Evaluating medications and adverse drug reactions in older ... - CECity

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Evaluating medications and adverse drug reactions in older ... - CECity

Evaluating medications

and adverse drug reactions

in older patients

Joshua S. Coren, DO, MBA

Kevin J. Overbeck, DO

Frank A. Filipetto, DO

As the U.S. population

ages there will be

substantial increases

in the number of older adults

who have type 2 diabetes mellitus.

Older adults with diabetes often

will be taking many other medications.

Health care professionals who coordinate

care for older patients with diabetes must

not only be able to treat hyperglycemia to target

individualized goals of care but also anticipate and

recognize the adverse effects of various pharmacologic

agents prescribed.

May 2011 DOs Against DIABETES

AOA Health Watch

3


Prescriber knowledge about drug

pharmacodynamics and pharmacokinetics

and their interaction with normally

aging physiology is critical in treating

the elderly patient with diabetes.

This knowledge is needed to minimize

and even avoid the potentially adverse

effects of hypoglycemia and the side

effects associated with polypharmacy.

When medications become necessary

to the management of diabetes in an

older patient, informed practitioners can

correctly and safely write a prescription

for the proper drug, dose and frequency.

Pharmacodynamics

When evaluating the pharmacodynamic

effects of a drug on a body, the patient’s

age, comorbid conditions and concurrent

medications should be considered. 1

An older patient may exhibit alterations

in receptor affinity or number and

signal transduction mechanisms,

and impairment of cellular response

in affected organs that influence

the pharmacodynamics of a particular

medication. 2,3

Pharmacodynamic effects commonly

encountered with regard to neurologic

and cardiac functioning via the

autonomic and central nervous system

also play a role in pharmacotherapy for

diabetes. Drug sensitivity may increase

in older patients when the cellular

response to a given pharmaceutical

concentration is enhanced. 4

Physicians must realize that enhanced

concentration of some medications,

such as the sulfonylureas, can increase

the incidence of hypoglycemia in older

patients more than in younger patients. 5

Evaluating each diabetic medication

and its respective pharmacodynamic

properties is imperative to reduce

the risk of these potential effects.

Pharmacokinetics

Pharmacokinetics involves the effect

of body on a drug during the course of

travel from absorption, bioavailability,

distribution and metabolism through

excretion. 6 Many classes of diabetic

medications are taken orally and

absorbed via the gastrointestinal tract.

A net neutral absorption effect

of decreased intestinal motility is likely

in the older patient, which increases

the time for drug absorption in the

otherwise normal gastrointestinal tract

that may be offset by the patient’s

increasing pH level. 7-9 With normal

aging, there is a decrease in lean body

mass, water volume and organ blood

flow, with a concomitant increase in

adipose tissue, making it imperative

that the practitioner choose the lowest

possible effective dose for the patient.

Renal and hepatic elimination of

diabetic medications is certainly a main

concern of providers caring for older

inpatient and outpatient populations.

Some of the most common diseaseinduced

changes can affect both liver

and kidney function, further leading

to varying pharmacokinetics and

drug elimination. These issues make

treating the older adult with diabetes

even more challenging.

Adverse drug reactions

The most common and one of the most

devastating side effects of pharmacologic

treatment of older patients is hypoglycemia.

The risk of severe or fatal hypoglycemia

exponentially increases with age. 10

The landmark trial Action to Control

Cardiovascular Risk in Diabetes, or

ACCORD, was discontinued early when

interim results indicated a statistically

significant increase in mortality in

patients who received intensive therapy

with the goal of achieving a glycated

hemoglobin level of 6% or less. Further

analysis of data from this trial showed

that individuals in this group used more

medication and had more hypoglycemic

events, greater weight gain and greater

fluid retention than individuals in the

group that received standard therapy

with the goal of a glycated hemoglobin

level of 7% to 7.9%. 11

Although the Action in Diabetes

and Vascular Disease: Preterax and

Diamicron Modified Release Controlled

Evaluation, or ADVANCE trial, which

similarly compared intensive blood sugar

control to standard therapy, did not

show a difference in mortality between

the two groups, it did demonstrate an

increase in the number of hypoglycemic

events and hospitalization in those who

were more intensively treated. 12 In light

of these findings, the American Diabetes

Association has recommended that goals

be individualized, with more flexible

goals for older adults, those with

advanced disease and complications

or those with limited life expectancy. 13

Older patients also may experience

delayed psychomotor responses as

a result of interventions designed

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AOA Health Watch

DOs Against DIABETES May 2011


to correct hypoglycemia. 14 Glucagon,

one of the main counter-regulatory

responses to hypoglycemia, is impaired

in older people and, to a greater

extent, older patients with diabetes. 15

Altered psychomotor and impaired

counter-regulatory responses must

be balanced with the functional and

cognitive status of the individual.

In addition to being aware of and

recognizing hypoglycemia, patients

must be able to access food or drink

to reverse this iatrogenic condition.

Hypoglycemia manifests through

an easily recognizable adrenergic

constellation of symptoms, most notably

tremor, sweats or weakness. However,

older patients commonly demonstrate

a primarily neuroglycopenic syndrome

(i.e., confusion, delirium, dizziness and

falls) that can be misdiagnosed as a

neurologic event such as a transient

ischemic attack or syncope.

Listed below are some common

classes of medications prescribed

for diabetes. Although this is not a

comprehensive list of medications

and corresponding adverse events,

notes are provided on the potential

for adverse reactions in this population.

Clear provider instructions and patient

(or caregiver) comprehension are

essential to ensure directed drug

dosing, timing and administration.

Commonly prescribed

medications

Thiazolidinediones

Adverse events associated with the

thiazolidinediones are weight gain,

edema, macular edema, congestive

heart failure, increased bone fracture

risk and, when combined with other

diabetic medications, hypoglycemia. 16

Of notable mention are several studies

that suggest the potential for adverse

cardiovascular events with rosiglitazone

and potential for benefits in cardiovascular

risk reduction from pioglitazone. 17-19

Further studies are needed regarding

these events and how they affect

the older population with diabetes.

Ongoing concerns about fluid retention

limit the utility of these studies for

older patients with diabetes.

Biguanide

Patients will commonly experience

gastrointestinal side effects that tend

to improve after the first few weeks of

treatment with metformin. Metformin

should not be used in individuals older

than age 80 until renal function has

been established. Lactic acidosis is

a potential side effect of metformin,

yet evidence is scant that it will

occur with contraindications to

metformin. 20,21 The biguanide class

is also contraindicated in patients

with renal disease, renal dysfunction

or abnormal creatinine clearance rates.

Sulfonylureas

As previously mentioned, hypoglycemia

is a notable adverse event that can

occur with the sulfonylurea class of

drugs. There are conflicting data on

whether the sulfonylurea class increases

the risk of cardiovascular events, and

further research is needed. 22-24 Older

patients should be instructed about the

potential for weight gain as more insulin

is produced and glucose is utilized.

Meglitinides

Weight gain is a common feature of

this class that includes the medications

repaglinide and nateglinide. Although

hypoglycemia is a possible side effect,

mealtime dosing of meglitinides enables

older patients to be flexible with their

dosing schedule. Repaglinide may also

be a good choice for an older patient or

a patient with renal disease, as 90% of

the drug can be recovered in the feces. 25

Insulin therapy

Insulin is often an underutilized

therapeutic modality in the older

patient with diabetes because of the

practitioner’s, patient’s or family’s

concerns about administration and

the risk of hypoglycemia. 26 Weight

gain is another common adverse effect

of insulin products. Patients should be

appropriately educated on the proper

administration, dosing and effects

of the various insulin products.

Visual and cognitive acuity

should be assessed prior to initiating

and tailoring products to ensure

that patients can easily administer

the amount of insulin prescribed.

Specifically, the use of insulin pens

can greatly assist older adults who

may have issues with vision or dexterity.

In some of the pens the correct dose

can be achieved even with clicks of

the pen, ensuring more accurate dosing.

With the advent of long-acting, oncedaily-administered

insulin formulations,

capable and willing caregivers can

often assist the older individual

with this pharmacologic intervention.

May 2011

DOs Against DIABETES

AOA Health Watch

5


Dipeptidyl Peptidase-4 Inhibitors

Sitagliptin, a dipeptidyl peptidase-4

(DPP-4) inhibitor, has a favorable

safety profile, and a low incidence

of hypoglycemia. Nausea generally

resolves with dosing strategies during

the introduction of the medication. 27

Sitagliptin is being investigated to

determine whether it is linked to acute

pancreatitis. 28,29 Abdominal pain and

substantially decreased appetite should

be cause to discontinue this medication.

Saxagliptin has a similar adverse effect

profile but is associated with a decrease

in the absolute lymphocyte count (this

was not observed at the 2.5 mg dose). 30

Although the clinical importance of

this laboratory finding has not been

firmly established, saxagliptin has been

associated with an increased number

of upper respiratory infections,

as well as urinary tract infections. 31

Repeated infections should prompt

a review of saxagliptin’s clinical utility

in the individual’s case. Despite an

increased financial burden for the

elderly, DPP-4 inhibitors may be

particularly useful in older adults,

since they exhibit few drug-to-drug

interactions. In addition, these

medications can be used in adults

with all stages of renal disease,

including end-stage renal disease

(but dosage adjustment is needed).

Incretin mimetics

Exenatide has a favorable safety

profile, with adverse events of

dizziness, headache and gastrointestinal

discomfort. 27 Incretin mimetics is

being investigated to determine whether

it is linked to acute pancreatitis and

thyroid cancer. 28, 29, 32 Liraglutide

has a similar safety concern but carries

the benefit of once daily dosing

administered in a pre-filled pen.

Since weight loss can be substantial in

patients using this medication, the role

of incretin mimetics is limited in the

vulnerable or frail elderly population. 33

Polypharmacy

The administration of multiple

pharmaceutical products in concert

(known as polypharmacy) may potentiate

or decrease the effects of common

diabetes medications in the older

population. Such patients commonly

have other systemic, related chronic

conditions; the physician must recognize

the variety of medications the patient

may be taking and the potential

interactions among these medications.

In one study of 18,968 patients with

diabetes, at least 16% were dispensed

a medicine that is associated with

adverse interactions, and 22.7% were

dispensed at least one potentially

inappropriate medicine. 34

Every six to 12 months, physicians

should request that their older patients

bring their medications with them to their

appointments as an audit for usage and

also as an educational opportunity. This

“brown bag” medication review is one

method to avert potential polypharmacy. 35

Physicians should also strive to partner

with family members who are often

caregivers for these patients.

Final notes

As aging is a risk factor for chronic

care conditions such as diabetes,

physicians are faced with a growing

population of older patients with this

disorder. Ensuring that patients are

educated on both their medications

and potential adverse events is a

necessity in every care plan to limit

potential treatment complications.

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AOA Health Watch

DOs Against DIABETES May 2011


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Joshua S. Coren, DO, MBA, is the acting chair and associate professor of the Department

of Family Medicine at the University of Medicine and Dentistry of New Jersey School of

Osteopathic Medicine in Stratford, New Jersey. He can be reached at corenjo@umdnj.edu.

Kevin J. Overbeck, DO, is assistant professor of family medicine and works as a geriatric

educator and clinician with the New Jersey Institute for Successful Aging at the University of

Medicine and Dentistry of New Jersey School of Osteopathic Medicine in Stratford, New Jersey.

Frank A. Filipetto, DO, is associate professor of the Department of Family Medicine at

the University of Medicine and Dentistry of New Jersey School of Osteopathic Medicine

in Stratford, New Jersey.

May 2011 DOs Against DIABETES AOA Health Watch 7

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