Drug Interactions Associated With Therapies for Pulmonary Arterial Hypertension.

Objective: To evaluate the potential for drug interactions with therapies for pulmonary arterial hypertension (PAH). Treatments include calcium channel blockers, phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin receptor agonists. Data Sources: A systemic literature search (January 1980-December 2021) was performed using PubMed and EBSCO to locate relevant articles. The mesh terms used included each specific medication available as well as "drug interactions." DAILYMED was used for product-specific drug interactions. Study Selection and Data Extraction: The search was conducted to identify drug interactions with PAH treatments. The search was limited to those articles studying human applications with PAH treatments and publications using the English language. Case reports, clinical trials, review articles, treatment guidelines, and package labeling were selected for inclusion. Data Synthesis: Primary literature and package labeling indicate that PAH treatments are subject to pharmacokinetic and pharmacodynamic interactions. The management of PAH is rapidly evolving. As more and more evidence becomes available for the use of combination therapy in PAH, the increasing use of combination therapy increases the risk of drug-drug interactions. Pulmonary arterial hypertension is also associated with other comorbidities that require concomitant pharmacotherapy. Conclusion: The available literature indicates that PAH therapies are associated with clinically significant drug interactions and the potential for subsequent adverse reactions. Clinicians in all practice settings should be mindful that increased awareness of drug interactions with PAH therapy will ensure optimal management and patient safety.

Vitamin D supplements: The pharmacists' perspective.

OBJECTIVE: The purpose of this narrative review was to provide guidance for pharmacists concerning vitamin D supplementation. METHODS: Relevant studies were identified in a search of MEDLINE/PubMed, EBSCOhost, and Google Scholar from January 1966 to September 2020 using the search terms vitamin D, vitamin D2, vitamin D3, calcitriol, and vitamin D deficiency. Abstracts were reviewed for relevance and, if relevant, full-text articles were retrieved and reviewed. References were checked, and citation searches using identified studies were conducted. The literature search included English-language studies involving administration of vitamin D monotherapy compared with placebo. RESULTS: Serum 25-hydroxyvitamin D levels of less than 12 ng/mL indicate a vitamin D deficiency. The Institute of Medicine recommends a daily intake of 600 IU of vitamin D in individuals aged up to 70 years and 800 IU in those aged above 70 years. Vitamin D is labeled for rickets, osetomalacia, hypophosphatemia (familial or secondary), renal osteodystrophy, and corticosteroid-induced osteoporosis. When used for these indications, vitamin D should be prescribed with appropriate monitoring by a qualified health care practitioner. There is evidence for vitamin D supplementation in individuals aged 75 years or older and in those with problems associated with mobility, gait, or balance. There is insufficient evidence to support vitamin D supplementation in the prevention of cardiovascular disease, cancer, asthma, chronic obstructive pulmonary disease exacerbations, new-onset type 2 diabetes, infectious lung diseases, cognitive dysfunction, Alzheimer disease, and depression, or in prenatal use. CONCLUSION: Pharmacists can provide evidence-based recommendations concerning the indications, dosing, monitoring, and adverse effects of vitamin D supplements.

Sepsis and the Obesity Paradox: Size Matters in More Than One Way.

OBJECTIVES: Multiple studies have demonstrated an obesity paradox such that obese ICU patients have lower mortality and better outcomes. We conducted this study to determine if the mortality benefit conferred by obesity is affected by baseline serum lactate and mean arterial pressure. DESIGN: Retrospective analysis of prospectively collected clinical data. SETTING: Five community-based and one academic medical center in the Omaha, NE. PATIENTS: 7,967 adults hospitalized with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized by body mass index as underweight, normal weight, overweight, or obese. Multivariable logistic regression models were used to estimate the odds of in-hospital death by body mass index category; two-way interactions between body mass index and each covariate were also evaluated. Subgroup and sensitivity analyses were conducted using an ICU cohort and Acute Physiology and Chronic Health Evaluation III scores, respectively. The overall unadjusted mortality rate was 12.1% and was consistently lower in higher body mass index categories (all comparisons, p < 0.007). The adjusted mortality benefit observed in patients with higher body mass index was smaller in patients with higher lactate levels with no mortality benefit in higher body mass index categories observed at lactate greater than 5 mmol/L. By contrast, the association between lower MAP and higher mortality was constant across body mass index categories. Similar results were observed in the ICU cohort. Finally, the obesity paradox was not observed after including Acute Physiology and Chronic Health Evaluation III scores as a covariate. CONCLUSIONS: Our retrospective analysis suggests that although patient size (i.e., body mass index) is a predictor of in-hospital death among all-comers with sepsis-providing further evidence to the obesity paradox-it adds that illness severity is critically important whether quantified as higher lactate or by Acute Physiology and Chronic Health Evaluation III score. Our results highlight that the obesity paradox is more than a simple association between body mass index and mortality and reinforces the importance of illness severity.

Evidence for the Efficacy of an Opioid-Sparing Effect of Intravenous Acetaminophen in the Surgery Patient: A Systematic Review.

BACKGROUND: Intravenous (IV) acetaminophen is used in multimodal analgesia to reduce the amount and duration of opioid use in the postoperative setting. METHODS: A systematic review of published randomized controlled trials was conducted to define the opioid-sparing effect of IV acetaminophen in different types of surgeries. Eligible studies included prospective, randomized, double-blind trials of IV acetaminophen compared with either a placebo- or active-treatment group in adult (age ≥18 years) patients undergoing surgery. Trials had to be published in English in a peer-reviewed journal. RESULTS: A total of 44 treatment cohorts included in 37 studies were included in the systematic analysis. Compared with active- or placebo-control treatments, IV acetaminophen produced a statistically significant opioid-sparing effect in 14 of 44 cohorts (32%). An opioid-sparing effect was more common in placebo-controlled comparisons. Of the 28 placebo treatment comparisons, IV acetaminophen produced an opioid-sparing effect in 13 (46%). IV acetaminophen produced an opioid-sparing effect in only 6% (one out of 16) of the active-control groups. Among the 16 active-control groups, opioid consumption was significantly greater with IV acetaminophen than the active comparator in seven cohorts and not significantly different than the active comparator in eight cohorts. CONCLUSIONS: The results of this systematic analysis demonstrate that IV acetaminophen is not effective in reducing opioid consumption compared with other adjuvant analgesic agents in the postoperative patient. In patients where other adjuvant analgesic agents are contraindicated, IV acetaminophen may be an option.

Alpha-1 Antitrypsin Replacement in Patients With COPD.

Chronic obstructive pulmonary disease can be attributed to genetic conditions and predispositions, among other factors. Alpha-1 antitrypsin deficiency (AATD) is a significant risk factor for COPD development and progression, and aggressive screening for all patients with COPD or adult-onset asthma is encouraged.

Clinically Significant Food-Drug Interactions.

OBJECTIVE: Provide an up-to-date review for health care providers regarding clinically significant food-drug interactions and summarize recommendations for optimal medication administration in older adults and long-term care patients. DATA SOURCES: A literature search was performed using MEDLINE, PUBMED, and IPA abstracts to locate relevant articles published between January 1982 and July 2017. DAILYMED was used to identify manufacturer-specific medication administration recommendations. STUDY SELECTION AND DATA EXTRACTION: Articles were reviewed for inclusion based on their relevance to this subject matter and the integrity of the information provided. Additionally, the package labeling of included products was reviewed. DATA SYNTHESIS: The current recommendations for specific medication administration with regard to food are summarized descriptively. CONCLUSION: Clinically significant food-drug interactions are common and have been reported with multiple classes of medications. However, there are a limited number of studies examining food-drug interactions, and the majority of recommendations are made by product-specific manufacturers. Pharmacists should be aware of common food-drug interactions in the community, assisted living, long-term care, subacute care, and hospital settings. To optimize medication therapy and improve therapeutic outcomes, it is important for pharmacists and other health care providers to identify agents with potential for food-drug interactions and to understand the clinical relevance of such interactions.

Management of Non-Cystic Fibrosis Bronchiectasis.

OBJECTIVE: The purpose of this report is to describe the case of a 43-year-old male with asthma who was hospitalized for an exacerbation of non-cystic fibrosis bronchiectasis (NCFB), a chronic lung disease that is characterized by dilation of the airways, persistent cough, chronic sputum production, and recurrent respiratory infections. He was treated with oral and inhaled antibiotics, inhaled bronchodilators, and aggressive airway-clearance techniques including nebulized 7% sodium chloride, flutter valve, and high-frequency chest wall oscillation. SETTINGS: Community pharmacy, nursing facility pharmacy, consultant pharmacy practice. PRACTICE CONSIDERATIONS: As the number of patients diagnosed with NCFB continues to increase, it is crucial to recognize that specific guidance for management of NCFB is warranted, as treatment responses differ from cystic fibrosis bronchiectasis or chronic obstructive pulmonary disease. CONCLUSION: It is important for pharmacists to understand the pharmacologic and nonpharmacologic treatments for NCFB to better assist physicians and patients and improve therapeutic outcomes.

Drug Interactions With Oral Inhaled Medications.

Objective: To evaluate the potential for drug interactions with oral inhaled medications (OIMs). OIMs include bronchodilators (ß-agonists and antimuscarinics), corticosteroids, combination products (2 or more agents combined within a single inhalation device), antibiotics, prostacyclins, anesthetics, acetylcysteine, mucolytics, insulin, antivirals, nitric oxide, and nicotine replacement. Data Sources: A systemic literature search (1980 to May 2018) was performed using PubMed and EBSCO to locate relevant articles. The MESH terms used included each specific medication available as an OIM as well as "drug interactions." DAILYMED was used for product-specific drug interactions. Study Selection and Data Extraction: The search was conducted to identify drug interactions with OIMs. The search was limited to those articles studying human applications with OIMs and publications using the English language. Case reports, clinical trials, review articles, treatment guidelines, and package labeling were selected for inclusion. Data Synthesis: Primary literature and package labeling indicate that OIMs are subject to pharmacokinetic and pharmacodynamics interactions. The most frequently identified clinically significant drug interaction is an inhaled corticosteroid when combined with a potent CYP 450 inhibitor such as a protease inhibitor or antifungal. Conclusions: The available literature indicates that OIMs are associated with clinically significant drug interactions and subsequent adverse reactions. Clinicians in all practice settings should be mindful of this potential to minimize adverse effects and optimize therapy.

Pharmacists can help prevent lipoid pneumonia: Two case reports.

OBJECTIVES: To report 2 cases of lipoid pneumonia. SUMMARY: Lipoid pneumonia is an inflammatory process in the lower airways due to the presence of lipid molecules in the alveoli. Exogenous lipoid pneumonia is due to the inhalation or aspiration of fat-containing substances. Historically, mineral oil is the most common medication cause but there have also been several reports of lipoid pneumonia associated with petroleum jelly, medicated vapor rub, and lip glosses. Two case reports are presented to illustrate the importance of identifying risk factors for lipoid pneumonia. RESULTS: Use of the Naranjo algorithm suggested that both cases of lipoid pneumonia were "possibly" due to aspiration of lipid-containing over-the-counter agents. The first case was associated with aspiration of mentholated topical ointment applied intranasally, whereas the second case was attributed to probable aspiration of mineral oil for management of chronic constipation. CONCLUSION: Pharmacists in many practice settings can play an integral role in preventing this condition and screening for patients who may warrant a diagnostic workup. During medication reconciliation, pharmacists should identify all prescription and nonprescription medications used by patients. Patients should specifically be asked about lipid-based over-the-counter products and cosmetic agents.

Role of pharmacists in the treatment of excessive daytime sleepiness.

The focus of this case is a 78-year-old female who is being referred to an assisted living community following several episodes of excessive daytime sleepiness (EDS). EDS in the geriatric patient is widespread and is often underdiagnosed and inadequately treated. It can affect an older patient?s quality of life, as well as increasing physical, psychological, cognitive, and mortality risks. There are many different etiologies for EDS including coexisting medical conditions, circadian misalignment, medications affecting the sleep/wake cycle, and psychiatric or psychosocial circumstances. This case illustrates how the pharmacist can help patients with EDS by recognizing symptoms; performing a targeted medical history, sleep history, and medication review; and offering screening with validated tools to refer patients to sleep specialists. There are both pharmacological and nonpharmacological treatment options. The consultant pharmacist is a vital member of the interprofessional health care team and can play a major role in the education, monitoring, and management of EDS.

Applying principles of formulary management to blood banking.

The pharmacy and therapeutics (P&T) committee or its equivalent has been a long-standing committee of the medical staff in almost every institution. The P&T committee is typically defined as the body that recommends policy to the medical staff and the administration of the organization on matters related to the safe and therapeutic use of medications as well as other matters relating to medication use. The Food and Drug Administration definition of a drug includes blood and blood components, and the American Society of Health-System Pharmacists guidelines suggest including blood derivatives in their definition of a drug. Clinicians and other health care providers have needed to become more familiar with blood and blood component therapy as more prescription blood products have become available. As such, the P&T committee could work collaboratively with blood bank personnel, who are experts in this area, to help ensure that blood derivative products undergo the same evidence-based formulary review process as other medications.

Theophylline for the management of respiratory disorders in adults in the 21st century: A scoping review from the American College of Clinical Pharmacy Pulmonary Practice and Research Network.

Theophylline is an oral methylxanthine bronchodilator recommended as alternate therapy for the treatment of asthma and chronic obstructive pulmonary disease (COPD). However, it is not generally recommended for the treatment of other respiratory disorders such as obstructive sleep apnea (OSA) or hypoxia. Most clinical practice guidelines rely on evidence published prior to the year 2000 to make these recommendations. This scoping review aimed to gather and characterize evidence describing theophylline for the management of respiratory disorders in adults between January 1, 2000 and December 31, 2020. Databases searched included Ovid MEDLINE, Embase, CINAHL Complete, Scopus, and International Pharmaceutical Abstracts. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Studies were included if they were published in English, theophylline was used for any respiratory disorder, and the study outcomes were disease- or patient-oriented. After removal of duplicates, 841 studies were screened and 55 studies were included. Results aligned with current clinical guideline recommendations relegating theophylline as an alternative therapy for the treatment of respiratory disorders, in favor of inhaled corticosteroids and inhaled bronchodilators. This scoping review identified the need for future research including: theophylline versus other medications deemed alternative therapies for asthma and COPD, meta-analyses of low-dose theophylline, and studies evaluating evidence-based patient-oriented outcomes for OSA, hypoxia, ventilator-induced diaphragmatic dysfunction, and spinal cord injury-related pulmonary function.

A Retrospective Analysis of the Effects of Time on Compliance and Driving Pressures in ARDS.

BACKGROUND: The evolution of compliance and driving pressure in ARDS and the effects of time spent on noninvasive respiratory support prior to intubation have not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (ie, noninvasive ventilation [NIV], high-flow nasal cannula [HFNC], or a combination of NIV and HFNC) on static compliance and driving pressure and retrospectively describe its trajectory over time for COVID-19 and non-COVID-19 ARDS while on mechanical ventilation. METHODS: This is a retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one rural magnet hospital, and 3 suburban community facilities. A total of 589 subjects were included: 55 COVID-19 positive, 137 culture positive, and 397 culture-negative subjects. Static compliance and driving pressure were calculated at each 8-h subject-ventilator assessment. RESULTS: Days of pre-intubation noninvasive respiratory support were associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19-positive subjects showed non-statistically significant worsening compliance by 0.08 units per subject-ventilator assessment (P = .24), whereas COVID-19-negative subjects who were either culture positive or negative showed statistically significant improvement (0.12 and 0.18, respectively; both P < .05); a statistically similar but inverse pattern was observed for driving pressure. CONCLUSIONS: In contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static compliance or driving pressures. Though there was no association between days of pre-intubation noninvasive respiratory support and mortality, its use was associated with worse overall compliance and driving pressure.

Synbiotics and probiotics in the critically ill after the PROPATRIA trial.

PURPOSE OF REVIEW: Recent clinical trials have furthered our understanding of the role of probiotic and synbiotic therapy across a variety of diverse diseases including antibiotic-associated diarrhea, Clostridium difficile associated diarrhea, acute pancreatitis, ventilator-associated pneumonia, and sepsis among others. Although each of these conditions has implications for critically ill patients, relatively few studies have specifically studied this vulnerable population. RECENT FINDINGS: One recent clinical trial studying probiotics in severe pancreatitis (the PROPATRIA trial) found an unexpected increase in mortality in probiotic-treated patients. These results stimulated an immediate, extensive, and badly overdue discussion focused on the need for improved safety monitoring during the execution of all clinical trials using probiotics. However, issues with the design, execution, and analysis of PROPATRIA ultimately created more questions than it answered. SUMMARY: Regardless of technical issues with the study, the increased mortality seen with probiotics cannot be ignored. As a result, various regulatory agencies have clarified their stance on the safety of probiotic research and the legacy of PROPATRIA is increasingly stringent regulation of this fledgling niche.

Probiotic, prebiotic, and synbiotic use in critically ill patients.

PURPOSE OF REVIEW: To summarize the existing data regarding the use of probiotics, prebiotics, and synbiotics in select disorders encountered in the intensive care unit setting. RECENT FINDINGS: Recent systematic reviews and meta-analyses have more rigorously aggregated the fragmented primary data which suffers from multiple limitations. SUMMARY: Probiotics are living microorganisms which, when ingested in adequate amounts, provide health benefits to the host. The mechanisms of these benefits include improved gastrointestinal barrier function, modification of the gut flora by inducing host cell antimicrobial peptides, releasing probiotic antimicrobial factors, competing for epithelial adherence, and immunomodulation to the advantage of the host. In the intensive care unit, probiotics appear to provide benefits in antibiotic-associated diarrhea, ventilator-associated pneumonia, and necrotizing enterocolitis. With increasing rates of antibiotic resistance among common nosocomial pathogens and fewer new antibiotics in the research pipeline, increasing attention has been placed on nonantibiotic approaches to the prevention and treatment of nosocomial infections. Existing studies of probiotics in critically ill patients are limited by heterogeneity in probiotic strains, dosages, duration of administration, and small sample sizes. Although probiotics are generally well tolerated and adverse events are very rare, the results of the PROPATRIA (Probiotics Prophylaxis in Patients with Predicted Severe Acute Pancreatitis) trial highlight the need for meticulous attention to safety monitoring. Better identification of the ideal characteristics of effective probiotics coupled with improved understanding of mechanisms of action will help to delineate the true beneficial effects of probiotics in various disorders.

Management of patients with fibrosing interstitial lung diseases.

PURPOSE: This article summarizes the appropriate use and pharmacology of treatments for fibrosing interstitial lung diseases, with a specific focus on the antifibrotic agents nintedanib and pirfenidone. SUMMARY: The interstitial lung diseases are a heterogenous group of parenchymal lung disorders with a common feature-infiltration of the interstitial space with derangement of the normal capillary-alveolar anatomy. Diseases characterized by fibrosis of the interstitial space are referred to as the fibrosing interstitial lung diseases and often show progression over time: idiopathic pulmonary fibrosis is the most common fibrotic interstitial lung disease. Historically, therapies for fibrosing lung diseases have been limited in number, questionable in efficacy, and associated with potential harms. Food and Drug Administration (FDA) approval of the antifibrotic agents nintedanib and pirfenidone for idiopathic pulmonary fibrosis in 2014 heralded an era of reorganization of therapy for the fibrotic interstitial lung diseases. Subsequent investigations have led to FDA approval of nintedanib for systemic sclerosis-associated interstitial lung disease and interstitial lung diseases with a progressive phenotype. Although supportive care and pulmonary rehabilitation should be provided to all patients, the role(s) of immunomodulators and/or immune suppressing agents vary by the underlying disease state. Several agents previously used to treat fibrotic lung diseases (N-acetylcysteine, anticoagulation, and pulmonary vasodilators) lack efficacy or cause harm. CONCLUSION: With the introduction of effective pharmacotherapy for fibrosing interstitial lung disease, pharmacists have an increasingly important role in the interdisciplinary team managing these patients.

Prolonged Prehospital Time Is a Risk Factor for Pneumonia in Trauma (the PRE-TRIP Study): A Retrospective Analysis of the United States National Trauma Data Bank.

BACKGROUND: Although multiple risk factors for development of pneumonia in patients with trauma sustained in a motor vehicle accident have been studied, the effect of prehospital time on pneumonia incidence post-trauma is unknown. RESEARCH QUESTION: Is prolonged prehospital time an independent risk factor for pneumonia? STUDY DESIGN AND METHODS: We retrospectively analyzed prospectively collected clinical data from 806,012 motor vehicle accident trauma incidents from the roughly 750 trauma hospitals contributing data to the National Trauma Data Bank between 2010 and 2016. RESULTS: Prehospital time was independently associated with development of pneumonia post-motor vehicle trauma (P < .001). This association was primarily driven by patients with low Glasgow Coma Scale scores. Post-trauma pneumonia was uncommon (1.5% incidence) but was associated with a significant increase in mortality (P < .001, 4.3% mortality without pneumonia vs 12.1% mortality with pneumonia). Other pneumonia risk factors included age, sex, race, primary payor, trauma center teaching status, bed size, geographic region, intoxication, comorbid lung disease, steroid use, lower Glasgow Coma Scale score, higher Injury Severity Scale score, blood product transfusion, chest trauma, and respiratory burns. INTERPRETATION: Increased prehospital time is an independent risk factor for development of pneumonia and increased mortality in patients with trauma caused by a motor vehicle accident. Although prehospital time is often not modifiable, its recognition as a pneumonia risk factor is important, because prolonged prehospital time may need to be considered in subsequent decision-making.

Pharmacotherapy for nontuberculous mycobacterial pulmonary disease.

PURPOSE: To provide an updated review of the diagnosis and pharmacotherapy of nontuberculous mycobacteria pulmonary disease (NTM-PD) and summarize guideline recommendations for an interdisciplinary treatment approach. SUMMARY: A systemic approach was taken in which all articles in English in MEDLINE and PubMed were reviewed. The US National Library of Medicine's DailyMed database was used to assess drug package inserts. Analysis of NTM treatment guidelines is summarized in the article with a focus on medications, dosing, interactions, and medication monitoring. CONCLUSION: It is critical to manage patients with NTM with a multidisciplinary team approach. Treatment is prolonged and expensive, and the potential for drug toxicity, adverse effects, and drug interactions requires monitoring. Clinical pharmacists play a role in the management of NTM.