Acute elevation of liver function test values following concomitant administration of dabigatran and primidone.

PURPOSE: We report a unique case of transiently elevated liver function test (LFT) values associated with concurrent use of dabigatran and primidone, which has not previously been described in the scientific literature. SUMMARY: Management of drug-drug interactions requires a fundamental understanding of pharmacodynamic and pharmacokinetic parameters. Despite the use of available best predictive models, idiosyncratic drug reactions may still occur when a newly approved medication begins to be used in the general population. We report a case of a possible interaction (Naranjo adverse drug reaction probability score of 3, Roussel Uclaf causality assessment method score of 3) between dabigatran and primidone in a 70-year-old Caucasian male resulting in a transient elevation of LFT values. The patient was transitioned from warfarin to dabigatran in the setting of persistently subtherapeutic international normalized ratio values. During a routine outpatient follow-up appointment approximately 1 month after dabigatran initiation, the patient was discovered to have LFT values greater than 5 times the upper limit of normal. Dabigatran was thus discontinued; the patient was returned to warfarin therapy and their LFT values returned to baseline. CONCLUSION: Studies have indicated a potential for reduced dabigatran efficacy with concurrent use of primidone due to P-glycoprotein induction, thereby potentiating the risk for thrombosis. To date, reports of this interaction resulting in hepatic injury are lacking. The present case suggests that this interaction may be clinically significant with regard to selection of antithrombotic medication therapy in patients on primidone therapy.

New Injectable Agents for the Treatment of Type 2 Diabetes Part 2-Glucagon-Like Peptide-1 (GLP-1) Agonists.

The US Food and Drug Administration has recently approved several new glucagon-like peptide-1 (GLP-1) agonists alone and in combination with various insulin products. The second of 2 articles in a series, this review will describe the potential advantages and disadvantages of the GLP-1 agonist class of products.

New Injectable Agents for the Treatment of Type 2 Diabetes Part 1 - Injectable Insulins.

The United States Food and Drug Administration has recently approved several new insulin products and new formulations of existing insulin products. These new products may provide advantages over older products, such as a lower risk of nocturnal hypoglycemia and ease of dosing; however, they are costly. The first of 2 articles in a series, this review will describe the potential advantages and disadvantages of these new insulin products.

Type 2 Diabetes Mellitus: Outpatient Insulin Management.

In patients with type 2 diabetes mellitus, insulin may be used to augment therapy with oral glycemic medications or as insulin replacement therapy. The American Diabetes Association suggests the use of long-acting (basal) insulin to augment therapy with one or two oral agents or one oral agent plus a glucagon-like peptide 1 receptor agonist when the A1C level is 9% or more, especially if the patient has symptoms of hyperglycemia or catabolism. Insulin regimens should be adjusted every three or four days until targets of self-monitored blood glucose levels are reached. A fasting and premeal blood glucose goal of 80 to 130 mg per dL and a two-hour postprandial goal of less than 180 mg per dL are recommended. Insulin use is associated with hypoglycemia and weight gain. Insulin analogues are as effective as human insulin at lowering A1C levels with lower risk of hypoglycemia, but they have significantly higher cost. Patients with one or more episodes of severe hypoglycemia (i.e., requiring assistance from others for treatment) may benefit from a short-term relaxation of glycemic targets. Several new insulin formulations have been approved recently that are associated with less risk of hypoglycemia compared with older formulations. The goals of therapy should be individualized based on many factors, including age, life expectancy, comorbid conditions, duration of diabetes, risk of hypoglycemia, cost, patient motivation, and quality of life.

Effect of diseases on response to vitamin K antagonists.

INTRODUCTION: The purpose of this review article is to summarize the literature on diseases that are documented to have an effect on response to warfarin and other VKAs. METHODS: We searched the English literature from 1946 to September 2015 via PubMed, EMBASE, and Scopus for the effect of diseases on response vitamin K antagonists including warfarin, acenocoumarol, phenprocoumon, and fluindione. DISCUSSION: Among many factors modifying response to VKAs, several disease states are clinically relevant. Liver disease, hyperthyroidism, and CKD are well documented to increase response to VKAs. Decompensated heart failure, fever, and diarrhea may also elevate response to VKAs, but more study is needed. Hypothyroidism is associated with decreased effect of VKAs, and obese patients will likely require higher initial doses of VKAs. CONCLUSION: In order to minimize risks with VKAs while ensuring efficacy, clinicians must be aware of the effect of disease states when prescribing these oral anticoagulants.

Management of Blood Glucose with Noninsulin Therapies in Type 2 Diabetes.

A comprehensive, collaborative approach is necessary for optimal treatment of patients with type 2 diabetes mellitus. Treatment guidelines focus on nutrition, exercise, and pharmacologic therapies to prevent and manage complications. Patients with prediabetes or new-onset diabetes should receive individualized medical nutrition therapy, preferably from a registered dietitian, as needed to achieve treatment goals. Patients should be treated initially with metformin because it is the only medication shown in randomized controlled trials to reduce mortality and complications. Additional medications such as sulfonylureas, dipeptidyl-peptidase-4 inhibitors, thiazolidinediones, and glucagon-like peptide-1 receptor agonists should be added as needed in a patient-centered fashion. However, there is no evidence that any of these medications reduce the risk of diabetes-related complications, cardiovascular mortality, or all-cause mortality. There is insufficient evidence on which combination of hypoglycemic agents best improves health outcomes before escalating to insulin therapy. The American Diabetes Association recommends an A1C goal of less than 7% for many nonpregnant adults, with the option of a less stringent goal of less than 8% for patients with short life expectancy, cardiovascular risk factors, or long-standing diabetes. Randomized trials in middle-aged patients with cardiovascular risk factors have shown no mortality benefit and in some cases increased mortality with more stringent A1C targets.

Flushing and pruritus secondary to prescription fish oil ingestion in a patient with allergy to fish.

BACKGROUND: A brand of fish oil capsules contains omega-3 fatty acids obtained from several fish sources. Although the manufacturer calls for caution in patients with fish hypersensitivity, insufficient data is available to make a definitive recommendation regarding its use in this population. CASE PRESENTATION: A patient with documented seafood allergy presented to the emergency department 4 days after the initiation of prescription brand name fish oil capsules complaining of chest tightness, shortness of breath, tingling of upper extremities, flushing, and pruritus that was minimally relieved by excessive nonprescription diphenhydramine administration. During subsequent follow-up, the patient reported that all symptoms had resolved within 5 days of discontinuing the medication and 3 days of disposing of her pillbox and all medications that had come in contact with the fish oil capsules. CONCLUSION: Due to the patient's allergic history, timing of onset/offset of the reaction, laboratory evidence, and the use of the Naranjo probability scale, prescription fish oil capsules were deemed the probable cause of this patient's pruritus and flushing of the face and trunk. Practitioners and patients should always ensure they have an updated list of allergies within the patient's medical record that includes medications as well as foods and food additives.

Graves' disease and treatment effects on warfarin anticoagulation.

Background. Hyperthyroidism causes an increased hypoprothrombinemic response to warfarin anticoagulation. Previous studies have demonstrated that patients with hyperthyroidism require lower dosages of warfarin to achieve a therapeutic effect. As hyperthyroidism is treated and euthyroidism is approached, patients may require increasing warfarin dosages to maintain appropriate anticoagulation. We describe a patient's varying response to warfarin during treatment of Graves' disease. Case Presentation. A 48-year-old African American female presented to the emergency room with tachycardia, new onset bilateral lower extremity edema, gradual weight loss, palpable goiter, and generalized sweating over the prior 4 months. She was admitted with Graves' disease and new onset atrial fibrillation. Primary stroke prophylaxis was started using warfarin; the patient developed a markedly supratherapeutic INR likely due to hyperthyroidism. After starting methimazole, her free thyroxine approached euthyroid levels and the INR became subtherapeutic. She remained subtherapeutic over several months despite steadily increasing dosages of warfarin. Immediately following thyroid radioablation and discontinuation of methimazole, the patient's warfarin dose and INR stabilized. Conclusion. Clinicians should expect an increased response to warfarin in patients with hyperthyroidism and close monitoring of the INR is imperative to prevent adverse effects. As patients approach euthyroidism, insufficient anticoagulation is likely without vigilant follow-up, INR monitoring, and increasing warfarin dosages.

Pharmacist-physician collaboration for diabetes care: cardiovascular outcomes.

BACKGROUND: Only 23% of patients are meeting all goals for cardiovascular complications of diabetes. OBJECTIVE: The purpose of our study is to evaluate the effect of a pharmacist-physician collaboration on attainment of cardiovascular-related goals in patients with type 2 diabetes. METHODS: This prospective, multicenter cohort enrolled patients from 7 practice sites that were members of the University of Tennessee Pharmacist Practice Based Research Network (UT Pharm Net). Patients were included if they were diagnosed with type 2 diabetes, at least 18 years of age and English speaking. Pregnant patients were excluded. Patients were followed for 12 months after enrollment. Primary cardiovascular outcomes included reduction in systolic blood pressure, diastolic blood pressure, and low-density lipoprotein (LDL) as well as the proportion of patients achieving a blood pressure goal of <130/80 mm Hg and proportion of patients achieving an LDL goal of <100 mg/dL. RESULTS: For the 206 patients enrolled, the average age was 59.7 years; the majority were male (59.7%) and white (66%). When compared with baseline, the postintervention mean systolic (P < .0001), diastolic blood pressure (P = .0003), and LDL (P < .0001) decreased significantly. The proportion of patients achieving a blood pressure of <130/80 mm Hg increased 21.8% (P < .0001), and the proportion of patients achieving an LDL of <100 mg/dL increased 12% (P = .0023). CONCLUSIONS: The results of our study indicate that collaborative management has a positive impact on decreasing cardiovascular risk and assists patients in attaining national goals for blood pressure and cholesterol.

Smoking and asthma.

BACKGROUND: The purpose of this review is to describe the current understanding of the prevalence and adverse effects of cigarette smoking and secondhand smoke (SHS) in asthmatics in terms of patient outcomes and response to inhaled corticosteroids. METHODS: We searched the English biomedical literature via PubMed, Embase, and Scopus using the terms "smoking and asthma," "secondhand smoke and asthma," "environmental tobacco smoke and asthma," and "smoking/secondhand smoke and corticosteroids." We also reviewed reference lists of identified articles for relevant citations. RESULTS: In asthmatic patients who smoke, disease control is poorer than in asthmatic nonsmokers. Of all forms of SHS, maternal exposure seems to have the largest impact on asthma by increasing the frequency and severity of the disease and decreasing lung function. Asthmatic children exposed to multiple household smokers face an increased risk for respiratory illness-related absences from school, and these effects persist during adolescence but weaken during adulthood. Airway mucosal permeability is increased in smokers, which could lead to increased clearance of inhaled corticosteroids from the airways. Smokers also have decreased histone deacetylase activity, which is necessary for corticosteroids to fully suppress cytokine production, and can lead to corticosteroid resistance. CONCLUSIONS: Cigarette smoking and SHS in asthmatics lead to detrimental effects in patient outcomes and effectiveness of steroid therapy.

Comparing team-based and mixed active-learning methods in an ambulatory care elective course.

OBJECTIVES: To assess students' performance and perceptions of team-based and mixed active-learning methods in 2 ambulatory care elective courses, and to describe faculty members' perceptions of team-based learning. METHODS: Using the 2 teaching methods, students' grades were compared. Students' perceptions were assessed through 2 anonymous course evaluation instruments. Faculty members who taught courses using the team-based learning method were surveyed regarding their impressions of team-based learning. RESULTS: The ambulatory care course was offered to 64 students using team-based learning (n = 37) and mixed active learning (n = 27) formats. The mean quality points earned were 3.7 (team-based learning) and 3.3 (mixed active learning), p < 0.001. Course evaluations for both courses were favorable. All faculty members who used the team-based learning method reported that they would consider using team-based learning in another course. CONCLUSIONS: Students were satisfied with both teaching methods; however, student grades were significantly higher in the team-based learning course. Faculty members recognized team-based learning as an effective teaching strategy for small-group active learning.

Heparin-induced thrombocytopenia complicated by warfarin-induced skin necrosis.

PURPOSE: A case of heparin-induced thrombocytopenia (HIT) complicated by warfarin-induced skin necrosis (WISN) is reported. SUMMARY: A patient with a history of hypertension, heart failure, and myocardial infarction was admitted to the hospital after complaining of a two-day history of shortness of breath, diaphoresis, and chest pain. The patient underwent a cardiac catheterization and received several medications, including heparin. Suspicions of HIT occurred when her platelets began to decrease severely and she developed a left groin hematoma and a pseudoaneurysm. Lepirudin was initiated and a heparin platelet factor 4 (PF4) antibody test was performed. The results were negative and lepirudin was discontinued. She was rechallenged with unfractionated heparin (UFH) after surgery of the pseudoaneurysm, but her platelets began to decrease again. A second PF4 test was performed, the results of which were positive. The UFH treatment was discontinued. Warfarin was also initiated after surgery and the patient's platelets rapidly increased after heparin was discontinued. She was discharged one week later. Three days after discharge, she was readmitted after complaining of severe pain and swelling of the fatty tissue of her right flank that began the day after she was discharged. Some blistering and necrosis were noted on the lesion. Histological sections showed focal thrombosis of vessels in the deep reticular dermis consistent with WISN. Local wound care was given to manage the WISN, lepirudin was initiated, and warfarin was discontinued and reinstated one week later at a low dosage. CONCLUSION: A patient with HIT developed severe skin necrosis after initiation of warfarin therapy.

Intracerebral hemorrhage secondary to a warfarin-metronidazole interaction.

BACKGROUND: It has been >25 years since the interaction between warfarin and metronidazole was last reported in the literature. The current case report represents the first documentation of this interaction associated with intracerebral hemorrhage. CASE SUMMARY: We present a case of a 78-year-old white woman started on metronidazole (250 mg every 8 hours for 5 days) and levofloxacin (500 mg QD for 6 days) for an upper respiratory tract infection after visiting a walk-in clinic. The patient did not notify any of the health care professionals involved that she was on concomitant warfarin therapy, which had been stable over the last 3 months. Her warfarin dose was 7 mg daily, and her most recent international normalized ratio (INR) reading was 2.5. Nine days after her clinic visit, the patient was admitted to the hospital for a profuse nosebleed with an INR of 8.0 and was found to have an intraparenchymal hemorrhage of the left occipital lobe. The Naranjo adverse drug reaction probability scale indicated that the association with metronidazole was probable and the association with levofloxacin was possible (scores of 7 and 4, respectively). After a 1-week hospital stay, she was discharged. CONCLUSIONS: This adverse event is highly suggestive of a drug interaction caused primarily by metronidazole, which produces an increase in S-warfarin concentrations. Treatment provided by health care providers who were not familiar with the patient and the use of a different pharmacy (where the pharmacist was unaware of her current medications) likely contributed to the event.

Elevated tobramycin concentrations following endotracheal administration in a premature infant.

The following case report describes a 1-month-old, 34-week-gestation premature neonate who had compromised renal function. The neonate received endotracheally administered tobramycin (300 mg every 12 hours) via a PARI PLUS reusable nebulizer to treat a documented Gram-negative tracheostomy infection. The patient also received systemic tobramycin (2.5 mg/kg intravenously every 18 hours). The tobramycin serum concentration obtained 45 hours after the last intravenous dose and 11.5 hours after the second nebulized dose was 17.6 mg/L. The tobramycin nebulizations were stopped.

Asthma treatment protocols in the emergency department: are they effective?

Management of asthma in emergency departments (ED) has been well documented to be deficient over many years, despite national and international guidelines. This review summarizes the effect of ED protocols aimed at improving the assessment and treatment of asthma in the ED. We performed a PubMed search of the English literature for ED asthma protocols published from 1986 to 2006 and identified 11 studies. Protocols were effective in improving at least some areas of management, including use of appropriate patient assessment, drug therapy per national guidelines, and patient education. A small number of protocols with the specific aims of reducing the length of stay in the ED as well as rates of hospital admission and return visits were effective. Persistent education of ED staff regarding protocols based on current management guidelines and adoption of easy-to-use forms can facilitate improved care of patients with asthma in the ED.