Exam1Lec5Pharmacokinetics Flashcards
As the concentration of a drug in contact with a tissue increases, what happens the magnitude of effect
Increases
What is EC 50 of a drug?
The concentration that produces one half the maximum efffect (Emax/2)
What does EC50 compare?
Potency of drug (x-axis) and Efficacy ( y-axis) of drugs with SAME RECEPTOR.
If the drug needs less concentration for same EC50=incr poteneny
What is KD?
Binding of the drug to a receptor. The KD of a drug is the concentration that produces one-half the maximum binding
The EC50 value for a response is often ____ than the Kd value, since there is often ____ between occupancy
smaller, amplification
Kd>EC50 b/c of amplification
What is an agonist?
Drug or ligand that binds to the same site as the endogenous ligand and produces a signal.
Agonsits can be ____ agonists or ____ agonists.
Full, partial
Full agonists have affinity for what?
Only for active state
Partial agonists have affinity for what?
Higher affinity only for active than inactive state. You wont reach 100%
still can bind to inactive state,
more than 50% effect but less than 100%
A ____ agonist can produce the greatest maximal response while the ____ agonsist produces a response that is less than a full agonist.
full, partial
What is potency?
Measurement of the amount of a drug needed to produce a given effect. It is used to differentiate between a series of compounds by comparing EC50 values
What would the most effacacious agonist do?
It would be the drug can produce the greatest maximum effect
ex: morphine is more effacacious than codeine
What is an antagonist?
A drug that binds to the site used by the endogenous ligand (or separate sire) and diminishes or blocks the signal produces by the endogenous ligand.
these inhibit the action of the agonst or receptor
Do antagonists initiate a response on their own?
NO AND IT DOESN’T CHANGE EQULIBRIUM OF ACTIVE TO INACTIVE
Are competitive antagonists reversible or irreversable?
reversible. You can incr the concentration of the agonist to overcome the antagonist to get the full effect. (on a graph, you see the sigmoidal curve shift to the right and its still reaching max effect)
compete for same binding site and whoever is at higher concentration dominates
Are non-competitive antagonists reversible or irreversable?
Irreversible, so it prevents the agonists, at any concentration from producing a maximum effect on a given receptor (on a graph, you see the sigmoidal curve move down)
What are inverse agonists?
Reduce the constitutive activity of a receptor
shifts the equilibrium to inactive state =decr.
What do inverse agonists have affinity for?
Only for inactive state and they shift equilibrium
What does continued stimulation of a receptor with its agonist result in?
A state of desensitization such that the effect that follows continued ot subsequent exposure to the same concentration drug is diminished.
What is an example of desensitization?
Attenuated response to the repeated use of beta-adrenergic agonits as branchodialtors for treatment if asthma.
also note for exapple that after you become desensitized, when you stop the drug, after some time, the effect of the drug incr again when taken again after stopping it
What happens to the number of receptors with continous or repeated exposure to an AGONIST?
decr the number of receptors
What happens to the number of receptors with continous or repeates exposure to an ANTAGONIST?
Incr the number of receptors.
Receptor desensitization and down regulation is often responsible for what?
Pharmacodynamic tolerance
What is pharmacodynamic tolerance?
Incr doses of drug are required to produce a given magnitude of effect. Also known as tachyphylaxis
Explain the concept of spare receptors?
A maximal apparent effect is achieved when a relatively small fraction of the receptors are occupied.
-Max effect with low number of receptors.
-more rececptors=more chance agonist will bind=full effect without occupying more receptors
What does the quantal dose-effect curve plot?
The number (percent) of indiv responding to the drug against dosage.
What is ED50 ?
Median effective dose
The median effective dose that causes 50% of individuals to respond.
gives us our therapeutic dose
What is TD50?
Median toxic dose
The dose that produces a toxic effect in 50% of individuals
What is LD50?
Medial lethal dose
The median lethal dose that kills 50% if the tested animals
Therapeutic index fomula
Therapeutic index=TD50/ED50
LD/ED for animals
For a drug to be safe what ratio do you want of TD50 and ED50?
High TD50 and Low ED50 so you can get a LARGE therapuetic index
Which is better
TD 50=10 and ED 50=1
OR
TD50=5 and ED50=2
TD 50=10 and ED 50=1
