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The American Journal of Medicine Mar 2024
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics
PubMed: 37423432
DOI: 10.1016/j.amjmed.2023.06.014 -
Clinical Pharmacology and Therapeutics Nov 2023Precision medicine has evolved from the application of pharmacogenetic biomarkers to the prospective development of targeted therapies in patients with specific... (Review)
Review
Precision medicine has evolved from the application of pharmacogenetic biomarkers to the prospective development of targeted therapies in patients with specific molecular/genetic subtypes of disease to truly "N-of-1" medicines targeted to very small numbers of patients - in some cases, a single identified patient. This latter iteration of precision medicine presents unprecedented opportunities for patients with severe, life-threatening, or life-limiting diseases. At the same time, these modalities present complex scientific, clinical, and regulatory challenges. To realize the promise of individualized medicines, a multistakeholder approach to streamlining medical diagnoses, advancing the technologies that enable development of these therapeutic modalities, and re-envisioning collaborative environments for access and evidence generation is of critical importance. Herein, we highlight some of these challenges and opportunities.
Topics: Humans; Prospective Studies; Precision Medicine; Pharmacogenetics
PubMed: 37620252
DOI: 10.1002/cpt.3030 -
Pharmacological Research Apr 2024Here we present an account on the history of pharmacology in Spain. Pharmacology as an independent science in Europe began with the creation of university chairs. Of...
Here we present an account on the history of pharmacology in Spain. Pharmacology as an independent science in Europe began with the creation of university chairs. Of particular relevance was the appointment in 1872 of Osswald Shmiedeberg as chairman of an Institute of Pharmacology at the University of Strassbourg, Germany. Teófilo Hernando pioneered in Spain the new emerging pharmacology at the beginning of the XX Century. He made a posdoctoral stay in the laboratory of Schmiedeberg, working on digitalis. In 1912 he won the chair of "Materia Médica y Arte de Recetar" at "Universidad Central of Madrid" (today, "Universidad Complutense de Madrid", UCM). He soon decided to transform such subject to the emerging modern pharmacology, with the teaching of experimental pharmacology in the third course of medical studies and clinical therapeutics (today clinical pharmacology) in the sixth course. This was the status of pharmacology in 1920, supporting the view that Hernando was a pioneer of clinical pharmacology. However, the Spanish Civil War and the II Word War interropted this division of preclinical and clinical pharmacology; only in the 1980's was clinical pharmacolgy partially developed in Spain. From a scientific point of view, Hernando directly trained various young pharmacologists that extended the new science to various Spanish universities. Some of his direct disciples were Benigno Lorenzo Velázquez, Francisco García Valdecasas, Rafael Méndez, Tomás Alday, Gabriel Sánchez de la Cuesta, Dámaso Gutiérrez or Ramón P é rez-Cirera. One of the central research subject was the analysis of the effects of digitalis on the cat and frog heart. In the initiation of the 1970 s pharmacologists trained by those Hernando's students grew throughout various universities and the "Consejo Superior de Investigaciones Científicas" (CSIC). And hence, in 1972 the "Sociedad Española de Farmacología" (SEF) emerged. Later on, in the 1990's the "Sociedad Española de Farmacología Clínica (SEFC) also emerged. The relationship between the two societies is still weak. Out of the vast scope of the pharmacological sciences, Spanish pharmacologists have made relevant contributions in two areas namely, neuropsychopharmacology and cardiovacular pharmacology. Nonetheless, in other areas such as smooth muscle, gastroenterology, pharmacogenetics and hepatic toxicity, Spanish pharmacologists have also made relevant contributions. A succint description of such contributions is made. Finally, some hints on perspectives for the further development of preclinical and clinical pharmacology in Spain, are offered.
Topics: Humans; Spain; Europe; Pharmacology, Clinical; Pharmacogenetics; Pharmacology
PubMed: 38364957
DOI: 10.1016/j.phrs.2024.107104 -
Clinical and Experimental Pharmacology... Jan 2024Children, as a special group, have their own peculiarities in terms of individualized medication use compared to adults. Adverse drug reactions have been an important... (Review)
Review
Children, as a special group, have their own peculiarities in terms of individualized medication use compared to adults. Adverse drug reactions have been an important issue that needs to be addressed in the hope of safe medication use in children, and the occurrence of adverse drug reactions is partly due to genetic factors. Anti-infective drugs are widely used in children, and they have always been an important cause of the occurrence of adverse reactions in children. Pharmacogenomic technologies are becoming increasingly sophisticated, and there are now many guidelines describing the pharmacogenomics of anti-infective drugs. However, data from paediatric-based studies are scarce. This review provides a systematic review of the pharmacogenomics of anti-infective drugs recommended for gene-guided use in CPIC guidelines by exploring the relationship between pharmacogenetic frequencies and the incidence of adverse reactions, which will help inform future studies of individualized medication use in children.
Topics: Adult; Humans; Child; Pharmacogenetics; Drug-Related Side Effects and Adverse Reactions; Anti-Infective Agents
PubMed: 37840030
DOI: 10.1111/1440-1681.13830 -
Pharmacy (Basel, Switzerland) Sep 2023Since the rebirth of pharmacogenomics (PGx) in the 1990s and 2000s, with new discoveries of genetic variation underlying adverse drug response and new analytical... (Review)
Review
Since the rebirth of pharmacogenomics (PGx) in the 1990s and 2000s, with new discoveries of genetic variation underlying adverse drug response and new analytical technologies such as sequencing and microarrays, there has been much interest in the clinical application of PGx testing. The early involvement of pharmacists in clinical studies and the establishment of organizations to support the dissemination of information about PGx variants have naturally resulted in leaders in clinical implementation. This paper presents an overview of the evolving role of pharmacists, and discusses potential challenges and future paths, primarily focused in the U.S. Pharmacists have positioned themselves as leaders in clinical PGx testing, and will prepare the next generation to utilize PGx testing in their scope of practice.
PubMed: 37736916
DOI: 10.3390/pharmacy11050144 -
The Pharmacogenomics Journal Nov 2023Personalized medicine is a novel frontier in health care that is based on each person's unique genetic makeup. It represents an exciting opportunity to improve the...
Personalized medicine is a novel frontier in health care that is based on each person's unique genetic makeup. It represents an exciting opportunity to improve the future of individualized health care for all individuals. Pharmacogenomics, as the main part of personalized medicine, aims to optimize and create a more targeted treatment approach based on genetic variations in drug response. It is predicted that future treatments will be algorithm-based instead of evidence-based that will consider a patient's genetic, transcriptomic, proteomic, epigenetic, and lifestyle factors resulting in individualized medication. A generative pretrained transformer (GPT) is an artificial intelligence (AI) tool that generates language resembling human-like writing enabling users to engage in a manner that is practically identical to speaking with a human being. GPT's predictive algorithms can respond to questions that have never been addressed. Chat Generative Pretrained Transformer (ChatGPT) is an AI chatbot's advanced with conversational capabilities. In the present study, questions were asked from ChatGPT about the future of personalized medicine and pharmacogenomics. ChatGPT predicted both to be a promising approach with a bright future that holds great promises in improving patient outcomes and transforming the field of medicine. But it still has several limitations that need to be solved.
Topics: Humans; Precision Medicine; Artificial Intelligence; Proteomics; Pharmacogenetics; Alanine Transaminase
PubMed: 37726551
DOI: 10.1038/s41397-023-00316-9 -
Clinical and Translational Science Dec 2023Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals'... (Review)
Review
Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals' (HCPs) and consumers' knowledge, attitudes, perspectives, and education needs to inform strategies for implementation of scalable and sustainable oncology PGx programs. Systematic review of original articles indexed in EMBASE, EMCARE, MEDLINE, and PsycInfo from January 2012 until June 2022, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using the Mixed Methods Appraisal Tool. PROSPERO registration number CRD42022352348. Of 1442 identified studies; 23 met inclusion criteria with 87% assessed high quality. Of these, 52% reported on HCPs, 35% on consumers, and 13% on both HCPs and consumers. Most were conducted in the United States (70%) and included multiple cancer types (74%). Across studies, HCPs and consumers mostly perceived value in PGx, however, both groups reported barriers to utilization, including cost, lack of consistent recommendations across guidelines, and limited knowledge among HCPs; test accuracy, clear testing benefits, and genomic information confidentiality among consumers. HCPs and consumers value and want to engage in PGx strategies in oncology care, however, are inhibited by unmet needs and practice and knowledge gaps. Implementation strategies aimed at addressing these issues may best support increased PGx uptake in oncology practice.
Topics: Humans; Pharmacogenetics; Health Knowledge, Attitudes, Practice; Health Personnel; Medical Oncology; Neoplasms
PubMed: 37991131
DOI: 10.1111/cts.13672 -
Drug Safety Jun 2024Rare diseases have become an increasingly important public health priority due to their collective prevalence and often life-threatening nature. Incentive programs, such... (Review)
Review
Rare diseases have become an increasingly important public health priority due to their collective prevalence and often life-threatening nature. Incentive programs, such as the Orphan Drug Act have been introduced to increase the development of rare disease therapeutics. While the approval of these therapeutics requires supportive data from stringent pre-market studies, these data lack the ability to describe the causes of treatment response heterogeneity, leading to medications often being more harmful or less effective than predicted. If a Goal Line were to be used to describe the multifactorial continuum of phenotypic variations occurring in response to a medication, the 'Goal Posts', or the two defining points of this continuum, would be (1) Super-Response, or an extraordinary therapeutic effect; and (2) Serious Harm. Investigation of the pharmacogenomics behind these two extreme phenotypes can potentially lead to the development of new therapeutics, help inform rational use criteria in drug policy, and improve the understanding of underlying disease pathophysiology. In the context of rare diseases where cohort sizes are smaller than ideal, 'small data' and 'big data' approaches to data collection and analysis should be combined to produce the most robust results. This paper presents the importance of studying drug response in parallel to other research initiatives in rare diseases, as well as the need for international collaboration in the area of rare disease pharmacogenomics.
Topics: Humans; Rare Diseases; Pharmacogenetics; Orphan Drug Production
PubMed: 38483768
DOI: 10.1007/s40264-024-01416-6 -
Pharmacological Research Feb 2024The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support,...
The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support, many research groups, composed of basic and clinical researchers, have been actively working for decades in this field. Their contributions made an international impact and paved the way for further studies and pharmacogenomics implementation in clinical practice. In this manuscript, that makes part of the Special Issue entitled Spanish Pharmacology, we present an analysis of the state of the art of Pharmacogenetics and Pharmacogenomics research in Europe, we compare it with the developments in Spain, and we summarize the most salient contributions since 1988 to the present, as well as recent developments in the clinical application of pharmacogenomics knowledge. Finally, we present some considerations on how we could improve translation to clinical practice in this specific scenario.
Topics: Pharmacogenetics; Precision Medicine; Europe
PubMed: 38199278
DOI: 10.1016/j.phrs.2024.107061