Module 2C Flashcards
What is pharmacodynamics
- The study of drug plasma concentration vs effect (dose- response) graphs
- Linear until receptors start to saturate
Compare drug-receptor interaction vs dose response curve
Drug receptor interactions
- B: bound fraction
- Bmax: total concentration of receptor sites (maximum binding capacity)
- Kd: concentration of free drug at half life-maximal binding (reciprocal relationship to affinity)
- C= free drug concentration
Dose- response curve
- E: effect or response
- Emax: maximum biological response
- EC50: unbound drug concentration that produces 50% maximal response
- C= unbound drug concentration
Similarities of drug-receptor interaction vs dose response curve
- Follow the same mathematical model for calculation
- As [D] increase drug effect increase in direct proportion until diminishing increases until no further increase in drug effect occurs (asymptote) even though [D] increases
Where are calculations more found
in hospital pharmacy
How can we do calculations safely
- Extent of the biological response is proportional to the number of receptors occupied by drug
- Max biological response is achieved when all receptors are occupied
- Binding of a drug to the receptor does not change the affinity of receptor for another drug
What is interindividual variable captured within
a) Differences in drug concentration that reaches receptor
- Variation in PK processes influence the unbound concentration of the drug
b) Variation in the concentration of an endogenous ligand
- Relevant for drugs that antagonize the function of endogenous agonists
c) Alterations in the function or number if receptors
- Genetics influence receptor number/ efficiency
- Different races don’t have different number of pain receptors
d) Changes in components of response other than at receptor
- Signal transduction or any response downstream
What is saturation
- Full receptor occupation
Efficacy
- The maximum response achievable (Emax)
- Magnitude of response
Potency
- A comparison of the concentration of drug needed to get a response in 50% of patients
What does a High/ Low EC50 mean within potency
a) High EC50: low potency
- You need a high drug concentration to achieve effect in 50% of patients
b) Low EC50: high potency
- You don’t need very much drug to see an effect in half of patients
What are the therapeutic outcomes (response)
- Onset
- Duration
Intensity of response
- Duration
What is the therapeutic window
- The range of drug plasma concentration (Cp) which produces desired clinical response in a patient
What is onset
- The length of time it takes for sufficient number of receptors to be occupied
What is the quantal dose response
- The response is all or nothing (yes or no)
- The curve is proportional or a percentage of individuals who exhibit a pre defined effect as a function of log dose
- Characterized by an ED50 value (dose where 50% of individuals exhibit the specific quantal effect
What is the graded dose response
- Intensity of response varies with dose or concentration
- Linear relationship between 20-80% of effect, maximal response is reached
Shape of the graph arise dependent upon potency and efficacy
- Linear relationship between 20-80% of effect, maximal response is reached
Which drugs are more potent and effective
i) potency: drugs 1 and 2 are more potent as they have lower EC50 values
ii) drugs 2,3,4 are more effective as they have a higher Emax
What type of interaction happens in each one
i) synergism
ii) potentiation
iii) additive
iv) antagonism
