Chapter 3 lecture 3-4 Flashcards
What is the difference between toxicokinetics and toxicodynamics?
- Toxicokinetics: What we do to the chemical
- Toxicodynamics: what the chemical does to us
The _ and _ of exposure is an important determinant of the ultimate dose
The route and duration of exposure is an important determinant of the ultimate dose
What are the 4 major routes of exposure/administration?
- GI tract
- Lungs
- Skin
- Other paprental routes
Compare the speed and degree of effect between
* Intravenous Injection
* Oral/dermal exposure
- Intravenous Injection: exact amount will reach target organ, quickest, cuz blood directly take chemical to organ
- Oral/dermal: there must be metabolism lost, lose effect
What are the 6 frequencies of exposure to toxic substances?
different from the toxicity in lecture 1
- Acute exposure
- Sub-acute
- Sub-chronic
- Chronic
- Life-time
- Exposures over generations
What is acute exposure?
- a single exposure to a chemical for less than 24 hours
- Repeated dose within 24 hrs also count
What is sub-acute exposure?
- Must be 13-40 doses
- Over a period of days, < 30 days
What is Sub-chronic exposure?
The repeated doses spreading 1-3 months
What is chronic exposure?
- The exposure > 3 months
- < lifetime, but experimental settings usually close to the expected lifetime
What is life-long exposure?
Repeated dose/ continuous throughout the whole lifespan.
What is exposures over generations?
- Impaired reproductive cabibility/
- genetically mediated damage
- the exposure can be maintained over several generations
What is the definition of dose?
The amount of a substance
administered at one time.
What are the other parameters that are needed togeteher with dose?
- no. of dose
- frequency
- Total time period
Why do we fractionate a total dose?
- To decrease the probability that the total dose will cause toxicity
- Body can repair the effect of each subtoxic dose in sufficient time
Why do we fractionate a total dose?
- To decrease the probability that the total dose will cause toxicity
- Body can repair the effect of each subtoxic dose in sufficient time
The clinical and toxic effects of a dose must be
related to _ and _.
The clinical and toxic effects of a dose must be
related to age and body size.
Why children and adult cannot recieve the same dose?
- Due to different metabolic rate
- Kids dun have much ability to detoxify the drug
A common dose measurement is mg/kg
Describe dose response
It correlates exposure with the spectrum of induced effects
By what ways can the dose-response relationship be determined?
Based on experimental animals, human clinical
NOT CELL STUDY CUZ CAN’T SHOW WHATS HAPPENING TO WHOLE BODY
What can dose-response relationship tell?
- establishes causality that the chemical has in fact induced the observed effects
- establishes the lowest dose where an induced effect occurs -the threshold effect
- determines the rate at which induced effect builds up - the slope for the dose response.
How to explain the variability within population?
Bell-shaped normal distribution curve.
What is the shape for the dose-response curve?
Sigmoidal shape
What is threshold value?
The point at which toxicity first appears
What does the threshold of toxic effect mean?
The ability to detoxify or repair injury has been exceeded.
eg: The development of cirrhosis needs 50% of liver replaced by firbous tissue.
To estimate acute toxicity, LD50 can be used. What is the meaning of this?
The dose at which 50% of the individuals will be expected to die
What is the difference between LD0 and threshold?
LD0: The dose at which no individuals are expected to die
Threshold: The dose at which toxicity has begun/first appears
What is Effective dose?
EDs are used to indicate the effectiveness
of a substance.
What is toxic dose?
TDs are utilized to indicate doses that cause adverse toxic effects.
ED is only used to describe toxic effect, T/F?
F
What is Therapeutic Index (TI)?
compare the
therapeutically toxic dose to the effective dose .
TD50/ED50
A statement of relative safety of a drug
TI can be used for drugs/ toxic substance?
Drugs, therapeutic
What does small/large TI indicate?
- A large TI indicates a safer drug
- A smaller TI indicates a more dangerous drug
Why TI can be misleading?
- It conly consider the slope for the response curves
- It does not take concentraton into consideration
What is MOS-Margin of Safety?
MOS = LD01/ED99
What does the extent of MOS value indicate?
Pharmist mus be considerate to prescribe drugs with MOS <1
NOAEL, LOAEL and Threshold are actual data point. T/F
True
What is NOAEL?
- No observed adverse effect level
- Highest data point at which there wasn‘t an observed adverse effect
What is LOAEL?
- Low observed adverse effect level
- The lowest datapoint at which there was and observable adverse effect
What substance gives a u shape dose response curve?
Inverted dose relationship
Vitamins
What substance gives a u shape dose response curve?
Inverted dose relationship
Vitamins
What is potentiation?
where one chemical/drug enhances the
effect of another
Substance A is not toxic by itself, but can enhance toxic effect of substance B
What is antigonism
The opposite effect where one compound
blocks or reduces the effect of the other
antidotes
Recall the example of naloxone and heroin
The receptor antagonist naloxone binds competitively to the receptor for opiate narcotics, thus reducing the toxic effects of heroin.
Describe what additivity is.
the combined effect of two or more chemicals is equal to the sum of the individual effects.
Describe what synergism is.
A toxicity that is greater when two compounds are
given simultaneously or sequentially than would be
expected from a consideration of the toxicities of
the compounds given alone.
