Applications in Pharmacogenetics are breaching the laboratory medicine and clinical environment. The testing of genetic variations in relation to differing response to drug metabolism and improvement of drug safety is an important and essential area in light of adverse drug reactions. This timely and comprehensive issue of the Clinics presents topics related to Pharmacology and Genetics, Pharmacogenetic Applications in Anticoagulation, Oncology, Pain Management, and Behavioral Disorders, Respiratory Disorders, as well as Education and Healthcare Economics of Pharmacogenetics.
Author(s): Roland Valdes Jr., Kristen Reynolds
Series: The Clinics: Internal Medicine
Edition: 1
Publisher: Saunders
Year: 2008
Language: English
Pages: 178
Cover......Page 1
Preface......Page 2
Overview of pharmacology......Page 5
Cytochrome P450 system and drug metabolism......Page 9
Genetic polymorphism in pharmacogenetics......Page 11
Clinical pharmacogenetics......Page 12
Pharmacogenetics and health needs......Page 13
The clinical laboratory and pharmacogenetics......Page 15
References......Page 16
Pharmacogenetics: From Description to Prediction......Page 18
Genetic markers predictive of human drug response......Page 21
Genetic markers predictive of outcomes and therapeutic benefits in cancer......Page 22
References......Page 27
Overview of Pharmacogenetics in Anticoagulation Therapy......Page 31
Metabolism of warfarin......Page 32
CYP2C9 polymorphisms......Page 33
Clinical implementation......Page 35
Challenges......Page 37
References......Page 39
Pharmacogenetic Testing for Warfarin Sensitivity......Page 43
Hybridization probes......Page 44
Invader......Page 46
xTAG CYP2C9-VKORC1 assay......Page 48
INFINITI 2C9-VKORC1 assay......Page 49
eSensor......Page 50
Single nucleotide primer extension......Page 51
Implementing warfarin sensitivity testing......Page 52
References......Page 53
Dynamic Pharmacogenetic Models in Anticoagulation Therapy......Page 56
VKORC1 genotype and warfarin dose requirement......Page 57
VKORC1 and CYP2C9 genotype and ethnic prevalence......Page 59
Induction phase of treatment......Page 60
Multivariate dose estimation equations......Page 61
Clinical scenarios......Page 63
Future practice......Page 65
References......Page 67
Irinotecan therapy in colorectal cancer......Page 70
Uridine diphosphate-glucuronyltransferase 1A1 polymorphisms and irinotecan toxicity......Page 71
Other uridine diphosphate-glucuronyltransferase 1A enzymes......Page 73
Tamoxifen therapy in breast cancer......Page 74
Cytochrome P450 2D6 polymorphisms and tamoxifen treatment......Page 75
Food and drug administration recommendations on tamoxifen......Page 78
Role of other polymorphisms in tamoxifen treatment outcome......Page 79
Future directions......Page 80
References......Page 81
Genetics of pain......Page 85
Low back pain......Page 86
Fibromyalgia......Page 87
Genetics of analgesia......Page 89
Melanocortin-1 receptor gene......Page 90
The spectrum of medication response......Page 91
References......Page 92
Opioid receptors......Page 96
Opioids......Page 97
Adverse drug reactions......Page 99
Undertreatment and fear of addiction......Page 100
Pharmacogenetic effects on opioid sensitivity......Page 103
Opioid Metabolism by CYP2D6......Page 104
Opioid response via mu-opioid receptor......Page 108
mu-opioid receptor genotyping......Page 109
References......Page 110
The AmpliChip CYP450 Test......Page 114
Pharmacogenetics and personalized medicine......Page 115
CYP testing......Page 116
Cytochrome P450 2D6......Page 117
CYP2C19......Page 118
CYP2C9......Page 120
The Tm Tag-It Mutation Detection Kit......Page 122
Metabolic syndrome......Page 123
Evaluation of pharmacogenetic testing in clinical practice......Page 124
Regulatory oversight......Page 126
CYP tests available......Page 121
References......Page 127
Rationale behind the development of pharmacogenetic diagnostics: genotype-based dosing......Page 133
Limitations of pharmacogenetic dose adjustments......Page 134
Clinical implications of pharmacogenetic testing in psychiatry......Page 135
Impact of CYP2D6 and CYP2C19 polymorphisms on pharmacokinetics and outcome of antidepressant drugs......Page 136
References......Page 138
Dopamine D2 receptor......Page 141
Schizophrenia......Page 142
Major depression......Page 143
CYP450 metabolic variants......Page 145
Receptor variants......Page 146
Serotonin transporter (5-HTT)......Page 149
The future of pharmacogenetics in psychiatric practice......Page 150
References......Page 151
Background on asthma......Page 158
Pharmacokinetics......Page 162
Measures of response to asthma therapy......Page 164
beta2-Agonists are controversial......Page 166
beta2-Adrenergic receptor pharmacogenetics......Page 167
In vivo acute response to beta2-agonists......Page 172
Response to chronic dosing with beta2-agonists is genotype-dependant......Page 174
Acknowledgments......Page 175
References......Page 176
