Role of the Funny Current Inhibitor Ivabradine in Cardiac Pharmacotherapy: A Systematic Review.

The pharmacology, pharmacokinetics, efficacy and safety of ivabradine are reviewed. Ivabradine is an oral medication that directly and selectively inhibits the hyperpolarization-activated cyclic-nucleotide gated funny (If) current in the sinoatrial node resulting in heart rate reduction. It has a plasma elimination half-life of 6 hours and is administered twice daily. Ivabradine is extensively metabolized by cytochrome P450 3A4, and its metabolism is affected by inducers and inhibitors of the 3A4 enzyme. Studies in patients with heart failure indicate that ivabradine improves surrogate markers such as exercise tolerance. The results of (1) phase III trial demonstrated ivabradine significantly reduced heart failure hospitalizations but had no effect on mortality. Ivabradine has been extensively evaluated for coronary artery disease wherein (2) large trials was shown to have no mortality benefit. Ivabradine has been associated with improved symptoms in stable chronic angina pectoris. Ivabradine has been evaluated for other cardiovascular conditions including tachycardias of various natures, arrhythmia prevention postcardiac surgery, in acute coronary syndrome, and for heart rate control during coronary computed tomography angiogram. The most common adverse events reported in clinical trials were bradycardia, new-onset atrial fibrillation, and phosphenes. Ivabradine, a novel cardiac medication, has been studied in numerous cardiac conditions. It is only currently approved in the United States to reduce hospitalizations for systolic heart failure. The role of this medication in other conditions has not been fully elucidated.

Buprenorphine for the Treatment of Neonatal Abstinence Syndrome.

Objective: To summarize the available data for using buprenorphine in neonatal abstinence syndrome and discuss these data in context of the current standard of care therapies, oral morphine and oral methadone. Data Sources: A literature search was conducted using PubMed (1949-May 2018) and EMBASE (1980-May 2018). Combinations of the search terms "buprenorphine," "neonatal," and "neonatal abstinence syndrome" were used. Study Selection and Data Extraction: All full-length, English-language studies were included in this review. Data Synthesis: A total of 4 studies were included in this review including 1 retrospective cohort study, 2 prospective single-center open-label randomized trials, and 1 prospective single-center, double-blind study. Oral morphine was the comparator in 3 studies, and oral methadone was the comparator in one. Buprenorphine was associated with a significant reduction in duration of treatment in 3 of the 4 studies and was associated with a significant reduction in duration of hospital stay in 3 of the 4 studies. In the randomized, double-blinded trial, buprenorphine had a significantly reduced duration of treatment (15 vs 28 days, P < .001) and duration of hospital stay (21 vs 33 days, P < .001). The requirement of adjunct treatment was similar between groups in all 4 studies, and buprenorphine did not have any significant adverse reactions in comparison with morphine and methadone. Conclusions: Buprenorphine appears to be a safe option for treating neonatal abstinence syndrome that is potentially superior to the current standard of care therapies with respect to duration of treatment and hospital length of stay.

Endovascular Interventions for Acute Ischemic Stroke: A Review of Recent Trials.

OBJECTIVE: To review recent endovascular intervention trials for acute ischemic stroke. DATA SOURCES: Recent, randomized controlled trials of endovascular interventions for acute ischemic stroke were identified. The search terms "endovascular" AND "stroke" were used and filter for "randomized controlled trial" was applied; the period searched was January 1, 2013, to October 31, 2015. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials of endovascular interventions in acute ischemic stroke published within the past 3 years (2013-2015). DATA SYNTHESIS: A total of 8 trials are reviewed: 3 trials published in 2013 demonstrated neutral results for endovascular interventions, and 5 trials published in 2015 demonstrated positive results for endovascular interventions. Potential reasons for the change in outcomes include better patient selection and improvement indevice technology. Patient selection improvements included selecting patients with salvageable brain tissue with an identifiable thrombus on perfusion imaging. The major improvement in device technology was the introduction of the Solitaire Flow Restoration stent retriever and the Trevo stent retriever, both of which have improved recanalization rates compared with earlier devices. Adjunctive medication considerations include the mode of sedation (general or conscious), intraprocedural anticoagulation with heparin, and intra-arterial tissue plasminogen activator. CONCLUSIONS: The use of endovascular devices for treating acute ischemic stroke is likely to increase as more centers become capable of integrating them into their stroke programs. It is important for pharmacists to understand the trials that evaluated endovascular interventions because differences exist with respect to device, adjunctive medication, and patient selection, all of which affect patient outcomes.

Systematic review of CETP inhibitors for increasing high-density lipoprotein cholesterol: where do these agents stand in the approval process?

The role that low levels of high-density lipoprotein cholesterol (HDL-C) plays in coronary artery disease and ischemic heart disease is well established. As such, therapies targeting low HDL-C levels have been of great therapeutic interest. These therapies include nonpharmacological methods such as exercise, tobacco cessation, weight reduction, moderate alcohol intake, and increasing dietary monounsaturated fatty acids and polyunsaturated fatty acids. Additionally, pharmacological methods of increasing HDL-C have been of great interest, with 2 classes of drugs, fibric acid derivatives and nicotinic acid, and have mixed trial results when used on top of standard lipid therapy. However, a new class of medications, cholesteryl ester transfer protein inhibitors, has shown increases in HDL-C of over 100%. However, early trial results with torcetrapib showed an increase in mortality, although this was attributed to off-target toxicity. Dalcetrapib was found to be safer than torcetrapib, but data released in 2012 showed no additional benefit in patients suffering an acute coronary syndrome event. Two newer agents, anacetrapib and evacetrapib, in early-phase clinical trials have shown to be safer than torcetrapib and significantly more potent than dalcetrapib (both increase HDL-C by a greater amount and both have a significant effect on low-density lipoprotein cholesterol). It remains to be seen whether the use of cholesteryl ester transfer protein inhibitors will result in clinical benefit in large, randomized double-blind trials and whether any agents in this class will ever be approved for clinical use.

Potential and emerging treatment options for Ebola virus disease.

OBJECTIVE: To describe the current Ebola virus epidemic and the potential options for treatment and prevention of Ebola virus disease. DATA SOURCES: A PubMed literature search (1976 through October 20, 2014) was conducted using the search term Ebola. STUDY SELECTION AND DATA EXTRACTION: Animal and human studies published in English were selected. Studies published within the past 5 years were the primary focus of this review. DATA SYNTHESIS: The current Ebola virus epidemic has primarily been contained in West Africa though it has subsequently spread to other areas, including the United States. The first patient in the United States infected with Ebola virus was diagnosed, treated, and expired in Texas. Two nurses caring for this patient also were diagnosed with Ebola virus and have been successfully treated. Treatment options for patients infected with Ebola virus are limited. Supportive therapy is centered on fluid resuscitation, electrolyte imbalance correction, treating complicating infections, and preventing complications of shock. Experimental therapies (ZMapp, brincidofovir, TKM-Ebola, and favipiravir) have been used during this current outbreak. Several medications such as amiodarone, chloroquine, and clomiphene may prevent the transmission of or treat Ebola virus. Different vaccine therapies are also in early-stage development. One of the vaccine strategies using recombinant vesicular stomatitis virus as a delivery vector has demonstrated efficacy when used for preexposure and postexposure prophylaxis. CONCLUSION: Ebola virus is highly virulent and fatal, and treatment options are limited. Several experimental and existing therapies may be options for preventing and treating Ebola virus disease.

Effect of introducing procalcitonin on antimicrobial therapy duration in patients with sepsis and/or pneumonia in the intensive care unit.

BACKGROUND: Utilizing procalcitonin (PCT) levels to limit antimicrobial overuse would be beneficial from a humanistic and economic perspective. OBJECTIVE: To assess whether introducing PCT at a teaching hospital reduced antimicrobial exposure in critically ill patients. METHODS: Patients wereadmitted to the intensive care unit (ICU) for >72 hours with sepsis and/or pneumonia. PCT levels were drawn on admission to the ICU or with new suspected infection, with at least 1 PCT level being drawn at least 48 hours later. Patients were matched in a 1:1 fashion to historical patients on age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, gender, and primary diagnosis. The primary outcome was duration of initial antimicrobial exposure defined as days from initiation of antimicrobial therapy to the intentional discontinuation of therapy by the physician. Secondary end points included length of stay, readmission to the hospital, and relapse of infection. RESULTS: There were 50 patients in the PCT group and 50 patients in the historical group. The initial duration of antimicrobials was 10 (±4.9) days compared with 13.3 (±7.2), which was statistically significant (P = .0238). The duration of stay in the hospital (13.5 compared with 17.8 days; P = .0299), readmission to the hospital (9 compared with 17; P = .055), and relapse of infection (3 compared with 11; P = .02) were seen less in the PCT group compared with controls. CONCLUSION: Introducing PCT levels resulted in a shorter duration of initial antimicrobial therapy and was not associated with adverse treatment outcomes.

MetaBase--the wiki-database of biological databases.

Biology is generating more data than ever. As a result, there is an ever increasing number of publicly available databases that analyse, integrate and summarize the available data, providing an invaluable resource for the biological community. As this trend continues, there is a pressing need to organize, catalogue and rate these resources, so that the information they contain can be most effectively exploited. MetaBase (MB) (http://MetaDatabase.Org) is a community-curated database containing more than 2000 commonly used biological databases. Each entry is structured using templates and can carry various user comments and annotations. Entries can be searched, listed, browsed or queried. The database was created using the same MediaWiki technology that powers Wikipedia, allowing users to contribute on many different levels. The initial release of MB was derived from the content of the 2007 Nucleic Acids Research (NAR) Database Issue. Since then, approximately 100 databases have been manually collected from the literature, and users have added information for over 240 databases. MB is synchronized annually with the static Molecular Biology Database Collection provided by NAR. To date, there have been 19 significant contributors to the project; each one is listed as an author here to highlight the community aspect of the project.

Effect of modifying dose alerts in an electronic health record on frequency of alerts.

PURPOSE: Results of a study to reduce the number of medication order-entry alerts and perceived alert fatigue by optimizing alert logic are reported. METHODS: Data on dosage alerts registered throughout a health system over 2 days per study phase (preintervention and postintervention) were collected from the electronic health record. The 5 medications most frequently associated with dosage alerts during computerized prescriber order entry (CPOE) were evaluated for appropriateness in relation to patient-specific characteristics. Additionally, the 10 alerts most frequently marked by prescribers as "inaccurate warning" during alert override were evaluated for appropriateness. Recommendations were made for all alerts deemed inappropriate or unnecessary. The percent change in the number of alerts from the preintervention to the postintervention period was determined. To evaluate clinician perceptions of the alert updates, a pre-post survey was distributed to hospitalists and pharmacists at 1 facility within the health system. RESULTS: Changes were recommended for 8 alerts; 2 alerts within the dosage category overlapped with alerts in the inaccurate-warning group, resulting in a total of 6 recommended changes. Two recommended alert changes were made within the clinical drug information system, and 4 alerts were changed at the health-system level. As a result, a 3.6% dosage alert decrease occurred. CONCLUSION: The proportion of dose alerts, among all CPOE-generated alerts, decreased after some of the alerts were modified in accordance with institution-specific medication and population evaluations.

Medication errors associated with transition from insulin pens to insulin vials.

PURPOSE: Three insulin administration errors that occurred after a hospital's transition from insulin pens to vials are described, and process improvement initiatives implemented to prevent future errors are reviewed. SUMMARY: In response to numerous reports and warnings related to the risk of insulin pen sharing, a 450-bed community hospital made a transition from insulin pens to insulin vials. Shortly after this transition, three major medication errors involving insulin occurred. Root-cause analysis of the errors identified numerous contributing factors, such as incomplete nursing staff education, issues with the electronic medical record, and lack of adherence to medication administration policies and procedures. In response to these errors, process improvement initiatives were implemented to prevent future errors from occurring. These process improvement initiatives consisted of (1) providing education to nurses, (2) revising the appearance of the electronic medical record, (3) emphasizing the importance of using insulin syringes exclusively for insulin administration, (4) performing safety rounds to confirm proper safety checks, and (5) implementing daily improvement huddles hospitalwide. Newly implemented initiatives to help ensure safe insulin use included involving frontline nursing staff in medication safety committee meetings and requiring that all insulin glargine doses be prepared in designated insulin syringes in the pharmacy for dispensing to patient care units. CONCLUSION: After three major insulin administration errors, a review of processes and contributing factors was conducted. With additional education of nurses, improved staff communication, and implementation of other safety initiatives, no insulin administration errors were reported in the following year.

National survey of pharmacy residents nearing completion of the 2014-15 residency year.

PURPOSE: The results of a national survey targeting postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) resident's perceptions of their residency programs and postresidency job prospects are presented. METHODS: An electronic survey was distributed to PGY1 and PGY2 residents identified through the ASHP membership database. The survey asked basic demographic questions, questions related to the residency experience (satisfaction, hours spent on various general activities such as patient care, research, and staffing), and various questions related to residents' job search and future career plans (search methods, outcomes, and satisfaction with the process). RESULTS: A total of 529 responses were received from the 2,766 surveys that were distributed, yielding a response rate of 19%. Most respondents reported having a favorable opinion of their residency. At the time of the survey, 71% of residents reported having found a full-time job; 17% of residents were still looking for a position. Eighty-five percent of PGY2 residents reported accepting a position in their specialty area and accepted clinical specialist roles in larger numbers than did PGY1 residents. Geographic location, practice/specialty area, and shift/schedule were the 3 areas of compromise most frequently mentioned when accepting a position and were the 3 areas ranked highest in terms of job importance. CONCLUSION: A survey of PGY1 and PGY2 pharmacy residents revealed that about one sixth of respondents entering the job market were having difficulty finding a position before finishing residency training and that most respondents were satisfied with their residency experience.

Antimicrobial Stewardship in the Emergency Department: Challenges, Opportunities, and a Call to Action for Pharmacists.

Antimicrobial resistance is a national public health concern. Misuse of antimicrobials for conditions such as upper respiratory infection, urinary tract infections, and cellulitis has led to increased resistance to antimicrobials commonly utilized to treat those infections, such as sulfamethoxazole/trimethoprim and flouroquinolones. The emergency department (ED) is a site where these infections are commonly encountered both in ambulatory patients and in patients requiring admission to a hospital. The ED is uniquely positioned to affect the antimicrobial use and resistance patterns in both ambulatory settings and inpatient settings. However, implementing antimicrobial stewardship programs in the ED is fraught with challenges including diagnostic uncertainty, distractions secondary to patient or clinician turnover, and concerns with patient satisfaction to name just a few. However, this review article highlights successful interventions that have stemmed inappropriate antimicrobial use in the ED setting and warrant further study. This article also proposes other, yet to be validated proposals. Finally, this article serves as a call to action for pharmacists working in antimicrobial stewardship programs and in emergency medicine settings. There needs to be further research on the implementation of these and other interventions to reduce inappropriate antimicrobial use to prevent patient harm and curb the development of antimicrobial resistance.

Pharmacotherapy Considerations in the Management of Transgender Patients: A Brief Review.

Transgender and transsexual individuals have unique health care needs and risks compared with the population at large. It is estimated that 1 in 100,000 individuals in the United States is a transgender woman and 1 in 400,000 is a transgender man, although these estimates of prevalence are likely conservative. Transgender individuals are at an increased risk of tobacco, alcohol, and substance abuse; they have an increased lifetime suicide attempt risk; and they are more likely to experience significant stressors in their lives. Transgender patients may elect to transition their appearance to the gender with which they identify. Hormone treatment (and possibly sex reassignment surgery) is a significant part of this transition, and pharmacists must understand the pharmacotherapeutic principles involved so they can better recommend therapeutic agents, provide dosing recommendations, and anticipate and manage adverse effects. It is critical to be culturally sensitive when providing care for transgender patients including using their preferred gender identity, preferred names, and preferred pronouns. It is also essential to be able to identify transgender and transsexual patients correctly within electronic health records to ensure that appropriate care and monitoring are provided. For pharmacists, this means they should know the biologic sex for performing calculations such as creatinine clearance and to prevent teratogenic agents from reaching a transgender or transsexual man who could be pregnant or is capable of becoming pregnant. Promoting knowledge of transgender health issues will enable pharmacists to provide better, more holistic care to their transgender patients.

Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, and role in therapy for riociguat are reviewed. SUMMARY: Riociguat is the first member of a new class of medications, soluble guanylate cyclase stimulators. Riociguat is indicated for patients with resistant or recurrent chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy who have World Health Organization (WHO) functional class IV pulmonary arterial hypertension (PAH) and in patients with inoperable CTEPH, regardless of WHO functional class, to improve exercise capacity and WHO functional class. Riociguat is indicated in patients with WHO functional class II PAH to improve exercise capacity, improve functional class, and delay clinical worsening. The mechanism of action of riociguat is within the nitric oxide pathway in the pulmonary vasculature. Clinical trials have demonstrated improvements in exercise capacity as measured by the six-minute walk distance test and in pulmonary arterial hemodynamics as measured by invasive pulmonary monitoring. Riociguat must be administered three times daily and requires dosage adjustments. Riociguat is a pregnancy category X drug and interacts with numerous medications. The two most serious adverse effects related to riociguat are hypotension and bleeding. Riociguat's role in the therapy of both PAH and CTEPH will be determined as more clinical experience and data are collected. Riociguat will likely cost approximately $90,000 annually. CONCLUSION: Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of CTEPH and PAH. It can be considered first-line therapy for the treatment of CTEPH and should be considered as an alternative to phosphodiesterase type-5 inhibitors in patients with PAH.

Practical considerations for the pharmacotherapy of pulmonary arterial hypertension.

Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.