Pharmacodynamic Drug Interactions

·       Alteration (Increase or Decrease) of effect of one drug, by the administration of another drug, is termed as “Pharmacodynamic Drug Interaction”.

·       Pharmacodynamic interactions either…

v Receptor mediated or

v Non receptor mediated

·       Pharmacodynamic interactions further classified in to…

v Additive (Summation) interactions

v Synergistic interactions

v Potentiation interactions

v Antagonism interactions

ü Functional antagonism

ü Chemical antagonism

ü Dispositional antagonism

ü Receptor antagonism

·       When the sum of individual effects of two drugs is equal to the combined effect of them, is known as “Additive interaction”.   

                   i.e. 1 + 1 = 2

       Ex: Aspirin + Ibuprofen

·       “Synergistic interaction” implies the combined effect of two drugs is greater than the sum of their individual effects at the same doses.

                  i.e. 1 + 1 > 2

      Ex: Aminoglycoside + Penicillin = Increased antibacterial activity

·       The creation of a toxic effect from one drug due to the presence of another drug, describes “Potentiation interaction”.

                   i.e. 1 + 0 = 2

          Ex: Fluoroquinolones + Macrolides = Excessive QT prolongation (Torsades de pointes)

           

·       “Antagonistic interaction” means the sum of individual effects of two drugs is less than the effect of the drugs taken independently of each other.

                  i.e. 1 - 1 = 0 or 0.5.

·       Functional or physiological antagonism occurs when one drug counteract the effects of another substance without binding to the same receptor.

       Ex: Adrenaline for hypersensitivity reaction (Histamine)

·       A drug counters the effect of another by simple chemical reaction or neutralization, in Chemical antagonism or Inactivation.

       Ex: Protamine sulphate is antidote for  Heparin overdosage

·       The alteration of the disposition of a substance (absorption, biotransformation, distribution, or excretion), known as Dispositional antagonism.

        Ex: Cholestyramine reduces the absorption of bile acids

·       Receptor antagonism involves the blockade of the effect of a drug (Agonist) by another drug (Antagonist) that competes at the receptor site.

·       Types of Receptor antagonists include…

v Competitive antagonists

v Reversible competitive antagonists

v Irreversible competitive antagonists

v Non competitive antagonists

v Uncompetitive antagonists

v Partial agonists

v Inverse agonists