9 Pharmacodynamics Flashcards
binding site bs receptor?
binding site-can bind substance but are not themselves capable of initiating response
receptor-can bind a substance and are capable of initiating a subsequent response
What is the percentage of receptors occupied dependent on?
the drugs
- affinity
- concentration
What does KD=
[D][R]/[DR]
What KD will drugs that have high affinity for receptors have?
low Kd values
WHat does KD the affinity constant represent ?
the concentration of that drug required to occupy 50% of a receptor population
What is the fractional occupancy equation tell you? What is it
-the binding of drugs to a receptor, dependent on drug affinity and drug concentration
1/(1+(KD/[D]))
How many log KD units to get to 91% occupied?
3 log units of concentration to occupy 91% of receptors
What is the magnitude of the response a function of?
some function f of the total number of receptors occupied
Does selectivity decrease as a dose increases?
yes
What is the dose response relationship?
increasing the dose increases the effect in a gradual manner but not right
What is potency?
the concentration or dose of a drug needed to produce 50% of that drugs maximal response
What is maximal efficacy?
-the maximal response produced by the drug
Can biological activity be determined from fractional occupancy?
no!
equal affinity but different biological activity
Are efficacy and potency independent properties of a drug?
yes
What is the clinical effectiveness of a drug dependent on?
Maximal efficacy (Emax) not potency (ED50)
To determine spare receptors you can take away number of total receptors, how can you tell when you exceed the reserves?
you see a reduction in E max
so like if it takes 20 receptors for E max and you take 10 away from 20 you cant get to Emax
Competitive antagonism
Surmountable!
- shift to the right in the DR Curve
- increases ED50
- No change in Emax
Competitive Antagonism
Insurmountable
-decrease Emax
-no change in ED50
(bad drug taking receptors and good drug has no reserves)
What is antagonism by partial agonists?
1+1/2 is less than 1
-decreases total response by decreasing full agonist component
What is chemical antagonism, physiological antagonism, and biologic antagonism?
chemical-chemical inactivation of drug
physiologic- opposing pathways to antagonize the effects of a drug
biologic-drug may affect metabolism of another drug
What is the quantal dose response curve?
the relationship between drug dose and a specified effect in a population of individuals
-cumulative frequency distribution of doses of a drug that produce a specified effect
What is the ED50 in the quantal dose response curve?
-median effective does
How do you know an index of selectivity from a quantal dose response curve/
comparing ED50 for specified effects
What can you compare on an quantal dose response curve to estimate the degree of safety for a drug for a specified effect? (therapeutic index )
LD50/ED50
