to categorize the severity of renal
dysfunction.
3
A national data system collects
and analyzes information about chronic and
end-stage kidney disease, and this information
shows that the prevalence of CKD is estimated to
be between 14% and 18% of the general popula-
tion and to be more than 35% in people who are
over the age of 60 years.
4
In addition, of those
individuals who have progressed to end-stage
renal disease, 20% are between the ages of 65
and 74 and 16% are 75 years of age or older.
4
As the prevalence of kidney disease continues to
be collected by the National Kidney Foundation,
rates of end-stage renal disease have stabilized
for middle-aged individuals but have increased
for those in the older age groups.
4
The National Kidney Foundation recom-
mends evaluation of patients on the basis of their
risk factors, initiation factors, and progression
factors.
3
One of the most important risk factors
that contributes to the development of CKD is
advanced age. Initiation factors are diseases
that cause renal damage and include diabetes
and hypertension, two diseases that are strongly
associated with age. Progression factors accel-
erate the damage to the kidney and include
hyperglycemia, hypertension, and proteinuria.
Other progression factors that can be modified
include smoking, hyperlipidemia, and obesity.
Progression factors occur commonly in older
individuals and are potentially modifiable by
medication therapy management.
3
Disease Progression in the Elderly
The natural course or progression of CKD to
end-stage renal disease is different between
younger and older people. CKD progresses
in association with factors such as proteinuria,
hypertension, diabetes, smoking cigarettes,
hyperlipidemia, and obesity. The effect of age
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9 - Renal and Urologic Disorders |
223
on the progression of CKD was evaluated in
a large cohort of elderly veterans, with kidney
disease showing an expected inverse relation-
ship between estimated GFR and rates of end-
stage renal disease and death.
5
In the older
men with initial moderate kidney disease, the
percentage who experienced a further decrease
in GFR each year increased with age. For men
with moderately severe disease, the percentage
of men who further decreased their GFR was
less with age. The older men with more severe
kidney disease were more likely to die than prog-
ress to end-stage renal disease.
5
This research
suggests that older age is a strong modifier of
disease course, with more rapid progression
from moderate to moderately severe disease
and less progression of moderately severe
disease to end-stage disease. This difference
in progression may be due to greater disease
comorbidity in older men that leads to death,
to a stabilization of moderate kidney disease in
older persons, or perhaps to a difference in the
underlying cause of kidney dysfunction in the
elderly.
Diagnosis of Chronic Kidney
Disease in the Elderly
Renal function, as defined by GFR, declines
with age by approximately 0.75–1.0 mL/
min/1.73 m
2
each year beginning by about 40
years of age.
2
Identification of CKD in older
persons is important for several reasons. Indi-
viduals with an estimated GFR of ≤60 mL/
min need to have adjustments of the doses
of renally eliminated medications. Preven-
tion of end-stage renal disease can become
a focus of medication therapy management if
CKD is documented. Frequently, CKD occurs
in older patients with diabetes and or hyper-
tension, which highlights the importance of
achievement of goal treatment values in the
management of these two chronic diseases.
Pharmacists who participate in medication
therapy management are uniquely situated
to help older people achieve goal treatment
values for chronic diseases, which can slow
progression of CKD.
Estimation of Renal Function
There is some controversy about the preferred
method for estimation of GFR in older people.
To estimate GFR, the serum concentration of
an endogenous filtration marker, such as creati-
nine, is measured and the clearance of creati-
nine is computed with a mathematical formula.
The mathematical equations have been devel-
oped from patient studies that use regres-
sion formulas to correlate the serum level of
creatinine to the measured GFR. Often, patient
factors are included in the formula such as age,
body weight, and sex to improve the correla-
tion between measured and estimated GFR.
6,7
Chapter 3 discusses the specific formulae
employed for estimating GFR and the pros and
cons of each, but, in general, it is the Cockcroft-
Gault equation that is used to estimate renal
function for the purposes of determining the
renal dose adjustment of medications.
8
The four-
variable Modification of Diet in Renal Disease
(MDRD) equation, which adjusts for age, sex,
creatinine, and race, yields an estimate of GFR
and is used to stage patients with CKD.
7
KEY POINT:
Estimation of GFR through
the use of the MDRD and estimation of
creatinine clearance through the Cockcroft-
Gault equation should both be performed for
older patients as a part of a comprehensive
medical and pharmaceutical assessment.
Treatment of Chronic Kidney
Disease
The goals of treatment for all ages of people with
CKD are to delay or prevent the progression to
more severe stages of disease, including end-
stage renal disease, and to prevent the occur-
rence of complications related to CKD. However,
because older patients generally have multiple
chronic diseases and are more likely to die with
kidney disease rather than from kidney disease
than younger individuals, interventions should
be tailored to meet the patient’s lifestyle prefer-
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224
| Fundamentals of Geriatric Pharmacotherapy
ences, to maintain optimal physical and mental
functioning, and to maintain quality of life. Inter-
ventions include nonpharmacologic (dietary
protein restriction) and pharmacologic. Drug
therapy recommendations may be different for
those with diabetic CKD than for those with CKD
because of other causes.
Dietary restriction of protein in amounts
up to 0.6 g/kg per day is recommended by the
National Kidney Foundation for individuals with
a GFR <25/mL/min/1.73 m
2
. The literature that
supports this recommendation is inconsistent
and suggests that a reduction in rate of decline
of the GFR is small at 0.5 mL/min per year.
Dietary protein restriction has not been specifi-
cally evaluated for efficacy or safety in older
people. Given that the benefits are small and the
risks for malnutrition and changes in quality of
life with protein restriction are significant, intake
levels of up to 0.75 g/kg/day are reasonable for
older people.
9
Pharmacologic erapy
To prevent progression of CKD, drug therapy is
specifically targeted toward control of the under-
lying disease that initiated the kidney disease,
generally either diabetes and/or hypertension.
Diabetes and hypertension both initiate CKD
as well as contribute to disease progression.
A comprehensive approach to the medical
management of older patients with diabetes,
hypertension, and renal diseases is vital.
Glycemic Control to Prevent Chronic
Kidney Disease in an Older Patient with
Diabetes
In older patients with type 2 diabetes, inten-
sive therapy that achieves goal HbA
1c
values
of ≤7.0% substantially reduces albuminuria,
10-12
but with the risk of more frequent hypoglycemic
reactions.
13,14
Clinical practice guidelines have
summarized the strong evidence that exists
between HbA
1c
and the emergence of albumin-
uria, although the evidence that links glycemic
improvement to a prevention of decline of the GFR
is weaker.
15
Two important publications highlight
both the risks and efficacy of intensive therapy
in older patients. More than 11,000 patients with
type 2 diabetes, who were 66 ± 6 years of age
(mean ± standard deviation) were randomized
to receive intensive therapy to achieve HbA
1c
values ≤6.5% or to standard therapy where the
HbA
1c
values were generally between 7% and
8%.
13
This cohort represents the younger end of
the age range referred to as elderly. Frail indi-
viduals of very advanced age or with multiple
comorbidities, disability, or dementia were not
well represented. All patients were treated with
multiple oral agents that most often included a
sulfonylurea with metformin. Patients in the inten-
sive arm of the study received a modified formu-
lation of gliclazide and were more likely to be
treated with insulin than the standard treatment
group (40% versus 24%, respectively). After
five years of treatment, patients in the intensive
arm of this study had a reduction by one-fifth of
new or worsening nephropathy. Rates of hypo-
glycemia were higher in the intensive versus
standard treated patients (2.7% versus 1.5%,
respectively).
13
For older patients with type 2
diabetes, the risk of hypoglycemia was even
higher, with an even more aggressive glycemic
goal regimen (HbA
1c
<6%) versus standard
management (HbA
1c
between 7% and 7.9%),
resulting in significantly more deaths in the
aggressive treatment arm.
14
Older patients are more likely to experi-
ence hypoglycemia, which may be due to their
underlying renal disease with a decreased ability
to eliminate both insulin and oral antidiabetic
drugs. Furthermore, patients with kidney disease
have decreased renal gluconeogenesis, which
reduces an important compensatory response
to counter hypoglycemia.
15,16
Due to these limi-
tations, glipizide is the preferred sulfonylurea
for use in older patients with kidney disease
because the drug is metabolized to inactive
compounds.
17
Metformin is recommended as
an effective and preferred beginning therapy for
patients with type 2 diabetes due to its broad
range of benefits and lack of hypoglycemia.
18
Use of metformin may be limited in older people
due to prescribing guidelines that recommend
individuals need adequate renal function to clear
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9 - Renal and Urologic Disorders |
225
this drug and prevent lactic acidosis.
In addition to recommendations to avoid
metformin with serum creatinine >1.4 mg/dL in
women and 1.5 mg/dL in men, creatinine clear-
ance should also be considered. Official product
information recommends a minimum creatinine
clearance of >60 mL/min, although there are
some data that suggest metformin can be used
in individuals with creatinine clearance as low
as 30 mL/min.
18,19
Although age >80 years is
not an absolute contraindication for use, caution
is required due to the increasing likelihood of
insufficient renal function with advancing age.
Other oral agents that may be preferable for use
in patients with impaired renal function include
repaglinide, a nonsulfonylurea secretogogue.
This class of oral agents is shorter acting and
lowers postprandial glucose more than fasting
glucose concentrations, which results in less
hypoglycemia. Pioglitazone may also be the
preferred thiazolidinedione for use in the elderly
with renal insufficiency, although concerns about
weight gain and fluid retention with this class
of medications warrants careful monitoring.
15-17
Based on the evidence that tight glycemic control
is associated with hypoglycemia that doesn’t
improve overall health outcomes for people
with comorbidities or limited life expectancy, the
2012 guideline updates recommend an HbA
1c
concentration in the 7% to 8% range.
15,17
Control of Cardiovascular Risk Factors
in Older Patients with Chronic Kidney
Disease
The Eighth Joint National Committee (JNC
8) guidelines suggest the appropriate blood
pressure goal for people with CKD is <140/90
mmHg.
16
Specific drug recommendations from
the JNC 8 guidelines are reviewed in Chapter
7. In general, the use of either an angiotensin-
converting enzyme (ACE) inhibitor or angio-
tensin receptor blocker (ARB) as first-line
therapy to treat hypertension or proteinuria in
patients with CKD is advised. Although the
long-term outcomes of this type of drug therapy
intervention is less clear in very frail individuals,
the prevention of further renal compromise is
important to preventing future morbidity among
younger groups of the geriatric population.
There are generally no significant age-related
pharmacokinetic or pharmacodynamic differ-
ences between older and younger patients in the
use of ACE inhibitors or ARBs.
20
To avoid renal toxicity in patients who may
be volume depleted from diuretics or for those
also receiving nonsteroidal anti-inflammatory
drugs, ACE inhibitors and ARBs should be
started at low dosages and slowly titrated to
effect. For those at high risk of renal toxicity, the
diuretic or nonsteroidal anti-inflammatory agent
can be held for 2–3 days to prevent an acute
decline in renal function related to any under-
lying dehydration.
20
ARBs may cause fewer side
effects, such as cough and angioedema, and
can be used as alternatives to ACE inhibitors.
The combined use of ACE inhibitors with ARBs
is sometimes recommended to prevent renal
angiotensin escape, thus providing for a greater
effect on blood pressure control and albumin-
uria.
20
However, elderly individuals with impaired
renal function are at increased risk for hyperka-
lemia with these medications, and for this reason
ACE inhibitors are often cited among the classes
of medications with a high prevalence of adverse
effects in the long-term care setting. Increased
monitoring of serum potassium may be required
for individuals receiving medications that alter
serum potassium, such as potassium supple-
ments, potassium-sparing diuretics, ACE inhibi-
tors, and ARBs.
Hyperlipidemia increases albuminuria,
which accelerates the progression of CKD. In
addition, death from atherosclerotic causes
is high in patients with CKD. The 2012 Kidney
Disease Outcomes Quality Initiative (KDOQI)
updates recommend treatment of patients with
CKD with an HMG-CoA reductase inhibitor
(statin).
15
However, the 2013 American College
of Cardiology/American Heart Association Blood
Cholesterol Guidelines do not specifically iden-
tify patients with CKD for treatment with statins.
The guidelines do recommend moderate-inten-
sity statin therapy in patients with CKD who also
have clinical atherosclerotic cardiovascular
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| Fundamentals of Geriatric Pharmacotherapy
disease or type 2 diabetes.
21
There is very little
information available about age-related changes
in either the pharmacokinetics or pharmaco-
dynamics with the use of statins.
20
Almost all
clinical trials with statins for the prevention of
adverse health consequences from hyperlip-
idemia have included at least some older indi-
viduals, with results supporting treatment.
17
This
research includes individuals who are in their
60s and 70s but generally does not evaluate
individuals in their 80s and 90s. Because the
risk of statin-associated myopathy is higher in
older patients receiving moderate to high doses
of statins, caution is advised when using higher
doses in older people. Even though there are
differences in the two guideline recommenda-
tions with respect to the use of statins in patients
with CKD, it is unlikely to yield differences in
treatment because almost all older patients with
CKD have comorbidities such as diabetes and
or atherosclerotic cardiovascular disease.
The management of other complications
related to CKD, such as anemia and bone
disease, is especially important in older people.
As the GFR decreases, erythropoietin secre-
tion diminishes, causing anemia of CKD. This
complication and its treatment are covered in
Chapter 16. Phosphate excretion decreases
with worsening renal disease, leading to an
increase in serum phosphorus, a decrease in
serum calcium, a decrease in vitamin D activa-
tion, hyperparathyroidism, and an increase in
calcium resorption from bone.
22
These adverse
effects on bone add further risks of bone
disease and fracture to the older person who
may already have coexisting osteoporosis. In
this setting, serum phosphorus, calcium, and
vitamin D
2
concentrations should be measured
so that appropriate supplementation can occur.
Phosphate binders are needed as the first step
in controlling this problem, although an ideal
formulation or regimen does not exist.
22
Calcium-
containing products are often used to bind phos-
phate and can be taken with meals in doses
that are often associated with side effects such
as nausea, vomiting, and constipation. These
regimens may also add to the pill burden in an
older patient’s medication regimen. Sevelamer
is a newer noncalcium-based agent that binds
to phosphorus in exchange for chloride and can
be used as sole therapy or in combination with
other phosphate binders. Because sevelamer is
a polymer that is not absorbed, older patients
should be carefully monitored for constipation to
prevent bowel obstruction.
22
Fluid and Electrolyte Disorders
The renal system has a remarkable capacity to
adjust to changes in our body from the envi-
ronment and disease processes. However, the
kidney’s ability to adapt and change decreases
with age, making older people more suscep-
tible to fluid and electrolyte imbalance. In addi-
tion, older people are much more likely to have
underlying diseases and drug treatments that
place them at further risk for fluid and electro-
lyte disorders. Due to the changes in the kidney
mentioned at the beginning of this chapter, older
people have a reduced ability to concentrate
their urine as well as a lessened ability to excrete
an increased water load. Vasopressin secretion
and thirst are the regulators of water balance.
Vasopressin levels tend to increase with age as
a result of a loss of sensitivity to this hormone by
the kidney. Also, older people have a decreased
thirst sensation and are more likely to have cogni-
tive impairments that, when coupled with the
decreased function of the kidney, place them at
great risk for dehydration.
1
In the elderly, the net
effect of vasopressin and thirst changes leads
to a loss in ability to compensate for changes in
fluid balance.
Dehydration is a common problem in
nursing home residents and is a frequent cause
for admission to the hospital. In the community,
the elderly are at great risk for dehydration and
death, particularly during heat waves in the
summer. Because of the loss of total body water
with aging, relatively mild dehydration can have
significant effects on serum electrolytes. The
recognition of this condition is more problem-
atic in the elderly due to diminished skin turgor
from ageing effects on the skin, and dry mucus
membranes can be present in those who breathe
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