The Clinical Significance of the Pharmacogenetics of Cardiovascular Medications

1992 ◽  
Vol 5 (6) ◽  
pp. 337-361 ◽  
Author(s):  
Robert J. Straka ◽  
Peter S. Marshall
Keyword(s):  
Clinical Practice ◽  
Drug Metabolism ◽  
Clinical Significance ◽  
Drug Response ◽  
Individual Variability ◽  
Metabolic Capacity ◽  
Cardiovascular Agents ◽  
Enzyme Systems ◽  
Cardiovascular Medications ◽  
Polymorphic Drug Metabolism

Inter-individual variability in the response to numerous drugs can be traced to a number of sources. One source of variability in drug response is the variability associated with the metabolic capacity of an individual. The component of metabolic capacity that will be the focus of this article is that determined by heredity. Pharmacogenetics is frequently referred to as the study of the effects of heredity on the disposition and response to medications. This article will review the pharmacokinetic and pharmacodynamic significance of pharmacogenetics as it pertains to a select number of cardiovascular agents. The enzyme systems responsible for drug metabolism discussed in this article will be limited to the P-450IID6 and N-acetylation pathways. Given the extensive use of cardiovascular agents in clinical practice that are affected by this genetic polymorphism, it is important for the practicing pharmacist to be aware of this phenomenon and its implications. Hopefully, the knowledge gained from this article will help practicing pharmacists to appreciate the clinical significance of polymorphic drug metabolism and provide a basis for the application of this knowledge to a variety of practice settings.

scholarly journals Distinct Effects of Inflammation on Cytochrome P450 Regulation and Drug Metabolism: Lessons from Experimental Models and a Potential Role for Pharmacogenetics

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1509
Author(s):  
Laura M. de Jong ◽  
Wim Jiskoot ◽  
Jesse J. Swen ◽  
Martijn L. Manson
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Drug Response ◽  
Genetic Factors ◽  
Potential Role ◽  
In Vitro Models ◽  
Experimental Models ◽  
Individual Variability ◽  
The Individual

Personalized medicine strives to optimize drug treatment for the individual patient by taking into account both genetic and non-genetic factors for drug response. Inflammation is one of the non-genetic factors that has been shown to greatly affect the metabolism of drugs—primarily through inhibition of cytochrome P450 (CYP450) drug-metabolizing enzymes—and hence contribute to the mismatch between the genotype predicted drug response and the actual phenotype, a phenomenon called phenoconversion. This review focuses on inflammation-induced drug metabolism alterations. In particular, we discuss the evidence assembled through human in-vitro models on the effect of inflammatory mediators on clinically relevant CYP450 isoform levels and their metabolizing capacity. We also present an overview of the current understanding of the mechanistic pathways via which inflammation in hepatocytes may modulate hepatic functions that are critical for drug metabolism. Furthermore, since large inter-individual variability in response to inflammation is observed in human in-vitro models and clinical studies, we evaluate the potential role of pharmacogenetic variability in the inflammatory signaling cascade and how this can modulate the outcome of inflammation on drug metabolism and response.

scholarly journals Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters

2021 ◽  
Vol 14 (3) ◽  
pp. 204
Author(s):  
Teresa Iannaccone ◽  
Carmine Sellitto ◽  
Valentina Manzo ◽  
Francesca Colucci ◽  
Valentina Giudice ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Drug Response ◽  
Current Knowledge ◽  
Individual Variability ◽  
Mood Stabilizers ◽  
Drug Metabolizing Enzymes ◽  
Efficacy And Safety ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Metabolizing Enzymes ◽  
Drug Pharmacokinetics

Pharmacogenomics can identify polymorphisms in genes involved in drug pharmacokinetics and pharmacodynamics determining differences in efficacy and safety and causing inter-individual variability in drug response. Therefore, pharmacogenomics can help clinicians in optimizing therapy based on patient’s genotype, also in psychiatric and neurological settings. However, pharmacogenetic screenings for psychotropic drugs are not routinely employed in diagnosis and monitoring of patients treated with mood stabilizers, such as carbamazepine and valproate, because their benefit in clinical practice is still controversial. In this review, we summarize the current knowledge on pharmacogenetic biomarkers of these anticonvulsant drugs.

scholarly journals Implementing Personalized Medicine in COVID-19 in Andalusia: An Opportunity to Transform the Healthcare System

2021 ◽  
Vol 11 (6) ◽  
pp. 475
Author(s):  
Joaquín Dopazo ◽  
Douglas Maya-Miles ◽  
Federico García ◽  
Nicola Lorusso ◽  
Miguel Ángel Calleja ◽  
...  
Keyword(s):  
Public Health ◽  
Health Care ◽  
Clinical Practice ◽  
Personalized Medicine ◽  
Local Level ◽  
Individual Variability ◽  
Response To Therapy ◽  
Control Measures ◽  
Response To Treatment ◽  
Specific Patient

The COVID-19 pandemic represents an unprecedented opportunity to exploit the advantages of personalized medicine for the prevention, diagnosis, treatment, surveillance and management of a new challenge in public health. COVID-19 infection is highly variable, ranging from asymptomatic infections to severe, life-threatening manifestations. Personalized medicine can play a key role in elucidating individual susceptibility to the infection as well as inter-individual variability in clinical course, prognosis and response to treatment. Integrating personalized medicine into clinical practice can also transform health care by enabling the design of preventive and therapeutic strategies tailored to individual profiles, improving the detection of outbreaks or defining transmission patterns at an increasingly local level. SARS-CoV2 genome sequencing, together with the assessment of specific patient genetic variants, will support clinical decision-makers and ultimately better ways to fight this disease. Additionally, it would facilitate a better stratification and selection of patients for clinical trials, thus increasing the likelihood of obtaining positive results. Lastly, defining a national strategy to implement in clinical practice all available tools of personalized medicine in COVID-19 could be challenging but linked to a positive transformation of the health care system. In this review, we provide an update of the achievements, promises, and challenges of personalized medicine in the fight against COVID-19 from susceptibility to natural history and response to therapy, as well as from surveillance to control measures and vaccination. We also discuss strategies to facilitate the adoption of this new paradigm for medical and public health measures during and after the pandemic in health care systems.

scholarly journals Hierarchy of evidence in interpretation of clinical significance of drug interactions

2012 ◽  
Vol 65 (1-2) ◽  
pp. 45-49
Author(s):  
Bozana Nikolic ◽  
Miroslav Savic
Keyword(s):  
Drug Metabolism ◽  
Drug Interactions ◽  
Clinical Significance ◽  
Health Professionals ◽  
Molecular Entity ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Potential Interactions

Introduction. Since drug interactions may result in serious adverse effects or failure of therapy, it is of huge importance that health professionals base their decisions about drug prescription, dispensing and administration on reliable research evidence, taking into account the hierarchy of data sources for evaluation. Clinical Significance of Potential Interactions - Information Sources. The sources of data regarding drug interactions are numerous, beginning with various drug reference books. However, they are far from uniformity in the way of choosing and presenting putative clinically relevant interactions. Clinical Significance of Potential Interactions - Interpretation of Information. The difficulties in interpretation of drug interactions are illustrated through the analysis of a published example involving assessment made by two different groups of health professionals. Systematic Evaluation of Drug-Drug Interaction. The potential for interactions is mainly investigated before marketing a drug. Generally, the in vitro, followed by in vivo studies are to be performed. The major metabolic pathways involved in the metabolism of a new molecular entity, as well as the potential of induction of human enzymes involved in drug metabolism are to be examined. In the field of interaction research it is possible to make use of the population pharmacokinetic studies as well as of the pharmacodynamic assessment, and also the postregistration monitoring of the reported adverse reactions and other literature data. Conclusion. In vitro and in vivo drug metabolism and transport studies should be conducted to elucidate the mechanisms and potential for drug-drug interactions. The assessment of their clinical significance should be based on well-defined and validated exposure-response data.

scholarly journals May be Urinary Excretion of α2-macroglobulin (MW 720 kDa) a Proteinuric Marker of Podocytopathy? Insight from Analysis of 204 Patients with Glomerulonephritis (GN) and Nephrotic Syndrome, 177 with Functional Outcome

2021 ◽  
Vol 8 (3) ◽  
pp. 01-06
Author(s):  
Claudio Bazzi
Keyword(s):  
Nephrotic Syndrome ◽  
Clinical Practice ◽  
Urinary Excretion ◽  
Functional Outcome ◽  
Clinical Significance ◽  
Α2 Macroglobulin ◽  
Progression Risk ◽  
Treatment Responsiveness

Background: In IgAN with cellular crescents (CIgAN) urinary excretion of α2-macroglobulin (α2m/C, MW 720 kDa) may be a marker of podocytes damage induced by crescents. The purpose of the study was the evaluation of the clinical significance of α2m/C excretion in 177 patients with glomerulonephritis (GN), nephrotic syndrome (NS) and functional outcome. Methods: In all 177 patients α2m/C excretion was measured; the patients were divided in 2 groups: α2mC=0 (n. 72) and α2m/C >0 (n. 105); for each group were assessed the outcomes considered in combination: Remission & persistent nephrotic syndrome (PNS) with long lasting NRF designed “Remission & NRF”; ESRD & eGFR < 50% & PNS with CRF designed “Progression and progression risk”. Results: In 72 patients with α2m/C=0 “Remission & NRF” was 78% and “Progression & progression risk” was 22%; in 105 patients with α2m/C>0 “remission & NRF” was 52% and “Progression & progression risk” was 48%. “Remission & NRF” in each GN type with α2m/C=0 was: 100% in MCD and LN; 82%, 79%, 67% in FSGS, IMN, MPGN; in α2m/C>0 “Progression and progression risk” was 0%, 38%, 46%, 54%, 56%, 85% in MCD, LN, IMN, MPGN, FSGS, CIgAN with cellular crescents, respectively. Conclusion: Urinary excretion of α2m is a very simple marker available in all clinical practice laboratories, marker of damage of podocytes at least in CIgAN and LN with crescents and marker of GFB damage in different GN types and useful to predict outcome and treatment responsiveness.

scholarly journals Epigenetics of Inflammatory Bowel Disease: Unraveling Pathogenic Events

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Beatriz Mateos ◽  
Cora Palanca-Ballester ◽  
Esteban Saez-Gonzalez ◽  
Inés Moret ◽  
Adrian Lopez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Inflammatory Bowel Diseases ◽  
Drug Response ◽  
Current Knowledge ◽  
Epigenetic Biomarkers ◽  
Bowel Diseases ◽  
Potential Applicability ◽  
Inflammatory Bowel ◽  
New Biomarkers

Abstract Epigenetics has emerged as a new and promising field in recent years. Because there exists a need to find new biomarkers and improve diagnosis, prognosis, and drug response for inflammatory bowel diseases, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to the clinical practice. In this review, we present an overview of the current knowledge and its potential applicability of this emerging field in inflammatory bowel diseases.

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