Cindy D. Stowe

Center for the Advancement of Pharmacy Education 2013 Educational Outcomes

An initiative of the Center for the Advancement of Pharmacy Education (formerly the Center for the Advancement of Pharmaceutical Education) (CAPE), the CAPE Educational Outcomes are intended to be the target toward which the evolving pharmacy curriculum should be aimed. Their development was guided by an advisory panel composed of educators and practitioners nominated for participation by practitioner organizations. CAPE 2013 represents the fourth iteration of the Educational Outcomes, preceded by CAPE 1992, CAPE 1998 and CAPE 2004 respectively. The CAPE 2013 Educational Outcomes were released at the AACP July 2013 Annual meeting and have been revised to include 4 broad domains, 15 subdomains, and example learning objectives.

24-Hour Ambulatory Blood Pressure Monitoring in Male Children Receiving Stimulant Therapy

OBJECTIVE: To determine whether cardiac indices are altered as assessed by 24-hour ambulatory blood pressure monitoring (ABPM) in male children receiving either chronic methylphenidate or dextroamphetamine/levoamphetamine (Adderall) therapy. METHODS: Boys 7–11 years old who were receiving methylphenidate or Adderall for a minimum of 2 months were asked to participate. Subjects wore ambulatory blood pressure monitors for 24-hour periods both off and on stimulant therapy. RESULTS: Subjects (n = 17; 8 methylphenidate, 9 Adderall) were well matched. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate differed between off and on stimulant therapy (p < 0.05). DBP load calculated from ABPM reference data was increased significantly (9.0% ± 5.6% on and 4.8% ± 4.5% off therapy; p < 0.05) while subjects were taking Adderall. There was a trend toward a greater elevation in blood pressure load during awake hours and a more pronounced decrease during the asleep hours for periods on compared with off-stimulant therapy. This trend resulted in significant (p < 0.05) nocturnal dipping on-stimulant phases compared with off-stimulant therapy for both SBP and DBP (Adderall) and SBP (methylphenidate). Two subjects (1 Adderall, 1 methylphenidate) met the criteria to be considered hypertensive based both on mean awake and 24-hour blood pressure load assessments during their on-treatment period. One additional subject receiving Adderall therapy met the criteria to be considered hypertensive based on blood pressure load criteria while off therapy only. Positive correlation coefficients (p < 0.05) were found when comparing stimulant dose (mg/kg) with the percent change of mean SBP, DBP, and heart rate between off and on therapy (r = 0.56, 0.61, and 0.58, respectively). CONCLUSIONS: These preliminary data suggest that blood pressure and heart rate appear to be altered in male patients while receiving stimulant therapy for attention-deficit hyperactivity disorder. Blood pressure and heart rate screening and monitoring during stimulant therapy to determine whether alterations become clinically significant is encouraged.

Intravenous voriconazole therapy in a preterm infant.

A preterm infant younger than 3 months developed a disseminated fluconazole‐resistant Candida albicans infection that was treated with liposomal amphotericin B for 52 days, followed by the combination of intravenous voriconazole and liposomal amphotericin B for an additional 19 days. The infant received concomitant phenobarbital throughout the hospital stay. The infection resolved after addition of voriconazole to the treatment regimen. Intravenous voriconazole was begun at a high dosage, 6 mg/kg every 12 hours, for anticipated developmental and drug‐induced changes in volume of distribution and clearance. On day 4 of therapy, serum concentrations of voriconazole were 3.27 μg/ml immediately after infusion and 0.33 μg/ml 6 hours after infusion. These levels were significantly lower than those achieved in adult pharmacokinetic and safety studies. After the infants dosage was increased to 6 mg/kg every 8 hours, serum concentrations were 5.33 μg/ml 30 minutes after infusion and 2.67 μg/ml 6 hours after infusion. These levels were similar to those observed in adults. Intravenous voriconazole 6 mg/kg every 8 hours was administered safely, with concomitant phenobarbital therapy, in this preterm infant with developmentally diminished renal function.

Acute mental status changes and hyperchloremic metabolic acidosis with long-term topiramate therapy.

Mental status changes and metabolic acidosis may occur with topiramate therapy. These adverse events were reported during dosage titration and with high dosages of the drug. A 20‐year‐old man receiving topiramate, valproic acid, and phenytoin experienced acute‐onset mental status changes with hyperchloremic metabolic acidosis. He had been receiving a modest dose of topiramate for 9 months. He was weaned off topiramate over 5 days, and his mental status returned to baseline within 48 hours of discontinuing the agent. This case illustrates the need for close evaluation of patients who experience acute‐onset mental status changes during topiramate therapy.

Pharmacokinetics and Pharmacodynamics of Famotidine in Infants

The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5‐mg/kg infusion of famotidine, timed serum (n = 6), urine (24‐hour collection), and repeated measurements of gastric pH were obtained. The mean ± standard deviation maximum plasma concentration (Cmax) was 640.66 ± 250.66 ng/mL, the elimination half‐life (t1/2β) was 10.51 ± 5.43 hours, and the apparent volume of distribution at steady state (Vdss) was 0.82 ± 0.29 L/kg. Plasma clearance (Cl) and renal clearance (ClR) were 0.132 ± 0.061 L/hr/kg and 0.093 ± 0.056 L/hr/kg, respectively. No significant correlations were found between t1/2β, Vdss, Cl, and ClR and age. Six of the nine infants who had intragastric pH monitoring maintained a gastric pH > 4 until the final 24‐hour sampling point. In this study, the t1/2β of famotidine was prolonged and the Vdss, Cl, ClR were reduced compared with corresponding parameters in previously reported studies of children older than one year of age and adults.

Human Recombinant Vascular Endothelial Growth Factor Reduces Necrosis and Enhances Hepatocyte Regeneration in a Mouse Model of Acetaminophen Toxicity

We reported previously that vascular endothelial growth factor (VEGF) was increased in acetaminophen (APAP) toxicity in mice and treatment with a VEGF receptor inhibitor reduced hepatocyte regeneration. The effect of human recombinant VEGF (hrVEGF) on APAP toxicity in the mouse was examined. In early toxicity studies, B6C3F1 mice received hrVEGF (50 μg s.c.) or vehicle 30 min before receiving APAP (200 mg/kg i.p.) and were sacrificed at 2, 4, and 8 h. Toxicity was comparable at 2 and 4 h, but reduced in the APAP/hrVEGF mice at 8 h (p < 0.05) compared with the APAP/vehicle mice. Hepatic glutathione (GSH) and APAP protein adduct levels were comparable between the two groups of mice, with the exception that GSH was higher at 8 h in the hrVEGF-treated mice. Subsequently, mice received two doses (before and 10 h) or three doses (before and 10 and 24 h) of hrVEGF; alanine aminotransferase values and necrosis were reduced at 24 and 36 h, respectively, in the APAP/hrVEGF mice (p < 0.05) compared with the APAP/vehicle mice. Proliferating cell nuclear antigen expression was enhanced, and interleukin-6 expression was reduced in the mice that received hrVEGF (p < 0.05) compared with the APAP/vehicle mice. In addition, treatment with hrVEGF lowered plasma hyaluronic acid levels and neutrophil counts at 36 h. Cumulatively, the data show that treatment with hrVEGF reduced toxicity and increased hepatocyte regeneration in APAP toxicity in the mouse. Attenuation of sinusoidal cell endothelial dysfunction and changes in neutrophil dynamics may be operant mechanisms in the hepatoprotection mediated by hrVEGF in APAP toxicity.

A Faculty Toolkit for Formative Assessment in Pharmacy Education

This paper aims to increase understanding and appreciation of formative assessment and its role in improving student outcomes and the instructional process, while educating faculty on formative techniques readily adaptable to various educational settings. Included are a definition of formative assessment and the distinction between formative and summative assessment. Various formative assessment strategies to evaluate student learning in classroom, laboratory, experiential, and interprofessional education settings are discussed. The role of reflective writing and portfolios, as well as the role of technology in formative assessment, are described. The paper also offers advice for formative assessment of faculty teaching. In conclusion, the authors emphasize the importance of creating a culture of assessment that embraces the concept of 360-degree assessment in both the development of a student’s ability to demonstrate achievement of educational outcomes and a faculty member’s ability to become an effective educator.

Lubiprostone for Constipation in Adults with Cystic Fibrosis: A Pilot Study

Background Constipation is prevalent in the cystic fibrosis (CF) population and yet there are few data demonstrating the effectiveness of currently used treatments. Lubiprostone is a laxative that works by activating the type 2 chloride channel in the gastrointestinal tract and thus has the potential to be especially effective for constipation associated with CR Objective: To evaluate the effectiveness of lubiprostone for the treatment of constipation in adults with CF. Methods: In this pilot study, participants acted as their own controls and comparisons were made between run-in and treatment periods. During the 2-week run-in period, participants continued their usual treatment for constipation; during the 4-week treatment period, participants received lubiprostone 24 μg twice daily. Efficacy outcomes Included spontaneous bowel movement frequency, Bristol Stool Scale scores, and Patient Assessment of Constipation Symptoms (PAC-SYM) survey scores. Outcomes were assessed during both the run-in and treatment periods (0, 2, and 4 weeks of treatment). Safety outcomes included spirometry, body weight, and serum chemistry. Results: Seven participants completed the study. Mean (SD) baseline forced expiratory volume in 1 second was 83.0% (9.4) of predicted and body mass index was 24.0 (2.8) kg/m2, indicating an overall healthy, well-nourished group of adults with CR Lubiprostone improved overall symptoms of constipation as measured by PAC-SYM survey scores (1.18 [0.56], 0,54 (0.27], and 0.44 [0.36] at 0, 2, and 4 weeks, respectively; p < 0.001). Spontaneous bowel movement frequency and Bristol Stool Scale scores were not statistically significantly different between periods. There were no differences in safety measures. Transient chest tightness and shortness of breath were reported by 2 separate participants, although neither participant withdrew due to these adverse effects. Conclusions: Lubiprostone may be an effective option for the treatment of constipation in adults with CF

Use of the Chloride Channel Activator Lubiprostone for Constipation in Adults with Cystic Fibrosis: A Case Series

Objective: To describe the use of lubiprostone for constipation in 3 adults with cystic fibrosis (CF). Case Summary: This case series describes the use of lubiprostone for the treatment of constipation in 3 adutts with CF (mean ± SD length of therapy 17.3 ± 1.5 mo). All 3 patients were prescribed lubiprostone 24 μg twice daily after hospitalization for treatment of intestinal obstruction. Patient 1 continues on chronic polyethylene glycol (PEG) 3350 and lubiprostone and has not had a recurrence of obstruction. Patient 2 requires aggressive chronic therapy with PEG 3350, lubiprostone, and methylnaltrexone. She has had 1 recurrence of obstruction. Patient 3 continues with lubiprostone taken several times per week with good control of constipation and no recurrence of obstruction to date. The adverse effect profile has been tolerable in all 3 patients. Discussion: CF is caused by a genetic mutation resulting in a dysfunctional or absent CF transmembrane conductance regulator that normally functions as a chloride channel. This results in viscous secretions in multiple organ systems including the lungs and intestinal tract. Accumulation of viscous intestinal contents contributes to constipation, which is common among adults with CF and can sometimes lead to intestinal obstruction. Lubiprostone is indicated for chronic constipation and works by activating type 2 chloride channels (CIC-2) in the intestinal tract. Because it utilizes an alternate chloride channel, lubiprostone may be especially effective for constipation in patients with CF. Conclusions: Lubiprostone provides an additional option for the treatment of constipation in adults with CF. Its use in the CF population deserves further study.

Candesartan Cilexetil Effectively Reduces Blood Pressure in Hypertensive Children

Background: The angiotensin-receptor blocker candesartan cilexetil is a well-toleraled antihypertensive agent with demonstrated benefits in adults with hypertension. However, there are few data supporting its use in children with hypertension. Objective: To determine the efficacy and tolerability of candesartan cilexetil in the treatment of pediatric hypertension. Methods: In an open-label, uncontrolled pilot study, hypertensive pediatric patients were eligible tor participation if untreated systolic and/or diastolic blood pressure (BP) exceeded the 95th percentile for sex, age, and height. Patients underwent a 7-day washout period prior to initiation of weight-based dosing of candesartan cilexetil (2-8 mg daily). The dose was doubled after 7 days of therapy if inadequate antihypertensive response was determined by clinic-measured casual BP monitoring (CBPM) and home BP monitoring (HBPM). Three methods of BP measurement were compared before and after 2 weeks of treatment with the final dose of candesartan cilexetil: CBPM, HBPM, and 24-hour continuous ambulatory BP monitoring (ABPM). Self-reported adverse effects and clinical laboratory analyses were used to determine tolerability. Results: Eleven patients (mean age 14.2 y) received a final candesartan cilexetil median daily dose of 8 mg (0.13 mg/kg, range 2-16 mg). Study treatment resulted in significant reductions in systolic and diastolic BP as measured by CBPM (-7.4%, p = 0,03 and -5.9%, p = 0.01, respectively) and by ABPM (-6.0%, p = 0.03 and -10.8%, p = 0.006, respectively), but no significant reductions as measured by HBPM. No clinically significant changes in laboratory measures were observed, and patients reported nonspecific mild adverse effects. Conclusions: Candesartan cilexetil effectively reduced BP as demonstrated by CBPM and ABPM measurements and was well tolerated in this group of hypertensive children.