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Using human genomic variation for individualisation of drug treatment
Published on Jul 21, 20141468 Views
There is inherent variation in the responses to drugs used in medicine. This can affect both efficacy and toxicity, which in some individuals leads to a poor benefit-risk ratio of drugs. Strategies
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Chapter list
Using Human Genomic Variation for Individualisation of Drug Treatment00:00
Current Paradigms00:40
“One Dose Fits All” –Variability In Improvement01:35
Adverse Drug Reactions (Side Effects)02:29
A Modern Concept of Personalised Medicine - 103:23
A Modern Concept of Personalised Medicine - 203:57
A Modern Concept of Personalised Medicine - 304:24
A Modern Concept of Personalised Medicine - 404:42
PharmacogenomicVariation in Drug Response05:23
When it works…06:10
Human LeucocyteAntigens (HLA)06:24
Technology-Based Reduction in the Burden of ADRs: The Case of Abacavir Hypersensitivity - 107:54
Technology-Based Reduction in the Burden of ADRs: The Case of Abacavir Hypersensitivity - 208:20
Technology-Based Reduction in the Burden of ADRs: The Case of Abacavir Hypersensitivity - 308:34
Technology-Based Reduction in the Burden of ADRs: The Case of Abacavir Hypersensitivity - 409:22
Effect of Pharmacogenetics on Drug Usage10:00
Change in Peptide Repertoire11:19
HLA-B*57:01 and AbacavirHypersensitivity11:42
When it makes sense…13:12
Genetic Variants in C5 and Poor Response to Eculizumab - 113:22
Genetic Variants in C5 and Poor Response to Eculizumab - 214:29
More often than not, it is difficult…15:14
Sources of Variation15:29
Warfarin - 116:51
Warfarin - 217:30
Variation in Dose Requirements18:23
Determinants of Anticoagulation Control - 119:33
Determinants of Anticoagulation Control - 220:32
GWAS Warfarin Mean Weekly Dose20:55
International Warfarin PharmacogeneticsConsortium (IWPC)22:02
Pharmacogenetic-Based Dosing: Warfarin Randomised Controlled Trial22:38
A RCT of Genotype-Guided Dosing of Warfarin24:26
Differences Between Genotyped-Guided Group and Control Group25:25
A Pharmacogenetic versus a Clinical Algorithm for Warfarin Dosing26:29
Genomeweb's verdict27:03
How can we explain the differences - 127:48
How can we explain the differences - 228:17
Dosing Algorithms - 128:24
Dosing Algorithms - 229:30
Dosing Algorithm –Day 1 - 130:47
Dosing Algorithm –Day 1 - 231:18
Ethnic Heterogeneity31:55
Control Arms in the Two Trials - 132:56
Control Arms in the Two Trials - 233:58
Efficacy and safety of dabigatran compared with warfrin34:54
Comparison Between COAG and EU-PACT35:29
EU-PACT: Effect of Number of Variants on % Time in Therapeutic Range (TTR)36:21
A RCT of Genotype-Guided Dosing of Acenocomumarol and Phenprocoumon37:53
Differences in Vitamin K antagonists39:01
Pharmacogenetic tests39:53
Drug Exposure: Differential Evidential Standards40:20
Differential Evidence Standards - 141:38
Differential Evidence Standards - 242:22
CYP2C19 genotype-based phase I studies42:57
Response to a drug, efficacy or toxicity, is a complex phenotype44:08
Systems Pharmacology Approaches44:27
Warfarin Dose Prediction45:08
Summary46:04
Future46:41
Acknowledgements47:47