Exam 3 Toxicology

Question 1

4 areas of study in toxicology

Answer 1

1. occupation safety
2. environmental toxicology
3. analytic toxicology
4. forensic toxicology

Question 2

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

Answer 2

biological variation

Question 3

term describing a greater than normal reaction to a drug

Answer 3

hypersusceptibility

Question 4

term describing the response of the patient to the drug when it is qualitatively different from the usual or expected response

Answer 4

drug idoiosyncrasy

Question 5

Geriatric patients have less ___ ___ (decreased plasma proteins), less _____ (decreased liver function) and decreased renal function which allows for normal doses of drugs to act at ____ levels. Give ___ dose

Answer 5

binding capacity
metabolism
overdose
lower

Question 6

In a pt with liver disease, drug ___ is reduced due to diminished function of ____ ____ system, dosing must be reduced.

Answer 6

metabolism

cytochrome P450

Question 7

In a pt with renal disease, renal impairment of ___ ___ occurs, dosing must be modified on the basis of renal ____ ___ of the drug

Answer 7

drug excretion

clearance values

Question 8

___ ____: increasing amounts of drug are required to produce a consistent effect, usually associated with drugs that cause ____ ____.

Answer 8

drug tolerance

physical dependence

Question 9

____: rapid development of tolerance

Answer 9

tachyphylaxis

Question 10

what does TD50/ED50 mean?

Answer 10

Therapeutic index
TD50 = dose of the drug that causes a toxic response in 50% of the popultion
ED50 = dose of the drug that is therapeutically effective in 50% of the population

Question 11

The therapeutic index provides a single number that quantifies the relative ____ of ___ of a drug in population of people. A large Ti represents a ___ therapeutic window and a small TI represents a ___ therapeutic window = requires monitoring

Answer 11

margin of safety
wide
narrow

Question 12

____ toxicity occurs as a result of a single, large ___ to the toxic agent. Effects are usually ____ within minutes to hours. Occasionally, signs of acute toxicity are not visible for ___ to ___ following the initial exposure.

Answer 12

Acute
exposure
visible
weeks to months

Question 13

____ toxicity = the effect of toxic insult that occurs over a ____ period of time. Often it is manifested after ___ of exposure. May also manifest long after the individual is no longer exposed to the ____.

Answer 13

Chronic
prolonged
years
toxin

Question 14

Study of the absorption, distribution, metabolism, and excretion of toxic parent compounds and metabolic products

Answer 14

toxicokinetics

Question 15

4 types of GI toxins

Answer 15

1. ingested
2. contaminants in food (mercury in fish)
3. majority of therapeutic agents (drugs)
4. lead in dirt and paint

Question 16

4 types of inhaled toxins

Answer 16

1. air pollutants
2. cigarette smoking
3. industrial chemicals
4. agents of chemical warfare

Question 17

What toxin can passively diffuse through the 7 layers of skin after prolonged contact?

Answer 17

insecticides

Question 18

8 mechanism of toxicity

Answer 18

1. Interference with cellular function
2. Macromolecular damage
3. Reactive species
4. inflam/immune mediated mechanisms
5. Enzyme/receptor mediated
6. Carcinogenesis
7. Teratogenesis
8. Organ directed toxicity

Question 19

What type of toxicity mechanism is described: carbon monoxide binds strongly to the iron in the active site of hemoglobin, preventing oxygen binding and reducing oxygen carrying capacity.

Answer 19

Receptor mediated

Question 20

What type of toxicity mechanism is described: nerve gasses/pesticides are acetylcholinesterase inhibitors which causes excessive concentration of ach in synaptic cleft resulting in slowed HR, difficulty breathing, sweating, pinpoint pupils

Answer 20

Enzyme mediated (common toxins interfere with NT, cardiac rhythm, oxygen deliver, ATP generation, or intracellular ca balance)

Question 21

What type of toxicity mechanism is described: cyanide binds to the heme iron in the active site of the enzyme cytochrome C oxidase causing reduction in the generation of ATP

Answer 21

Enzyme mediated (many compounds are toxic bc they alter important metabolic pathways, signaling pathways, or interact with critical receptors)

Question 22

What type of toxicity mechanism is described: toxins damage tissue by altering the structure of proteins, lipids, carbs, and nucleic acids so severely that cellular integrity is lost

Answer 22

macromolecular damage - tissue damaging agents are nonspecific

Question 23

What type of toxicity mechanism is described: React chemically with biologic macromolecules and other chemicals, more specific in their site of action, example: carbon tetrachloride

Answer 23

Reactive species - when carbon tetrachloride is metabolized by the liver, reacts with oxygen to form toxic organic free radicals which cause toxicity

Question 24

What type of toxicity mechanism is described: hypersensitivity and autoimmune reactions

Answer 24

Inflammatory and immune mediated mechanisms - the immune system removes cell damaged by toxins and releases immune mediators that are important in repairing tissue damage

Question 25

What type of toxicity mechanism is described: the transformation of a normal cell to a neoplastic cell

Answer 25

carcinogenesis - involves multiple genetic changes

Question 26

Development of cancer: Initiators damage ____, interfere with DNA replication or ___ mechanisms. Most initiators are ___ ___ that chemically modifies the structures of DNA, preventing accurate ____ which causes DNA _____. Mutations are passed along during cell ____.

Answer 26

``` DNA repair reactive species replication mutation replication ```

Question 27

Carcinogens can also promote the development of cancer by causing what?

Answer 27

chronic tissue damage in organs capable of tissue repair (alcoholism -> cirrhosis -> liver cancer)

Question 28

What type of toxicity mechanism is described: substances that can inhibit intracellluar signals are potent, they can induce a birth deft and also alter DNA or chromosomes

Answer 28

Teratogenesis - effect of any substance is dependent on the development timing of the exposure

Question 29

What type of toxicity mechanism is described: organs with regenerative capacity may recover after toxic exposure and organs with limited or no regenerative function lose function as tissue is destroyed from toxic exposure (heart/nerves)

Answer 29

Organ directed toxicity - blood brain barrier prevents many toxins from entering the CNS

Question 30

3 mechanisms of selected toxicity by drugs 1. Attack targets that are unique to the pathogen but are not ______ 2. Attack target in the pathogen or cancer cell that are similar ___________ 3. Attack targets in the pathogen/cancer cell that are shared _________

Answer 30

1. present in the host 2. but not identical to those in the host 3, by the host but that vary in importance between pathogen and the host

Question 31

Drugs exhibit the ____ toxicity when they target a ___ ___ between the pathogen and host cell Drugs exhibit the ___ toxicity when they target ___ ___ shared by both the pathogen and the host cell.

Answer 31

Least unique difference most common pathway

Question 32

A highly ___ drugs like penicillin is prescribed ___ because of the large difference between the therapeutic and ___ concentrations.Drugs that are less selective means that they affect both the pathogen and host cells and are ___ ___ and have a ____ therapeutic index.

Answer 32

``` selective safely toxic not safe narrow ```

Question 33

4 examples of unique targets (present in pathogen bu lacking in host)

Answer 33

1. metabolic pathways 2. enzymes 3. mutated genes 4. gene products

Question 34

_______: when the host and the pathogen share a common biochemical or physiologic pathway

Answer 34

Common targets - narrow therapeutic index

Question 35

With common targets their are adverse side effects, name 5

Answer 35

1. loss of hair 2. mouth sores 3. skin problems 4. GI problems 5. infertility

Question 36

drugs that affect only 1 phase of the cell cycle

Answer 36

cell cycle specific

Question 37

drugs that affect any/all phases of the cell cycle

Answer 37

cell cycle non specific (most antineoplastic drugs affect either S or M phase)

Question 38

3 phases of carcinogenesis

Answer 38

1. transformation 2. proliferation 3. metastasis