PHARMACOLOGY

 PROTEIN BINDING ::

Protein binding is a very important factor in pharmacokinetics that may produce serious drug interactions Protein binding of drug is the reversible interaction between the drug and plasma proteins generally albumin The importance of protein binding can be visulized from the following 

1.Protein binding renders the drug inactive 

2.The drug becomes impermeable to membrane after protein binding This delays the metabolism and excretion of drugs 

3.Protein binding serves as a storage of drugs 

4.Changes in protein binding may change the distribution of drug 

    For such changes the following criteria must be fulfilled ::

(a) The bound drug must constitute more then 90% of the total drug in the plasma For example digoxin which is bound to proteins to the extent of 20% will not be affected by a 5% change in protein binding However if 5% change in protein binding occurs for phenytoin that is bound to the extent of 90% the unbound and active form available will be increased significantly resulting in toxicity 

(b) The extent of distribution of drugs to tissues must be small if a drug is widely distributed to the tissues then even large increase in the amount of unbound drug in the plasma will be unimportant in such cases the increment of unbound drug which through small in comparison with total body content will be readily distributed to body tissues and the unbound concentration in the plasma will rise only by negligible amount 

        Drugs having high affinity for protein can displace the drugs having low affinity but high capacity for proteins e.g. salicylates or sulphonamides can displace coumarin or warfarin leading to serious interactions resulting in bleeding tendencies 

    Factors affecting -protein binding of drugs : 

1.Renal impairment altering the characteristics of drugs for albumin 

2.Hypoalbuminaemia causing decrease in protein binding 

3.Pregnancy -Protein binding is decreased during last trimester of pregnancy due to hypoalbuminaemia and other unknown factors 

4.Age -Protein binding is lower in neonates and children 

5.Uremia also decreases protein binding