Introduction

Question 1

define orphan receptors:

Answer 1

receptors with no know endogenous ligand

Question 2

Immediate (acute) vs delayed (chronic)

Answer 2

acute example would be like an acute poisoning where as delayed would be cancer. Most cansers take 10-20 years to progress.

Question 3

define setereoisomers?

Answer 3

have the same molecular formula but can have very different effects

Question 4

the affinity of a xenobiotic for a receptor depends on what?

Answer 4

its chemical structure (stereochemistry)

Question 5

What are the spectrum of toxic effects.

Answer 5

1. Local vs systemic
2. Reversible vs irreversible
3. Immediate (acute) vs delayed (chronic)
4. Morphological, functional, and biochemical effects. 5. Allergic Vs idiosyncratic reactions
5. Graded (continous) vs quantal (all-or-none) responses.

Question 6

define toxicodynamics?

Answer 6

Toxicodynamics is essential what the xenobiotic does to the body—the effect, response.

Question 7

Risk assessment of a toxicant has 4 steps:

Answer 7

1. identification of a hazard 2. exposure and dose response 3. mechanisms of toxicity 4. predict if adverse effects do occur

Question 8

describe functional effect?

Answer 8

biological functions are effected like reproduction or kidney functions!

Question 9

Nuclear receptors:

Answer 9

sterpid and thyroid hormones bind here and is located by the nucleus.

Question 10

what are all the receptors in this image?

Answer 10

1. G protein coupled receptors
2. Nuclear receptors
3. Tyrosine kinase coupled receptors
4. Ion channel receptors

Question 11

decsribe the difference bewteen the spectrum of toxic effects between local vs systemic

Answer 11

Systemic is like the systemic circulation. Vast majority of xenobiotics has to get into your blood stream to cause effects. Local toxic effects are more rare. Acid burning a hole in your arm is a local effect.

Question 12

what physical factors could influence toxilogical effects?

Answer 12

1. Temperature. 2. barometric pressure 3. Photoperiod 4. electromagnetic readiation 5. cell phones?

Question 13

Tyrosine kinase- coupled receptors

Answer 13

similar to G protein but the enzyme is actually built into the receptor.

Question 14

what is a good example of stereoisomers?

Answer 14

Dextromethorpan is the same chemical formula as codeine but we cannot sell it over the counter because it does not decrease pain or get us addicted, it is just a cough suppressant.

Question 15

Once we are exposed to a xenobiotic is this delivery phase of ADME: what are for happy face pathways and 4 sad face pathways during the delivery phase

Answer 15

:)

1. Presystemic elimination
2. Distribuiton away from target
3. Excretion
4. Detoxification

:(

1. Absorption

2 Distribution toward target

3. reabsorption
4. toxication

Question 16

what is a broader definition for receptors?

Answer 16

Enzymes, transport proteins, nucleic acids, structural proteins, membrane lipids

Question 17

describe the comparison between allergic vs idiosyncratic?

Answer 17

idiosyncratic reactions are things we do not understand.d They are unexplinable genetically based adverse response. Very rare. Allergies are the immune system working good but on the wrong thing.

Question 18

describe the significance of receptor subtypes?

Answer 18

receptors can have alpha and beta adrenergic receptors. Even with these sub types there are alpha 1, and alpha 2 and beta 1 and beta 2. Depending on which subtype it binds to it can create very different responses. If norepinephrine binds t alpha 1 receptors the response is vasconstriction and increases blood pressure but if it bids to beta 2 receptor you get vasodilation

Question 19

compare graded vs quantal responses

Answer 19

graded like growth of enzyme activity. It is a continous response. Quantal is an all or none response like death, pregnant. do you have an arm? yes or no answers.

Question 20

Define receptors:

Answer 20

Cellular proteins that normally serve as receptors for endogenous ligands (e.g. hormones, neurotransmitters, cytokines)

Question 21

what are modifying factors of toxicity? what are the two most important ones?

Answer 21

1. Dose
2. Duration and frequency of exposure
3. Species, strain, individual
4. Gender, pregnancy
5. Age
6. Nutritional status
7. Disease
8. Physical (environmental) factors
9. social factors

Question 22

what does the ultimate toxicant do?

Answer 22

it interacts with the target molecule

Question 23

Many xenobitoics cause their :) and :( by interacting with ————

Answer 23

receptors

Question 24

describe biochemical effects?

Answer 24

biochemical effects are often used as biochemical markers in toxicity and can act as early warnings!

Question 25

Big picture question: a xenobiotic gets absorbed into a cell, what are the different events that can happen?

Answer 25

The xenobitoic can then be pumped out of cell :). Or it can interact with a cellular molecule and have toxicodynamics. This can cause toxicity disruption of function or structure. This can result in function failure, cell failure, organ failure etc.

Question 26

the terattogenic activity of thalidomide is —————-

Answer 26

stereoselective.

Question 27

Ion channel receptors:

Answer 27

involved in the essential electrolytes or ions into the cell

Question 28

describe two dynamic natures of receptors?

Answer 28

1. Receptors can be desensitized. The main way this occurs is by down regulation. ex.) drugs of abuse.
2. Occassionally, receptors can be up-regulated as well but this is very rare.

Question 29

Draw out the 4 step scheme:

Answer 29

Question 30

in terms of age who is more susceptible?

Answer 30

young and very old

Question 31

Describe morphological effect:

Answer 31

would be like thalidomide with babies with no arms. It is a super obvious effect. Can be less noticeable in cellular or tissue morphology.

Question 32

why are mechanisms underlying the toxicity of a particular xenobiotic helpful and important?

Answer 32

1. Improves risk assessment to human health
2. Defining high-risk subgroups in human populations
3. Defining threshold exposure level for toxic compound including carcinogenic compounds
4. Guiding and accelarating the development of safer pharmaceutical drugs.
5. Developing antidotes for prevention of acute intoxications.
6. developing targeted approaches for the treatment of diseases and develping therapeutic measures in chemically induced toxicity.
7. understanding and preventing drug-drug interactions
8. Developing biomarkers
9. Targeting and selectively killing cells or tissues.

Question 33

define G protein coupled receptors:

Answer 33

hormones bind to receptor that causes this cascading effects. These receptors are located on the cell membrane because hprmones are water solbule and cannot get into the cell.

Question 34

what is an example of social factors?

Answer 34

crowding, when humans or lab animals are crowded it makes toxicological effects worse. Related to stress.

Question 35

compare Reversible vs irreversible mechanisms of toxicity

Answer 35

Reversible effects are shorter doses at short time periods. Ireversible are larger doses for long time periods.

Question 36

how does thalidomide cause birth defects?

Answer 36

binds to and blocks promotore region of specifc genes involved in angiogenesis and limb bud development.

Question 37

what are three examples of orphan receptors?

Answer 37

1. Opiod receptors
2. cannabinoud receptors
3. aryl hydrocrabon receptor (AhR)