Module 5 Toxicology Patho

Question 1

Define toxicology

Answer 1

study of the adverse affects of chemical or physical agents on living systems

Question 2

toxin vs. toxicant

Answer 2

toxin is a poisonous substance produced by living cells while toxicant is a man-made chemical

Question 3

determine whether a specific activity/intervention is a descriptive, mechanistic, or regulatory toxicology

Answer 3

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

Question 4

local vs systemic, immediate versus delayed, and reversible versus irreversible toxic responses

Answer 4

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

Question 5

given a case of toxic exposure, identify three means by which toxic responses may be mitigated

Answer 5

1. Prevent/reduce exposure
2. Enhance elimination from body
3. Block/repair cellular effects

Question 6

given a case of toxic exposure, determine which of the three phases of toxic responses are ongoing

Answer 6

1. Exposure
2. Disposition
3. Toxicodynamics

Question 7

identify three levels of risk-benefit analysis that occur related to drug therapy

Answer 7

-accessibility (evaluates benefits/risks for the population)
-applicability (evaluates benefits/risks for a patient)
-acceptability (evaluates benefits/risks in terms of personal values)

Question 8

state the three elements of information needed for application of an Investigational New Drug with the Food and Drug Administration

Answer 8

-Animal pharmacology and toxicology, manufacturing information, and clinical protocol and investigator information

Question 9

Differentiate the No Adverse Effect Level and Minimal Anticipated Biological Effect Level for determining the first dose in man for an investigational drug

Answer 9

NOAEL- max level before no adverse effects are seen
MABEL- when an effect is observed

Question 10

identify primary reasons adverse drug events are often not detected until after the drug is approved and marketed for a period of time

Answer 10

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

Question 11

Provided key information about a potential pharmaceutical excipient–determine whether or not preclinical toxicology studies are needed for its inclusion in a dosage form

Answer 11

-if pick from GRAS, preclinical studies are not needed
-if want to develop new excipient, new ones would be needed

Question 12

name the five categories of preclinical studies typically completed in the development of a new drug

Answer 12

-Acute studies
-repeated dose studies
-genetic toxicity
-reproductive toxicity
-Carcinogenicity

Question 13

Given a patient response to drug, identify the nature of the adverse reaction (side effect, augmented response, or toxic response)

Answer 13

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

Question 14

identify the four determinants of toxic drug responses and provide an example of each

Answer 14

1. Individual susceptibility
2. Accessibility of Drug to Target
3. Compensatory Mechanisms
4. Reactivity of Drug with target

Question 15

given the mechanisms by which a drug provokes a toxic response, provide potential interventions to prevent or minimize the toxic response

Answer 15

mechanisms by which a drug provokes a toxic response: Cellular Dysfunction, Cellular Destruction, Genotoxicity

Question 16

given a cell type that experiences genomic damage, identify the likely clinical outcome

Answer 16

Somatic Cell- cancers
Germ cell- Birth defects/Childhood cancers
Developing Embryo- miscarriages, stillbirths, birth defects

Question 17

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

Answer 17

1-2 weeks is embryo death
3-8 weeks major congenital abnormalities
9-38 weeks functional defects and minor anomolies

Question 18

state the criteria for classification of an agent as a teratogen

Answer 18

1. exposure results in a characteristic set of malformations
2. Effect occurs with exposure at a specific stage of development
3. effect is dose-dependent

Question 19

Define drug-induced hypersensitivity

Answer 19

a low frequency serious adverse drug reaction with an immunological cause to an otherwise safe and effective therapeutic agent

Question 20

State the 4 key characteristics of DIHR

Answer 20

rare, unpredictable, complex and potentially fatal

Question 21

Distinguish between the two types of DIHR

Answer 21

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)

Question 22

State the two primary reasons most people who claim to have an allergy to penicillin actually tolerate the drug

Answer 22

-after 10 years many are not allergic anymore
-can lose immunological memory and tolerate it
-rash can be caused by concurrent viral infection

Question 23

State the two phases of delayed hypersensitivity reactions

Answer 23

Sensitization (prior exposure or repeated dosing) phase and Effector phase

Question 24

identify the most common organ effected by delayed hypersensitivity reactions

Answer 24

Skin

Question 25

state the time frame at which most drug eruptions occur

Answer 25

1 week?

Question 26

describe how DRESS is differentiated from other DIHR

Answer 26

internal organ involvement