Gefapixant in two randomised dose-escalation studies in chronic cough

Background and objectivesGefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.Materials and methodsTwo randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50–200 mg, study 2: 7.5–50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.ResultsIn clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.ConclusionsP2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.

Medication-induced hyperglycemia: pediatric perspective

Medication-induced hyperglycemia is a frequently encountered clinical problem in children. The intent of this review of medications that cause hyperglycemia and their mechanisms of action is to help guide clinicians in prevention, screening and management of pediatric drug-induced hyperglycemia. We conducted a thorough literature review in PubMed and Cochrane libraries from inception to July 2019. Although many pharmacotherapies that have been associated with hyperglycemia in adults are also used in children, pediatric-specific data on medication-induced hyperglycemia are scarce. The mechanisms of hyperglycemia may involve β cell destruction, decreased insulin secretion and/or sensitivity, and excessive glucose influx. While some medications (eg, glucocorticoids, L-asparaginase, tacrolimus) are markedly associated with high risk of hyperglycemia, the association is less clear in others (eg, clonidine, hormonal contraceptives, amiodarone). In addition to the drug and its dose, patient characteristics, such as obesity or family history of diabetes, affect a child’s risk of developing hyperglycemia. Identification of pediatric patients with increased risk of developing hyperglycemia, creating strategies for risk reduction, and treating hyperglycemia in a timely manner may improve patient outcomes.

EVALUASI RASIONALITAS PENGOBATAN HIPERTENSI DI PUSKESMAS PELAMBUAN BANJAR MASIN TAHUN 2017

Irrational use of drugs is still found in Puskesmas which is the First Level Health Facilities. The use of irrational drugs based on appropriate drugs and precise indications. In the use of various types of drugs there may be an irrationality of treatment, one of which is hypertension.This study aims to determine the antihypertensive drugs used in Pelambuan Puskesmas Banjarmasin and to determine the percentage of rationality of hypertension treatment at Pelambuan Puskesmas Banjarmasin. evaluating the rationale for the use of antihypertensive drugs that include the accuracy of indication, drug, dose, patient, mode of administration, and duration of administration in hypertensive patients at Puskesmas Pelambuan Banjarmasin during 2017. This type of research was descriptive non-experimental research with retrospective data retrieval based on medical records of hypertensive patients in 2017. The population in this study amounted to 333 medical records and the number of samples that met the inclusion and exclusion criteria as much as 37 medical records. The tools / instruments in this study were observation sheets and interview sheets. The results of the research on antihypertensive drugs used in Pelambuan Banjarmasin Health Center were amlodipine, nifedipine, captopril, lisinopril. The results of the evaluation of the rationality of the use of antihypertensive drugs were seen based on the exact indication criteria as many as 18 patients (48,65%), right medication as many as 18 patients (48,65%), right dose of 17 patients (45,95%), right patients as many as 33 patients (89,19%), the exact method of administration was 31 patients (83,79%), and the exact duration of administration was 22 patients (59,46%).

Insights on Localized and Systemic Delivery of Redox-Based Therapeutics

Reactive oxygen and nitrogen species are indispensable in cellular physiology and signaling. Overproduction of these reactive species or failure to maintain their levels within the physiological range results in cellular redox dysfunction, often termed cellular oxidative stress. Redox dysfunction in turn is at the molecular basis of disease etiology and progression. Accordingly, antioxidant intervention to restore redox homeostasis has been pursued as a therapeutic strategy for cardiovascular disease, cancer, and neurodegenerative disorders among many others. Despite preliminary success in cellular and animal models, redox-based interventions have virtually been ineffective in clinical trials. We propose the fundamental reason for their failure is a flawed delivery approach. Namely, systemic delivery for a geographically local disease limits the effectiveness of the antioxidant. We take a critical look at the literature and evaluate successful and unsuccessful approaches to translation of redox intervention to the clinical arena, including dose, patient selection, and delivery approach. We argue that when interpreting a failed antioxidant-based clinical trial, it is crucial to take into account these variables and importantly, whether the drug had an effect on the redox status. Finally, we propose that local and targeted delivery hold promise to translate redox-based therapies from the bench to the bedside.

Elevated International Normalized Ratio in a Patient Taking Warfarin and Mauby: A Case Report

We describe a 70-year-old Haitian man who had been taking warfarin for 5 years for atrial fibrillation and pulmonary hypertension. This patient had his international normalized ratio (INR) checked in the pharmacist-run anticoagulation clinic and was followed monthly. Prior to the interaction, his INR was therapeutic for 5 months while taking warfarin 10.5 mg/d. The patient presented with an INR > 8.0. Patient held 4 days of warfarin and restarted on warfarin 8.5 mg/d. Two weeks later, his INR was 2.5. After continuing dose, patient presented 2 weeks later and INR was 4.8. Upon further questioning, the patient stated he recently began ingesting mauby. Mauby is a bitter dark liquid extracted from the bark of the mauby tree that is commonly used in the Caribbean population as a folk remedy with many health benefits. This case report illustrates that mauby may have a probable drug–herb interaction (Naranjo Algorithm Score of 6) when given with warfarin. There is a lack of published literature and unclear information on the Internet describing the interaction of mauby and warfarin. Health professionals should be cautious regarding interactions between warfarin and mauby until the interaction is fully elucidated.