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 duration
- The length of time Cp remains above the minimum effective concentration
- The higher the Cp the more intense the response until Emax is reached
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 are the pharmacodynamic interactions
a) Additive
- A combined effect of two drugs administered together (with same or different efficacy) thavt is equal to the sum of the individual responses
b) Synergism
- A combined effect of two drugs administered together (with some or different efficacy) that is greater than the sum of individual response
c) Potentiation
The increase in effect of one effective drug when it is taken with an ineffective drug
d) Antagonism
one drug decreases the effect of another drug
What type of interaction happens in each one
i) synergism
ii) potentiation
iii) additive
iv) antagonism
