Pharmacodynamics 101: Agonist Dose Response Curves

Agonist and Antagonist

When drug combines with a drug target (receptor, ion channel, enzyme, carrier molecule) this may lead to one of the following:

Agonist effect: the drug binds and causes the same action as the normal substance that bind to receptor
Antagonist effect: the drug binds and stops the action or effect of another substance

The interaction between the drug and its target can be described by a curve because the drugs affects natural regulatory processes so their effect follows a natural curve

Affinity: the probability of drug occupying certain receptor at a given concentration , the higher the affinity the higher the binding to receptor
Occupancy: measures the extent to which drug occupying the receptors

it is all or none response
Example is prevention of convulsions by antiepileptic drugs
It is response to few drugs
The response could not be tested in one animal and must be tested in a group of animals or humans by randomized clinical trials

Efficacy refers to the effect of a drug. The more effect the drug does, the higher the efficacy of the drug
E max is maximal effect that a drug can elicit at specific concentration
Full agonist occupy all receptors at certain dose and it activates all of them leading to maximal response
Partial agonist occupy all receptors but it doesn’t activate all of them so we get less than the maximal effect
ED50 (dose that achieve 50% of effect) dose that gives 50% of E max in graded response or it is the dose that gives the desired effect in 50% of tested population in quantal response
EC50 same as ED50 (concentration that achieve 50% effect)
Drug that has smaller ED50 than another drug is described as more potent than the another drug
Potency of a drug is less clinically important than efficacy because you can increase the dose of a less potent drug that has better effect and we get the better effect than potent drug with less effect

Therapeutic index: it is ratio between the TD50 and the ED50
TD50: dose that achieve toxicity (harmful effect) in 50% of population
Example: if toxic dose is 10 times the therapeutic dose, therapeutic index is 10
TI is a measure of safety of drugs
High therapeutic index means there is large difference between the dose of a drug that produces the desired effect and the dose that produces toxic effect and vice versa for small TI
Drugs with high TI are more safe for clinical use and vice versa (warfarin has a narrow TI and requires careful therapeutic monitoring)
Some drugs are toxic drugs in any dose like the cancer chemotherapeutic drugs