Genomics Flashcards
What is a SNP
Single Nucleotide Polymorphism- different people can have a different nucleotide or base at a given location on a chromosome
Pharmacogenomics
Larger scale, smaller effect with multiple variants
Pharmacogenetics
Smaller scale- large single-variant effect
Pharmacodynamics & genomics
What a drug does to the body- variations in drug targets
Pharmacokinetic & genomics
What a body does to a drug- often affects receptor proteins- mostly in metabolism of the drug
What is a phenotype
Characteristic
Genomics & succ
Prolonged apnea after administration- structural effect on enzyme (pseudocholinesterase) metabolizing succ
Genomics & MH
RYR1 gene in about 50% of cases
Genomics & red hair
Require 20% more des, more resistant to SC lidocaine, MC1R gene- reduced sensitivity to noxious stimuli, increased analgesic response to M-6-G
Genomics & PONV
CYP450 enzymes metabolism of 5-HT3 antagonists
Genomics & mu opioid receptor
OPRM1 is gene of interest, influences binding site on mu receptor- Homozygous (GG) require larger doses- have less PONV & less risk for opioid toxicity, A allele at risk for opioid toxicity. Also Beta-arrestin may desensitize opioid receptors after prolonged exposure
Genomics & COMT
Reduced COMT activity increases catecholamines which increases pain sensitivity BUT lower doses of opioids may be required
Genomics & p-glycoprotein efflux transporter
Variant combinations associated with opioid side effects- homozygous carriers of variant C>T experience greater pain relief than carriers of 1 C allel
Order of magnitude of CYPs on medication metabolism
CYP3A4>2C>1A2>2E1>2D6>2B6
CYP2D6 metabolizes which drugs related to anesthesia
Codeine, tramadol, oxycodone
CYP3A4/3A5 metabolizes which drugs related to anesthesia
Codeine, dihydrocodeine, fentanyl, tramadol, methadone, oxycodone, benzos, locals
Ultrarapid metabolizers
Variation in CYP2D6 (multiple copies)- therapeutic effects cannot be obtained at conventional doses
Extensive metabolizers
Normal enzyme activity in CYP2D6 (2 wild type alleles)
Intermediate metabolizers
Reduced metabolism by CYP2D6- one inactive allele and one wild type allele
Poor metabolizers
Increased risk of adverse side effects, therapeutic failure
What is epigenetics
Heritable changes in gene function not explained by differences in DNA sequence
What is the only syndrome 23&me can effect
Bloom syndrome–changes DNA copying & repair–higher risk of cancer
