1. [Pharmacovigilance update]
F Livio Rev Med Suisse. 2013 Jan 9;9(368):72-5.
Main pharmacovigilance updates in 2012 are reviewed here. Dabigatran: elderly patients with renal failure are at higher risk of bleeding. Dual renin-angiotensin-aldosterone system blockade comprising aliskiren is harmful. Incretins: low risk of acute pancreatitis. Interaction between fusidic acid and statins: many reports of rhabdomyolysis. Interactions between boceprevir/telaprevir and antiretroviral therapies: complex, but manageable. Citalopram, ondansetron: maximum recommended doses are reduced. Atomoxetine: significant increase in blood pressure and heart rate in a fraction of exposed patients. Agomelatine: elevated liver enzymes are common. Fingolimod: bradycardia and heart blocks after first dose - stronger safety recommendations regarding use in patients with heart conditions and strengthened cardiovascular monitoring.
2. Pharmacological agents for adults with acute respiratory distress syndrome
Sharon R Lewis, Michael W Pritchard, Carmel M Thomas, Andrew F Smith Cochrane Database Syst Rev. 2019 Jul 23;7(7):CD004477. doi: 10.1002/14651858.CD004477.pub3.
Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition caused by direct or indirect injury to the lungs. Despite improvements in clinical management (for example, lung protection strategies), mortality in this patient group is at approximately 40%. This is an update of a previous version of this review, last published in 2004. Objectives: To evaluate the effectiveness of pharmacological agents in adults with ARDS on mortality, mechanical ventilation, and fitness to return to work at 12 months.
3. Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?
Pavel Klein, et al. Epilepsia. 2020 Mar;61(3):359-386. doi: 10.1111/epi.16450.
Prevention of epilepsy is a great unmet need. Acute central nervous system (CNS) insults such as traumatic brain injury (TBI), cerebrovascular accidents (CVA), and CNS infections account for 15%-20% of all epilepsy. Following TBI and CVA, there is a latency of days to years before epilepsy develops. This allows treatment to prevent or modify postinjury epilepsy. No such treatment exists. In animal models of acquired epilepsy, a number of medications in clinical use for diverse indications have been shown to have antiepileptogenic or disease-modifying effects, including medications with excellent side effect profiles. These include atorvastatin, ceftriaxone, losartan, isoflurane, N-acetylcysteine, and the antiseizure medications levetiracetam, brivaracetam, topiramate, gabapentin, pregabalin, vigabatrin, and eslicarbazepine acetate. In addition, there are preclinical antiepileptogenic data for anakinra, rapamycin, fingolimod, and erythropoietin, although these medications have potential for more serious side effects. However, except for vigabatrin, there have been almost no translation studies to prevent or modify epilepsy using these potentially "repurposable" medications. We may be missing an opportunity to develop preventive treatment for epilepsy by not evaluating these medications clinically. One reason for the lack of translation studies is that the preclinical data for most of these medications are disparate in terms of types of injury, models within different injury type, dosing, injury-treatment initiation latencies, treatment duration, and epilepsy outcome evaluation mode and duration. This makes it difficult to compare the relative strength of antiepileptogenic evidence across the molecules, and difficult to determine which drug(s) would be the best to evaluate clinically. Furthermore, most preclinical antiepileptogenic studies lack information needed for translation, such as dose-blood level relationship, brain target engagement, and dose-response, and many use treatment parameters that cannot be applied clinically, for example, treatment initiation before or at the time of injury and dosing higher than tolerated human equivalent dosing. Here, we review animal and human antiepileptogenic evidence for these medications. We highlight the gaps in our knowledge for each molecule that need to be filled in order to consider clinical translation, and we suggest a platform of preclinical antiepileptogenesis evaluation of potentially repurposable molecules or their combinations going forward.
