What is drug tolerance?

• A. An immediate decrease in response
• B. Reduction in response after repeated administration
• C. A temporary enhancement of effect with drug withdrawal
• D. A permanent loss of receptor function

Answer: (B)

Tolerance is the diminished response to a drug after repeated exposure, so the same dose produces a smaller effect and a higher dose is often needed to achieve the same level of action. This happens because the body adapts in two main ways: pharmacokinetic changes, where the drug is cleared more efficiently due to increased enzyme activity or other processes; and pharmacodynamic changes, where target cells become less responsive, such as receptor desensitization or downregulation and alterations in downstream signaling. A common example is opioid analgesia, where continued use can require higher doses for the same relief. Tolerance is usually reversible with time off the drug. It’s not an immediate decrease in effect (that would be tachyphylaxis), nor is it a temporary enhancement after withdrawal, and it isn’t typically a permanent loss of receptor function.