Introduction to toxicology

Question 1

Define a toxin and toxicant

Answer 1

Toxin: From a biological source- animal, plant or bacteria
Toxicant: anthropogenic (human made)

Question 2

Define EC50, TC50, ED50, TD50, and LD50

Answer 2

EC50: concentration at which 50% of the maximal effect is observed
TC50: 50% of a toxic maximal effect is observed in cells
ED50: the dose at which 50% of the max therapeutic effect is observed
TD50: dose at which 50% of the max toxic effect is observed
LD50: dose at which 50% of subjects experience mortality

Question 3

What is the therapeutic index?

Answer 3

Ratio of TD50 to ED50

Question 4

Define NOAEL and LOAEL

Answer 4

NOAEL: no observed adverse effect level
LOAEL: lowest observed adverse effect level

Question 5

What causes most adverse reactions?

Answer 5

Dose related issues- increasing the dose increases the chance of observing an ADR

Question 6

What are non-dose related ADRs?

Answer 6

Allergic reactions: immune system mediated, can vary from skin rashes to anaphylactic shock
Idiosyncratic reactions: unexpected, abnormal reactions, often unexplained

Question 7

What are the 3 ways we can classify ADRs?

Answer 7

Their relationship to the therapeutic mechanism of action:

1) Extensions of the primary effect of the drug
2) Off-target effects
3) Reversibility

Question 8

What are off target effects?

Answer 8

Effects that are related to another mechanism of action that isn’t the therapeutic one.
Ex. promethazine, which causes sedation but also orthostatic hypotension since it is an a1 adrenergic receptor antagonist

Question 9

What are the three pathways acetaminophen is metabolized by? Which ones produce toxic metabolites?

Answer 9

Glucoronidation
Sulfation
CYP2E1+CYP3A4 (produces toxic metabolites)