Opioid Overdose: Limitations in Naloxone Reversal of Respiratory Depression and Prevention of Cardiac Arrest.

Opioids are effective analgesics, but they can have harmful adverse effects, such as addiction and potentially fatal respiratory depression. Naloxone is currently the only available treatment for reversing the negative effects of opioids, including respiratory depression. However, the effectiveness of naloxone, particularly after an opioid overdose, varies depending on the pharmacokinetics and the pharmacodynamics of the opioid that was overdosed. Long-acting opioids, and those with a high affinity at the µ-opioid receptor and/or slow receptor dissociation kinetics, are particularly resistant to the effects of naloxone. In this review, the authors examine the pharmacology of naloxone and its safety and limitations in reversing opioid-induced respiratory depression under different circumstances, including its ability to prevent cardiac arrest.

Influence of age on the relationship between apixaban concentration and anti-factor Xa activity in older patients with non-valvular atrial fibrillation.

BACKGROUND/OBJECTIVES: Despite lower major bleeding rates associated with direct oral anticoagulants (DOACs) as compared to conventional warfarin therapy, bleeding rates remain higher in older patients compared to younger patients suggesting a potential role for DOAC measurements. The objective of this study is to examine the effect of age on the relationship between apixaban concentrations and anti-Factor Xa activity in patients with non-valvular atrial fibrillation (NVAF). METHODS: This is a retrospective analysis based on a database created using data from the ARISTOTLE study. Outpatient, stable adult patients with NVAF receiving apixaban were included in this study. Data collection consisted of apixaban concentration, anti-Factor Xa activity, age, weight, creatinine, and co-medications. RESULTS: The database composed of 2058 patients receiving apixaban. Distribution of race, NVAF subtype, and aspirin use was fairly similar across each age quantile. Older patients received a higher number of co-medications and received the 2.5 mg apixaban dose more often as compared to younger patients (22% vs. < 1%). Linear regression demonstrated that the unadjusted slope for apixaban concentration effect on anti-Factor Xa activity was similar across each age quantile. Although, the overall adjusted linear regression analysis demonstrated that the age by concentration interaction was statistically significant, relative differences in anti-Factor Xa activity (< 8%) were not clinically meaningful. CONCLUSION: Data on apixaban concentrations and anti-Factor Xa activity from a pivotal randomized double-blind study of apixaban for the prevention of stroke in NVAF patients have confirmed that the chromogenic anti-Factor Xa activity assay can accurately assess apixaban concentrations in patients regardless of age. Age was not associated with a clinically relevant change in the apixaban vs. anti-Factor Xa activity response relationship and target ranges are unchanged.

Leveraging Big Data in Pediatric Development Programs: Proceedings From the 2016 American College of Clinical Pharmacology Annual Meeting Symposium.

This article discusses the use of big data in pediatric drug development. The article covers key topics discussed at the ACCP annual meeting symposium in 2016 including the extent to which big data or real-world data can inform clinical trial design and substitute for efficacy and safety data typically obtained in clinical trials. The current states of use, opportunities, and challenges with the use of big data in future pediatric drug development are discussed.