Which of the following is true: (DNB Dec 2012)
|A||As the concentration of drug increases over the therapeutic range, the bound form of the drug increases|
|B||The bound form is not available for metabolism but is available for excretion|
|C||Acidic drug binds to albumin; and basic drug binds β globulin|
|D||Binding sites are non-specific and one drug can displace the other|
Considering each option separately:
Option 'a' : As concentration of drug increases over the therapeutic range, it is the free form of the drug
that increases (because most protein binding sites are already saturated).
Option 'b' : The bound form is not available for metabolism, excretion and action.
Option 'c' : Plasma protein binding of drug
-1 acid glycoprotein
All the acidic drugs bind to plasma protein albumin
Ex. Valproic acid, phenytoin, barbiturate Benzodiazepines, sulphonamides, Tetracycline, Tolbutamide, Warfarin, NSAIDs
All the basic drugs bind to -1 acid glycoprotein
Ex: Beta blocker, Prazosin, Bupivacaine Lignocaine, Verapamil, Disopyramide Imipramine, Methadone.
Protein binding of drug affects:
- Metabolism of drug
- Elimination of drug
Protein binding limits the glomerular filtration of drug but dose not affect the renal tubular secretion.
Binding sites are nonspecific and one drug can displace the other at therapeutic plasma concentration. Only a tiny fraction is unbounded. Sulphonamides are an exception because they occupy 50% of binding sites at therapeutic concentration and so can cause unexpected effect by displacing other drugs.