Module 5 Toxicology Patho Flashcards
Define toxicology
study of the adverse affects of chemical or physical agents on living systems
toxin vs. toxicant
toxin is a poisonous substance produced by living cells while toxicant is a man-made chemical
determine whether a specific activity/intervention is a descriptive, mechanistic, or regulatory toxicology
descriptive- area of focus in toxicology which is concerned with determining the toxic responses to agents
mechanistic- area of focus in toxicology concerned with determining why (how) agents provoke a toxic response
regulatory- area of focus in toxicology that is concerned with assessing the risks of toxic substances and determining how that risk is best managed
local vs systemic, immediate versus delayed, and reversible versus irreversible toxic responses
local- effect is observed at portal of entry
systemic- effect is observed at site distant from contact/portal of entry
immediate- seconds to hours
delayed- days to years
reversible- effect stops after stopping exposure
irreversible- effect persists after stopping exposure
given a case of toxic exposure, identify three means by which toxic responses may be mitigated
- Prevent/reduce exposure
- Enhance elimination from body
- Block/repair cellular effects
given a case of toxic exposure, determine which of the three phases of toxic responses are ongoing
- Exposure
- Disposition
- Toxicodynamics
identify three levels of risk-benefit analysis that occur related to drug therapy
-accessibility (evaluates benefits/risks for the population)
-applicability (evaluates benefits/risks for a patient)
-acceptability (evaluates benefits/risks in terms of personal values)
state the three elements of information needed for application of an Investigational New Drug with the Food and Drug Administration
-Animal pharmacology and toxicology, manufacturing information, and clinical protocol and investigator information
Differentiate the No Adverse Effect Level and Minimal Anticipated Biological Effect Level for determining the first dose in man for an investigational drug
NOAEL- max level before no adverse effects are seen
MABEL- when an effect is observed
identify primary reasons adverse drug events are often not detected until after the drug is approved and marketed for a period of time
extreme adverse effects would not be picked up in a population study of phase I-III trials (size is too small), duration also a factor
Provided key information about a potential pharmaceutical excipient–determine whether or not preclinical toxicology studies are needed for its inclusion in a dosage form
-if pick from GRAS, preclinical studies are not needed
-if want to develop new excipient, new ones would be needed
name the five categories of preclinical studies typically completed in the development of a new drug
-Acute studies
-repeated dose studies
-genetic toxicity
-reproductive toxicity
-Carcinogenicity
Given a patient response to drug, identify the nature of the adverse reaction (side effect, augmented response, or toxic response)
Side Effect- off target response, marginal impact on health, impacts patient compliance
Augmented Responses- extension of pharmacologic effect, dose-dependent, bradycardia with propranolol
Toxic reactions- not predicted from pharmacology of drug, can seriously impact health
identify the four determinants of toxic drug responses and provide an example of each
- Individual susceptibility
- Accessibility of Drug to Target
- Compensatory Mechanisms
- Reactivity of Drug with target
given the mechanisms by which a drug provokes a toxic response, provide potential interventions to prevent or minimize the toxic response
mechanisms by which a drug provokes a toxic response: Cellular Dysfunction, Cellular Destruction, Genotoxicity
given a cell type that experiences genomic damage, identify the likely clinical outcome
Somatic Cell- cancers
Germ cell- Birth defects/Childhood cancers
Developing Embryo- miscarriages, stillbirths, birth defects
provided a specific gestational stage for a woman, identify whether a teratogen is likely to result in 1. embryo death 2. major congenital anomalies 3. functional defects and minor anomalies
1-2 weeks is embryo death
3-8 weeks major congenital abnormalities
9-38 weeks functional defects and minor anomolies
state the criteria for classification of an agent as a teratogen
- exposure results in a characteristic set of malformations
- Effect occurs with exposure at a specific stage of development
- effect is dose-dependent
Define drug-induced hypersensitivity
a low frequency serious adverse drug reaction with an immunological cause to an otherwise safe and effective therapeutic agent
State the 4 key characteristics of DIHR
rare, unpredictable, complex and potentially fatal
Distinguish between the two types of DIHR
classified as immediate hypersensitivity (within 1 hour, Type I, IgE-mediated) or delayed hypersensitivity (Occurs over an hour, Type IV or III, T cell-mediated)
State the two primary reasons most people who claim to have an allergy to penicillin actually tolerate the drug
-after 10 years many are not allergic anymore
-can lose immunological memory and tolerate it
-rash can be caused by concurrent viral infection
State the two phases of delayed hypersensitivity reactions
Sensitization (prior exposure or repeated dosing) phase and Effector phase
identify the most common organ effected by delayed hypersensitivity reactions
Skin
state the time frame at which most drug eruptions occur
1 week?
describe how DRESS is differentiated from other DIHR
internal organ involvement
