Lecture 8+9: Toxicology Flashcards
Toxin
-poisonous substance from living thing
Toxicology
-study of adverse effects of agents on living systems
toxicant
man-made chemical introduced to environment
Risk assessment
-regulatory toxicology (safety)
-mechanistic toxicology (why)
-descriptive toxicology (is it toxic)
types of toxic responses
-local vs systemic
-immediate vs delayed
-reversible vs irreversible
Phases of toxic response
-exposure
-disposition
-toxicodynamics
Mitigation of toxic responses
-prevent exposure
-enhance elimination
-block/repair effects
OAEL (observable adverse effect level)
-LOAEL: lowest
-NOAL: no
LOAEL
-lowest observable adverse effect level
-lowest dose where toxicity starts
NOAEL
-no observable adverse effect level
-highest dose at which no toxicity
Variability in response
-resistant vs sensitive individuals
-set exposure levels where even sensitive individuals will be okay
-fuck pregnant ppl tho
Toxicology and Public policy
-BAC
Levels of risk-benefit analysis
-accessibility
-applicability
-acceptability
Accessibility
FDA evaluates risk for population
applicability
provider to patient
acceptability
patient to self
Investigational new drug (IND)
-filed after early discovery and preclinical development
-followed by 4 phases (NDA filed after phase III)
elements required for IND
-animal pharma and toxicology
-manufacturing information
-clinical protocol and investigator information
objective of preclinical toxicology studies
-limit risk to humans in administration of new agent
preclinical studies
-acute (effect of one dose)
-repeated dose
-genetic toxicity
-reproductive toxicity
-carcinogenicity
How to predict first dose of new drug
- determine NOAEL in animal
- calculate human equivalent dose (HED)
- determine safety factor
- divide HED by safety factor
MRSD
-max recommended starting dose
-window between NOAEL and MABEL
-safety factor based on risk
Minimal anticipated biological effect level (MABEL)
-guide first dose
-pharmacology instead of toxicology
Why adverse effects are missed
- rare events vs study participants
- common events vs duration (age)
