1. Efficacy, Potency and Safety of Drugs
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture-10
October 17, 2011

2. Receptor
Macromolecular protein on the plasma membrane or cytoplasm that binds the drugs and initiates its effects
Site where drug binds and initiates its effect
The drug binding may (1) do nothing, (2) lead to some undesirable effect, or (3) initiate a sequence of biochemical reactions that ultimately results in a desirable therapeutic effect
The binding reaction is driven by chemical/physical forces

3. Drug-Receptor Interaction
Drug-Receptor Interactions is a Lock and Key Model, drug as a key and the receptor as a lock
Two important properties of drugs (keys) should be considered
First, will the drug bind to the receptor (will the key fit in the lock)?
Second, will the drug activate the receptor (will the key turn and open the lock)?

4. Log Dose-Response Curve
Dose-response curves are most often mathematically transformed to a semi-logarithmic scale
This is a mathematical calculation
It allows easier graphical comparison of different dose-response curves because it expands the scale of the concentration axis at low concentrations and compresses the axis at high concentrations

5. Log Dose-Response Curve

6. Efficacy of Drug
Efficacy refers to the capacity of a drug to produce a pharmacological response. It is maximal response produced by a drug (Emax)
Depends on the no. of drug-receptor complexes formed
Efficacy extending from (1) "full" agonists that produce a maximal response to (2) "full" antagonists that bind to receptors but which do not produce any measurable response

7. Intrinsic Activity of Drug
Intrinsic activity relates to whether the drug can activate the receptor
Some drugs (agonists) can change the conformation of the receptor (turn in the lock) and cause activation of a response (open the lock)
Other drugs (antagonists) can bind to the receptor, but cannot activate it (cannot turn in the lock and open it)

8. Intrinsic Activity of Drug
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

9. Potency of Drug
Potency is a measure of how much drug is required to elicit a response
If a drug binds tightly to a receptor (i.e. receptor has high affinity for the drug), the drug will be a potent modulator of effects mediated by that receptor
Conversely, a drug that binds very weakly with a receptor will not be very potent

10. Graded Response of Drug
Any action or effect of drug that is continuously variable (graded) from no response up to a maximal response
For example, a drug-dependent increase in heart rate could vary with the dose of the drug in an individual from zero beats/minute to 10,22,35, or 50 beats/min…
May not be applicable to other patients because of potential variability between patients in their absorption, distribution, or metabolism of the drug

11. Graded Response of Drug

12. Quantal Response of Drug
Quantal responses are of the "either yes or no" variety
Examples of quantal responses are as follows: 1) relief of headache, 2) sleep, or 3) prevention of convulsions
Quantal responses corresponding to clinically relevant endpoints are determined in a large population of patients in clinical trials
Quantal response data are used to establish the safety and efficacy of a drug

13. Characteristic Parameters obtained from Dose-Effect Curves:
ED50; LD50; TD50
ED50: (1) A specified effect is produced in 50% of the population at that dose (Quantal curve) OR (2) the dose that produces 50% of the maximum response (graded curve).  
LD50: dose that kills (lethal) or elicits toxicity (TD50) in 50% of the population
Therapeutic Index (TI)= LD50/ED50 (or TD50/ED50)

14. QUANTAL DOSE-RESPONSE CURVES
TI = -----
Therapeutic range = TD50 - ED50
ED50