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25 febbraio 2014 In collegamento con:

Progetto Formativo ANMCO - AIAC UNIVERSO TROMBOSI ROMPERE IL LEGAME TRA FIBRILLAZIONE ATRIALE & ICTUS CONSIGLI D’AUTORE. POLITERAPIA E PRINCIPI DI INTERAZIONI FARMACOLOGICHE. 25 febbraio 2014 In collegamento con:

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25 febbraio 2014 In collegamento con:

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  1. Progetto Formativo ANMCO - AIAC UNIVERSO TROMBOSI ROMPERE IL LEGAME TRA FIBRILLAZIONE ATRIALE & ICTUS CONSIGLI D’AUTORE POLITERAPIA E PRINCIPI DI INTERAZIONI FARMACOLOGICHE 25 febbraio 2014 In collegamento con: Torino, Bergamo, Mestre, Bologna, Lucca, Roma, Napoli, Bari, Catania, Cagliari

  2. Drug–drug interactions and pharmacokinetics of new oral anticoagulants • Treatment with VKAs requires careful consideration of multifold food and drug interactions. • Despite high expectations of less interactions with the NOAC drugs, physicians will have to consider pharmacokinetic effects of accompanying drugs and of comorbidities when prescribing NOACs. 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  3. Can Pharm J 2014; 147:1

  4. Absorption and metabolism of the different new anticoagulant drugs 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  5. P-gp System • P-glycoprotein (P-gp) is a transporter system located in the epithelial cells of the intestine (enterocytes). • As the drug molecules diffuse through the enterocytes, P-gp picks up the drug molecules and carries them back to the luminal side of the cell, preventing them from reaching the circulation. • Therefore, when a drug inhibits the P-gp pump system, it increases the systemic availability of a P-gp–sensitive drug, with a resultant enhanced activity/toxicity. • Conversely, if a drug induces the P-gp system, less of the drug reaches the systemic circulation and therefore its activitywill be decreased.

  6. P-gp = P-glycoprotein Adapted from Lin J. Adv Drug Deliv Rev 2003;55:53–81 Intestinal apical cell Drug P-gp Drug plasma level Metab Gastrointestinal lumen Blood circulation NOACs and P-glycoprotein High concentrations of a strong P-gp inhibitor in the gut at the time a NOAC is ingested can lead to increased systemic delivery of the drug as the P-gp-mediatedefflux of the drug back into the gut is blocked

  7. CYP 450 3A4 • CYP 450 3A4 is an enzyme located in the liver, which metabolizes a wide variety of drugs. • Inhibition will decrease the metabolism of drugs that depend on this enzyme for their elimination, thereby increasing the activity/toxicity of these agents. • Conversely, if a drug induces this enzyme, the drugs that depend on this enzyme for their elimination will have a higher rate of elimination and their activity will be diminished.

  8. Absorption and metabolism of the different new anticoagulant drugs 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  9. Can Pharm J 2014; 147:1

  10. Can Pharm J 2014; 147:1

  11. Interazioni farmacologiche dei NAO Red, contraindicated. Orange, reduce dose (from 150 mg bid to 110 mg bid for dabigatran; from 20 mg to 15 mg qd for rivaroxaban; from 5 mg bid to 2.5 mg bid for apixaban). Yellow, consider dose reduction if another ‘yellow’ factor is present. Hatching, no data available; recommendation based on pharmacokinetic considerations. 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  12. Interazioni farmacologiche dei NAO • Età avanzata, peso corporeo ridotto, funzionalità renale ridotta ed altri fattori (HAS-BLED) possono determinare un incremento nelle concentrazioni plasmatiche dei NAO e richiedere una riduzione delle dosi, • Si deve ridurre la dose in caso siano presenti due caselle gialle; ad esempio in caso di terapia con Dabigatran ed Amiodarone in paziente con età> 75 aa. 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  13. Funzionalità Renale e Dosaggio NAO 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  14. Can Pharm J 2014; 147:1

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