Principles of Toxicology

Question 1

Define the term “toxicology.”

Answer 1

the study of deleterious effects of physical chemicals or biological substances “toxins”; study of the interaction between poisons and living organisms

Question 2

Definite biologic variation.

Answer 2

range of response per dose (an individual may require a higher/lower dose to produce the desired effect

Question 3

Define hypersusceptibility

Answer 3

greater-than-normal reaction to a drug

Question 4

Define drug idiosyncracy

Answer 4

response of the patient to the drug that is qualitatively different from the usual or expected response

Question 5

Define pathological state

Answer 5

liver diseases (may diminish function of cytochromie P-450 system decreasing drug metabolism and necessitating lower drug dosing) renal diseases (results in impairment of drug excretion)

Question 6

Define tolerance

Answer 6

increasing amounts of drug are reuquired to produce a consistent effect (often associated w/addiction)

Question 7

Define tachyphylaxis

Answer 7

rapid development of tolerance (major example in dentistry is local anesthetic)

Question 8

Discuss the concept of the therapeutic index.

Answer 8

Therapeutic index = (TD50/ED50) and is a quantitative measure of the therapeutic window: Wide/large window is good and small window requires regular monitoring

Question 9

Explain the differences between TD50 and ED50.

Answer 9

TD50=dose of drug that causes toxic response in 50% of population and ED50=dose of drug that is therapeutically effective in 50% of the population

Question 10

Compare and contrast acute toxicity with chronic toxicity.

Answer 10

acute occurs as a result of a single, large exposure and chronic toxicity is the effect of toxic insults that occur over a prolongued period of time

Question 11

Discuss the pathophysiology of toxic exposures, as it relates to toxicokinetics.

Answer 11

toxins must cross an epithelial layer to be absorbed systemically (GI and respiratory tracts and skin are the 3 primary sites of absorption)

Question 12

Describe various mechanisms of toxicity related to macromolecular damage

Answer 12

toxins damage tissues by altering the structure of proteins, lipids, carbohydrates and nucleic acids so severely that cellular integrity is lost (tissue-damaging agents are non-specific)

Question 13

What are some examples of enzyme-mediated toxicity?

Answer 13

nerve gases and pesticides are acetylacholinesterase inhibitors; cyanide binds to the heme ion in the active site of cytochrome C oxidase thereby preventing generation of ATP

Question 14

What is an example of receptor-mediated toxicity?

Answer 14

Carbon monoxide binds strongly to the iron in the active site of hemoglobin preventing oxygen binding.

Question 15

What are three methods of selective toxicity?

Answer 15

attack targest unique to pathogen/cancer cell that are not present in the host, targets that are similar but not identical to those in the host and targets that are shared by the host but vary in importance.

Question 16

With respect to selective toxicity, when do drugs exhibit the least/most toxicity?

Answer 16

least: when they target a unique difference between pathogen/cancer cell and normal host; most: when they target common pathways

Question 17

Discuss 3 mechanisms of selected toxicity by drugs.

Answer 17

interference with cellular/molecular functions, forming species that react with biological macromolecules, generating inflammatory or immune responses

Question 18

Describe the relationship between selective drug toxicity to the Therapeutic Index and range of the therapeutic window.

Answer 18

highly selective drugs (like penicillin) may be prescribed safely because of the large difference between the therapeutric and toxic concentrations

Question 19

Give examples of common targets that are associated with adverse drug effects.

Answer 19

GI (diarrhea), sex cells (infertility), skin problems, mouth sores, loss of hair