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Dúvidas denucci@dglnet.br Arquivo Farmacogenômica (Eurofarma) Site gdenucci

Dúvidas denucci@dglnet.com.br Arquivo Farmacogenômica (Eurofarma) Site www. gdenucci.com. Drug Distribution. Drug Excretion. Drug Absorption. Pharmacogenomics. Drug Receptor Affinity. Drug Targeting Gene Products. Curr Probl Cardiol, May 2003. Apolipoprotein e 4. 1.00 0.95 0.90

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Dúvidas denucci@dglnet.br Arquivo Farmacogenômica (Eurofarma) Site gdenucci

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  1. Dúvidas denucci@dglnet.com.br Arquivo Farmacogenômica (Eurofarma) Site www.gdenucci.com

  2. Drug Distribution Drug Excretion Drug Absorption Pharmacogenomics Drug Receptor Affinity Drug Targeting Gene Products Curr Probl Cardiol, May 2003

  3. Apolipoprotein e4 1.00 0.95 0.90 0.85 0.80 Not e4-Carriers N=312 Proportion Alive e4-Carriers N=166 0 500 1000 1500 2000 2500 Days Since Randomization (a) Treatment with Placebo Curr Probl Cardiol, May 2003

  4. Alelos da apo e • apo e2 • apo e3 • apo e4

  5. Simvastatin treatment reduces mortality • 13% in non apo e4 • 50% in apo e4

  6. 1.00 0.95 0.90 0.85 0.80 Not e4-Carriers N=301 e4-Carriers N=187 Proportion Alive 0 500 1000 1500 2000 2500 Days Since Randomization (b) Treatment with Simvastatin Curr Probl Cardiol, May 2003

  7. ACE genotype 1.00 0.80 0.60 0.40 0.20 0.00 p = 0.04 Transplant-free Survival ACE II (N=69) ACE ID (N=154) ACE DD (N=105) 0 6 12 18 24 30 Months Follow Up (a) Curr Probl Cardiol, May 2003

  8. ACE DD 1.00 0.80 0.60 0.40 0.20 0.00 p = 0.007 Transplant-free Survival Beta Blocker (N=154) No Beta Blocker (N=105) 0 6 12 18 24 30 Months Follow Up (b) Curr Probl Cardiol, May 2003

  9. Established Pharmacotherapies With Strong Clinical Efficacy and Percentage of Patients Benefiting and Not Benefiting With Treatment Lack of Benefit/100 Event Rates (%) Trial Drug Benefit /100 Placebo Treated Hope APTC FTT 4S EPIC CURE Ramipril Aspirin Thrombolytics Simvastatin Abciximab Clopidogrel 17.8 14 11.5 28 12.8 11.5 14 10 9.6 19 8.3 9.3 3.8 4 1.9 9 4.5 2.2 96.2 96 98.1 91 95.5 97.8

  10. Selected Examples of Clinically Relevant Polymorphisms Influencing Medication Efficacy and Safety Gene Polymorphism Effect Related to Polymorphism Medications CYP2C9 CYP2D6 Thiopurine methyl-transferase CYP3A4 Warfarin, phenytoin β-blockers, codeine, debrisoquin, flecainide, propafenone, sparteine Mercaptopurine, thioguanine, azathioprine Mibefradil Anticoagulant effect, bleeding risk β–blocker effect, inadequate pain relief Safety, efficacy Safety, efficacy

  11. Selected Examples of Clinically Relevant Polymorphisms Influencing Medication Efficacy and Safety Gene Polymorphism Effect Related to Polymorphism Medications Angiotensin converting enzyme HERG Potassium channel KvLQT1 hKCNE2 β2–adrenargic receptor Enalapril, lisinopril, captopril Quindine, cisapride Terfenadine, disopyramide, mefloquine Clarithromycin Albuterol Renal protection effects, blood pressure, cardiac indices Long QT syndrome, torsade de pointes Long QT syndrome Arrhythmias Airway responsiveness

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