Richard Loiacono; Week 2 MED1022; Pharmacology
Drug reactions vary greatly from person to person, depend on physiological/pathological factors, environmental and genetic factors. Pharmacogenetics is study of inter-individual variation in DNA related to pharmacokinetics or pharmacodynamics. Bimodal drugs have two prominent plasma concentration per dosage in a group.
Sources of variation can be single base mutations (single nucleotide polymorphisms), insertion or deletion of one or more nucleotides (tandem repeat polymorphisms, insertion/deletion polymorphisms).
All genes encoding CYP1/2/3 are polymorphic (have more than one variant of the gene). CYP2D6 has a large consequence on drug metabolism and many people either lack the enzyme or have gene duplications, creating metabolism changes.
In b2 adrenoreceptors, arg/arg rather than gly/gly phenotype reduce sensitivity to salbutamol quickly, should not use b2 agonist bronchodilators.
Pharmacogenomics is use of genetic information to guide drug therapy. Responses to drugs can be predicted. Tratuzumab is used in HER2 (a tyrosine kinase) breast cancers, diagnostic tests for HER2 give prospective efficacy rather than retrospective analyses.