Pharmodynamics I Flashcards
What is the difference between biological receptors and binding sites?
Biological receptors can bind substances AND initiate a subsequent response while binding sites only bind substances.
What kind of relationship is there between the fractional occupancy of a drug and the dose?
Non-linear
What relationship is there between the response and the dose?
Non-linear
What does the occupancy fraction depend upon?
- Affinity
- Concentration (of the dose)
Kd
Dissociation constant.
It is the concentration of drug required to bind HALF (50%) of the receptors.
What do small Kd values indicate?
High affinity for the receptor
ED50
Median effective dose.
The dose required to achieve a QUANTAL effect in 50% of the population.
Potency
Concentration necessary to produce 50% of a drug’s max response and is expressed as an EC50 or ED50 value
What does the potency of a drug depend on?
- Affinity which is the Kd
- Efficiency of the receptor interaction with the response
What does the clinical effectiveness of a drug depend upon?
Emax (maximal efficiency)
EC50
Half maximal effective concentration.
Concentration where 50% of its maximal effect is observed (GRADED)
-> Can be quantal, then it is ED50
When does EC50 = Kd?
When all spare receptors are bound
How does a competitive antagonist change the DR curve?
- Shifts it right
- Increases the ED50
- Emax remains the same
How does a non-competitive antagonist change the DR curve?
- Curve does not shift
- ED50 remains the same
- Decrease Emax
What happens to the DR curve with more spare receptors?
It gets steeper
How does competition with drugs occur?
Dynamic equilibrium is how the competition occurs.
Displacement does NOT occur with drugs on receptor.
What is the Fractional Occupancy equation?
F.O. = 1/( 1+(Kd/[D]) )
What happens to selectivity as drug dose is increased?
Selectivity will decrease.
The Dose-Response Relationship
This is the correspondence between the amount of drug and the magnitude of the effect; increasing the dose, increases the effect in a graded manner.
How do Full Agonists affect activity?
Efficacy = 100%
How do Partial Agonists affect activity?
Efficacy = 0 - X - 100%
How do Neutral Antagonists affect activity?
Efficacy = 0%
How do Inverse Antagonists affect activity?
0 > Efficacy
How do partial agonists affect the DR curve?
They compete with the normal agonist (drug) and bring the level of response below one.
“One + a half is less than one and a half”
Chemical Antagonism
Done via chemical inactivation of a drug
Physiologic Antagonism
The use of opposing pathways to antagonize the effects of a drug
Biologic Antagonism
One drug may affect the metabolism or pharmacokinetics of another drug
What is the quantal DR curve?
The relationship between drug dose and a SPECIFIED effect in a population of individuals
TD50
The dose required to get 50% of the population reporting this specific toxic effect
LD50
The dose required to achieve 50% mortality from toxicity
What is the therapeutic index?
Ratio of the TD50 or LD50 to the ED50
What is the therapeutic window?
This is the Dosage Range between the minimum effective therapeutic dose and the minimum toxic dose
What is the best assessment of drug toxicity?
Therapeutic window
