module 4 medication therapy problems 2012

7/31/2019 Module 4 Medication Therapy Problems 2012

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Module 04: Medication Therapy Problems

Current Content Expert

Kevin W. Chamberlin, PharmDAssistant Clinical ProfessorUniversity of Connecticut School of Pharmacy&UConn Center on Aging

Legacy Content Expert

H.E. Davidson, PharmD, MPHPartner, and Assistant Professor of Internal Medicine

Insight Therapeutics, and Eastern Virginia Medical School, Norfolk, VA

Course Objectives:

At the conclusion of this application based activity, the participant will beable to:

Develop the primary responsibilities of the consulting pharmacist throughidentifying, prioritizing, resolving and preventing medication therapy

problems.

Develop strategies for determining if a given drug is appropriate for ageriatric patient.

Examine the major types of medication problems that can occur based onthe administration of drug therapy.

Examine the major types of medication problems that can occur based on

the patients response to therapy.


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04.01.01 Introduction to Medication Therapy Problems

Medication Therapy Problem: any undesirable event experienced by the patient

that is thought to involve drug therapy and that actually or potentially interfereswith a desired patient outcome (Strand LM, Morley PC, Cipolle RJ. Drug-relatedproblems: their structure and function. DICP 1990; 24:1093-7).

A medication therapy problem is any undesirable event experienced by thepatient that is thought to involve drug therapy, and that actually or potentiallyinterferes with a desired patient outcome. Medication therapy problems arecentral to the practice of pharmaceutical care.

Not only are such problems costly in terms of wasted resources, they alsoprevent patients from experiencing the benefits of appropriate therapy, delayingrecovery and compromising health. For these reasons, it is important that theconsulting pharmacist not only understands the causes of medication therapyproblems, but also assumes responsibility for identifying, resolving when theyoccur and preventing such problems in the future.

The elderly are at higher risk for medication therapy problems because:

A. The pharmacists that treat such patients have less training

B. There is wide individual variation in the rate of age-related changes thataffect pharmacology

C. They tend to substitute other drugs for those prescribed in the therapeuticregimen

D. There is little research to guide decisions in geriatric pharmacology

ANSWER: B


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04.01.02 Incidence of Medication Therapy Problems

Percentage of patients who experience medication therapy problems


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Nursing facility elderly residents with at least 4 risk factors for medicationtherapy problems: 23.8%

Not surprisingly, the most frequently encountered drug therapy problems arethose involving the most frequently seen patients and most frequently usedmedications. According to data collected for the Minnesota Pharmaceutical CareProject, drug therapy problems were identified in 37% of the nearly 1000 patientsreceiving pharmaceutical care in the study. Almost 15% had multiple medicationtherapy problems at some time during their care.

A study by Fouts, et al., found that 23.8% of long-term care facility residents hadfour or more risk factors for medication therapy problems.

04.01.03 Risk Factors for Medication Therapy Problems in the Elderly

Specific Medications Prevalence (%)

digoxin 17.1

warfarin 6.0

lithium 2.4

Classes of Medications: Prevalence (%)

anticholinergics 36.5

narcotic analgesics 19.4

benzodiazepines with half-life 10-24 h 11.5

antipsychotics 11.1

anticonvulsants 10.7

benzodiazepines with half-life > 24 h 4.0


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sedative/hypnotics 0.8

Patient Characteristics: Prevalence (%)

no. of active chronic medical diagnoses (> 6) 73

renal function < 50ml/min 70.2

low body weight 42.9

prior adverse drug reactions 42.1

age > 85 40.5

no. of doses of medications/day (> 12) 36.9

9 or more medications 24.2

Source: Fouts, M., Hanlon, J., Peiper, C., Perfetto, E., & Feinberg, J.(1997).Identification of elderly nursing facility residents at high risk for drug-relatedproblems. Consult Pharm; 12:1103-11

The Fouts study identified 18 risk factors for medication therapy problems amongelderly residents of long-term care facilities. They are listed here, with theirprevalence. The risk factors include specific medications such as digoxin andwarfarin, classes of medications such as anticonvulsants and antipsychotics, andpatient factors, such as more than 6 concurrent diagnoses, poor renal function,history of an adverse drug reaction and 9 or more medications.

04.01.04 Costs of Medication-related Morbidity and Mortality

In LTC facilities:The cost of medication-related morbidity and mortality = $7.6 billion

In other words:For every $1 spent on drugs in the LTCF. . $1.33 is spent in the treatment ofdrug-related problems!


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Source: Bootman, J.L., Harrison, D. L. & Cox, E.(1997). The healthcare cost ofdrug-related morbidity and mortality in nursing facilities. Arch Intern Med;157:2095.

Medication-related morbidity and mortality within the long-term care facilityrepresents not only a serious health concern, but a major economic problem aswell. Medication-related problems in ambulatory facilities, hospitals, and nursing

homes combined cause thousands of deaths a year and may cost as much asone hundred billion dollars annually in health care resources.

Without pharmaceutical care, Bootman estimates the cost of medication-relatedproblems in long-term care facilities alone to be $7.6 billion. For every $1 dollarspent on drugs in the nursing home, it has been estimated that $1.33 worth ofhealth care resources are consumed on medication related problems.

04.01.05 Responsibilities of the Consulting Pharmacist

Ensure that the patients drug therapy is indicated, is the most effectiveavailable, is the safest possible, and can be taken as indicated

Identify, resolve, and prevent any drug therapy problems

Ensure that the goals of the patients therapy are met and optimaloutcomes are realized

With current federally mandated drug regimen reviews, it is estimated thatconsulting pharmacists can help cut the costs of medication-related problems in

long-term care facilities in half, from $7.6 to $4 billion (Bootman et al., 1997).There are at least three ways that consulting pharmacists help reduce the humanand financial costs of medication-related problems.

First, the pharmacist makes sure that the patients drug therapy is indicated, isthe most effective available, is the safest possible, and can be taken asindicated. Second, the pharmacist identifies, resolves, and prevents drug


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therapy problems where possible. Third, the consulting pharmacist ensures thatthe goals of the patients therapy are met and that optimal outcomes are realized.

04.01.06 Difficulties in Selecting Appropriate Medication Therapy in theElderly

Multiple interacting factors influence age-related changes in drugpharmacology

There is wide individual variation in the rate of age-related changes thataffect pharmacology

The clinical status of each patient (e.g., nutrition and hydration, cardiacoutput, intrinsic renal and liver disease) must be considered in addition tothe effects of aging

Research in geriatric pharmacology is still in its infancy

Source: Kane, R. L., Ouslander, J. G., & Abrass, I. B.(1994). Essentials ofclinical geriatrics. New York: McGraw-Hill. p. 360.

The role of the consulting pharmacist is especially challenging in the geriatricsetting. Several factors make the development of specific recommendations forelderly patients very difficult.


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04.01.07 Other Factors that May Interfere with the Successful MedicationTherapy in the Elderly

Image: http://flylib.com/books/en/1.431.1.20/1/


In addition to these biophysical factors, compliance plays a major role in thesuccess of geriatric medication therapy. Some of the barriers to compliance

faced by the elderly include complex dosing schedules, polypharmacy, and thechronic nature of illness. The potential effects of these barriers on the success ofmedication therapy are shown in the chart.


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04.01.08 Categories of Medication Therapy Problems

Medication Problems Related to Choice of Therapy:

Patient has a need for additional drug therapy

Patient is being treated with unnecessary drugs

Patient is using the wrong drug

Medication Problems Related to the Administration of Therapy:

Dosage of the drug is too low

Dosage of the drug is too high

Drug adversely interacts with other drugs and substances

Medication Problems Related to Patients Response to Therapy:

Patient does not comply with therapeutic regimen

Patient has an adverse reaction to drug therapy

Patients condition does not improve with therapy

While medication therapy problems tend to be multifaceted, it is possible tocategorize problems with similar characteristics. Categorizing medication-relatedproblems clarifies the distinctions between one type of problem, such as adversedrug reactions, and other types of problems. Another benefit is that enablesconsulting pharmacists to identify and clarify their own professionalresponsibilities in the prevention or resolution of such problems.

The categories may help the consulting pharmacist develop systematicprocesses for achieving successful therapeutic outcomes, and providing acommon vocabulary for the discussion of medication-related problems withcolleagues and patients alike.

04.01.09 Stating the Medication Therapy Problem

Poor method of stating the problem:

Inappropriate drug therapy


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Good method of stating the problem:

Toxic trough concentrations resulting from too high a dose of theophylline

Source: Cipole, R. J., Strand, L. M. & Morley, P. C. (2004). Pharmaceutical care

practice. New York: McGraw Hill.

With these categories serving as a map, the pharmacist must give seriousconsideration to how specific medication therapy problems should be stated.How a medication therapy problem is stated not only determines how theproblem will be resolved, but also how it will affect other aspects of the care planas well.

Keep in mind that specific is better. Inappropriate drug therapy is not as usefulas toxic trough concentrations resulting from too high a dose of theophylline.

04.01.10 Prioritizing the Urgency of a Medication Therapy Problem

The extent of potential harm to the patient + the rate at which harm islikely to occur = RISK

The patients perception of the potential harm

Once the medication therapy problem has been properly defined, it must beprioritized in terms of urgency. Prioritization is important, since data from theMinnesota Pharmaceutical Care Project reveals that almost fifteen percent of allpatients have two or more medication therapy problems, and five percent havemore than four problems.

The urgency of any given medication therapy problem depends on three things:the extent of potential harm to the patient, the rate at which harm is likely tooccur, and the patients perception of the potential harm. The first two constitutethe risk confronting the patient.

04.01.11 Medication Therapy Problems: Role of the Patient

Self-reported problem

Perceived benefit of therapy


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Sometimes the patient him-/her-self will identify a medication therapy problem,either through self-examination and diagnosis, or comparisons with similarexperiences of family or friends. While the philosophy of patient-centered care

dictates that such self-reports are given the full attention of the consultingpharmacist, there is an even more compelling reason to pay attention to thesereports: compliance. Studies have shown that 65% of elderly patients will stoptaking a medication if they do not feel they are experiencing its benefits. Thepower of patient perceptions of drug therapy problems should not beunderestimated.

04.01.12 Algorithm Resolving a Medication Therapy Problem


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Once a medication therapy problem has been assessed in terms of its riskpotential and related patient perceptions, the consulting pharmacist mustconsider which problems can be solved immediately and which problems canwait. The pharmacist must also considerwho is best equipped to resolve each

problem. Is it a primary responsibility of the pharmacist? Does it need to becollaboratively resolved by the pharmacist and patient? Or does it require theintervention of a family member, a primary physician, or a medical specialist?Once these questions have been answered, the consulting pharmacist canmobilize the necessary resources to resolve or prevent the problem.

04.01.13 General Guidelines for Preventing Medication Therapy Problems

Evaluate elderly patients thoroughly

Manage medical conditions without drugs as often as possible

Know the pharmacology of the drug being prescribed and how it mightadversely interact with other drugs

Consider how the clinical status of each patient could influence thepharmacology and effectiveness of the drug(s)

Be sensitive to potential barriers to compliance (e.g., impaired cognitivefunction, diminished vision and hearing, cultural barriers)

For drugs or their active metabolites that are renally eliminated, makeappropriate age-related adjustments in dosages

If there is a question about drug dosage, start small and increase

gradually Use drug blood concentrations to monitor potentially toxic drugs used

frequently in the elderly

Monitor elderly patients frequently for compliance, drug effects and toxicity


Medication therapy problems in the elderly may be minimized by applying the

guidelines listed here. While many of these guidelines will seem obvious to theconsulting pharmacist, they are worth repeating here.

For example, a thorough evaluation of the patient will help identify all conditionsthat may benefit from drug treatment and any conditions that will be adverselyaffected by drug treatment. Carefully consider how the clinical status of thepatient might affect the pharmacology an effectiveness of the drugs beingprescribed. Consider also how the cognitive and psychosocial status of the


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patient might affect compliance with the therapeutic regimen. If there isuncertainty about the correct dosage, start low and go slow. Monitor the patientfrequently for compliance, drug effects and toxicity.

04.01.14 Resources

For additional information, see:

Bootman, J.L., Harrison, D. L. & Cox, E.(1997). The healthcare cost of drug-related morbidity and mortality in nursing facilities. Arch Intern Med; 157:2089-96.

Cipole, R. J., Strand, L. M. & Morley, P. C. (2004).Pharmaceutical carepractice.New York: McGraw Hill.

Fouts, M., Hanlon, J., Peiper, C., Perfetto, E., & Feinberg, J.(1997). Identificationof elderly nursing facility residents at high risk for drug-related problems.ConsultPharm; 12(10): 1103-11

Gurwitz, J. H., Soumerai, S. B. & Avorn, J.(1990).Improving medicationprescribing and utilization in the nursing home.J Geriatr Soc; 38(5): 542-52.

Meade, V.(1994). Solving problems in board and care facilities. Consult Pharm,9(7), 735-744.

Riegelman, R. K.(1991). Minimizing medical mistakes. Boston:Little, Brown, andCo.

Strand L.M., Morley P.C., Cipolle R.J. (1990) Drug-related problems: theirstructure and function.DICP; 24:1093-7

Williams, B. R., Thompson, J. F., & Brummel-Smith, K. V.(1993). Improvingmedication use in the nursing home. In Rubenstein, L.Z. & Wieland, D. (eds.).Improving Care in the Nursing Home. Newbury Park, CA: Sage Publications.

Websites:

Cole, Michele R., Suboptimal Medication Use in the Geriatric Population, ASCPConsultants Forum, January, 1997.http://www.ascp.com/public/pubs/tcp/1997/jan/consultant.html


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Losben, Nancy L., Using the MDS 2.0 to Identify and Monitor the At-Risk Elderly,ASCP, The Consultant Pharmacist, May 1997.http://www.ascp.com/public/pubs/tcp/1997/may/mds.html


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Module 4, Section 2: Problems Based on Choice of Therapy

04.02.01 Medication Problems Related to Choice of Therapy

Patient has a need for additional drug therapy

Patient is being treated with unnecessary drugs

Patient is using the wrong drug

Prescribing cascade occurs


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Medication therapy problems can arise when inappropriate interventions arechosen. At one end of the spectrum, the patient may have a medical conditionthat requires new or additional drug therapy.

Problems can occur when the patient is at high risk to develop a condition forwhich therapy is indicated as primary or secondary prevention. At the other endof the spectrum, the patient may be taking a drug for which there is no medicalindication. In this case, problems occur when the patient develops a newcondition based on the use of this unnecessary drug.

This is illustrated in the prescribing cascade, where a new medication is addedbased on a new medical condition caused by a medication. In the exampleshown, as the dose of metoclopramide increases, the odds of starting levodopa,based on Parkinsons symptoms, increased.

In addition to this, are all the problems that can occur when the patient developsa new condition based on the use of a drug, which is inappropriate for his or hercurrent medical disorder.


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04.02.02 Inadequate Drug Therapy: Causes

Patient has a new medical condition that requires new therapy

Patient has a chronic disorder requiring continuation of drug therapy

Patient has a medical condition that requires combinationpharmacotherapy to obtain synergism/potentiate effects

Patient is at risk to develop a new medical condition which could beprevented by the use of prophylactic drug therapy or and/or premedication

Source: Cipole, R. J., Strand, L. M. & Morley, P. C. (2004). Pharmaceutical carepractice. New York: McGraw Hill.

Consider the first of these potential problems. Data from the MinnesotaPharmaceutical Care Project reveal that almost twenty percent of medicationtherapy problems involve patients who need additional or new drug therapy.

The need for additional therapy can be caused by a variety of circumstances. Forexample, the patient may have a new medical condition that requires newtherapy. Or he or she may have a chronic disorder requiring the continuation ofdrug therapy.

The patient may require combination pharmacotherapy to treat a currentcondition, or prophylactic (i.e. preventive) therapy to treat an anticipatedcondition. The use of low risk prophylactic therapy, such as low dose aspirin forsecondary prevention of myocardial infarction or stroke, is often overlooked in theelderly.

04.02.03 Inadequate Drug Therapy: Continuity Issues

Continuity in drug therapy is a common issue with these types of medicationproblems. Geriatric patients with chronic disorders such as rheumatoid arthritisor heart failure often require prolonged treatment for relief of discomforting signsand symptoms and to decrease morbidity and mortality. Drug therapy can bedisrupted if these patients are transferred from one facility to another, from onephysician to another, or even one from one pharmacy to another.


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04.02.05 Unnecessary Drug Therapy

No medical indication

Addictive/recreational drug use

Non-drug therapy more important

Duplicative therapy

Treating an avoidable adverse drug reaction

Source: Cipole, R. J., Strand, L. M. & Morley, P. C. (2004). Pharmaceutical carepractice.New York: McGraw Hill.

The Centers for Medicare and Medicaid Services (CMS) define unnecessarymedications as any medication used without adequate indications for its use.Examples include:

Improper medication selection (i.e. wrong medicine for the condition beingtreated

Use of a high-risk medication without clear justification in an individual

who may have experienced an ADR Receiving a medication and experiencing symptoms that could represent

an ADR Receiving a medication despite a known allergy

Source: Department of Health and Human Services, Centers for Medicare &Medicaid Services (2004) State Operations Manualhttp://www.cms.hhs.gov/manuals/107_som/som107ap_pp_guidelines_ltcf.pdf.

Among the patients who might experience inadequate drug therapy are thosewho require combination drug therapy, such as patients with a recent history ofmyocardial infarction or heart failure. Following a myocardial infarction, multipleagents from different classes have been shown to reduce morbidity and the riskfor future MI, stroke, and death. With diseases such as heart failure, multipleagents are often prescribed to mitigate symptoms and improve quality of life andsurvival.


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The second potential medication problem related to choice of therapy is the useof drugs that are unnecessary. This type of problem is often overlooked by thepharmacist, who is responsible for ensuring that patients are protected from thetoxic effects of drugs for which there is no valid medical indication. Unnecessarydrug therapy can also occur as a result of recreational drug use, self-selected

herbal remedies, duplicative therapy, and treatment of avoidable adverse drugreactions.

According to the Minnesota Pharmaceutical Care Project, 7% of drug therapyproblems identified and resolved by pharmacists are due to the use ofunnecessary drugs. Additionally, the CMS definition for an unnecessarymedication has been provided along with examples.

04.02.06 Unnecessary Drug Therapy: Combination Therapy

Sometimes patients receive combination therapy when a single agent would beequally effective. This problem often occurs with patients in long-term carefacilities. That is why pharmacists who consult to such facilities are expected toidentify patients who receive more than one agent for any given condition whenonly one medication is indicated.

04.02.07 Unnecessary Drug Therapy: Use of Illicit Drugs

More ambiguous is the pharmacists role with respect to prescribing drugs thatare potentially addictive and abused. While the laws regarding illegal drug taking

may vary from place to place, the ethical obligation of the practicing pharmacistto provide pharmaceutical care to patients remains constant. The pharmacistmust act to reduce harm to anyone at medical risk, regardless of legal status ofthe drugs being considered for treatment, or the societal consequences of thepatients conduct.


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04.02.08 Wrong Drug Therapy: Incidence

Using the wrong drug = 17% of medication problems

Any time a patient does not experience expected positive outcomes of aparticular drug, the clinician must consider the possibility that the drug isinappropriate. Data from the Minnesota Pharmaceutical Care Project reveal that17% of medication problems encountered by pharmacists involve patientsreceiving the wrong drugs. The high percentage of such errors is especiallydisturbing considering the extent to which the use of drugs are controlled throughformularies, patient management protocols, drug utilization reviews andelectronic feedback mechanisms associated with cost reimbursement.

04.02.09 Wrong Drug Therapy: Influence of Patient Factors

Nature of the medical condition Severity of the condition

Infectious process and organism involved

Age

General health status

Preferences

The success of any therapy is dependent on correct identification and diagnosisof the patients medical condition. Factors that contribute to making a particularmedication the right or wrong choice for a given patient include the nature of thepatients medical condition, the severity of the condition, the infectious processand the organism involved, and the age and general health status of the patient.

For example, an asthma patient using propranolol to treat hypertension may beusing the wrong drug for blood pressure control, especially if they are using abeta-agonist for asthma treatment.

Although propranolol may adequately control the patients blood pressure, it issaid that the patient has a drug therapy problem because of thebronchoconstrictive properties of the beta-blocker. A patient may also be usingthe wrong drug if he or she is allergic to the agent.

04.02.10 Age-related Changes Relevant to Drug Pharmacology

Changes in Absorption:


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Decreases in absorptive surface and splanchnic blood flow

Increased gastric pH

Rate, but not extent of absorption

Changes in Distribution:

Decreases in total body water, lean body mass, and albumin

Increased fat

Altered protein binding

Changes in Metabolism:

Decrease in liver blood flow

Enzyme activity and inducibility

Changes in Excretion:

Decrease in renal blood flow, GFR, tubular secretion

Changes in Tissue Sensitivity:

Alterations in receptor number and affinity

Second messenger function

Cellular and nuclear responses

Kane, R. L., Ouslander, J. G., & Abrass, I. B.(1994). Essentials of clinicalgeriatrics. New York:McGraw-Hill. p. 360.

Natural age-related changes also play a role in the success of medicationtherapy. In the elderly, changes in absorption, distribution, metabolism,excretion, and tissue sensitivity can alter the effectiveness or toxicity of a givenagent, leading to medication therapy problems.

04.02.11 Wrong Drug Therapy: Influence of Cost

Brand vs. generic

The patient may be using the wrong drug if there is an equally effectivealternative that is less expensive. In these situations it is important to ensure thatthere is objective evidence to support the claim that both medications are equallyeffective, and that there is no significant difference in potential toxicities.


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04.02.12 Key Medications That May be Potentially Inappropriate for SomeOlder Adults

amiodarone ergot mesyloids mineral oilamitriptyline estrogens nitrofurantoin

amphetamines ethacrynic acid orphenadrine

barbiturates flurazepam pentazocine

chlordiazepoxide guanadrel phenylbutazone

chlorpropamide guanethidine potassium supplements

cimetidine indomethacin propoxyphene

clonidine isoxsuprine reserpine**

cyclandelate ketardac short-acting nifedipine

daily fluoxetine lorazepam stimulant laxatives

dessicated thyroid meperidine thioridazine

digoxin* meprobamate ticlopidinediphenydramine mesoridazine trimethobenzamide

dipyridamole methocarbamol

disopyramide Methylfopa

doxazosin methyltestosterones

doxepin

* digoxin >0.125 mg in heart failure

** reserpine >0.1 mg/day

2012 Beers Criteria:

http://www.americangeriatrics.org/health_care_professionals/clinical_practice/clinical_guidelines_recommendations/2012

A consensus panel of geriatric experts, including pharmacists, has developed alist of explicit criteria for determining whether or not certain medications areappropriate for elderly patients. The criteria also outline medical conditionsunder which selected medications may be inappropriately used in the geriatric

population. Some of these medications may be inappropriate only for individualswith selected medical conditions.


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All of the following medications are included in the list of medications consideredinappropriate for use in the elderly, according to Beers and colleagues, except:

A. AmitriptylineB. Diphenhydramine

C. CiprofloxacinD. MethyldopaE. Meperidine

ANSWER: C. Fluoroquinolones are generally not considered inappropriate foruse in the elderly according to the Beers List critieria.

04.02.13 Assessing the Appropriateness of Medication Therapy

Is there an indication for the drug?

Is the medication effective for the condition?

Is the dosage correct?

Are the directions correct?

Are the directions practical?

Are there clinically significant drug-drug interactions?

Are there clinically significant disease-drug interactions?

Is there unnecessary duplication with other drugs? Is the duration of therapy acceptable?

Is this drug the least expensive alternative compared to others of equalutility?

Source: Hanlon, J. T., Schmader, K. E., Samsa, G. P., et al.(1992). A method forassessing drug therapy appropriateness. J Clin Epidemiol; 45(10): 1045-51.

An indexing system, like the one developed by Hanlon and associates, may alsobe helpful in assessing the appropriateness of medication therapy in the elderly.The assessment process consists of a series of questions that, when answeredand tabulated, provide an index of the appropriateness of a given medication.The types of questions asked during this assessment process are listed on yourscreen.


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The Medication Appropriateness Index (MAI), as proposed by Hanlon et al,considers all of the following, except:

A. Is there unnecessary duplication with other drugs?B. Is the duration of therapy of therapy acceptable?

C. Is the dosage form appropriate based on patient specific factors?D. Is there an indication for the drug?

CORRECT ANSWER: C

04.02.14 Wrong Drug Therapy: Justification for Change

Does the alternative drug demonstrate a significant advantage inproducing desirable outcomes?

Does the alternative drug demonstrate a significant advantage in reducingundesirable outcomes?

Does the alternative drug offer significant cost savings?

Is the patient open to the idea of changing medications?

In summary, a drug is said to be wrong or inappropriate when there are otheragents that have a higher probability of producing the desired outcomes, when

there are other agents with a lower probability of producing undesirableoutcomes, or when there are other agents equally effective but less costly.

However, it is important to keep in mind that the difference between alternativemedications may not be enough to justify a change in therapy. A drug that isexpected to be effective in seventy-five percent of patients and another that isexpected to be effective in ninety-five percent can still both be appropriate drugfor a patient experiencing positive outcomes. Patient preferences also play arole.

The patient who is accustomed to using a particular medication may be reluctant

to change if the alternatives provide only minor advantages over alternatives.

04.02.15 Resources



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Beers, M. H.(1997). Explicit criteria for determining potentially inappropriatemedication use by the elderly. Arch Intern Med; 157:1531-1536.

Cipole, R. J., Strand, L. M. & Morley, P. C. (1998).Pharmaceutical carepractice.New York: McGraw Hill.

Fick DM, Cooper JW, Wade WE et al. Updating the Beers Criteria for potentiallyinappropriate medication use in older adults. Arch Intern Med2003;163:2716-24.

Hanlon, J. T., Schmader, K. E., Samsa, G. P., et al.(1992).A method forassessing drug therapy appropriateness. J Clin Epidemiol; 45(10): 1045-51.

Montamat, S. C. & Cusack, B.(1992). Overcoming problems with polypharmacyand drug misuse in the elderly. Clinical Geriatric Medicine, 8(1), 143-158.

Pinneke, S. (1993).Showing the reduction of unnecessary drugs. Consult

Pharm, 8(3), 305-306.

Riegelman, R. K.(1991). Minimizing medical mistakes. Boston:Little, Brown, andCo.

Websites:

Agency for Healthcare Research and Quality (AHRQ)http://www.ahrq.gov/


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Module 4, Section 3: Problems Related to the Administration ofTherapy

04.03.01 Medication Problems Related to the Administration of Therapy

Dosage of the drug is too low

Dosage of the drug is too high

Drug adversely interacts with other drugs and substances

Sometimes variations in drug administration can lead tomedication problems. Apatient may receive too little of the appropriate drug, negating the best diagnosticand therapeutic efforts. Or a patient may receive too much of the appropriate

drug, with the potential for adverse effects. Finally, a patient may experience anadverse reaction based on the interaction of an otherwise appropriate drug andother medications.

04.03.02 Drug Dosage Too Low: Causes

The amount of drug administered is too low

The dosing frequency is inappropriate

The duration of therapy is too short The drug has lost its potency due to improper storage

The drug is administered inappropriately


Drug therapy problems resulting from patients receiving inadequate doses ofpotentially effective medications are a serious concern. The MinnesotaPharmaceutical Care Project estimated that 14% of patients are beingunderdosed on their medications. The causes of underdosing are many andvaried.


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04.03.03 Drug Dosage Too Low: Safety Issues

One of the more insidious causes of underdosing is misplaced concern aboutpatient safety. Although frequently prescribed medications such as amoxicillin,ibuprofen, and ciprofloxacin are both effective and safe,clinicians mayfavor

more conservative therapeutic regimens, especially at the outset.

However, considering that published dosing guidelines tend to be conservative tobegin with, such strategiesoften condemn the patient to days or weeks ofineffective drug therapy. Conservative start-up regimens require frequent follow-up to evaluate patient status and adjust dosage accordingly.

04.03.04 Drug Dosage Too Low: Patient Factors

Patient factors can also lead to underdosing. Age and body weight can have a

significant impact on dosing requirements and must be taken into account whenprescribing any therapeutic regimen.

Patients may deliberately underuse their medications to avoid unpleasant sideeffects. It is important to consider that this form of intelligent noncompliancemay be a valid response by patients who may be compensating for physiologicalattributes that alter their response to medication.

04.03.05 Drug Dosage Too Low: Schedule and Duration of Therapy

Sometimes inadequate dosing is related to the timing of treatment rather than theabsolute amount of the drug being taken. For example, a patient may bereceiving too little medication if the dosing interval is inappropriately prolonged.This can happen when preparations designed for extended use are replacedwith preparations that are more rapidly absorbed.

Patients may also receive inadequate medication if therapeutic regimen isdiscontinued prematurely, before its full benefits are realized. This oftenhappens when dosages effective with one type of disorder, such as anuncomplicated urinary tract infection, are applied to related but more complexdisorders, such as pyelonephritis.


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04.03.06 Drug Dosage Too Low: Importance of Testing

As new technologies have increased our ability to individualize drug dosing,clinicians are beginning to realize that many patients require higher drug doses

than previously suggested. Remember that serum and blood-drug concentrationtests are necessary not only to avoid overdoses and toxicities, but also to ensurethat patients receive enough medication to meet their therapeutic needs.

04.03.07 Drug Dosage Too High: The Importance of Renal Function

Just as inadequate amounts of medication can lead to drug therapy problems, socan excessive amounts of medication. Reduced renal function and a diminishedability to eliminate certain types of drugs makes older adults especiallysusceptible to overdoses and their toxic effects.

Many elderly patients also have diminished cardiac reserve, making themvulnerable to the hypotensive effects of cardiovascular drugs, as well asantidepressant and antipsychotic agents.

04.03.08 Drug Dosage Too High: Causes

The amount of drug administered is too high

The dosing frequency is inappropriate

The duration of therapy is too long

Patients may experiencedrug therapy problems related to excessive amounts ofmedication if the absolute dosage or concentration of the drug is too high, if thepatient receives the drug too often, or if the duration of therapy is too long.Patients may decide to increase the dosage deliberately if they are notexperiencing the anticipated benefits of medication. An elderly patient, forexample, may increase the recommended dose of arthritis medication to relieveresidual pain. The systemic or localized effects of excessive medication aregenerally predictable, based on the known pharmacological action of the agent.

04.03.09 Drug Dosage Too High: Prevention

Measurement of blood drug concentration

Dosage individualization

Pharmacokinetic monitoring


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When the risk of drug accumulation and toxicity is high, measurement of serumor blood drug concentration is essential. Pharmacokinetic monitoring with

dosage individualization is also invaluable in preventing this type of drugproblem. For example, patients who require acute, short-term antithrombotictherapy with heparin depend on coagulation tests to determine the appropriatedose and reduce the risk of excessive bleeding. Patients who are on long-termanticoagulation therapy with warfarin similarly benefit from measurements of theINR (International Normalized Ratio).

04.03.10 Drug Dosage Too High: Legislative Efforts

Measurement of blood drug concentration Dosage individualization

Pharmacokinetic monitoring

Drug regimen review to reduce dosage levels

In a national effort to reduce the frequency and severity of toxic complicationsassociated with psychotropic drugs, the 1990 Omnibus Budget Reconciliation Actrequires biannual documentation of efforts to reduce dosage levels for Medicaidrecipients. Rather than determining specific dosage regimens for individual

patients, these guidelines are intended to encourage regular drug regimenreviews in long-term care facilities. Guidelines from the CMS also specifysuggested maximum doses of antipsychotic medications.

04.03.11 Drug-Drug Interactions

The patient may experience the effects of underdosing or overdosing whenever

one drug negatively interacts with another drug. Drug-drug interactions are themost frequently cited cause of drug therapy problems, yetthey are the leastunderstood. Some interactions are simply the pharmacology of one drugcombined with the pharmacology of another drug. Others are not only difficult toidentify and characterize, but their resolution is often very complex because ofthe intricate nature of the interaction.


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04.03.12 Top Ten Dangerous Drug Interaction in Long-Term Care

1. Warfarin and NSAIDs2. Warfarin and Sulfa Drugs

3. Warfarin and Macrolides4. Warfarin and Quinolones5. Warfarin and Phenytoin6. ACE Inhibitors and Potassium Supplements7. ACE Inhibitors and Spironolactone8. Digoxin and Amiodarone9. Digoxin and Verapamil10. Theophylline and Quinolones

A survey of physicians and pharmacists with experience in treating older

adultsidentified the top 10 drug interactions in long term care. The list was basedon frequency of use in older adults and the potential for adverse consequences ifused together.

04.03.13 Problems Resulting from Drug-Drug Interactions

Problem Example Potential Effects

Interference withdrug absorption

antacid+digoxin, INH,ciprofloxacin

decreased effectiveness

Displacement frombinding protein

warfarin, ASA, oralhypoglycemics

enhanced effects, greatertoxicity

Altered distribution digoxin+quinidine greater toxicity

Altered metabolism clarithromycin +carbamazepine,digoxin

decreased drug clearance,enhanced effect, greatertoxicity

Altered excretion lithium+diureticsimbalance

greater toxicity, electrolyteimbalance

PharmacologicalAntagonism

levodopa+clonidine decreased anti-Parkinsonianeffects

PharmacologicalSynergism antihypertensives +TCAs increased risk of hypotension

Adapted from: Kane, R. L., Ouslander, J. G., & Abrass, I. B.(1994).Essentials ofclinical geriatrics.New York:McGraw-Hill. p. 358


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For example,anticonvulsants, which are commonly associated with drug-druginteractions, can induce the metabolism of other anticonvulsants takenconcurrently. Competition between agents for similar binding sites can elevateconcentrations of one or both drugs to toxic levels. Drugs can even disrupt theirown metabolism.

For example, initial carbamazepine therapy for the control of seizure often makespatients drowsy and lethargic. This is due to auto-induction of the hepaticenzyme systems that are responsible for the metabolism of the carbamazepineitself that takes roughly 3-4 weeks to complete with initiation of therapy orsubsequent change in dosage.

Which of the following combinations is most likely to produce a negative drug-

drug interaction by altering the distribution of medication?

A. Lithium + furosemideB. Cimetidine + phenytoinC. Digoxin + quinidineD. Levodopa + clonidineE. All of the above

CORRECT ANSWER: C. Lithium and diuretics produce negative drug-druginteractions via altered excretion that leads to electrolyte abnormalities and

increased potential for lithium toxicity.

Cimetidine and phenytoin interact likely via inhibition of CYP450 2C19-mediatedphenytoin metabolism, prompting elevated phenytoin levels and decreasedclearance of phenytoin. Literature and case reports suggest clonidine decreasesthe effects of levodopa in Parkinsons patients. Quinidine likely inhibits the p-glycoprotein transport system that digoxin is dependent upon, reducing digoxinsclearance and volume of distribution, resulting in a likely digoxin toxic situation inthe patient.


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04.03.14 Polypharmacy and Potentially Inappropriate Drug Combinations

Drug-drug interactions are especially problematic in the elderly because of theirincreased need for polypharmacy. Studies show that the average nursing homeresident is prescribed 5-8 regularly scheduled medications in addition to thoseadministered on an as-needed basis. One reason for this is that the patient withmultiple chronic diseases is often seen by more than one medical specialist whocontributes to the health care plan.

A recent study of polypharmacy in Canadian elderly found that the number ofpotentially inappropriate drug combinations increased in direct relation to thenumber of physicians involved in the patients management.

The same study showed that the use of multiple dispensing pharmacies and theprescribing habits of individual physicians also increased the risk of inappropriatedrug combinations.


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04.03.15 Other Potential Sources of Drug-Drug Interactions

Medications from previous treatment programs

Medications shared by family and friends

Nonprescription medications

o laxatives

o analgesics

o vitamins/minerals

o cold or cough preparations

The use of prescription medications from previous treatment programs andmedications shared by family and friends can also contribute todrug-drug

interactions. Such medications are often past the expiration date.Nonprescription medications, used by the majority of older adults, may alsoprovoke drug-drug interactions.

Laxatives, for example, must be used with caution by elderly patients takingdigitalis preparations. Other nonprescription medications used frequently by theelderly include analgesics, laxatives, vitamins/minerals, and cold or coughpreparations.

04.03.16 Resources


Cipole, R. J., Strand, L. M. & Morley, P. C. (2004). Pharmaceutical care practice.New York: McGraw Hill.

Kane, R. L., Ouslander, J. G., & Abrass, I. B.(1994). Essentials of clinicalgeriatrics. New York: McGraw-Hill

Monette, J., Gurwitz, J. H. & Avorn, J. (1995). Epidemiology of adverse drugevents in the nursing home setting. Drugs Aging; 7(3): 203-11.

Regal RE, Vue CO. Drug interactions between antibiotics and selectivemaintenance medications: seeing more clearly through the narrow therapeuticwindow of opportunity. Consult Pharm 2004;12:119-28.


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Riegelman, R. K.(1991). Minimizing medical mistakes. Boston: Little, Brown,and Co.

Stewart, R. B. & Hale, W. E.(1992). Acute confusional states in older adults andthe role of polypharmacy. Ann Rev. Public Health, 13, 415-430.

Tamblyn, R. M., McLeod,P.J., Abrahamowicz, M., Laprise, R.(1996). Do toomany cooks spoil the broth? Multiple physician involvement in medicalmanagement of elderly patients and potentially inappropriate drug combinations.Can Med Assoc J; 154(8): 1177-84.

Thomas, J. A. (1995). Drug-nutrient interactions. Nutrition Rev; 53(10): 271-282.

Websites:

Multidisciplinary Medication Management Project. Top ten dangerous drug

interactions in long term care. Available athttp://www.amda.com/tools/clinical/m3/topten.cfm

The Merck Manual of Geriatrics-Clinical Pharmacologyhttp://www.merck.com/!!wC8L80tbNwC8LS04YV/pubs/mm_geriatrics/21x.htm


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Module 4, Section 4: Problems Related to PatientsResponse to Therapy

04.04.01 Medication Problems Related to Patients Response to Therapy

Patient does not comply with therapeutic regimen

Patient has an adverse reaction to drug therapy

Patients condition does not improve with therapy

It is the responsibility of the pharmacist to take whatever steps are necessary toensure that the patients drug therapy is effective. Such steps may bedeliberately or inadvertently undermined by the patients own behavior. Or, they

may be subverted by an adverse reaction to therapy. Sometimes, despite theclinicians best efforts, the patient simply fails to improve with treatment.

04.04.02 Reasons for Nonadherence

The patient prefers not to take the drug for personal reasons

The drug is not available

The patient cannot afford to obtain the medication

The patient does not understand the instructions

The patient forgets to take the medication

The dosage form cannot be swallowed or tolerated

Source:Cipole, R. J., Strand, L. M. & Morley, P. C. (2004).Pharmaceutical carepractice.New York: McGraw Hill.

While data from the Minnesota Pharmaceutical Care Project indicate that 12% ofmedication therapy problems are related to nonadherence, the percentage

suggested in the literature is much higher. It has been estimated that as manyas 70% of patients do not fully comply with their therapeutic regimens, for avariety of reasons.

Patients may feel that the drug has caused or will cause them harm, or at leastinconvenience. Some patients may feel the cost of the drug is too high, or theymay not be able to afford it. Some may not be able to understand theinstructions, while others may forget to take the medication entirely. Then there


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are patients who cannot tolerate the dosage form of the medication. Forexample, as salivary flow declines with age, older patients may have troubleswallowing capsules that adhere to the relatively drier mucous membranes.

04.04.03 Age-related Changes that Can Affect Adherence

Changes in Vision (affects 90% of people over age 60):

decreased lens elasticity increased lens opacity and papillary response

yellowing of lens with concomitant loss of color differentiation

Changes in Hearing (affects 60% of people over age 65):

loss of hearing acuity sound distortion

increased sensitivity to loud and extraneous sounds

Changes in Memory:

decreased short term memory

The patients comprehension and knowledge about his or her illness andmedications are important issues in determining the success of therapy. Someof the physical and cognitive changes associated with aging may affect theelderly patients ability to understand regimen demands and take medicationsappropriately.

Sensory changes, such as impaired vision, and hearing, may affect the patientsability to read labels or understand the pharmacists instructions for use. Theage-related decline in short-term memory makes it imperative that newtherapeutic information be integrated with existing habits or past experience.


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04.04.04 Self-Medication Problems with the Elderly

Age-related changes in sensory ability and cognitive function explain some of the

self-medication problems experienced by older adults. Cases have beenreported in the literature in which patients swallowed chewable tablets whole,and had to undergo surgery to remove them. Aspirin tablets that patientsallowed to dissolve in their mouth resulted in painful burns of the mucosa. Bulklaxatives have been taken without adequate fluids, necessitating surgicalintervention.

04.04.05 The Roles of Knowledge and Understanding in Adherence

Consider:

sensory ability

cognitive ability

memory

literacy level

language barriers

Provide:

clear explanations with a minimum of technical terms

learning aids such as auxiliary directions, uncomplicated schedules, largereadable print on labels, etc.

memory aids such as drug dosing calendars, telephone reminders forrefills, etc.

Recognition of these age-related changes is important in promoting patientcompliance. The psychological impact of illness must also be considered. Anelderly patient who has been diagnosed with a chronic illness may initiallyexperience a high level of anxiety that interferes with his or her ability to

comprehend and remember medication instructions.

Compliance has been found to improve when the pharmacist takes the time tocounsel patients and explain the purpose of and appropriate use of eachmedication. Conveying drug information in simple terms, with frequent repetitionand follow-up, is more likely to promote compliance.


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Learning and memory aids such as drug-dosing calendars, the use of large,readable print on prescription labels, and telephone reminders for refills are alsouseful in improving compliance with the elderly.

04.04.06 Assessing Other Patient Sources of Nonadherence

Health care beliefs

Expectations

Concerns

Negative experiences

Fears

Cultural influences

Habits

Coping mechanisms

Personality traits

As important as knowledge and understanding are to patient adherence, it isimportant to remember that much of nonadherence is learned behavior ratherthan a simple lack of knowledge about drug therapy. Assessing patients healthcare beliefs, as well as their expectations and concerns about taking medicationis critical.

Adherence is, after all, a leap of faith on the part of the patient that therapy will bein their best interest. Negative experiences, fears, cultural influences, habits,coping mechanisms and personality traits all play a role in adherence. Patientswho are nonadherent must be cared for in the context of altering their behavior.

Patient sources of nonadherence include all of the following except:

A. The patient's health care beliefsB. The patient's health care plan does not approve reimbursement for the

drugC. The patient does not understand the instructionsD. The patient's vision limitations

CORRECT ANSWER: B.


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04.04.07 Administrative Sources of Nonadherence

The drug the patient needs is not in the pharmacy

The drug product is not on the approved formulary list

The drug product is not approved for reimbursement The drug is lost in the mail

The wrong drug is dispensed

The caregiver fails to administer the drug

The drug delivery device is not working properly


While the vast majority of nonadherence problems are rooted in the knowledgeand behavior of the patient, you must also consider administrative sources ofnonadherence. Despite the sophistication of todays drug distribution systems,mistakes do occur.

For example, a drug the patient needs may not be stocked in the pharmacy,either because of an inventory oversight or because the product is not on theapproved formulary. The drug may not be approved for reimbursement, and istherefore not available to the patient.

If ordered by post, the drug may be lost in the mail. The wrong drug may bedispensed, or the clinician may simply fail to administer it on schedule. Or theremay be a technical problem with the drug delivery device or pump. It is importantto establish the existence of these problems and take prompt corrective action.

Administrative sources of patient nonadherence with therapy include all of thefollowing except:

A. The wrong drug is dispensedB. The drug product is not approved for reimbursementC. The patient does not understand the instructions

D. The caregiver fails to administer the drug

CORRECT ANSWER: C.

For more information on Medication Adherence, see:http://www.adultmeducation.com/


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04.04.08 Adverse Drug Reactions

Adverse Drug Reaction (ADR): any undesirable negative effects caused by amedication that were not predicted based on the dosage, concentration

dependency, or known pharmacology of the drug

Incidence:

24% of all medication therapy problems

half of all reported deaths due to ADRs occur in patients over age 60

In long term care, ADRs have been reported to occur at a rate of 9.8 per100 resident-months

Source: Gurwitz JH, Field TS, Judge J, et al. The incidence of adverse drugevents in two large academic long-term care facilities. Am J Med2005;118:251-8

Adverse drug reactions have been described, analyzed, and quantified morethan any other type of medication therapy problem. However, the lack of aconsistent definition and an infrastructure to identify, document, and resolve

ADRs has limited the amount of practical information available to clinicians.

For our purposes here, we define adverse drug reactions as any undesirablenegative effects caused by a medication that were not predicted based on thedosage, concentration dependency, or known pharmacology of the drug. Thedata from the Minnesota Pharmaceutical Care Project suggest that as many as24% of patients experience an adverse drug reaction.

Nearly half of all deaths attributed to adverse drug reactions occur in patients agesixty or over. In long term care, ADRs occur often, in about 1 in 10residents/month, and about half of these events are judged to be preventable.

04.04.09 Causes of Adverse Drug Reactions

The patient is receiving a drug considered to be unsafe

The patient has an allergic reaction to the drug

The drug is improperly or incorrectly administered

The dosage is increased or decreased too rapidly

The drug interacts negatively with another drug

The patient experiences an undesirable effect that was not predicted


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Most adverse drug reactions occur within the first two weeks of administration.ADRs are experienced for a variety of reasons. The patient may be receiving adrug product considered to be unsafe. Or the patient may have an allergicreaction to the drug. The drug may be administered improperly, or the dosageincreased or decreased too rapidly. The drug may interact negatively withanother drug, or the patient may simply have an adverse reaction that wasotherwise unpredictable.

04.04.10 Types of Drugs Likely to Cause ADRs in the Elderly

Overall:

antihyhpertensives

antiparkinson agents

psychotropics

cardiac glycosides

In LTC Facilities:

antipsychotic agents anticoagulants diuretics anticonvulsants

Although a wide variety of drugs can cause adverse reactions, four classes ofmedications should be used with particular precaution in the elderly. Theyinclude antihypertensives, antiparkinson agents, psychotropics, and cardiacglycosides. In the nursing home, medications most often associated with ADRsinclude antipsychotic agents, anticoagulants, diuretics, and anticonvulsants.

04.04.11 Criteria for Confirming Adverse Drug Reactions

The temporal relationship between patient exposure to the drug and theonset of undesirable effects


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Whether or not the patients condition improves when the drug isdiscontinued

Whether the adverse event recurs when the patient is re-exposed to thedrug

The patients health status can make it difficult to determine if an adverse drugreaction is directly attributable to the active ingredient of the drug, itspreservatives, vehicles or metabolites. Nonspecific symptoms such as fatigue,headache, or drowsiness may be attributable to the use of medication, andunderlying illness, or the patients natural constitution.

Criteria which are often applied to make this determination include the temporalrelationship between patient exposure to the drug and the onset of undesirableeffects, whether or not the patients condition improves when the drug isdiscontinued, and whether the adverse event recurs when the patient is re-

exposed to the drug.

Based on the extent to which it meets these criteria, an adverse reaction isclassified as highly probable, probable, or remote.

04.04.12 Patient Factors that Affect Adverse Drug Responses

Age

Gender

Body weight

Diet

Natural sensitivity to drug

General health status

Underlying disease(s)

Current medical condition

Individual patient sensitivity to certain drugs also makes it difficult to predict orprevent adverse drug reactions. For example, patients may vary widely in theirsensitivity to heparin and the risk of bleeding, even when dosage regimens takeinto account patient factors such as age, gender, and body weight.


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04.04.13 Responses to Drug Therapy Not Considered Adverse Reactions

Inadequate dosing, resulting in continued illness

Bioavailabilty problems that result in therapeutic failure

Drug abuse Noncompliance

Accidental or intentional poisoning


While many undesirable medication effects can be properly classified as adversedrug reactions, some cannot. Undesirable effects that are not consideredadverse drug reactions include inadequate dosing, resulting in continued illness;bioavailability problems that result in therapeutic failure; drug abuse;noncompliance, and accidental or intentional poisoning.

Some of these events are described in the context of other types of medicationtherapy problems. Adverse drug-drug interactions are presented as a separatemedication therapy problem in another section of this module.

04.04.14 Resources


Atkin, P. A. & Shenfield, G. M.(1995). Medication-related adverse reactions andthe elderly:A literature review. Adv Drug Reac Toxicol Rev, 14(3), 175-191.

Cipole, R. J., Strand, L. M. & Morley, P. C. (2004). Pharmaceutical care practice.New York: McGraw Hill.

Corlett, A. J. (1996). Aids to compliance with medications. BMJ, 313(7062).926-

929.

Fitten, L J., et al.(1995). Assessment of capacity to comply with medicationregimens in older patients. J Am Geri Soc, 43, 361-367.

Gurwitz JH, Field TS, Judge J, et al. The incidence of adverse drug events intwo large academic long-term care facilities. Am J Med2005;118:251-8.


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Monette, J., Gurwitz, J. H. & Avorn, J.(1995). Epidemiology of adverse drugevents in the nursing home setting. Drugs Aging, 7(3), 203-211.

Riegelman, R. K.(1991). Minimizing medical mistakes. Boston: Little, Brown,and Co.

Salzman, C. (1995).Medication compliance in the elderly. J Clin Psych, 56(Suppl1), 18-22.

Szeinbach, et al.(1992). Role of consulting pharmacists in adverse drug reactionmonitoring. Consult Pharm, 7(9), 948-949.

Thomas, J. A.(1995). Drug-nutrient interactions. Nutrition Rev., 53(10), 271-282.

Walker, J. & Wynne, H.(1994). Review: The frequency and severity of adversedrug reactions in elderly people. Age & Aging, 23(3), 255-259.

Websites:

The Merck Manual of Pharmacology The Role of the Pharmacisthttp://www.merck.com/!!wC8L80tbNwC8LS04YV/pubs/mm_ geriatrics/22x.htm

module 4 medication therapy problems 2012

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