Module 04: Medication Therapy Problems

Current Content Expert Kevin W. Chamberlin, PharmD Assistant Clinical Professor University of Connecticut School of Pharmacy & UConn Center on Aging Legacy Content Expert H.E. Davidson, PharmD, MPH Partner, 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 be able to: Develop the primary responsibilities of the consulting pharmacist through identifying, prioritizing, resolving and preventing medication therapy problems. Develop strategies for determining if a given drug is appropriate for a geriatric patient. Examine the major types of medication problems that can occur based on the administration of drug therapy. Examine the major types of medication problems that can occur based on the patients response to therapy.

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 interferes with a desired patient outcome (Strand LM, Morley PC, Cipolle RJ. Drug-related problems: their structure and function. DICP 1990; 24:1093-7).

A medication therapy problem is any undesirable event experienced by the patient that is thought to involve drug therapy, and that actually or potentially interferes with a desired patient outcome. Medication therapy problems are central to the practice of pharmaceutical care. Not only are such problems costly in terms of wasted resources, they also prevent patients from experiencing the benefits of appropriate therapy, delaying recovery and compromising health. For these reasons, it is important that the consulting pharmacist not only understands the causes of medication therapy problems, but also assumes responsibility for identifying, resolving when they occur 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 that affect pharmacology C. They tend to substitute other drugs for those prescribed in the therapeutic regimen D. There is little research to guide decisions in geriatric pharmacology ANSWER: B

04.01.02 Incidence of Medication Therapy Problems Percentage of patients who experience medication therapy problems

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

Not surprisingly, the most frequently encountered drug therapy problems are those involving the most frequently seen patients and most frequently used medications. According to data collected for the Minnesota Pharmaceutical Care Project, drug therapy problems were identified in 37% of the nearly 1000 patients receiving pharmaceutical care in the study. Almost 15% had multiple medication therapy problems at some time during their care. A study by Fouts, et al., found that 23.8% of long-term care facility residents had four or more risk factors for medication therapy problems.

04.01.03 Risk Factors for Medication Therapy Problems in the Elderly Specific Medications digoxin warfarin lithium Classes of Medications: Prevalence (%) 17.1 6.0 2.4 Prevalence (%)

anticholinergics narcotic analgesics benzodiazepines with half-life 10-24 h antipsychotics anticonvulsants benzodiazepines with half-life > 24 h

36.5 19.4 11.5 11.1 10.7 4.0

sedative/hypnotics

0.8

Patient Characteristics:

Prevalence (%) 73 70.2 42.9 42.1 40.5 36.9 24.2

no. of active chronic medical diagnoses (> 6) renal function < 50ml/min low body weight prior adverse drug reactions age > 85 no. of doses of medications/day (> 12) 9 or more medications

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

The Fouts study identified 18 risk factors for medication therapy problems among elderly residents of long-term care facilities. They are listed here, with their prevalence. The risk factors include specific medications such as digoxin and warfarin, classes of medications such as anticonvulsants and antipsychotics, and patient 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 of drug-related problems!

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

Medication-related morbidity and mortality within the long-term care facility represents not only a serious health concern, but a major economic problem as well. Medication-related problems in ambulatory facilities, hospitals, and nursing homes combined cause thousands of deaths a year and may cost as much as one hundred billion dollars annually in health care resources. Without pharmaceutical care, Bootman estimates the cost of medication-related problems in long-term care facilities alone to be $7.6 billion. For every $1 dollar spent on drugs in the nursing home, it has been estimated that $1.33 worth of health 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 effective available, 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 optimal outcomes are realized

With current federally mandated drug regimen reviews, it is estimated that consulting 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 human and financial costs of medication-related problems. First, the pharmacist makes sure that the patients drug therapy is indicated, is the most effective available, is the safest possible, and can be taken as indicated. Second, the pharmacist identifies, resolves, and prevents drug

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

04.01.06 Difficulties in Selecting Appropriate Medication Therapy in the Elderly

Multiple interacting factors influence age-related changes in drug pharmacology There is wide individual variation in the rate of age-related changes that affect pharmacology The clinical status of each patient (e.g., nutrition and hydration, cardiac output, intrinsic renal and liver disease) must be considered in addition to the effects of aging Research in geriatric pharmacology is still in its infancy

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

The role of the consulting pharmacist is especially challenging in the geriatric setting. Several factors make the development of specific recommendations for elderly patients very difficult.

04.01.07 Other Factors that May Interfere with the Successful Medication Therapy in the Elderly

Image: http://flylib.com/books/en/1.431.1.20/1/ Source: Kane, R. L., Ouslander, J. G., & Abrass, I. B.(1994). Essentials of clinical geriatrics. New York: McGraw-Hill. p. 353. In addition to these biophysical factors, compliance plays a major role in the success of geriatric medication therapy. Some of the barriers to compliance faced by the elderly include complex dosing schedules, polypharmacy, and the chronic nature of illness. The potential effects of these barriers on the success of medication therapy are shown in the chart.

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 to categorize problems with similar characteristics. Categorizing medication-related problems clarifies the distinctions between one type of problem, such as adverse drug reactions, and other types of problems. Another benefit is that enables consulting pharmacists to identify and clarify their own professional responsibilities in the prevention or resolution of such problems. The categories may help the consulting pharmacist develop systematic processes for achieving successful therapeutic outcomes, and providing a common vocabulary for the discussion of medication-related problems with colleagues and patients alike.

04.01.09 Stating the Medication Therapy Problem Poor method of stating the problem: Inappropriate drug therapy

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 serious consideration to how specific medication therapy problems should be stated. How a medication therapy problem is stated not only determines how the problem will be resolved, but also how it will affect other aspects of the care plan as well. Keep in mind that specific is better. Inappropriate drug therapy is not as useful as 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 is likely to occur = RISK The patients perception of the potential harm

Once the medication therapy problem has been properly defined, it must be prioritized in terms of urgency. Prioritization is important, since data from the Minnesota Pharmaceutical Care Project reveals that almost fifteen percent of all patients have two or more medication therapy problems, and five percent have more 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 to occur, and the patients perception of the potential harm. The first two constitute the risk confronting the patient.

04.01.11 Medication Therapy Problems: Role of the Patient

Self-reported problem Perceived benefit of therapy

Sometimes the patient him-/her-self will identify a medication therapy problem, either through self-examination and diagnosis, or comparisons with similar experiences of family or friends. While the philosophy of patient-centered care dictates that such self-reports are given the full attention of the consulting pharmacist, there is an even more compelling reason to pay attention to these reports: compliance. Studies have shown that 65% of elderly patients will stop taking a medication if they do not feel they are experiencing its benefits. The power of patient perceptions of drug therapy problems should not be underestimated. 04.01.12 Algorithm Resolving a Medication Therapy Problem

Once a medication therapy problem has been assessed in terms of its risk potential and related patient perceptions, the consulting pharmacist must consider which problems can be solved immediately and which problems can wait. The pharmacist must also consider who is best equipped to resolve each problem. Is it a primary responsibility of the pharmacist? Does it need to be collaboratively resolved by the pharmacist and patient? Or does it require the intervention of a family member, a primary physician, or a medical specialist? Once these questions have been answered, the consulting pharmacist can mobilize 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 might adversely interact with other drugs Consider how the clinical status of each patient could influence the pharmacology and effectiveness of the drug(s) Be sensitive to potential barriers to compliance (e.g., impaired cognitive function, diminished vision and hearing, cultural barriers) For drugs or their active metabolites that are renally eliminated, make appropriate 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

Source: Kane, R. L., Ouslander, J. G., & Abrass, I. B.(1994). Essentials of clinical geriatrics. New York: McGraw-Hill. p. 373. Medication therapy problems in the elderly may be minimized by applying the guidelines listed here. While many of these guidelines will seem obvious to the consulting pharmacist, they are worth repeating here. For example, a thorough evaluation of the patient will help identify all conditions that may benefit from drug treatment and any conditions that will be adversely affected by drug treatment. Carefully consider how the clinical status of the patient might affect the pharmacology an effectiveness of the drugs being prescribed. Consider also how the cognitive and psychosocial status of the

patient might affect compliance with the therapeutic regimen. If there is uncertainty about the correct dosage, start low and go slow. Monitor the patient frequently 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 drugrelated morbidity and mortality in nursing facilities. Arch Intern Med; 157:208996. Cipole, R. J., Strand, L. M. & Morley, P. C. (2004).Pharmaceutical care practice.New York: McGraw Hill. Fouts, M., Hanlon, J., Peiper, C., Perfetto, E., & Feinberg, J.(1997). Identification of elderly nursing facility residents at high risk for drug-related problems.Consult Pharm; 12(10): 1103-11 Gurwitz, J. H., Soumerai, S. B. & Avorn, J.(1990).Improving medication prescribing 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, and Co. Strand L.M., Morley P.C., Cipolle R.J. (1990) Drug-related problems: their structure and function.DICP; 24:1093-7 Williams, B. R., Thompson, J. F., & Brummel-Smith, K. V.(1993). Improving medication 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, ASCP Consultants Forum, January, 1997. http://www.ascp.com/public/pubs/tcp/1997/jan/consultant.html

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

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

Medication therapy problems can arise when inappropriate interventions are chosen. At one end of the spectrum, the patient may have a medical condition that requires new or additional drug therapy. Problems can occur when the patient is at high risk to develop a condition for which therapy is indicated as primary or secondary prevention. At the other end of the spectrum, the patient may be taking a drug for which there is no medical indication. In this case, problems occur when the patient develops a new condition based on the use of this unnecessary drug. This is illustrated in the prescribing cascade, where a new medication is added based on a new medical condition caused by a medication. In the example shown, 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 develops a new condition based on the use of a drug, which is inappropriate for his or her current medical disorder.

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 combination pharmacotherapy to obtain synergism/potentiate effects Patient is at risk to develop a new medical condition which could be prevented by the use of prophylactic drug therapy or and/or premedication

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

Consider the first of these potential problems. Data from the Minnesota Pharmaceutical Care Project reveal that almost twenty percent of medication therapy problems involve patients who need additional or new drug therapy. The need for additional therapy can be caused by a variety of circumstances. For example, the patient may have a new medical condition that requires new therapy. Or he or she may have a chronic disorder requiring the continuation of drug therapy. The patient may require combination pharmacotherapy to treat a current condition, or prophylactic (i.e. preventive) therapy to treat an anticipated condition. The use of low risk prophylactic therapy, such as low dose aspirin for secondary prevention of myocardial infarction or stroke, is often overlooked in the elderly.

04.02.03 Inadequate Drug Therapy: Continuity Issues

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

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 care practice.New York: McGraw Hill. The Centers for Medicare and Medicaid Services (CMS) define unnecessary medications as any medication used without adequate indications for its use. Examples include:

Improper medication selection (i.e. wrong medicine for the condition being treated 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 Manual http://www.cms.hhs.gov/manuals/107_som/som107ap_pp_guidelines_ltcf.pdf.

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

The second potential medication problem related to choice of therapy is the use of drugs that are unnecessary. This type of problem is often overlooked by the pharmacist, who is responsible for ensuring that patients are protected from the toxic effects of drugs for which there is no valid medical indication. Unnecessary drug therapy can also occur as a result of recreational drug use, self-selected herbal remedies, duplicative therapy, and treatment of avoidable adverse drug reactions. According to the Minnesota Pharmaceutical Care Project, 7% of drug therapy problems identified and resolved by pharmacists are due to the use of unnecessary drugs. Additionally, the CMS definition for an unnecessary medication has been provided along with examples.

04.02.06 Unnecessary Drug Therapy: Combination Therapy

Sometimes patients receive combination therapy when a single agent would be equally effective. This problem often occurs with patients in long-term care facilities. That is why pharmacists who consult to such facilities are expected to identify patients who receive more than one agent for any given condition when only 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 that are potentially addictive and abused. While the laws regarding illegal drug taking may vary from place to place, the ethical obligation of the practicing pharmacist to provide pharmaceutical care to patients remains constant. The pharmacist must act to reduce harm to anyone at medical risk, regardless of legal status of the drugs being considered for treatment, or the societal consequences of the patients conduct.

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 a particular drug, the clinician must consider the possibility that the drug is inappropriate. Data from the Minnesota Pharmaceutical Care Project reveal that 17% of medication problems encountered by pharmacists involve patients receiving the wrong drugs. The high percentage of such errors is especially disturbing considering the extent to which the use of drugs are controlled through formularies, patient management protocols, drug utilization reviews and electronic 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 diagnosis of the patients medical condition. Factors that contribute to making a particular medication the right or wrong choice for a given patient include the nature of the patients medical condition, the severity of the condition, the infectious process and the organism involved, and the age and general health status of the patient. For example, an asthma patient using propranolol to treat hypertension may be using the wrong drug for blood pressure control, especially if they are using a beta-agonist for asthma treatment. Although propranolol may adequately control the patients blood pressure, it is said that the patient has a drug therapy problem because of the bronchoconstrictive properties of the beta-blocker. A patient may also be using the wrong drug if he or she is allergic to the agent.

04.02.10 Age-related Changes Relevant to Drug Pharmacology Changes in Absorption:

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 clinical geriatrics. New York:McGraw-Hill. p. 360. Natural age-related changes also play a role in the success of medication therapy. In the elderly, changes in absorption, distribution, metabolism, excretion, and tissue sensitivity can alter the effectiveness or toxicity of a given agent, 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 effective alternative that is less expensive. In these situations it is important to ensure that there is objective evidence to support the claim that both medications are equally effective, and that there is no significant difference in potential toxicities.

04.02.12 Key Medications That May be Potentially Inappropriate for Some Older Adults amiodarone amitriptyline amphetamines barbiturates chlordiazepoxide chlorpropamide cimetidine clonidine cyclandelate daily fluoxetine dessicated thyroid digoxin* diphenydramine dipyridamole disopyramide doxazosin doxepin ergot mesyloids estrogens ethacrynic acid flurazepam guanadrel guanethidine indomethacin isoxsuprine ketardac lorazepam meperidine meprobamate mesoridazine methocarbamol Methylfopa methyltestosterones mineral oil nitrofurantoin orphenadrine pentazocine phenylbutazone potassium supplements propoxyphene reserpine** short-acting nifedipine stimulant laxatives thioridazine ticlopidine trimethobenzamide

* digoxin >0.125 mg in heart failure ** reserpine >0.1 mg/day 2012 Beers Criteria: http://www.americangeriatrics.org/health_care_professionals/clinical_practice/clin ical_guidelines_recommendations/2012

A consensus panel of geriatric experts, including pharmacists, has developed a list of explicit criteria for determining whether or not certain medications are appropriate for elderly patients. The criteria also outline medical conditions under which selected medications may be inappropriately used in the geriatric population. Some of these medications may be inappropriate only for individuals with selected medical conditions.

All of the following medications are included in the list of medications considered inappropriate for use in the elderly, according to Beers and colleagues, except: A. B. C. D. E. Amitriptyline Diphenhydramine Ciprofloxacin Methyldopa Meperidine

ANSWER: C. Fluoroquinolones are generally not considered inappropriate for use 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 equal utility?

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

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

The Medication Appropriateness Index (MAI), as proposed by Hanlon et al, considers all of the following, except: A. B. C. D. Is there unnecessary duplication with other drugs? Is the duration of therapy of therapy acceptable? Is the dosage form appropriate based on patient specific factors? 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 in producing desirable outcomes? Does the alternative drug demonstrate a significant advantage in reducing undesirable 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 other agents that have a higher probability of producing the desired outcomes, when there are other agents with a lower probability of producing undesirable outcomes, or when there are other agents equally effective but less costly. However, it is important to keep in mind that the difference between alternative medications may not be enough to justify a change in therapy. A drug that is expected to be effective in seventy-five percent of patients and another that is expected to be effective in ninety-five percent can still both be appropriate drug for a patient experiencing positive outcomes. Patient preferences also play a role. 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 For additional information, see:

Beers, M. H.(1997). Explicit criteria for determining potentially inappropriate medication use by the elderly. Arch Intern Med; 157:1531-1536. Cipole, R. J., Strand, L. M. & Morley, P. C. (1998).Pharmaceutical care practice.New York: McGraw Hill. Fick DM, Cooper JW, Wade WE et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med 2003;163:2716-24. Hanlon, J. T., Schmader, K. E., Samsa, G. P., et al.(1992).A method for assessing drug therapy appropriateness. J Clin Epidemiol; 45(10): 1045-51. Montamat, S. C. & Cusack, B.(1992). Overcoming problems with polypharmacy and 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, and Co. Websites: Agency for Healthcare Research and Quality (AHRQ) http://www.ahrq.gov/

Module 4, Section 3: Problems Related to the Administration of Therapy

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 to medication problems. A patient may receive too little of the appropriate drug, negating the best diagnostic and therapeutic efforts. Or a patient may receive too much of the appropriate drug, with the potential for adverse effects. Finally, a patient may experience an adverse reaction based on the interaction of an otherwise appropriate drug and other 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

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

Drug therapy problems resulting from patients receiving inadequate doses of potentially effective medications are a serious concern. The Minnesota Pharmaceutical Care Project estimated that 14% of patients are being underdosed on their medications. The causes of underdosing are many and varied.

04.03.03 Drug Dosage Too Low: Safety Issues One of the more insidious causes of underdosing is misplaced concern about patient safety. Although frequently prescribed medications such as amoxicillin, ibuprofen, and ciprofloxacin are both effective and safe, clinicians may favor more conservative therapeutic regimens, especially at the outset. However, considering that published dosing guidelines tend to be conservative to begin with, such strategies often condemn the patient to days or weeks of ineffective drug therapy. Conservative start-up regimens require frequent followup 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 when prescribing any therapeutic regimen. Patients may deliberately underuse their medications to avoid unpleasant side effects. It is important to consider that this form of intelligent noncompliance may be a valid response by patients who may be compensating for physiological attributes 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 the absolute amount of the drug being taken. For example, a patient may be receiving too little medication if the dosing interval is inappropriately prolonged. This can happen when preparations designed for extended use are replaced with preparations that are more rapidly absorbed. Patients may also receive inadequate medication if therapeutic regimen is discontinued prematurely, before its full benefits are realized. This often happens when dosages effective with one type of disorder, such as an uncomplicated urinary tract infection, are applied to related but more complex disorders, such as pyelonephritis.

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 concentration tests are necessary not only to avoid overdoses and toxicities, but also to ensure that 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, so can excessive amounts of medication. Reduced renal function and a diminished ability to eliminate certain types of drugs makes older adults especially susceptible to overdoses and their toxic effects. Many elderly patients also have diminished cardiac reserve, making them vulnerable to the hypotensive effects of cardiovascular drugs, as well as antidepressant 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 experience drug therapy problems related to excessive amounts of medication if the absolute dosage or concentration of the drug is too high, if the patient 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 not experiencing the anticipated benefits of medication. An elderly patient, for example, may increase the recommended dose of arthritis medication to relieve residual pain. The systemic or localized effects of excessive medication are generally 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

When the risk of drug accumulation and toxicity is high, measurement of serum or blood drug concentration is essential. Pharmacokinetic monitoring with dosage individualization is also invaluable in preventing this type of drug problem. For example, patients who require acute, short-term antithrombotic therapy with heparin depend on coagulation tests to determine the appropriate dose and reduce the risk of excessive bleeding. Patients who are on long-term anticoagulation therapy with warfarin similarly benefit from measurements of the INR (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 complications associated with psychotropic drugs, the 1990 Omnibus Budget Reconciliation Act requires biannual documentation of efforts to reduce dosage levels for Medicaid recipients. Rather than determining specific dosage regimens for individual patients, these guidelines are intended to encourage regular drug regimen reviews in long-term care facilities. Guidelines from the CMS also specify suggested 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 the most frequently cited cause of drug therapy problems, yet they are the least understood. Some interactions are simply the pharmacology of one drug combined with the pharmacology of another drug. Others are not only difficult to identify and characterize, but their resolution is often very complex because of the intricate nature of the interaction.

04.03.12 Top Ten Dangerous Drug Interaction in Long-Term Care 1. Warfarin and NSAIDs 2. Warfarin and Sulfa Drugs 3. Warfarin and Macrolides 4. Warfarin and Quinolones 5. Warfarin and Phenytoin 6. ACE Inhibitors and Potassium Supplements 7. ACE Inhibitors and Spironolactone 8. Digoxin and Amiodarone 9. Digoxin and Verapamil 10. 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 based on frequency of use in older adults and the potential for adverse consequences if used together.

04.03.13 Problems Resulting from Drug-Drug Interactions Problem Interference with drug absorption Displacement from binding protein Altered distribution Altered metabolism Altered excretion Pharmacological Antagonism Pharmacological Synergism Example antacid+digoxin, INH, ciprofloxacin warfarin, ASA, oral hypoglycemics digoxin+quinidine clarithromycin + carbamazepine, digoxin lithium+diuretics imbalance levodopa+clonidine antihypertensives + TCAs Potential Effects decreased effectiveness enhanced effects, greater toxicity greater toxicity decreased drug clearance, enhanced effect, greater toxicity greater toxicity, electrolyte imbalance decreased anti-Parkinsonian effects increased risk of hypotension

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

For example, anticonvulsants, which are commonly associated with drug-drug interactions, can induce the metabolism of other anticonvulsants taken concurrently. Competition between agents for similar binding sites can elevate concentrations of one or both drugs to toxic levels. Drugs can even disrupt their own metabolism.

For example, initial carbamazepine therapy for the control of seizure often makes patients drowsy and lethargic. This is due to auto-induction of the hepatic enzyme systems that are responsible for the metabolism of the carbamazepine itself that takes roughly 3-4 weeks to complete with initiation of therapy or subsequent change in dosage.

Which of the following combinations is most likely to produce a negative drugdrug interaction by altering the distribution of medication? A. B. C. D. E. Lithium + furosemide Cimetidine + phenytoin Digoxin + quinidine Levodopa + clonidine All of the above

CORRECT ANSWER: C. Lithium and diuretics produce negative drug-drug interactions via altered excretion that leads to electrolyte abnormalities and increased potential for lithium toxicity. Cimetidine and phenytoin interact likely via inhibition of CYP450 2C19-mediated phenytoin metabolism, prompting elevated phenytoin levels and decreased clearance of phenytoin. Literature and case reports suggest clonidine decreases the effects of levodopa in Parkinsons patients. Quinidine likely inhibits the pglycoprotein transport system that digoxin is dependent upon, reducing digoxins clearance and volume of distribution, resulting in a likely digoxin toxic situation in the patient.

04.03.14 Polypharmacy and Potentially Inappropriate Drug Combinations

Drug-drug interactions are especially problematic in the elderly because of their increased need for polypharmacy. Studies show that the average nursing home resident is prescribed 5-8 regularly scheduled medications in addition to those administered on an as-needed basis. One reason for this is that the patient with multiple chronic diseases is often seen by more than one medical specialist who contributes to the health care plan.

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

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

04.03.15 Other Potential Sources of Drug-Drug Interactions

Medications from previous treatment programs Medications shared by family and friends Nonprescription medications
o o o o

laxatives analgesics vitamins/minerals cold or cough preparations

The use of prescription medications from previous treatment programs and medications shared by family and friends can also contribute to drug-drug interactions. Such medications are often past the expiration date. Nonprescription medications, used by the majority of older adults, may also provoke drug-drug interactions. Laxatives, for example, must be used with caution by elderly patients taking digitalis preparations. Other nonprescription medications used frequently by the elderly include analgesics, laxatives, vitamins/minerals, and cold or cough preparations.

04.03.16 Resources For additional information, see: 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 clinical geriatrics. New York: McGraw-Hill Monette, J., Gurwitz, J. H. & Avorn, J. (1995). Epidemiology of adverse drug events in the nursing home setting. Drugs Aging; 7(3): 203-11. Regal RE, Vue CO. Drug interactions between antibiotics and selective maintenance medications: seeing more clearly through the narrow therapeutic window of opportunity. Consult Pharm 2004;12:119-28.

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 and the role of polypharmacy. Ann Rev. Public Health, 13, 415-430. Tamblyn, R. M., McLeod,P.J., Abrahamowicz, M., Laprise, R.(1996). Do too many cooks spoil the broth? Multiple physician involvement in medical management 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 at http://www.amda.com/tools/clinical/m3/topten.cfm

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

Module 4, Section 4: Problems Related to Patients Response 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 to ensure that the patients drug therapy is effective. Such steps may be deliberately or inadvertently undermined by the patients own behavior. Or, they may be subverted by an adverse reaction to therapy. Sometimes, despite the clinicians 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 care practice.New York: McGraw Hill. While data from the Minnesota Pharmaceutical Care Project indicate that 12% of medication therapy problems are related to nonadherence, the percentage suggested in the literature is much higher. It has been estimated that as many as 70% of patients do not fully comply with their therapeutic regimens, for a variety of reasons. Patients may feel that the drug has caused or will cause them harm, or at least inconvenience. Some patients may feel the cost of the drug is too high, or they may not be able to afford it. Some may not be able to understand the instructions, while others may forget to take the medication entirely. Then there

are patients who cannot tolerate the dosage form of the medication. For example, as salivary flow declines with age, older patients may have trouble swallowing 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 and medications are important issues in determining the success of therapy. Some of the physical and cognitive changes associated with aging may affect the elderly patients ability to understand regimen demands and take medications appropriately. Sensory changes, such as impaired vision, and hearing, may affect the patients ability to read labels or understand the pharmacists instructions for use. The age-related decline in short-term memory makes it imperative that new therapeutic information be integrated with existing habits or past experience.

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 been reported in the literature in which patients swallowed chewable tablets whole, and had to undergo surgery to remove them. Aspirin tablets that patients allowed to dissolve in their mouth resulted in painful burns of the mucosa. Bulk laxatives have been taken without adequate fluids, necessitating surgical intervention. 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, large readable print on labels, etc. memory aids such as drug dosing calendars, telephone reminders for refills, etc.

Recognition of these age-related changes is important in promoting patient compliance. The psychological impact of illness must also be considered. An elderly patient who has been diagnosed with a chronic illness may initially experience 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 to counsel patients and explain the purpose of and appropriate use of each medication. Conveying drug information in simple terms, with frequent repetition and follow-up, is more likely to promote compliance.

Learning and memory aids such as drug-dosing calendars, the use of large, readable print on prescription labels, and telephone reminders for refills are also useful 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 is important to remember that much of nonadherence is learned behavior rather than a simple lack of knowledge about drug therapy. Assessing patients health care beliefs, as well as their expectations and concerns about taking medication is critical. Adherence is, after all, a leap of faith on the part of the patient that therapy will be in their best interest. Negative experiences, fears, cultural influences, habits, coping mechanisms and personality traits all play a role in adherence. Patients who 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 beliefs B. The patient's health care plan does not approve reimbursement for the drug C. The patient does not understand the instructions D. The patient's vision limitations CORRECT ANSWER: B.

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

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

While the vast majority of nonadherence problems are rooted in the knowledge and behavior of the patient, you must also consider administrative sources of nonadherence. 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 the approved formulary. The drug may not be approved for reimbursement, and is therefore not available to the patient. If ordered by post, the drug may be lost in the mail. The wrong drug may be dispensed, or the clinician may simply fail to administer it on schedule. Or there may be a technical problem with the drug delivery device or pump. It is important to establish the existence of these problems and take prompt corrective action. Administrative sources of patient nonadherence with therapy include all of the following except: A. B. C. D. The wrong drug is dispensed The drug product is not approved for reimbursement The patient does not understand the instructions The caregiver fails to administer the drug

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

04.04.08 Adverse Drug Reactions Adverse Drug Reaction (ADR): any undesirable negative effects caused by a medication 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 per 100 resident-months

Source: Gurwitz JH, Field TS, Judge J, et al. The incidence of adverse drug events in two large academic long-term care facilities. Am J Med 2005;118:2518 Adverse drug reactions have been described, analyzed, and quantified more than any other type of medication therapy problem. However, the lack of a consistent 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 undesirable negative effects caused by a medication that were not predicted based on the dosage, concentration dependency, or known pharmacology of the drug. The data from the Minnesota Pharmaceutical Care Project suggest that as many as 24% of patients experience an adverse drug reaction. Nearly half of all deaths attributed to adverse drug reactions occur in patients age sixty or over. In long term care, ADRs occur often, in about 1 in 10 residents/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

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

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 a drug product considered to be unsafe. Or the patient may have an allergic reaction to the drug. The drug may be administered improperly, or the dosage increased or decreased too rapidly. The drug may interact negatively with another drug, or the patient may simply have an adverse reaction that was otherwise 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 of medications should be used with particular precaution in the elderly. They include antihypertensives, antiparkinson agents, psychotropics, and cardiac glycosides. In the nursing home, medications most often associated with ADRs include 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 the onset of undesirable effects

Whether or not the patients condition improves when the drug is discontinued Whether the adverse event recurs when the patient is re-exposed to the drug

The patients health status can make it difficult to determine if an adverse drug reaction is directly attributable to the active ingredient of the drug, its preservatives, vehicles or metabolites. Nonspecific symptoms such as fatigue, headache, or drowsiness may be attributable to the use of medication, and underlying illness, or the patients natural constitution. Criteria which are often applied to make this determination include the temporal relationship between patient exposure to the drug and the onset of undesirable effects, whether or not the patients condition improves when the drug is discontinued, and whether the adverse event recurs when the patient is reexposed to the drug. Based on the extent to which it meets these criteria, an adverse reaction is classified 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 or prevent adverse drug reactions. For example, patients may vary widely in their sensitivity to heparin and the risk of bleeding, even when dosage regimens take into account patient factors such as age, gender, and body weight.

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

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

While many undesirable medication effects can be properly classified as adverse drug reactions, some cannot. Undesirable effects that are not considered adverse 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 medication therapy problems. Adverse drug-drug interactions are presented as a separate medication therapy problem in another section of this module.

04.04.14 Resources For additional information, see: Atkin, P. A. & Shenfield, G. M.(1995). Medication-related adverse reactions and the 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).926929. Fitten, L J., et al.(1995). Assessment of capacity to comply with medication regimens in older patients. J Am Geri Soc, 43, 361-367. Gurwitz JH, Field TS, Judge J, et al. The incidence of adverse drug events in two large academic long-term care facilities. Am J Med 2005;118:251-8.

Monette, J., Gurwitz, J. H. & Avorn, J.(1995). Epidemiology of adverse drug events 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(Suppl 1), 18-22. Szeinbach, et al.(1992). Role of consulting pharmacists in adverse drug reaction monitoring. 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 adverse drug reactions in elderly people. Age & Aging, 23(3), 255-259. Websites: The Merck Manual of Pharmacology The Role of the Pharmacist http://www.merck.com/!!wC8L80tbNwC8LS04YV/pubs/mm_ geriatrics/22x.htm