PHARMACODYNAMICS

1. ONCE A DRUG REACHES ITS target WHAT EXACTLY DOES IT DO, AND HOW DOES THIS PRODUCE A
CELLULAR RESPONSE?
THE STUDY OF THIS PROCESS IS CALLED pharmacodynamics
THE STUDY OF HOW A DRUG AFFECTS OUR bodies
THE VAST MAJORITY OF DRUGS ELICIT (GET OR OBTAIN) A PHYSIOLOGICAL RESPONSE BECAUSE OF
THE WAY THAT THEY interact WITH A PARTICULAR PROTEIN. MOST OFTEN THIS WILL BE A receptor
protein, WHICH MAY BE EMBEDDED IN THE CELL MEMBRANE, OR IT MAY BE FOUND INSIDE THE CELL,
WHETHER IN THE cytoplasm OR THE NUCLEUS.
2. TALKING ABOUT BIOCHEMISTRY, ANY receptor WILL HAVE A ligand, WHICH IS A MOLECULE THAT FITS
INTO THE ACTIVE SITE OF THE RECEPTOR, AND IN ESSENCE TURNS THE RECEPTOR ON, EVOKING A
conformational change THAT THEN PROPAGATES THE SIGNAL IN ONE OF SEVERAL WAYS.
3. WHEN DRUGS interact WITH RECEPTORS, THERE ARE TWO MAIN WAYS THAT THIS COULD GO:
4. A DRUG COULD BE AN agonist FOR A PARTICULAR RECEPTOR, MEANING THAT IT fits INTO THE
ACTIVE SITE AND MIMICS THE NATIVE LIGAND, ELICITING OR GET THE TYPICAL PHYSIOLOGICAL
RESPONSE. WE CAN CALL THIS facilitators
5. A DRUG COULD BE AN antagonist FOR THIS RECEPTOR, MEANING THAT IT binds TO THE ACTIVE
SITE, BUT DOES NOT ACTIVATE THE RECEPTOR, THEREBY LOCKING IT IN AN INACTIVE STATE. WE
CAN CALL THESE inhibitors , OR blockers.
6. IT IS IMPORTANT TO DEFINE TWO TERMS:

● POTENCY: REFERS TO THE STRENGTH OF A DRUG AT A PARTICULAR CONCENTRATION OR dosage,

OR THE amount OF A DRUG THAT IS REQUIRED TO PRODUCE A PARTICULAR effect. TECHNICALLY, IT
REFERS TO THE CONCENTRATION OR DOSAGE REQUIRED TO PRODUCE fifty -50%- OF THE MAXIMUM
EFFECT THAT DRUG CAN ACHIEVE.

FOR EXAMPLE: IF A DRUG IS EXTREMELY POTENT, ONLY A very small OF IT WILL NEED TO BE
ADMINISTERED IN ORDER TO ACHIEVE ITS maximum EFFECT.

● EFFICACY : REFERS TO THE maximum EFFECT THAT CAN BE ACHIEVED BY A DRUG, SO THAT AFTER
THIS IS REACHED, NO HIGHER DOSE WILL PRODUCE ANY FURTHER EFFECT. TWO DIFFERENT DRUGS
MAY HAVE SIMILAR POTENCIES, MEANING THAT THE RESPONSE INCREASES OVER THE SAME
INCREASE IN DOSAGE, BUT ONE WILL achieve A MORE SIGNIFICANT response THAN THE OTHER OR A
MORE SIGNIFICANT EFFECT, DUE TO ITS HIGHER EFFICACY.

FOR EXAMPLE: TWO DRUGS CAN HAVE THE same EFFICACY, BUT DIFFER IN THEIR POTENCY, SINCE
ONE REQUIRES A smaller DOSAGE TO ACHIEVE ITS MAXIMUM EFFECT THAN THE OTHER.

7. WHAT DETERMINES THE efficacy OF A DRUG?

WE HAVE TO LOOK AT HOW THE DRUG interacts WITH ITS target .

IF THE PURPOSE OF THE DRUG IS TO bind TO THE ACTIVE SITE OF A receptor OR enzyme,

8. HOW WELL DOES IT BIND?

WHAT IS THE BINDING affinity?

 HOW WELL DOES THE DRUG fit INTO THE ACTIVE SITE?

9. IF THE DRUG IS ACTING AS AN inhibitor, THEN A HIGH BINDING AFFINITY WILL BE CRUCIAL IN ORDER
TO HAVE REASONABLE efficacy , BECAUSE IF THE BINDING AFFINITY IS LOW, THEN WHEN THE native
ligand COMES ALONG, WHICH IS THE MOLECULE THAT IS SUPPOSED TO GO IN THE ACTIVE SITE, IT
WILL MOST LIKELY HAVE A HIGHER BINDING AFFINITY THAN THE DRUG, AND WILL displace IT, THUS
NO INHIBITION CAN BE ACHIEVED.

10. IF THE DRUG IS ACTING AS AN agonist , AGAIN BINDING AFFINITY WILL BE RELEVANT, AND IT WILL
ALSO HAVE TO HAVE THE RIGHT FUNCTIONAL GROUPS NECESSARY TO PROMOTE THE SAME
conformational change IN THE PROTEIN AS THE native ligand , SO THAT PROTEIN WILL PRODUCE THE
SAME CELLULAR RESPONSE.

11. POTENCY AND EFFICACY USING receptors AS EXAMPLES

POTENCY IS THE affinity OF A DRUG FOR A RECEPTOR: IF THE AFFINITY IS VERY HIGH, MOST OF THE
DRUG WILL BE BOUND AT ANY GIVEN TIME, AND THUS VERY LITTLE OF THE DRUG WILL BE needed TO
OCCUPY ALL THE RECEPTORS.

EFFICACY DESCRIBES THE effect THE DRUG HAS ON THE receptor ONCE IT IS BOUND, OR THE
DEGREE OF ITS ABILITY TO ACT AS AN agonist (PROMOTES THE NORMAL FUNCTION OF THE
PROTEIN) OR antagonist (SILENCES THE PROTEIN AND PREVENTS FUNCTION).

POTENCY IS RELATED TO affinity (BINDING AFFINITY FOR THE PROTEIN)

EFFICACY IS RELATED TO THE CLINICAL effect OF THE DRUG (CLINICAL AFFECT ON THE PROTEIN)