8 Drug Toxicity Flashcards
What is a therapeutic index?
toxic dose/ therapeutic dose
-the higher the number the better
What is on target adverse effects?
- drug binding to its intended receptor
- adverse effect may be exaggeration of intended action - duration of drug
ex. anti-psychotics-tardive dyski
What happens with off target adverse effects?
drug binds to
off target within same cell
intended target on different cell
off target on different cell
WHat is an example of an off target adverse effect?
- anti histimine terfenadine-H1 angonist-theraputic stie
- binds to herG )potassium channels and inhibits potassium currents
- increasing hr corrected QT interval
- arrhythmias and death
- all new drug candidates tested for binding to herG initro and if makes it to clinical trial evaluated for ability to prolong QT interval
2. non selective b-blockers contraindicated in asthmatics
3. Enantiomers–>morning sickness-Presently enantiomers are evaluated by FDA as separate entities
What are idiosyncratic effects?
unknown cause -not seen in practical or clinical trials
- linked to genetic polymorphisms
- if cause organ failure or death-drugs removed from market
What factors affect drug toxicity?
- interaction absorption
- interaction with protein binding
- interaction of metabolism
- interaction of receptor binding
- interaction of therapeutic
What is interaction of absorption?
A drug may cause increase or decrease in absorption of a second drug from the intestinal lumen
What is acetaminophen primary metabolized by? What is a small amount metabolized by? What are the two byproducts of this? How does alcohol affect this?
- primarily metabolized in phase 2 by
1. glucuronidation
2. sulfation - small amount met by CYP2E1 to NAPQ1
- NAPQ1 can go to excreted from using GSH or it can go to a metabolite that causes cell death
- alcohol consumption can induce expression of CYP2E1
What is potentiation?
creation of a toxic effect from one drug due to presence of another drug ?
-enhance agonist binding to site of action-PAM (positive allosteric modulator)
What is antagonism?
interference of one drug with the action of another
What is functional antagonism?
two drugs have opposite effects on the same physiological function
What is chemical antagonism?
chemical reaction between two drugs to neutralize their effects-chelation therapy
What is dispositional antagonism?
alter absorption/distribution/excretion so that less drug gets to the site of action
What is receptor antagonism?
block drug binding to receptor with another drug
What are the four types of hypersensitivity reactions?
type 1-allergic
type 2-antibody directed against self tissue antigens
type 3-immune complex mediated disease
type 4-delayed hypersensitivity
