What is an on target adverse effect?

• A. The result of the drug binding to an unintended receptor/target
• B. An immune-mediated reaction to the drug
• C. A metabolic interaction with another drug
• D. The result of the drug binding to its intended receptor/target, but at an inappropriate concentration, or in the incorrect tissue

Answer: (D)

On-target adverse effects happen when the drug hits its intended receptor or target, but the adverse outcome occurs because the interaction happens in the wrong context—either the dose is inappropriate (too high) or the target is present in a tissue where its modulation causes harm. In other words, the mechanism of action is correct, but the effect becomes adverse due to concentration or tissue distribution. This distinguishes it from effects caused by hitting an unintended target (off-target), or from immune-mediated reactions or pharmacokinetic interactions with other drugs. For example, inhibiting a receptor that's present in multiple tissues can produce beneficial effects in one tissue but adverse effects in another if the target is blocked there as well or if dose is excessive.