Prevalence of potential drug-drug interactions in the intensive care unit of a Brazilian teaching hospital

Abstract Patients in intensive care unit are prescribed large numbers of drugs, highlighting the need to study potential Drug-Drug Interactions in this environment. The aim of this study was to delineate the prevalence and risk of potential drug-drug interactions between medications administered to patients in an ICU. This cross-sectional observational study was conducted during 12 months, in an adult ICU of a teaching hospital. Inclusion criteria were: prescriptions with 2 or more drugs of patients admitted to the ICU for > 24 hours and age of ≥18 years. Potential Drug-Drug Interactions were quantified and classified through MicromedexTM database. The 369 prescriptions included in this study had 205 different drugs, with an average of 13.04 ± 4.26 (mean ± standard deviation) drugs per prescription. Potential Drug-Drug Interactions were identified in 89% of these, with an average of 5.00 ± 5.06 interactions per prescription. Of the 405 different pairs of potentially interacting drugs identified, moderate and major interactions were present in 74% and 67% of prescriptions, respectively. The most prevalent interaction was between dipyrone and enoxaparin (35.8%), though its clinical occurrence was not observed in this study. The number of potential Drug-Drug Interactions showed significant positive correlations with the length of stay in the intensive care unit, and with the number of prescribed drugs. Acknowledging the high potential for Drug-Drug Interactions in the ICU represents an important step toward improving patient safety and best therapy results

Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.Da identificação do HIV como o agente causador da AIDS, ao desenvolvimento de fármacos antirretrovirais eficazes, os avanços científicos na pesquisa sobre o HIV nos últimos vinte e seis anos foram marcantes. Atualmente, existem vinte e cinco fármacos anti-HIV formalmente aprovados pelo FDA para utilização clínica no tratamento da AIDS. Estes compostos são divididos em seis classes: inibidores nucleosídeos de transcriptase reversa (INTR), inibidores nucleotídeos de transcriptase reversa (INtTR), inibidores não-nucleosídeos de transcriptase reversa (INNTR), inibidores de protease (IP), inibidores da entrada celular ou inibidores de fusão (IF), inibidores de co-receptores (ICR) e inibidores de integrase (INI). O metabolismo consiste em um dos maiores determinantes do perfil farmacocinético de um fármaco. A formação de metabólitos ativos ou tóxicos terá impacto nas respostas farmacológicas ou toxicológicas do fármaco. Portanto, é amplamente reconhecido que estudos do metabolismo de uma nova entidade química devem ser realizados durante as fases iniciais do processo de desenvolvimento de fármacos. Este artigo descreve uma abordagem do metabolismo dos fármacos anti-HIV atualmente disponíveis na terapêutica

New constraints on ultraheavy dark matter from the LZ experiment

Searches for dark matter with liquid xenon time projection chamber experiments have traditionally focused on the region of the parameter space that is characteristic of weakly interacting massive particles, ranging from a few GeV/c2 to a few TeV/c2. Models of dark matter with a mass much heavier than this are well motivated by early production mechanisms different from the standard thermal freeze-out, but they have generally been less explored experimentally. In this work, we present a reanalysis of the first science run of the LZ experiment, with an exposure of 0.9  tonne×yr, to search for ultraheavy particle dark matter. The signal topology consists of multiple energy deposits in the active region of the detector forming a straight line, from which the velocity of the incoming particle can be reconstructed on an event-by-event basis. Zero events with this topology were observed after applying the data selection calibrated on a simulated sample of signal-like events. New experimental constraints are derived, which rule out previously unexplored regions of the dark matter parameter space of spin-independent interactions beyond a mass of 1017  GeV/c2. Published by the American Physical Society 2024 </jats:sec