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Lecture 21 Variability – Role of Pharmacogenetics
Prescribed drugs are generally effective in about 50% of patients. Inappropriate
prescriptions adverse reactions (ADRs) death.
Cost of treating ADRs > Cost of medications themselves.
Current “trial and error” method of drug prescribing.
Gnenetically-enabled “personalized medicine”
•Use genetic technology to develop better medications, predictive genotype tests to
determine ideal dose, drug, in right patient at right time.
Variation in drug response
•Genetic and environmental factors contribute to ADME
Pharmacogenetics: study of influence of genetic factors on response to and toxicity of
Patients with same diagnosis may not be homogenous; may require different treatments.
Need technology to identify segregation of: responders who are not predisposed to toxicity
(given conventional drug/dose), and non-responders who are toxic responders (require
SNPs correlate with disease predisposition, influence response to medications.
Classification of pharmacogenetic variants
oPharmacokinetic: body drug
oPharmacodynamic: drug body
Significant environmental effects
Pharmacogenetics of drug metabolism: variation in how body “hits” drug
Polymorphic gene extensive and poor metabolizers of drug, foreign chemicals
variable plasma drug levels, drug responses, drug toxicity after standard doses
Discovery of pharmacogenetic traits
•Astute clinical observation of unexpected/abnormal phenotype of drug
Polymorphism of CYP2D6
Variation in effectiveness, toxicity of debrisoquine and sparteine