Introduction Flashcards
define orphan receptors:
receptors with no know endogenous ligand
Immediate (acute) vs delayed (chronic)
acute example would be like an acute poisoning where as delayed would be cancer. Most cansers take 10-20 years to progress.
define setereoisomers?
have the same molecular formula but can have very different effects
the affinity of a xenobiotic for a receptor depends on what?
its chemical structure (stereochemistry)
What are the spectrum of toxic effects.
- Local vs systemic
- Reversible vs irreversible
- Immediate (acute) vs delayed (chronic)
- Morphological, functional, and biochemical effects. 5. Allergic Vs idiosyncratic reactions
- Graded (continous) vs quantal (all-or-none) responses.
define toxicodynamics?
Toxicodynamics is essential what the xenobiotic does to the body—the effect, response.
Risk assessment of a toxicant has 4 steps:
- identification of a hazard 2. exposure and dose response 3. mechanisms of toxicity 4. predict if adverse effects do occur
describe functional effect?
biological functions are effected like reproduction or kidney functions!
Nuclear receptors:
sterpid and thyroid hormones bind here and is located by the nucleus.
what are all the receptors in this image?
- G protein coupled receptors
- Nuclear receptors
- Tyrosine kinase coupled receptors
- Ion channel receptors
decsribe the difference bewteen the spectrum of toxic effects between local vs systemic
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.
what physical factors could influence toxilogical effects?
- Temperature. 2. barometric pressure 3. Photoperiod 4. electromagnetic readiation 5. cell phones?
Tyrosine kinase- coupled receptors
similar to G protein but the enzyme is actually built into the receptor.
what is a good example of stereoisomers?
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.
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
:)
- Presystemic elimination
- Distribuiton away from target
- Excretion
- Detoxification
:(
- Absorption
2 Distribution toward target
- reabsorption
- toxication
what is a broader definition for receptors?
Enzymes, transport proteins, nucleic acids, structural proteins, membrane lipids
describe the comparison between allergic vs idiosyncratic?
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.
describe the significance of receptor subtypes?
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
compare graded vs quantal responses
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.
Define receptors:
Cellular proteins that normally serve as receptors for endogenous ligands (e.g. hormones, neurotransmitters, cytokines)
what are modifying factors of toxicity? what are the two most important ones?
- Dose
- Duration and frequency of exposure
- Species, strain, individual
- Gender, pregnancy
- Age
- Nutritional status
- Disease
- Physical (environmental) factors
- social factors
what does the ultimate toxicant do?
it interacts with the target molecule
Many xenobitoics cause their :) and :( by interacting with ————
receptors
describe biochemical effects?
biochemical effects are often used as biochemical markers in toxicity and can act as early warnings!
Big picture question: a xenobiotic gets absorbed into a cell, what are the different events that can happen?
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.
the terattogenic activity of thalidomide is —————-
stereoselective.
Ion channel receptors:
involved in the essential electrolytes or ions into the cell
describe two dynamic natures of receptors?
- Receptors can be desensitized. The main way this occurs is by down regulation. ex.) drugs of abuse.
- Occassionally, receptors can be up-regulated as well but this is very rare.
Draw out the 4 step scheme:
in terms of age who is more susceptible?
young and very old
Describe morphological effect:
would be like thalidomide with babies with no arms. It is a super obvious effect. Can be less noticeable in cellular or tissue morphology.
why are mechanisms underlying the toxicity of a particular xenobiotic helpful and important?
- Improves risk assessment to human health
- Defining high-risk subgroups in human populations
- Defining threshold exposure level for toxic compound including carcinogenic compounds
- Guiding and accelarating the development of safer pharmaceutical drugs.
- Developing antidotes for prevention of acute intoxications.
- developing targeted approaches for the treatment of diseases and develping therapeutic measures in chemically induced toxicity.
- understanding and preventing drug-drug interactions
- Developing biomarkers
- Targeting and selectively killing cells or tissues.
define G protein coupled receptors:
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.
what is an example of social factors?
crowding, when humans or lab animals are crowded it makes toxicological effects worse. Related to stress.
compare Reversible vs irreversible mechanisms of toxicity
Reversible effects are shorter doses at short time periods. Ireversible are larger doses for long time periods.
how does thalidomide cause birth defects?
binds to and blocks promotore region of specifc genes involved in angiogenesis and limb bud development.
what are three examples of orphan receptors?
- Opiod receptors
- cannabinoud receptors
- aryl hydrocrabon receptor (AhR)
