Key Principles of Pharmacology
4. Pharmacodynamics
Pharmacodynamics (PD) is the study of the effect of a medicine on the body.
There are two ways a medicine can affect the body:
A medicine can change conditions within the body, or
A medicine can interact with specific parts of the body on a cellular or sub-cellular level.
The primary objective of pharmacodynamic studies is to gather information on how the medicine affects the body this can be biochemical, physiologic, and molecular effects and involves receptor binding (including receptor sensitivity), postreceptor effects, and chemical interactions).). It allows scientists to assess the efficacy of the medicine – that is, whether or not the medicine is having the desired effect on the target, and if so, how strong that effect is.
It also allows a better understanding of the relationship between the concentration of the medicine in the body and the strength of its effect. This means that PK and PD both together influence dosing, benefit, and adverse effects (for example, addressed in PK/PD models).
The majority of medicines either mimic or inhibit normal physiological/biochemical processes or inhibit pathological processes.
There are 7 main medicine actions:
stimulating action through direct receptor agonism and downstream effects
depressing action through direct receptor agonism and downstream effects
blocking/antagonizing action, the medicine binds the receptor but does not activate it
stabilizing action, the medicine seems to act neither as a stimulant or as a depressant
exchanging/replacing substances or accumulating them to form a reserve
direct beneficial chemical reaction as in free radical scavenging
direct harmful chemical reaction which might result in damage or destruction of the cells, through induced toxic or lethal damage
Pharmacodynamics places particular emphasis on dose–response relationships, In principle, then the goal would be to dose for an optimal plasma concentration of the medicine for a desired level of response. In reality, there are many factors affecting this goal. Pharmacokinetic factors determine peak concentrations, and concentrations cannot be maintained with absolute consistency because of metabolic breakdown and excretory clearance. Genetic factors may exist which would alter metabolism or drug action itself, and a patient's immediate status may also affect indicated dosage.
A simplified schematic of PK and PD parameters and their interrelation is given in the following figure (Fig. 6).
Figure.6: Relationship between the plasma concentration – time curve obtained following a single extravascular (e.g. oral) dose of a medicine and parameters associated with the therapeutic or pharmacological response
Two parameters, as shown in the above figure, deserve specific mention because they give an indication of the efficacy and safety of the medication tested:
The therapeutic window is the amount of a medication between the amount that gives an effect (minimum effective concentration) and the amount that gives more adverse effects than desired effects (maximum safe concentration). To note: adverse effects (side effects) of various nature can occur while the medicine is effective (benefit) but their influence (risk) must be less than the positive effect (a favourable benefit – risk ratio) over the range of intensity (from minimum effective concentration to Cmax) to make the medicine acceptable. Therefore, medication with a small therapeutic window must be administered with care and control, e.g. by frequently measuring blood concentration of the drug.
The duration of action of a medicine is the length of time that the particular drug is effective (from reaching the minimum effective concentration in the absorption phase back to this level in the elimination phase). Duration of action is a function of several parameters including plasma half-life, the time to equilibrate between plasma and target (compartments), and the off rate of the drug from its biological target.