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Pharmacogenomics
lecture 25 kraus
| Question | Answer |
|---|---|
| pharmacogenetics | relationship btwn individual gene variants (alleles) and variations in drug effects (how an individual responds to a certain drug based on their genetic influences) |
| pharmacogenomics | relationship btwn variants in a large collection of genes, up to the whole genome and variations in drug effects; usually using SNPs (pharmacological responses across populations, genetic basis for differences in drug responses btwn individuals) |
| CYP2D6 allelism | differences in copy number, affects nortriptyline metabolism - poorest metabolizers tend to have null allele |
| phase I drug metabolism | P450 enzymes that make drug metabolites with modified activity by oxidizing, reducing and hydrolyzing |
| phase II drug metabolism | makes drugs hydrophilic by conjugating endogeous substrates onto metabolites (glutathione transferase) so they can be excreted |
| 2 most common phase I enzymes | CYP3A4 first (over half of all drugs, has various induces and inhibitors) and CYP2D6 second (highest genetic variability) |
| CYP2C9 allelism | due to missense substitutions, has major influence on warfarin metabolism |
| adrenergic beta2 receptor allelism | ADRB2 has a poor response to albuterol with the arginine (R16) polymorphism as opposed to 16 being a glycine residue |
| "susceptible" individual | think genetic predisposition |
| malignant hyperthermia | RyR overstimulated by halothane and other inhalation anesthetics causing increased release of Ca++ from SR into muscle = sx seen. AD transmission |
| antidote for malignant hyperthermia | dantrolene sodium |
| protein or receptor has to be present within ca cells in order for the molecular target tx to work | ER- breast ca cells won't respond to Tamoxifen |
| tamoxifen pharmacogenomics | CYP2D6 makes active metabolites, but they are antagonized competitively by SSRIs that are given for hot flash relief |
| azathioprine pharmacogenomics | 1/300 Caucasians are homozygous for defective thiopurine S-methyltransferase allele with low to no activity and resultant myelotoxicity seen |
| designer drugs | pharmacological agents that are designed or selected in accordance with an individual's genetic or physiologic status |
| pharmacological rescue | tailoring production or design of a drug to reverse deleterious effects of a particular genetic mutation that alters the activity of an expressed gene product |
Created by:
sirprakes
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