Current Reviews in Clinical and Experimental Pharmacology最新文献

Therapy with exogenous interferon and human conditions that feature endogenous interferon upregulation may be associated with endothelial damage that primarily involves small blood vessels. Endothelial injury associated with interferon may display different clinical expression, including thrombotic microangiopathy, Raynaud's phenomenon, vasculopathy of dermatomyositis and atrophic papulosis, interferon-associated skin angiopathy, systemic capillary leak syndrome, collapsing glomerulopathy, interstitial lung disease, pulmonary hypertension, and retinopathy. Interferon- induced endothelial damage involves complement-mediated injury, although pathogenic mechanisms by which interferon promote abnormal complement activation on endothelial cells are not fully understood. Human interferon-γ (type II interferon) binds to heparan sulfate on the endothelial surface, suggesting that overproduction of interferon-γ may hinder factor H attachment to the same location. Absence of factor H on self surfaces promotes activation of the alternative pathway of complement and complement-mediated endothelial damage. Type I interferon typically induces the generation of antibodies. Type I interferon upregulation may elicit the formation of autoantibodies against factor H. These autoantibodies block factor H binding to endothelial surfaces, abolishing the protective effect of factor H on complement-mediated damage. In addition, interferon induces insulin resistance which is associated with reduced heparan sulfate in the extracellular matrix, including the endothelial surface. Decreased amount of heparan sulfate suppresses factor H attachment, promoting activation of the alternative pathway of complement. Complement blockade with eculizumab (a monoclonal antibody against C5) improves endothelial damage in patients with thrombotic microangiopathy and other situations associated with interferon upregulation and interferon-induced endothelial injury, suggesting that complement-mediated injury is clinically relevant under conditions that feature interferon overproduction.

Objective: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning.

Methodology: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer.

Results: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group.

Conclusion: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.

Previous genetic studies on the genetic makeup of Arab populations highlight the diversity resulting from the distribution of specific genetic markers among various Arab descendant populations. Different genetic variants classified as clinically significant have been identified, impacting the response to administered drugs. Absorption, distribution, and excretion of drugs throughout the human body are managed through the actions of drug transporters and receptor proteins, which are expressed on the cellular membrane. Drug metabolism involves activating or inactivating various compounds, transforming them into therapeutically active or toxic metabolites. With the rapid advancement of pharmacogenetic testing techniques and increased genetic studies involving Arab populations, insights into genetic polymorphisms have emerged, leading to a better understanding of the diverse phenotypes of drug response associated with genotype variation. Variations in transporters and receptor genes have significantly contributed to generating variant phenotypes that affect individuals' responses to treatments and substrates. This necessitates administering individualized drug doses based on the patient's haplotype, which can be determined through advanced genetic diagnosis. This review summarizes the findings of recent pharmacogenetic studies in the Arab world, emphasizing the benefits of pharmacogenetic research and applications to enhance therapeutic aspects of healthcare and treatment among patients in Arab countries.

Predictions are made by artificial intelligence, especially through machine learning, which uses algorithms and past knowledge. Notably, there has been an increase in interest in using artificial intelligence, particularly generative AI, in the pharmacovigilance of pharmaceuticals under development, as well as those already in the market. This review was conducted to understand how generative AI can play an important role in pharmacovigilance and improving drug safety monitoring. Data from previously published articles and news items were reviewed in order to obtain information. We used PubMed and Google Scholar as our search engines, and keywords (pharmacovigilance, artificial intelligence, machine learning, drug safety, and patient safety) were used. In toto, we reviewed 109 articles published till 31st January 2024, and the obtained information was interpreted, compiled, evaluated, and conclusions were reached. Generative AI has transformative potential in pharmacovigilance, showcasing benefits, such as enhanced adverse event detection, data-driven risk prediction, and optimized drug development. By making it easier to process and analyze big datasets, generative artificial intelligence has applications across a variety of disease states. Machine learning and automation in this field can streamline pharmacovigilance procedures and provide a more efficient way to assess safety-related data. Nevertheless, more investigation is required to determine how this optimization affects the caliber of safety analyses. In the near future, the increased utilization of artificial intelligence is anticipated, especially in predicting side effects and Adverse Drug Reactions (ADRs).

Introduction: Genomic variations among individuals can greatly affect their responses to different medications. Pharmacogenomics is the area of study that aims to understand the relationship between these various genetic variations and subsequent drug responses. Many medications used to optimize cardiovascular health are affected by these genetic variants and these relationships can subsequently impact dosing strategies in patients.

Objective: This study aims to review the current literature on the clinical applications of pharmacogenomics for commonly used cardiovascular medications such as Warfarin, Clopidogrel, Statins, Beta Blockers, and ACE-I/ARBs.

Methods: Databases like PubMed were accessed to gather background information on pharmacogenomics and to collect data on relationships between genetic variants and subsequent drug response. Information on clinical applications and guidelines was obtained by accessing the CPIC and DPWG databases.

Results: This article describes the most up-to-date data on pharmacogenomics relating to commonly used cardiovascular medications. It also discusses the clinical application of pharmacogenomic data as it pertains to medication selection/dosing by detailing current guidelines published by organizations such as the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group.

Conclusion: In conclusion, this paper will help medical providers not only better understand pharmacogenomics but also apply it in their day-to-day practice. Clinical guidelines relating to the application of pharmacogenomic data were discussed both in text and graphical format, allowing providers to confidently select medications and adjust doses for common cardiovascular medications so that patients receive the maximum therapeutic benefit with minimal toxicity.