dúvidas [email protected] arquivo farmacogenômica (eurofarma) site gdenucci
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Dúvidas [email protected] 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 - PowerPoint PPT PresentationTRANSCRIPT
Dúvidas [email protected]
Arquivo FarmacogenômicaFarmacogenômica
(Eurofarma)(Eurofarma)
Sitewww.gdenucci.com
Dúvidas [email protected]
Arquivo FarmacogenômicaFarmacogenômica
(Eurofarma)(Eurofarma)
Sitewww.gdenucci.com
PharmacogenomicsPharmacogenomics
Drug Receptor AffinityDrug Receptor AffinityDrug Receptor AffinityDrug Receptor Affinity Drug Targeting Gene ProductsDrug Targeting Gene ProductsDrug Targeting Gene ProductsDrug Targeting Gene Products
Drug ExcretionDrug ExcretionDrug ExcretionDrug ExcretionDrug DistributionDrug DistributionDrug DistributionDrug Distribution
Drug AbsorptionDrug AbsorptionDrug AbsorptionDrug Absorption
Curr Probl Cardiol, May 2003
Apolipoprotein 4
Days Since Randomization(a) Treatment with Placebo
Pro
por
tion
Ali
veNot Not -Carriers-Carriers
N=312N=312
-Carriers-CarriersN=166N=166
Curr Probl Cardiol, May 2003
1.00
0.95
0.90
0.85
0.800 500 1000 1500 2000 2500
Alelos da apo
• apo 2
• apo 3
• apo 4
Simvastatin treatment reduces mortality
• 13% in non apo 4
• 50% in apo 4
Days Since Randomization(b) Treatment with Simvastatin
Pro
por
tion
Ali
veNot -Carriers
N=3014-Carriers
N=187
Curr Probl Cardiol, May 2003
1.00
0.95
0.90
0.85
0.800 500 1000 1500 2000 2500
ACE genotype
Months Follow Up(a)
Tra
nsp
lan
t-fr
ee S
urv
ival
ACE II (N=69)ACE ID (N=154)ACE DD (N=105)
p = 0.04p = 0.04
Curr Probl Cardiol, May 2003
1.00
0.80
0.60
0.40
0.20
0.000 6 12 18 24 30
ACE DD
Months Follow Up(b)
Tra
nsp
lan
t-fr
ee S
urv
ival
Beta Blocker (N=154)No Beta Blocker (N=105)
p = 0.007p = 0.007
Curr Probl Cardiol, May 2003
1.00
0.80
0.60
0.40
0.20
0.000 6 12 18 24 30
Trial DrugEvent Rates (%)
Benefit /100Lack of
Benefit/100Placebo 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
Established Pharmacotherapies With Strong Clinical Efficacy and Percentage of Patients Benefiting and Not
Benefiting With Treatment
Gene Polymorphism
Medications Effect Related to Polymorphism
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
Selected Examples of Clinically Relevant Polymorphisms Influencing Medication Efficacy and Safety
Gene Polymorphism
Medications Effect Related to Polymorphism
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
Selected Examples of Clinically Relevant Polymorphisms Influencing Medication Efficacy and Safety