Pathophysiology
Clinical meaning
The therapeutic window (therapeutic index/TI) is the range between the minimum effective concentration (MEC โ lowest drug concentration that produces the desired therapeutic effect) and the minimum toxic concentration (MTC โ lowest concentration that produces toxic effects). Drugs with a NARROW therapeutic index (NTI) have a small margin between therapeutic and toxic doses โ requiring precise dosing, therapeutic drug monitoring (TDM), and close clinical monitoring. Examples: warfarin, lithium, digoxin, phenytoin, theophylline, aminoglycosides, vancomycin, cyclosporine, carbamazepine, valproic acid. The therapeutic index is quantified as TI = TDโ โ/EDโ โ (toxic dose in 50% of population / effective dose in 50% of population); higher TI = wider safety margin. Potency vs. Efficacy: POTENCY refers to the amount of drug needed to produce an effect โ a more potent drug achieves the same effect at a LOWER dose (leftward shift on dose-response curve); this relates to receptor binding affinity. EFFICACY (Emax) refers to the MAXIMUM effect a drug can produce regardless of dose โ a more efficacious drug achieves a higher ceiling of therapeutic effect. Example: hydromorphone is more POTENT than morphine (achieves analgesia at...
