Joe R. Anderson

Pharmacotherapeutic management of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a disabling chronic disorder of the pulmonary vasculature, which is characterized by increased pulmonary artery pressure as a result of increased pulmonary vascular resistance. The pathology of PAH is characterized by pulmonary vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. These changes are a result of an imbalance between vasodilators (prostacyclin, nitric oxide, vasoactive intestinal peptide) and vasoconstrictors (thromboxane A2, endothelin, serotonin), growth inhibitors and mitogenic factors, and antithrombotic and prothrombotic factors. Recent advances in treatment are directed at restoring the balance between these systems. Endothelin receptor antagonists (bosentan, ambrisentan, sitaxsentan), phosphodiesterase type 5 inhibitors (sildenafil, tadalafil), and prostacylin (epoprostenol, iloprost, treprostinil, beraprost) represent the different classes of medications that are currently used in monotherapy and in combination to treat PAH. The purpose of this drug highlight is to provide the reader with an update of the pharmacotherapeutic treatment of PAH.

CARDIOVASCULAR DRUG-DRUG INTERACTIONS

The drug-drug interactions discussed in this article have either documented or suspected clinical relevance for patients with cardiovascular disease and the clinician involved in the care of these patients. Oftentimes, drug-drug interactions are difficult, if not impossible, to predict because of the high degree of interpatient variability in drug disposition. Certain drug-drug interactions, however, may be avoided through knowledge and sound clinical judgment. Every clinician should maintain a working knowledge of reported drug-drug interactions and an understanding of basic pharmacokinetic and pharmacodynamic principles to help predict and minimize the incidence and severity of drug-drug interactions.

Elevated serum creatinine levels associated with fenofibrate therapy.

PURPOSE The case of a patient who developed clinically relevant increases in serum creatinine (SCr) levels while receiving fenofibrate therapy is reported. SUMMARY Fenofibrate therapy was initiated for a 60-year old Hispanic man with stage 4 chronic kidney disease (CKD) for the treatment of hypertriglyceridemia. Two weeks after taking 48 mg of fenofibrate daily, the patients SCr and blood urea nitrogen concentrations increased from 3.0 and 25 mg/dL, respectively, to 3.5 and 30 mg/dL, respectively. His estimated glomerular filtration rate (eGFR) had decreased from 24.8 to 17.9 mL/min/1.73 m(2). One month after initiating fenofibrate, his SCr concentration had increased to 3.7 mg/dL, a 32% increase from baseline. Because of persistently high triglyceride concentrations (e.g., 402 mg/dL), the fenofibrate dosage was increased to 145 mg daily. The patients SCr concentration rose to 4.7 mg/dL (a 62% increase from baseline), and his eGFR was calculated as 13 mL/min/1.73 m(2). The patient was referred by the nephrology service for vascular-access placement in preparation for hemodialysis. Four days after discontinuation of fenofibrate, the patients SCr concentration dropped to 3.3 mg/dL and returned to baseline approximately six weeks later, with an eGFR of 20.5 mL/min/1.73 m(2). Preparation for hemodialysis was terminated, and the patients eGFR remained stable at 20.2 mL/min/1.73 m(2) for the 12 months after fenofibrate discontinuation. A score of 4 on the Naranjo et al. probability scale indicated that there was a possible association between fenofibrate and renal dysfunction in this patient. CONCLUSION A 60-year-old patient developed renal impairment after receiving fenofibrate for the treatment of hypertriglyceridemia.

Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review

Pulmonary arterial hypertension (PAH) is a chronic and disabling condition characterized by an elevated pulmonary vascular resistance and an elevated mean pulmonary arterial pressure. Despite recent improvements in treatment availability, PAH remains challenging to treat, burdensome for patients, and ultimately incurable. Tadalafil is a phos-phodiesterase-5 inhibitor that is administered once daily by mouth for the treatment of PAH. Current treatment guidelines recommend tadalafil as an option for patients with World Health Organization functional class II or III PAH. In a placebo-controlled clinical trial, patients taking tadalafil demonstrated significantly improved exercise capacity as measured by the 6-minute walk distance. Patients also experienced decreased incidence of clinical worsening, increased quality of life, and improved cardiopulmonary hemodynamics. Uncontrolled studies and smaller trials have indicated a possible role for tadalafil as a suitable alternative to sildenafil and as a beneficial add-on option when used in combination with other treatments for PAH. Tadalafil is generally safe and well tolerated. Adverse events are typically mild-to-moderate in intensity, and discontinuation rates are usually low. The purpose of this review is to provide an evidence-based evaluation of the clinical utility of tadalafil in the treatment of PAH.

Smoking Cessation and Its Predictors: Results from a Community-Based Pharmacy Tobacco Cessation Program in New Mexico

BACKGROUND: The New Mexico Pharmaceutical Care Foundation received funding through the Tobacco Use Prevention and Control Program (TUPAC) to provide support for pharmacist-delivered tobacco cessation services. The goal of the program was to increase the availability of tobacco cessation services to residents of New Mexico. Program outcomes are presented, using data from the first 2 fiscal years. OBJECTIVE: To assess tobacco quit rates among smokers who participated in the community pharmacist–based program and identify the predictors of quitting at the end of a 6-month program. METHODS: Pharmacists, who had received Rx for Change training, provided tobacco cessation services. Patients were scheduled for an initial visit and then were seen at regularly scheduled follow-up visits at 1 month, 3 months, and 6 months from the initial visit. Data collected at the initial visit included demographics, smoking history, and readiness for quitting. Smoking status was collected at each of the follow-up visits. Data were analyzed using SAS (SAS Institute) and STATA (StataCorp LP) statistical software. Tobacco quit rates were calculated at 1, 3, and 6 months. Multivariate regression analysis was performed to assess predictors of quitting. Standard errors were adjusted for repeated observation. RESULTS: Data were available for 346 participants. The average quit rate at the end of 6 months was 25%. Significant predictors of quitting were high confidence levels in quitting at baseline, individuals who had first cigarettes at least 30 minutes after waking up, first cessation attempt, and nonwhite patients. CONCLUSIONS: A smoking cessation program delivered through trained community pharmacists with prescriptive authority is an effective approach to reducing smoking. Further research should be conducted to compare the effectiveness of pharmacists with that of other providers of tobacco cessation services.

Statin Loading Before Percutaneous Coronary Intervention to Reduce Periprocedural Myocardial Infarction

Periprocedural myocardial infarction (PMI) is a common complication associated with percutaneous coronary intervention (PCI), occurring in approximately 15% to 20% of patients undergoing the procedure. The established diagnostic criteria for PMI is an increase in cardiac biomarkers, specifically creatine kinase-MB levels > 3 times the upper limit of normal. As PMI has been associated with an increased risk of mortality after PCI, investigative efforts have been directed at therapies that can potentially decrease PMI. One such therapy is the use of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) administered as a loading dose before PCI. Multiple small, randomized, controlled trials have demonstrated significant reductions in the incidence of PMI with statin loading before PCI. The risk reduction was seen in patients with stable and unstable coronary artery disease, as well in statin-naive patients or those on chronic statin therapy. Potential mechanisms for the rapid benefits of statin loading include: anti-inflammatory effects, reversal of endothelial dysfunction, decrease in oxidative stress, and inhibition of the thrombotic system. None of the current studies were of sufficient power or duration to detect benefits on mortality, though a recent meta-analysis did demonstrate a reduction in major adverse cardiovascular events. In addition to long-term effects, several additional questions remain with regard to statin loading, such as statin type, dose, and optimal timing of administration. However, given the current evidence of benefit and the low risk of adverse events, it can be recommended that all patients undergoing PCI be considered for statin loading before the procedure.

Association of serum aryl hydrocarbon receptor activity and RBC omega-3 polyunsaturated fatty acids with flow-mediated dilation in healthy, young Hispanic cigarette smokers.

Impaired flow-mediated dilation (FMD) occurs prior to clinical disease in young cigarette smokers. We investigated two potential biomarkers of FMD: serum aryl hydrocarbon receptor (AHR) activity and RBC omega-3 polyunsaturated fatty acids in healthy young Hispanic cigarette smokers. We recruited never (n=16) and current (n=16) Hispanic smokers (32 ± 7 years old), excluding individuals with clinical cardiovascular disease. We measured FMD with duplex ultrasound, RBC fatty acids and serum AHR activity using a luciferase reporter assay. FMD was significantly impaired in smokers (5.8 ± 4%) versus never smokers (12.3 ± 7.4%, p=0.001). Serum AHR activity was significantly increased in smokers (1467 ± 358 relative light units (RLU)) versus never smokers (689 ± 251 RLU, p<0.001), and correlated positively with FMD only in smokers (r=0.691, p<0.004). RBC percentage of α-linolenic acid (ALA%) was significantly increased in smokers (0.14 ± 0.03%) versus never smokers (0.11 ± 0.03%, p=0.018), and correlated inversely with FMD only in smokers (r=-0.538, p=0.03). The combination of serum AHR activity, ALA%, and systolic blood pressure significantly correlated with FMD in a multivariable regression model (r=0.802, p<0.008). These results suggest that serum AHR activity and RBC ALA% could serve as biomarkers of FMD in healthy, young Hispanic cigarette smokers.

Improving the Effectiveness of Pharmacist-Assisted Tobacco Cessation: A Study of Participant- and Pharmacy-Specific Differences in Quit Rates

Background: The New Mexico Pharmaceutical Care Foundation provided a pharmacist-assisted tobacco cessation program from 2004 to 2010. In evaluating the program, discrepant 6-month quit rates were observed between pharmacies. Objective: To identify participant- and pharmacy-specific factors associated with improved quit rates. Methods: To supplement data regarding participant characteristics and quit rates, semistructured interviews of 7 participating pharmacists were conducted. Multivariate logistic regression quantified associations between successful abstinence at 6 months and participant characteristics and pharmacy-specific factors. Results: Quit rates by pharmacy ranged from 1.1% to 59.4% (mean = 19.1%). There were 1235 participants enrolled at 7 pharmacies, and because of missing participant data, 883 were included in the quantitative analysis. Three pharmacy-specific characteristics distinguished 6-month success rates: number and duration of follow-ups and format of counseling sessions. Participants followed up at least 3 times were more likely to quit at 6 months than those contacted once or twice (odds ratio [OR] =4.9; 95% CI = 1.6-15.0). Compared with follow-ups of <15 minutes, longer durations of follow-ups were associated with higher success rates: 15 to 30 minutes, OR = 7.2, 95% CI = 3.7-14.3); >30 minutes, OR = 10.0, 95% CI = 3.5-28.9. Participants who attended group sessions were more likely to quit at 6 months than those who attended individual sessions: OR = 8.2; 95% CI = 2.8-23.9. Most pharmacists (88%) noted that participants’ high or low commitment to quit was associated with success or failure, respectively. Several pharmacists (43%) noted difficulties with follow-up associated with participants’ relapse. Time constraints were an obstacle noted by 70% of pharmacists. Conclusions: Pharmacy-specific factors, including counseling format and program intensity, affected success.

Psychometric Properties of the Purdue Pharmacist Directive Guidance (PPDG) Scale in a Sample of Diabetes Patients in the Southwestern United States

Despite the fairly widespread adoption of the 10-item Purdue Pharmacist Directive Guidance Scale (PPDG) over the last decade, only one study has assessed its psychometric properties. The present study examined the validity and reliability of the scale in a sample of 99 diabetic patients in the Southwestern United States. Principal axis factor analysis with Varimax rotation yielded two factors, “Instruction” and “Feedback and Goal Setting,” similar to those found when the scale was originally developed. Cronbachs alphas for the total scale and the two factors were 0.95, 0.95, and 0.92, respectively. The scale and the two factors correlated significantly and positively with number of visits by patients to the pharmacist in the past 3 mo. These results provide further evidence for the internal consistency, and construct and criterion-related validities of the scale.

Split-half and parallel reliabilities of the Purdue Pharmacist Directive Guidance Scale.

Using R and SPSS, various forms of split-half and parallel reliabilities were calculated. Robust split-half and parallel reliability coefficients for the Purdue Pharmacist Directive Guidance Scale are presented with coefficients greater than .84.