1. Drug-Receptor Interaction
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture-3
September 20, 2011

2. Dose Response Relationship
To understand drug–receptor interactions, it is necessary to quantify the relationship between the drug and the biological effect it produces
Since the degree of effect produced by a drug is generally a function of the amount administered, we can express this relationship in terms of a dose–response curve
Because we cannot always quantify the concentration of drug in the biophase in the intact individual, it is customary to correlate effect with dose administered

3. Dose Response Relationship
When a graded dose–response relationship exists, the response to the drug is directly related to the number of receptors with which the drug effectively interacts
The principles derived from dose–response curves are the same in animals and humans
However, obtaining the data for complete dose–response curves in humans is generally difficult or dangerous

4. Quantal Relationship
In addition to the responsiveness of a given patient, one may be interested in the relationship between dose and some specified quantum of response among all individuals taking that drug
Such information is obtained by evaluating data obtained from a quantal dose–response curve
Anticonvulsants can be suitably studied by use of quantal dose–response curves
The construction of a quantal dose–response curve requires that data be obtained from many individuals

5. Quantal Dose-Response Curve: Effective Dose
The quantal dose–response curve represents estimates of the frequency with which each dose elicits the desired response in the population
This is done through
the calculation of an
ED50, the dose that
would protect 50%
of the animals

6. Quantal Dose-Response Curve: Lethal Dose
Important characteristic of a drug’s activity is its toxic effect and, the ultimate toxic effect is death
A curve can be constructed by plotting percent of animals killed by any drug against dose
This can calculate by
the LD50, the dose
that would kill 50%
of animals

7. Therapeutic Index The ratio LD50/ED50
As a general rule, a drug should have a high therapeutic index; however, some important therapeutic agents have low indices
The therapeutic index is a rough measure of safety and represents only the starting point in determining whether a drug is safe enough for human use

8. Graded Response
A single animal gives graded responses to graded doses; that is, as the dose is increased, the response increases
With graded responses, one can obtain a complete dose–response curve in a single animal

9. Idealized dose–response curves of three agonists (a, b, c) that increase heart rate but differ in potency, maximum effect, or both. Broken lines indicate 50% of maximum response (horizontal) and individual ED50 values (vertical)

10. Potency and Intrinsic Activity
Another drug characteristic that can be compared by use of ED50 values is potency
From the previous curve,
less of drug ‘a’ is needed to produce a given response
ED50b/ED50a= 3/.3=10, i.e., ‘a’ is 10 times more potent than ‘b’
In contrast, drug c has less maximum effect than either drug a or drug b. Drug c is said to have a lower intrinsic activity than the other two

11. Equation from Drug-Receptor InteractionK1
D + R
D-R K2 K3
Response
Affinity is k1/k2, and efficacy is represented by k3
Affinity and efficacy represent kinetic constants that relate the drug, the receptor, and the response at the molecular level
Affinity is the measure of the net molecular attraction between a drug and its receptor
Efficacy is a measure of the efficiency of the drug–receptor complex in initiating the signal transduction process