Case Presentation

B.L. is a 58-year-old white woman who has been referred to the pharmacist clinician for pharmacotherapy assessment and diabetes management. Her multiple medical conditions include type 2 diabetes diagnosed in 1995, hypertension, hyperlipidemia, asthma, coronary artery disease, persistent peripheral edema, and longstanding musculoskeletal pain secondary to a motor vehicle accident. Her medical history includes atrial fibrillation with cardioversion, anemia, knee replacement, and multiple emergency room (ER) admissions for asthma.

B.L.’s diabetes is currently being treated with a premixed preparation of 75% insulin lispro protamine suspension with 25% insulin lispro preparation (Humalog 75/25), 33 units before breakfast and 23 units before supper. She says she occasionally “takes a little more” insulin when she notes high blood glucose readings, but she has not been instructed on the use of an insulin adjustment algorithm.

Her other routine medications include the fluticasone metered dose inhaler (Flovent MDI), two puffs twice a day; salmeterol MDI (Serevent MDI), two puffs twice a day; naproxen (Naprosyn), 375 mg twice a day; enteric-coated aspirin, 325 mg daily; rosiglitazone (Avandia), 4 mg daily; furosemide (Lasix), 80 mg every morning; diltiazem (Cardizem CD), 180 mg daily (per cardiologist consult); lanoxin (Digoxin), 0.25 mg daily (per cardiologist consult); potassium chloride, 20 mEq daily; and fluvastatin (Lescol), 20 mg at bedtime. Medications she has been prescribed to take “as needed” include sublingual nitroglycerin for chest pain (has not been needed in the past month); furosemide, additional 40 mg later in the day if needed for swelling (on most days the additional dose is needed); and albuterol MDI (Proventil, Ventolin), two to four puffs every 4–6 hours for shortness of breath. She denies use of nicotine, alcohol, or recreational drugs; has no known drug allergies; and is up to date on her immunizations.

B.L.’s chief complaint now is increasing exacerbations of asthma and the need for prednisone tapers. She reports that during her last round of prednisone therapy, her blood glucose readings increased to the range of 300–400 mg/dl despite large decreases in her carbohydrate intake. She reports that she increases the frequency of her fluticasone MDI, salmeterol MDI, and albuterol MDI to four to five times/day when she has a flare-up. However, her husband has been out of work for more than a year, and their only source of income is her Social Security check. Therefore, she has been unable to purchase the fluticasone or salmeterol and so has only been taking prednisone and albuterol for recent acute asthma exacerbations.

B.L. reports eating three meals a day with a snack between supper and bedtime. Her largest meal is supper. She states that she counts her carbohydrate servings at each meal and is “watching what she eats.” She has not been able to exercise routinely for several weeks because of bad weather and her asthma.

The memory printout from her blood glucose meter for the past 30 days shows a total of 53 tests with a mean blood glucose of 241 mg/dl (SD 74). With a premeal glucose target set at 70–140 mg/dl, there were no readings below target, 8% within target, and 91% above target. By comparison, her results from the same month 1 year ago averaged 112 mg/dl, with a high of 146 mg/dl and a low of 78 mg/dl.

Physical Exam

B.L. is well-appearing but obese and is in no acute distress. A limited physical exam reveals:

• Weight: 302 lb; height 5′1″

• Blood pressure: 130/78 mmHg using a large adult cuff

• Pulse 88 bpm; respirations 22 per minute

• Lungs: clear to auscultation bilaterally without wheezing, rales, or rhonchi

• Lower extremities +1 pitting edema bilaterally; pulses good

B.L. reports that on the days her feet swell the most, she is active and in an upright position throughout the day. Swelling worsens throughout the day, but by the next morning they are “skinny again.” She states that she makes the decision to take an extra furosemide tablet if her swelling is excessive and painful around lunch time; taking the diuretic later in the day prevents her from sleeping because of nocturnal urination.

Lab Results

For the sake of brevity, only abnormal or relevant labs within the past year are listed below.

• Hemoglobin A_1c (A1C) measured 6 months ago: 7.0% (normal range: <5.9%; target: <7%)

• Creatinine: 0.7 mg/dl (normal range: 0.7–1.4 mg/dl)

• Blood urea nitrogen: 16 mg/dl (normal range: 7–21 mg/dl)

• Sodium: 140 mEq/l (normal range: 135–145 mEq/l)

• Potassium: 3.4 mg/dl (normal range: 3.5–5.3 mg/dl)

• Calcium: 8.2 mg/dl (normal range: 8.3–10.2 mg/dl)

• Lipid panel

      • Total cholesterol: 211 mg/dl (normal range <200 mg/dl)

      • HDL cholesterol: 52 mg/dl (normal range: 35–86 mg/dl; target: >55 mg/dl, female)

      • LDL cholesterol (calculated): 128 mg/dl (normal range: <130 mg/dl; target: <100 mg/dl) Initial LDL was 164 mg/dl.

      • Triglycerides: 154 mg/dl (normal range: <150 mg/dl; target: <150 mg/dl)

• Liver function panel: within normal limits

• Urinary albumin: <30 μg/mg (normal range: <30 μg/mg)

Assessment

• Poorly controlled, severe, persistent asthma

• Diabetes; control recently worsened by asthma exacerbations and treatment

• Dyslipidemia, elevated LDL cholesterol despite statin therapy

• Persistent lower-extremity edema despite diuretic therapy

• Hypokalemia, most likely drug-induced

• Hypertension JNC-VI Risk Group C, blood pressure within target and stable

• Coronary artery disease, stable

• Obesity, stable

• Chronic pain secondary to previous injury, stable

• Status post–atrial fibrillation with cardioversion

• Status post–knee replacement

• Financial constraints affecting medication behaviors

• Insufficient patient education regarding purposes and role of specific medications

• Wellness, preventive, and routine monitoring issues: calcium/vitamin D supplement, magnesium supplement, depression screening, osteoporosis screening, dosage for daily aspirin

Discussion

Strand et al.1 proposed a systematic method for evaluation of and intervention for a patient’s pharmacotherapy, using a process called the Pharmacist’s Work-Up of Drug Therapy (PWDT). The PWDT has been modified by subsequent authors,2–4 but the process remains grounded in the following five questions:

1. What are reasonable outcomes for this patient?

2. Based on current guidelines and literature, pharmacology, and pathophysiology, what therapeutic endpoints would be needed to achieve these outcomes?

3. Are there potential medication-related problems that prevent these endpoints from being achieved?

4. What patient self-care behaviors and medication changes are needed to address the medication-related problems? What patient education interventions are needed to enhance achievement of these changes?

5. What monitoring parameters are needed to verify achievement of goals and detect side effects and toxicity, and how often should these parameters be monitored?

Outcomes and Endpoints

Clinical outcomes are distinctly different from therapeutic or interventional endpoints. The former refers to the impact of treatment on patients’ overall medical status and quality of life and should emphasize patient-oriented evidence that matters (POEMs) rather than disease-oriented evidence (DOEs).

Therapeutic endpoints include the anticipated and desired clinical effects from drug therapy that are expected, ultimately, to achieve the desired outcome(s). As such, therapeutic endpoints are used as surrogate markers for achievement of outcomes. Commonly, more than one endpoint will be needed to achieve an outcome. For example, near-normal glycemic control and normalization of blood pressure (endpoints) would be necessary to significantly reduce the risk of end-stage renal disease (outcome).

Therapeutic endpoints should be specific, measurable, and achievable within a short period of time. Achievement of clinical outcomes usually cannot be determined except by long-term observation or retrospective analysis.

Outcomes and endpoints for any given patient should be determined collaboratively between patient and provider before selecting or initiating pharmacotherapy or nonpharmacological interventions. Taking the time to identify these components up front (and periodically revise them later on) helps ensure that subsequent medications or strategies are appropriately directed. It further ensures a common vision and commitment for ongoing patient care and self-management among the care team (including the patient), thus maximizing the potential for optimal disease control and patient satisfaction.

The outcomes and endpoints for a patient such as B.L. are numerous and obviously would not be addressed or attained in a single session. Therefore, after desired outcomes and endpoints are determined, they should be prioritized according to medical urgency and patient preference. Implementation and goal setting related to these priorities can then be undertaken, thus establishing a treatment plan for the eventual attainment of the full list.

During ongoing and follow-up visits, this care plan should be reviewed and modified as indicated by changes in patient status, preferences, and medical findings. Examples of desired outcomes and endpoints for B.L. are given in Tables 1 and 2. For the sake of brevity, these tables are not intended to be inclusive.

Medication-Related Problems and Proposed Interventions

With agreement between patient and clinician concerning desired outcomes and endpoints, the next logical step is to evaluate whether the current treatment plan is likely to achieve those goals, or, if treatment is to be initiated, which therapies or interventions should be selected.

According to Strand et al.,1 a medication-related problem is any aspect of a patient’s drug therapy that is interfering with a desired, positive patient (therapeutic) outcome or endpoint. The PWDT proposes a systematic and comprehensive method to identify, resolve, or prevent medication-related problems based on the following major categories:

1. No indication for a current drug

2. Indication for a drug (or device or intervention) but none prescribed

3. Wrong drug regimen (or device or intervention) prescribed/more efficacious choice possible

4. Too much of the correct drug

5. Too little of the correct drug

6. Adverse drug reaction/drug allergy

7. Drug-drug, drug-disease, drug-food interactions

8. Patient not receiving a prescribed drug

9. Routine monitoring (labs, screenings, exams) missing

10. Other problems, such as potential for overlap of adverse effects

Once problems are identified, resolutions must be developed, prioritized, and implemented. Patient or caregiver input is especially helpful at this stage because the individual can describe subjective as well as objective data, expectations or concerns that may be affecting drug therapy, and deficits in drug knowledge, understanding, or administration.

Resolutions may result from numerous strategies, including dose alteration, addition or discontinuation of medication, adjunct medications, regimen adjustment, complementary therapies, instruction on medication administration or devices, disease or medication education, development of “cues” as compliance reminders (e.g., pill boxes), and identification of ways to avoid, detect, or manage side effects or toxicities. Needless to say, the involvement of patients and family or caregivers is critical for successful implementation of most resolution strategies and for optimal disease management.

Because of the extent of B.L.’s medication-related problems and potential interventions (Tables 3 and 4), it was agreed to tackle first her asthma exacerbations and high blood glucose levels. To this end, B.L. was counseled about the role of maintenance asthma medications versus rescue drugs. The root of her confusion between these agents was easy to understand—because the prednisone and fluticasone were both called steroids, it seemed likely that the tablets were a cheaper and easier way to take the medicine. Likewise, since albuterol and salmeterol were both called bronchodilators, it seemed that the albuterol was the cheaper way to take the medicine.

Having grasped the concept of asthma prevention, she was willing to convert to a product combining fluticasone and salmeterol (Advair Diskus) for maintenance/prevention and to reserve the albuterol for quick relief of acute symptoms. Free samples of the new product were dispensed, and B.L. was enrolled in the manufacturer’s indigent drug program for subsequent supplies.

She was further instructed on the use of a peak flow meter and advised to monitor her readings and symptoms. At the next visit, these data will be used to determine her maximal expiratory effort (“personal best”) and to construct an asthma action plan.

B.L.’s insulin was changed to a basal-based regimen utilizing bedtime glargine (Lantus) insulin and premeal lispro (Humalog) insulin. Education was provided on this dosing concept. She and the pharmacist discussed how this regimen can give greater flexibility in dosing, especially for responding to changes in diet, exercise, and disease exacerbations or medications. She was also given an initial supplementary adjustment algorithm (sliding scale) to correct for any temporary elevation of blood glucose. She agreed to test four times daily and to record her blood glucose results, carbohydrate intake, and insulin doses. At the next visit, these data will be used to modify the adjustment algorithm and to construct a prospective algorithm for matching premeal bolus insulin to the anticipated carbohydrate intake (insulin-to-carbohydrate ratio).

The final interventions for this visit were to increase the dose of potassium chloride and change the fluvastatin to atorvastatin (Lipitor) to further reduce B.L.’s LDL cholesterol. Medication education for atorvastatin was provided, and patient questions were answered.

Other medication-related problems and interventions identified for B.L. are listed and briefly discussed in Tables 3 and 4. For the sake of brevity, these lists are not inclusive nor are all pharmacotherapy issues discussed.

Monitoring for Effectiveness, Side Effects, and Toxicity

The last step in the PWDT process is to develop a plan to evaluate the patient’s progress in attaining desired outcomes, therapeutic endpoints, and behavior changes; to assess effectiveness of pharmacotherapy; and to identify side effects, drug interactions, or toxicity issues that need to be addressed.

The monitoring/follow-up component is the most tedious aspect of the PWDT. For each medication or intervention, key parameters must be identified as markers for effectiveness, for side effects, for drug interactions, and for toxicity. In addition, the time frame and process for assessing those parameters must be determined. Finally, the desired range for the parameter must be listed or a “decision point” must be identified to signal that additional action will be required.

It should be noted that only a limited number of parameters are selected for a given patient. For example, it is not necessary to list and monitor for every possible side effect with equal intensity and frequency. Selection of the monitoring parameters is based on the positive effects (efficacy) that are most important to the care of that patient, as well as the adverse effects (side effects, toxicity, or drug interactions) that are most important to avoid for the safety of that patient or to which that patient is most prone.

Because the monitoring component is usually extensive, examples listed for B.L. in Table 5 have been limited to three of the medication or regimen changes that were made at the first pharmacist visit: switching from fluvastatin to atorvastatin; switching from two shots of premixed 75/25 lispro to bedtime glargine with premeal lispro; and substituting the combination inhaler product for her fluticasone and salmeterol MDI prescriptions. Because atorvastatin and fluvastatin differ chemically, the monitoring parameters for this change are similar to those for initiation of a new medication. Monitoring for the new insulin regimen (basal insulin with premeal bolus) focuses primarily on glycemic control patterns and hypoglycemic episodes. Because B.L. has previously used the two ingredients of her new inhaler product (fluticasone and salmeterol) without adverse effect, monitoring of her new asthma therapy is focused on effectiveness, tolerance of inhalation of its dry powder formula, and use of the administration device.

Summary

Diabetes patients with multiple co-morbidities have concerns about all of their problems, not just the diabetes; therefore, BC-ADM pharmacists must comprehensively explore all the ramifications of comorbidities as well as patients’ feelings, expectations, and concerns for total health. B.L. is a good example of this; even though her referral was for “diabetes management,” her greatest concern at this visit was her asthma exacerbations.

As can be seen in this case, each coexisting disease or coprescribed drug has a domino effect, affecting other diseases or drugs and ultimately affecting quality of life. With input from B.L., the pharmacist clinician was able to develop a PWDT that addresses her diabetes as well as her other health care needs.

B.L. was able to leave the health center with a few achievable self-care goals and medication changes that address her acute concerns and with the knowledge and confidence that, at each subsequent visit, additional progress will be made toward her personalized health status goals.