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Thiopurines, represented by three medicines: the 6-mercaptopurine (6-MP, Purinéthol), the azathioprine (Imuran) and the 6-thioguanine (6-TG, Lanvis), are a part of first drugs used to handle the autoimmune diseases, in particular the intestinal chronic inflammatory diseases (MICI). Endowed with anti-metabolic and immunosuppressive properties, this medicine plays a major role of savings in corticoid and a preservation of the effect in time, positioning them as a first line maintenance treatment of the Crohn’s disease and as a second line treatment in the rectocolitis disease. Although their precise mechanisms of action remain partially unknown, several factors such as the best knowledge of their profile of short-term and long term tolerance, their mode of administration as once daily oral dose, their methods of use in monotherapy or in association and their low cost make of these drugs an important therapeutic class in the treatments of the MICI. All these factors mean that this class is interesting to know for a future pharmacist. Les thiopurines actuellement représentées par trois médicaments :la 6-mercaptopurine (6-MP, Purinéthol®), l'azathioprine ( Imuran ®) et la 6-thioguanine (6-TG, Lanvis®) font partie des premiers médicaments utilisés pour traiter les maladies auto-immunes notamment les maladies inflammatoires chroniques intestinales (MICI).Dotés de propriétés anti-métaboliques et immunosuppressives, ces médicaments jouent un rôle majeur d'épargne en corticoïde et un maintien de l'effet dans le temps, ceux-ci les positionnent comme le traitement d'entretien de première ligne dans la maladie de Crohn et de deuxième ligne dans la rectocolite hémorragique. Bien que leurs mécanismes d'action précis restent en partie inconnus, plusieurs facteurs tels que la meilleure connaissance de leur profil de tolérance à court terme et à long terme, leur mode d'administration facile en uni dose quotidienne par voie orale, ainsi leurs méthodes d'utilisation en monothérapie ou en association et leur coût peu élevé font en sorte que cette classe médicamenteuse conserve une place importante dans le traitement des MICI. Tous ces facteurs réunis font que cette classe est un sujet potentiellement intéressant à connaitre en tant que futur pharmacien.
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The personalized medicine is supported by the pharmacogenetics. This new branch of genetics evolves thanks to the news of molecular biology and the complete sequencing of the human genome. Thanks to its progressive use in the current clinic, it is possible to choose and adapt the treatment appropriately. This is of great importance when it comes to molecules with narrow therapeutic window or which could de the cause of potentially serious side effects. In this work, we reviewed the treatments for psoriasis and lupus and in particular those that are the subject of pharmacogenetics studies. The identified polymorphisms of thiopurine methyltransferase are responsible for the variation of its activity. Homozygous carriers of wild-type alleles have normal thiopurine methyltransferase activity and may be treated with thiopurines such as azathioprine. The presence of one or two mutated alleles reduces thiopurine methyltransferase activity. Once identified the deficient patients, the doctor adjusts the dosage of azathioprine or prescribes another medication more suitable. La pharmacogénétique est un des outils de la médecine personnalisée. Cette nouvelle branche de la génétique a émergé suite aux récents développements de la biologie moléculaire et du séquençage complet du génome humain. Grace à son installation progressive dans la clinique courante, on arrive à choisir et mieux adapter le traitement pour chaque patient. Ceci est d'une grande importance quand il s'agit de molécules à fenêtre thérapeutique étroite ou qui sont la cause d'effets secondaires potentiellement graves. Dans ce travail, nous avons passé en revue les traitements contre le psoriasis et le lupus et en particulier ceux qui sont objet d'études pharmacogénétiques. Les polymorphismes identifiés de la thiopurine methyltransferase sont responsables de la variation de son activité. Les porteurs homozygotes des allèles sauvages ont une activité normale de la thiopurine methyltransferase et peuvent se voir attribuer un traitement à base de thiopurines telles que l'azathioprine. La présence d'un seul ou de deux allèles variants réduisent l'activité de la thiopurine methyltransferase. Une fois les patients déficients en activité thiopurine methyltransferase identifiés, le médecin adapte la posologie de l'azathioprine ou prescrit un autre médicament plus adéquat.
Pharmacogenetics --- Psoriasis --- Lupus Vulgaris --- Azathioprine
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Cyclosporins --- Kidney Transplantation --- Azathioprine --- adverse effects --- therapeutic use
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Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient’s genetic features. In recent years, several pharmacogenetic guidelines have been published by international scientific consortia, but the uptake in clinical practice is still poor. Many coordinated international efforts are ongoing in order to overcome the existing barriers to pharmacogenomic implementation. On the other hand, existing validated pharmacogenomic markers can explain only a minor part of the observed clinical variability in the therapeutic outcome. New investigational approaches are warranted, including a study of the pharmacogenomic role of the immune system genetics and of previously neglected rare genetic variants, reported to account for a large part of inter-individual variability in drug metabolism. In this book, we have collected a series of articles covering many aspects of pharmacogenomics. These include clinical implementation of pharmacogenomics in clinical practice, development of tools or infrastructures to support this process, research of new pharmacogenomics markers to increase drug efficacy and safety, and the impact of rare genetic variants in pharmacogenomics.
Medicine --- CYP2C9 --- VKORC1 --- warfarin --- warfarin initiation phase of therapy --- INR --- pharmacogenetics study --- pharmacogenomics --- pharmacogenetics --- genotype --- phenotype --- alleles --- precision medicine --- pharmacotranscriptomics --- high-throughput analysis --- childhood acute lymphoblastic leukemia --- clopidogrel --- acenocoumarol --- CDSS --- implementation --- azathioprine --- inflammatory bowel disease --- glutathione-S transferase --- pharmacokinetics --- nucleoside analogs --- microRNAs --- gene expression --- drug resistance --- AML --- cisplatin --- nephrotoxicity --- kidney injury --- genetic polymorphisms --- pre-emptive --- panel --- breast cancer subtype --- miRNA --- pathway --- crosstalk network --- precision drugs --- ovarian cancer --- platinum resistance --- focal copy number alterations --- whole exome sequencing --- personalized medicine --- human genetics --- pharmacology --- CYP2C9 --- VKORC1 --- warfarin --- warfarin initiation phase of therapy --- INR --- pharmacogenetics study --- pharmacogenomics --- pharmacogenetics --- genotype --- phenotype --- alleles --- precision medicine --- pharmacotranscriptomics --- high-throughput analysis --- childhood acute lymphoblastic leukemia --- clopidogrel --- acenocoumarol --- CDSS --- implementation --- azathioprine --- inflammatory bowel disease --- glutathione-S transferase --- pharmacokinetics --- nucleoside analogs --- microRNAs --- gene expression --- drug resistance --- AML --- cisplatin --- nephrotoxicity --- kidney injury --- genetic polymorphisms --- pre-emptive --- panel --- breast cancer subtype --- miRNA --- pathway --- crosstalk network --- precision drugs --- ovarian cancer --- platinum resistance --- focal copy number alterations --- whole exome sequencing --- personalized medicine --- human genetics --- pharmacology
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Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient’s genetic features. In recent years, several pharmacogenetic guidelines have been published by international scientific consortia, but the uptake in clinical practice is still poor. Many coordinated international efforts are ongoing in order to overcome the existing barriers to pharmacogenomic implementation. On the other hand, existing validated pharmacogenomic markers can explain only a minor part of the observed clinical variability in the therapeutic outcome. New investigational approaches are warranted, including a study of the pharmacogenomic role of the immune system genetics and of previously neglected rare genetic variants, reported to account for a large part of inter-individual variability in drug metabolism. In this book, we have collected a series of articles covering many aspects of pharmacogenomics. These include clinical implementation of pharmacogenomics in clinical practice, development of tools or infrastructures to support this process, research of new pharmacogenomics markers to increase drug efficacy and safety, and the impact of rare genetic variants in pharmacogenomics.
CYP2C9 --- VKORC1 --- warfarin --- warfarin initiation phase of therapy --- INR --- pharmacogenetics study --- pharmacogenomics --- pharmacogenetics --- genotype --- phenotype --- alleles --- precision medicine --- pharmacotranscriptomics --- high-throughput analysis --- childhood acute lymphoblastic leukemia --- clopidogrel --- acenocoumarol --- CDSS --- implementation --- azathioprine --- inflammatory bowel disease --- glutathione-S transferase --- pharmacokinetics --- nucleoside analogs --- microRNAs --- gene expression --- drug resistance --- AML --- cisplatin --- nephrotoxicity --- kidney injury --- genetic polymorphisms --- pre-emptive --- panel --- breast cancer subtype --- miRNA --- pathway --- crosstalk network --- precision drugs --- ovarian cancer --- platinum resistance --- focal copy number alterations --- whole exome sequencing --- personalized medicine --- human genetics --- pharmacology
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Pharmaceutical Preparations --- analysis --- Drugs --- Pharmaceutical chemistry --- Médicaments --- Chimie pharmaceutique --- Analysis --- Yearbooks. --- Analyse --- Pharmaceutical Preparations - analysis --- Atenolol --- Camphre --- Chloroquine --- Cholecalciferol --- Cimetidine --- Disopyramide (phosphate) --- Indomethacine --- Ketofifene --- Melphalan --- Moxalactam (disodium) --- Oxyphenbutazone --- Pentazocine --- Phenytoine --- Pyridoxine --- Reserpine --- Saccharine --- Salicylamide --- Sulfadadiazine argent --- Sulindac --- Tetracycline (chlorhydrate --- Tolbutamide --- Vitamine d3 --- CHLORTHALIDONE --- IMIPRAMINE HCl --- CISPLATIN --- ANALYTICAL PROFILE --- TRIPELENNAMINE HCl --- XYLOMETAZOLINE HCl --- MEFLOQUINE HCl --- ACIDE IOPOANOIQUE --- LIDOCAINE --- LIDOCAINE HCl --- BENPERIDOL --- HYDRATE DE TERPINE --- ATROPINE --- ISOPROTERENOL --- WARFARIN --- NALOXONE HCl --- DIFLUNISAL --- BACLOFEN --- ACETAMINOPHEN --- HALOTHANE --- Bacitracine --- Bretylium --- Carbamazepine --- Ccyproheptadine --- Cefaclor --- Cefamandole --- Dibenzepine --- Digoxine --- Doxorubicine --- Fluphenazine --- Gentamicine (sulfate) --- Griseofulvine --- Haloperidol --- Khellin --- Lorazepam --- Methadone --- Methoxsalen --- Monographies medicaments --- Nadolol --- Nitrazepam --- Nitroglycerin --- Trifluoroperazine --- Acide ascorbique --- Acide flufenamique --- Aminophylline --- Captopril --- Cefotaxime --- Cefoxitine sodium --- Clofibrate --- Clotrimazole --- Dopamine chlorhydrate --- Ergonovine maleate --- Hexestrol --- Mestranol --- Noscapine --- Penicilline-g benzathine --- Phenylbutazone --- Sulfadiazine --- Amantadine --- Amikacine sulfate --- Benzocaine --- Dibucaine --- Dibucaine chlorhydrate --- Dioctylsulfosuccinate de sodium --- Estrone --- Etomidate --- Heparine sodium --- Hydrocortisone --- Isopropamide --- Metoprolol tartrate --- Phenylpropanolamine chlorhydrate --- Pilocarpine --- Pyrazinamide --- Pyrimethamine --- Quinine chlorhydrate --- Quinine sulfate --- Rutine --- Trimipramine maleate --- AMILORIDE CHLORHYDRATE --- AMINOGLUTETHIMIDE --- CAFEINE --- COCAINE CHLORHYDRATE --- EPHEDRINE CHLORHYDRATE --- OESTRADIOL --- GUANABENZ ACETATE --- IODAMIDE --- LITHIUM CARBONATE --- MAPROTILINE CHLORHYDRATE --- PENICILLIN G --- POTASSIUM --- PIROXICAM --- RANITIDINE --- STRYCHNINE --- VIDARABINE --- ZOMEPIRAC --- SODIUM --- CHLORAMPHENICOL --- LIDOCAINE CHLORHYDRATE --- SODIUM NITROPRUSSIATE --- Acide aminosalicylique --- Azathioprine --- Benzoate de benzyle --- Chlorhydrate d'emetine --- Chlorhydrate de clindamycine --- Chlorhydrate de methylphenidate --- Colchicine --- Cyanocobalamine --- Glibenclamide --- Heroine --- Hydrochlorothiazide --- Ketoprofen --- Nabinole --- Natamycine --- Oxytocine --- Penicillamine --- Phosphate de codeine
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