Pharmacogenomics Flashcards
What are the three main mechanisms for pharmacogenetic differences?
alterations in drug metabolism, alterations in the target of the drug, and altered drug transport tissues
What are the two general outcomes for altered drug metabolism?
undesired effects and an inactive drug
What are the three types of undesirable effects of altered drug metabolism?
prolonged effect, toxic effect, and side effect
What is an example of something that can cause a prolonged drug effect?
portosystemic shunt
What is an example of a consequence of a toxic effect?
sulfonamides and Stevens-Johnson syndrome causing photosensitivity
What is an example of a drug side effect? (discussed in class)
enrofloxacin and depression in humans
What is the mechanism for acetaminophen toxicity in cats?
it is usually metabolized by glucuronidation and since cats are bad at that, the other metabolic conversions lead to electrophiles being formed resulting in hepatocellular injury
What is the evolutionary base for acetaminophen toxicity in cats?
acetaminophen is a phytoalexin and carnivores are not efficient at metabolizing plant derivatives
What are the two types of alterations in drug metabolism that an lead to treatment failures?
Toxic metabolite formed following drug metabolism
Unwanted, unrelated, unexpected side effect (non-toxic)
What are two outcomes related to alterations of a drug target?
no activity of the drug or drug side effect
How can erythromycin cause GI upset?
Erythromycin is a motilinR agonist for motolinR subtype A so patients with subtype A will develop this problem (other motilin R subtypes do not recognize erythromycin)
How can drug transportation differences be a double-edged sword?
bad -toxic accumulation
good - selective tissue distribution
What are the five overall outcomes of pharmacogenoomic differences?
toxicity, prolonged effect, unwanted effect, drug failure, exploitable
What are the pharmacological basesfor ivermectin toxicity in collies?
Collies have a mutated mdr1 gene. The mdr1 gene encodes for a large transmembrane protein that is an important part of the blood brain barrier pumping out drugs into the blood and therefore out of the brain. In collies, it is not flushed out of the brain due to the mutation
Describe how auto-active receptors present a pharmacologic problem.
the biochemical reaction is always going so the drug antagonist have no effects
