Pharmacokinetic Drug Interactions

       

Alteration (Increase or Decrease) of concentration of one drug, by the administration of another drug in the system, is termed as “Pharmacokinetic Drug Interaction”.

·       Interacting drugs have unrelated actions and it is difficult to predict pharmacokinetic drug interactions.

·       Pharmacokinetic interactions involve in the alteration of drugs’

v Absorption

v Distribution

v Metabolism

v Excretion

·       Absorption interactions involve

v Changes in gastrointestinal pH

v Adsorption, chelation and other complexing mechanisms

v Changes in gastrointestinal motility

v Induction or inhibition of drug transporter proteins

v Malabsorption caused by drugs

·       Distribution interactions involve

v Protein-binding interactions

v Induction or inhibition of drug transporter proteins

·       Metabolism interactions involve

v Changes in first-pass metabolism

ü Changes in blood flow through the liver

ü Inhibition or induction of first-pass metabolism

v Enzyme induction

v Enzyme inhibition

·       Excretion interactions involve

v Changes in urinary pH

v Changes in active renal tubular excretion

v Changes in renal blood flow

v Biliary excretion and the entero-hepatic shunt

v Enterohepatic recirculation

v Drug transporter proteins

General Introduction to Drug Interactions

General Introduction to Drug Interactions:

·       Modification of effects of one drug, by the administration of another substance such as a drug, a nutrient (food), an herb, alcohol or tobacco smoke is termed as “Drug Interaction”.

·       The drug interaction may produce increased / decreased beneficial effects or increased adverse effects. 

·       The drug interaction which leads to undesirable effects is called as “Adverse Drug Interaction”.

·       The factors like Polypharmacy, Genetic factors, Old age, Liver or Kidney disease, other underlying diseases, Lifestyle (diet, exercise), the duration of combined therapy, Time of administration of the two substances and Therapeutic index of drugs affect the appearance of drug interactions.

Mechanisms of Drug Interactions:

v Pharmaceutical Interactions

v Pharmacokinetic interactions

·       Absorption Interactions

·       Distribution Interactions

·       Metabolism Interactions

·       Excretion Interactions

v Pharmacodynamic interactions

·       Receptor mediated Interactions

·       Non receptor mediated Interactions