Donald S. Nuzum

Nebivolol: A Third-Generation β-Adrenergic Blocker

Objective: TO describe the pharmacologic and pharmacokinetic properties of a new β-adrenergic blocker, nebivolol, and review the literature evaluating its efficacy in the treatment of hypertension and heart failure. Data Sources: Articles were identified through searches of MEDLINE (1996–May 2006) and International Pharmaceutical Abstracts (1970–May 2006), using the key word nebivolol. Additional references were selected from the bibliographies of the articles cited. Searches were not limited by language, time, or human subject. Study Selection and Data Extraction: Preclinical studies evaluating the pharmacologic and pharmacokinetic properties of nebivolol in humans were selected for review. Randomized, controlled, blinded clinical trials assessing the efficacy of nebivolol for the treatment of hypertension and heart failure were also included. Data Synthesis: Preclinical data have established nebivolol as a third-generation β-adrenergic blocker, as it possesses vasodilatory properties that contribute to its hemodynamic effects beyond those achieved at β-adrenergic receptors. Short-term, randomized, controlled clinical trials have shown nebivolol to be as effective as other antihypertensive therapies at lowering blood pressure. One long-term trial showed a significant reduction in death and hospital admissions for cardiovascular causes when nebivolol was compared with placebo in patients with heart failure (31.1% vs 65.3%; HR 0.86; 95% CI 0.74 to 0.99). Conclusions: Nebivolol is a novel β-adrenergic blocker that possesses unique pharmacologic properties, compared with other agents in its class. Nebivolol appears to be as effective as other antihypertensive agents at lowering blood pressure and possesses benefits for patients with heart failure. Additional studies are needed to address the long-term benefits of nebivolol for hypertension, to compare nebivolol with other β-adrenergic blockers for heart failure, and to investigate the clinical relevance of nitric oxide-mediated vasodilation.

Evaluating Second-Line Treatment Options for Type 2 Diabetes: Focus on Secondary Effects of GLP-1 Agonists and DPP-4 Inhibitors

OBJECTIVE To discuss the controversy surrounding selection of second-line type 2 diabetes mellitus (T2DM) therapy by reviewing available data regarding secondary effects of glucagon-like peptide-1 receptor (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, which include low hypoglycemia risk, weight loss, and cardiovascular (CV) and β-cell function benefits. DATA SOURCES A MEDLINE search (1966–March 2013) was conducted using the following key terms: β-cell protection, blood pressure, DPP-4 inhibitors, exena tide, exenatide extended-release, GLP-1 agonists, hypoglycemia, lina glip tin, lipid, liraglutide, pancreatitis, saxagliptin, sitagliptin, and type 2 diabetes. STUDY SELECTION AND DATA EXTRACTION Identified articles published in English were evaluated for inclusion, with priority given to randomized controlled trials in humans receiving incretin monotherapy or incretin combination therapy with metformin. References identified in these articles were reviewed for additional trials. DATA SYNTHESIS Most patients with T2DM use combination therapy; however, determination of the second-line agent that is most appropriate is debatable. Prior to the use of incretin therapies, traditional second-line agents included sulfonylureas, thiazolidinediones, and basal insulin, all of which demonstrate undesirable adverse effects. In addition to improving glycemic control, incretin therapies have demonstrated benefits concerning hypoglycemic risk and weight loss in addition to potential improvements in CV risk factors and β-cell function. While there are risks associated with using incretins, most patients with T2DM are good candidates for incretins and could benefit from their potential secondary effects. Cost remains a barrier to initiating these agents. CONCLUSIONS Demonstrated secondary benefits in addition to efficacy may make GLP-1 agonists and DPP-4 inhibitors a more favorable option than other second-line T2DM therapies.

Risk of cancer associated with the use of angiotensin II-receptor blockers

PURPOSE The proposed mechanism by which angiotensin II and angiotensin II-receptor blockers (ARBs) may influence the risk of cancer and the literature describing a possible causal relationship between ARB use and specific types of cancers are reviewed. SUMMARY A number of cell-signaling pathways have been identified to establish a relationship between angiotensin II and cancer. Preclinical data support agonism of the angiotensin type-1 receptor by angiotensin II and unopposed stimulation of the angiotensin type-2 receptor as possible causes of proliferative and angiogenic processes. Results from a large meta-analysis suggested that ARB use is associated with a modest increase in risk of new cancer incidence. The publication of that meta-analysis led to subsequent large population analyses. A comprehensive literature review was conducted to identify studies evaluating the relationships among angiotensin II, ARBs, cancer, and malignancy. Preclinical studies evaluating the effects of angiotensin II and ARBs on proliferation and angiogenesis were selected to review how the renin-angiotensin system is involved in cellular proliferation and growth. Human studies evaluating the role of ARBs in specific types of cancer were also analyzed. The literature review found limited patient-specific data in humans to support the association. The Food and Drug Administration has concluded that there is no evidence of an increased risk of cancer with ARBs. CONCLUSION At this time there is insufficient evidence to conclude that ARBs increase the risk of cancer. Blockade of the angiotensin system through both AT(1) and AT(2) receptors may have a protective effect against malignancy.

Long-acting nifedipine in the management of the hypertensive patient

Hypertension is a global condition affecting billions worldwide. It is a significant contributor to cardiovascular events, cardiac death and kidney disease. A number of medication classes exist to aid healthcare providers and their patients in controlling hypertension. Nifedipine, a dihydropyridine calcium channel blocker, was once one of the most widely used medications for hypertension, but safety and tolerability concerns along with the introduction of new classes of antihypertensive medications and an increasing pool of data showing mortality benefit of other classes caused nifedipine to fall out of favor. More recently, long-acting formulations were developed and made available to clinicians. These newer formulations were designed to address many of the concerns raised by earlier formulations of nifedipine. Numerous clinical trials have been conducted comparing long-acting nifedipine to many of the more commonly prescribed antihypertensive medications. This review will address the pharmacology, pharmacokinetics and the available clinical trial data on long-acting nifedipine and summarize its role in the management of hypertension.

Pharmacy Students’ Ability to Identify Plagiarism After an Educational Intervention

Objective. To determine if an educational intervention in a doctor of pharmacy (PharmD) degree program increases pharmacy students’ ability to identify plagiarism. Methods. First-year (P1), second-year (P2), and third-year (P3) pharmacy students attended an education session during which types of plagiarism and methods for avoiding plagiarism were reviewed. Students completed a preintervention assessment immediately prior to the session and a postintervention assessment the following semester to measure their ability. Results. Two hundred fifty-two students completed both preintervention and postintervention assessments. There was a 4% increase from preintervention to postintervention in assessment scores for the overall student sample (p<0.05). The mean change was greatest for P1 and P2 students (5% and 4.8%, respectively). Conclusion. An educational intervention about plagiarism can significantly improve students’ ability to identify plagiarism.

Alternative dosing strategies for liraglutide in patients with type 2 diabetes mellitus.

PURPOSE Alternative dosing strategies for liraglutide in patients with type 2 diabetes mellitus are described. SUMMARY Nausea is the most common adverse effect of liraglutide, affecting upward of 40% of patients depending on the dose of liraglutide and concomitant medications. The frequency of nausea is dose dependent, with a lower rate of nausea reported with 0.6 mg (5.2-10.7%) compared with 1.2 mg (10.5-29.2%) or 1.8 mg (6.8-40%). Due to dose-related adverse effects, it is reasonable to assume that smaller or slower dosage adjustments may improve tolerability and increase the likelihood that the patient will be able to continue therapy long term. Depending on the degree of nausea and the necessary reduction in blood glucose levels, it is reasonable to consider a smaller or slower increase in liraglutide dosage than what is currently recommended by the manufacturer. For instance, increasing the dose of liraglutide by 0.3 mg weekly instead of 0.6 mg weekly may help prevent or decrease the severity of nausea. Alternative dosing strategies may also include increasing the dosage every two weeks or even monthly rather than weekly. Depending on the degree of nausea and glycemic control, providers may recommend patients stop increasing the dosage. It is important to proactively assess each patients ability to comply with special instructions to ensure safe use of the product. CONCLUSION Alternative dosing strategies that allow for slower dosage adjustments or smaller dosages may offer improved tolerability and increase the likelihood that patients will be able to continue long-term therapy with liraglutide.

Evaluating Sample Medications in Primary Care: A Practice-Based Research Network Study

BACKGROUND No reports have objectively evaluated safety of samples in primary care practices. A study was conducted to determine adherence to the Institute for Safe Medication Practices (ISMP) recommendations for safe distribution of medication samples to minimize medication errors. METHODS In 2004, 17 urban and rural primary care practices participated in a two-phase observational study: (1) a site visit to collect inventory data and perform assessment of medication sample dispensing procedures and (2) a survey questionnaire for providers and patients upon sample medication provision. RESULTS No practices were compliant with all seven ISMP recommendations. Twelve of 17 practices had policies for sample medication dispensing, and 7 had policies for labeling. Sample medication use was evaluated for 585 office visits and 27 patient surveys. Fifty-eight sample medications were dispensed during 55 of 585 patient visits. Common reasons for using sample medications included availability and need for a short-term trial for a chronic medication. Verbal communication only was provided most of the time for patient education regarding appropriate sample medication use and side effects. DISCUSSION Primary care practices in this research network did not follow safe and appropriate sample medication dispensing procedures as outlined by ISMP. Both labeling and patient instructions were inadequate and may increase the risk for medication errors.

Pycnogenol for chronic venous insufficiency

Chronic venous insufficiency (CVI) is a vascular disorder affecting 1–5% of the population and is most common in the elderly.[1][1],[2][2] Complications of CVI include edema and venous stasis ulcers, which can contribute to increased morbidity and health care costs.[3][3],[4][4] Unfortunately, few

Oral ivermectin for the treatment of head lice infestation

PURPOSE Published literature describing the use of oral ivermectin for the treatment of head lice infestation is reviewed. SUMMARY In the United States and globally, head lice infestation, or pediculosis capitis, remains a public health issue with both social and medical implications. Treatment with oral or topical medications is typically required for head lice eradication. Resistance to traditional topical therapies for head lice infestation is increasing, creating a need for consideration of additional treatment options. A growing body of data describing the potential role of oral ivermectin for the treatment or prevention of head lice infestation is available. A literature search identified 5 clinical trials that evaluated safety and/or effectiveness outcomes of oral ivermectin use as an alternative to malathion, other topical prescription medications, and traditional, nonprescription remedies; those studies were conducted in various parts of the world (e.g., Australia, Brazil, Mexico, Egypt) and likely involved varying types and degrees of lice resistance. Clinical research findings to date, while not consistently robust, suggest that oral ivermectin is comparable or superior in effectiveness to other topical treatment options for head lice infestation while being well tolerated and favorably perceived by patients and caretakers. CONCLUSION Oral ivermectin is an option for the treatment of head lice infestation, especially in individuals who have experienced a treatment failure. Published evidence from clinical trials indicates that oral ivermectin is as effective as currently available topical treatments.

Creating and Assessing Student Perception of an Examination Mastery Score Report for a Pharmacotherapy Course.

Objective. To compare student-perceived utility of two types of score reports. Methods. Assessment standards were followed to create a new examination score report for pharmacotherapy coursework. Student examination scores were returned using the traditional score report, the utility of which students rated along 9 dimensions. A mastery score report was also distributed, and students rated it on the same 9 dimensions. The ratings were compared to determine which the students perceived as more useful. Results. The students rated the mastery score report significantly better on each of the 9 dimensions and in aggregate. Conclusion. Pharmacy students perceived the mastery score report as more useful in helping them improve their achievement of educational outcomes.