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Vitamin K antagonists are medicines which are widely prescribed throughout the world. The effectiveness of these treatments is dependent on a delicate balance, which is influenced by many factors both specific to the patient and the environment: a low dose may be insufficient for therapeutic effectiveness, while a high dose may increase the risk of bleeding. A regular measurement of a biological parameter called International Normalized Ratio is required in order to provide a personalised adaptation of the dose. In order to optimise the anticoagulation, each patient treated by vitamin K antagonists has to reach a target value of this biological indicator. Since the anticoagulant response is influenced by many factors and varies from one patient to another, we propose to study the potential influence of the genetic constitution of each individual, as a basis of individual variations. Pharmacogenetics assesses the role played by genetic factors on the clinical response to drugs. In the case of vitamin K antagonists, the genes that influence the response to the drug are those involved in their metabolism and in the synthesis of the target on which they act. Many studies have been conducted in order to highlight the importance of these genes and their polymorphisms in the therapeutic effect of oral anticoagulants. These have demonstrated a clear relationship between some genetic polymorphisms and the anticoagulant effect of vitamin K antagonists. Dosage algorithms can help the practitioner to determine the initial dose to be prescribed. Unfortunately, these algorithms are only available for warfarin, which remains the most widely prescribed anticoagulant in the world. In Belgium, the use of acenocoumarol is more frequent compared to warfarin. However, genetic data in relation to warfarin are more abundant compared to acenocoumarol. We will analyse several clinical trials showing that both compounds have similar characteristics and suggesting the importance of pharmacogenetics for their clinical use Les antagonistes de la vitamine K sont des médicaments largement prescrits partout dans le monde. L’efficacité et la sécurité de ces traitements reposent sur un équilibre fragile, influencé par des facteurs environnementaux et des facteurs propres au patient: une dose trop faible est insuffisante pour obtenir une efficacité thérapeutique alors qu’une dose trop élevée peut augmenter les risques de saignements. Une adaptation strictement individuelle du traitement est nécessaire par mesures régulières d’un paramètre biologique appelé International Normalized Ratio. Pour chaque patient traité par antagonistes de la vitamine K on détermine une valeur cible de cet indicateur biologique pour obtenir un niveau anticoagulant optimal. Puisque la réponse anticoagulante est influencée par de nombreux facteurs et qu’elle est variable d’un patient à l’autre, pourquoi ne pas s’intéresser à la constitution génétique de chaque individu qui est une des bases de la variabilité individuelle? La pharmacogénétique s’engage à étudier l’influence des caractéristiques génétiques des patients sur la réponse clinique aux traitements médicamenteux. Dans le cas des antagonistes de la vitamine K, les gènes qui influencent la réponse aux médicaments sont ceux qui interviennent dans leur métabolisme et dans la synthèse de la cible sur laquelle ils agissent. De nombreuses études ont été menées dans le but de mettre en évidence l’importance de ces gènes dans la réponse aux anticoagulants oraux. Elles ont démontré une association claire entre certains gènes et la réponse anticoagulante aux antagonistes de la vitamine K. Des algorithmes de dosage peuvent aider le praticien à déterminer la dose initiale à administrer au patient. Malheureusement, ces algorithmes ne sont actuellement disponibles que pour la warfarine qui reste l’anticoagulant le plus prescrit dans le monde. En Belgique, l’utilisation de l’acénocoumarol est plus fréquente que celle de la warfarine. Cependant, les données génétiques concernant la warfarine sont plus abondantes. Nous analyserons plusieurs essais cliniques montrant que ces deux molécules ont des caractéristiques proches et l’importance de la pharmacogénétique dans ce type de traitement
Vitamin K --- International Normalized Ratio --- Pharmacogenetics --- Acenocoumoral --- Warfarin
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Derived from the comprehensive two-volume set, Genomic and Personalized Medicine also edited by Drs. Willard and Ginsburg, this work serves the needs of the evolving population of scientists, researchers, practitioners and students that are embracing one of the most promising avenues for advances in diagnosis, prevention and treatment of human disease. From principles, methodology and translational approaches to genome discoveries and clinical applications, Essentials of Genomic and Personalized Medicine will be a valuable resource for various professionals and students across me
Medical genetics. --- Pharmacogenetics. --- Pharmacology --- Biochemical genetics --- Clinical genetics --- Diseases --- Heredity of disease --- Human genetics --- Medical sciences --- Pathology --- Genetic disorders --- Genetic aspects
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Epigenetics has emerged recently as an important area of molecular biological studies. Epigenetic modifications lead to potentially heritable but reversible alterations in the expression of genes that determine cell fate. Epigenetic misregulation is thus often linked to degenerative diseases, cancer and neuronal disorders. Recent biomedical interest in this regulatory system stems from the fact that epigenetic, in contrast to genetic, alterations are in principle amenable to pharmacological intervention. A few epigenetically active drugs, for example histone deacetylase inhibitors (HDACi) and DNA methyltransferase (DNMT) inhibitors, have been approved by FDA for treatment of cancers such as CTCL, MDS, and AML. This volume explores the scientific background for clinical applications of epigenetically active drugs. Included are descriptions of epigenetic controls over gene expression, the post-transcriptional silencing of genes by RNA interference (RNAi) and microRNAs, as well as new findings from stem cell research which are relevant to pharmacological applications.
DNA --- Epigenesis. --- Genetic regulation. --- Pharmacogenetics. --- Methylation. --- Medicine. --- Medical genetics. --- Biomedicine. --- Gene Function. --- Pharmacology --- Biochemical genetics --- Gene expression --- Gene expression regulation --- Gene regulation --- Biosynthesis --- Cellular control mechanisms --- Molecular genetics --- Embryology --- Evolution (Biology) --- Genetics --- Deoxyribonucleic acid --- Desoxyribonucleic acid --- Thymonucleic acid --- TNA (Nucleic acid) --- Deoxyribose --- Nucleic acids --- Genes --- Genetic aspects --- Regulation --- Clinical genetics --- Diseases --- Heredity of disease --- Human genetics --- Medical sciences --- Pathology --- Genetic disorders
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Chemotherapy has made a dramatic difference to improved survival in patients with cancer. However, not all patients respond and some experience serious side effects. "Pharmacogenetics: Making cancer treatment safer and more effective" is an up to date summary of the exciting new field of how genetic testing can tailor more effective prescription in oncology. It is targeted at oncologists and professionals involved in the treatment of patients with cancer. It provides a core background in genetics and pharmacological principles before providing chapters from acknowledged experts in the field on genetic tests in specific cancer types, including breast, bowel and lung cancer. Clinical cases are used to illustrate the practical application of this knowledge. Chapters on ethics, health economics and the industry aspects of pharmacogenetics set out the challenges and opportunities afforded by this new science.
Cancer -- Chemotherapy. --- Cancer -- Genetic aspects. --- Pharmacogenetics. --- Antineoplastic agents --- Cancer --- Genetic screening --- Drug targeting --- Biology --- Genetic Techniques --- Pharmacology --- Diagnostic Techniques and Procedures --- Therapeutics --- Diseases --- Genetic Services --- Therapeutic Uses --- Diagnostic Services --- Metabolic Phenomena --- Diagnosis --- Health Services --- Analytical, Diagnostic and Therapeutic Techniques and Equipment --- Biological Science Disciplines --- Investigative Techniques --- Preventive Health Services --- Health Occupations --- Pharmacologic Actions --- Phenomena and Processes --- Metabolism --- Pharmacogenetics --- Genetic Testing --- Antineoplastic Agents --- Neoplasms --- Genetics --- Drug Delivery Systems --- Drug Therapy --- Community Health Services --- Chemical Actions and Uses --- Health Care Facilities, Manpower, and Services --- Disciplines and Occupations --- Natural Science Disciplines --- Health Care --- Chemicals and Drugs --- Health & Biological Sciences --- Medicine --- Oncology --- Pharmacy, Therapeutics, & Pharmacology --- Physiological effect --- Genetic aspects --- Genetic screening. --- Drug targeting. --- Physiological effect. --- Genetic aspects. --- Drugs --- Site-specific drug delivery --- Targeting of drugs --- Cancer genetics --- Anticancer agents --- Antineoplastic drugs --- Antineoplastics --- Antitumor agents --- Antitumor drugs --- Cytotoxic drugs --- Inhibitors, Neoplasm --- Neoplasm inhibitors --- Targeting --- Medicine. --- Cancer research. --- Human genetics. --- Pharmacology. --- Oncology. --- Biomedicine. --- Cancer Research. --- Pharmacology/Toxicology. --- Human Genetics. --- Biomedicine general. --- Target organs (Anatomy) --- Human chromosome abnormalities --- Medical screening --- Cancer genes --- Dosage forms --- Chemotherapy --- Toxicology. --- Oncology . --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Tumors --- Heredity, Human --- Physical anthropology --- Chemicals --- Poisoning --- Poisons --- Toxicology --- Health Workforce --- Biomedicine, general. --- Drug effects --- Medical pharmacology --- Pharmacy --- Cancer research --- Cancer. --- Medical genetics. --- Cancer Biology. --- Medical Genetics. --- Biomedical Research. --- Research. --- Biological research --- Biomedical research --- Clinical genetics --- Heredity of disease --- Human genetics --- Genetic disorders --- Cancers --- Carcinoma --- Malignancy (Cancer) --- Malignant tumors
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