The concept of 'therapeutic index' (TI) is not simply a ratio but reflects different pharmacokinetic-pharmacodynamic considerations depending on the drug's concentration-response curve. For a drug with a STEEP concentration-effect curve, a narrow TI is MOST concerning because:

• A Small increases in plasma concentration (within or just above the therapeutic range) produce large increases in pharmacological effect, rapidly reaching toxic effects — leaving little margin between efficacy and toxicity ✓
• B Small increases in dose produce proportionally small increases in effect, requiring large overdoses to produce toxicity
• C Steep curves indicate irreversible receptor binding, making toxicity permanent even after drug discontinuation
• D Steep curves are associated with zero-order kinetics, causing exponential accumulation at toxic levels

Explanation

The steepness of the concentration-response (E-C) curve determines how sensitive drug effect is to concentration changes. A steep Emax-model curve (high Hill coefficient 'n') means that even small increments in plasma concentration produce disproportionately large increases in pharmacological effect, rapidly transitioning from sub-therapeutic to toxic concentrations. This creates a narrow margin between therapeutic and toxic doses that is difficult to manage clinically. Classic examples: digoxin (steep curve, narrow TI), warfarin. In contrast, a shallow curve provides more room to titrate. Steep curves do not imply irreversible binding or zero-order kinetics directly.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.