Which statement about opioid tolerance is true?

Which statement about opioid tolerance is true?

• A. Repeated opioid exposure leads to desensitization and down-regulation of opioid receptors.
• B. Tolerance always accompanies physical dependence.
• C. Tolerance increases analgesic efficacy.
• D. Tolerance is the same as dependence.

Answer: (A)

Repeated opioid exposure causes pharmacodynamic changes that blunt the drug’s effect. Receptors become less responsive (desensitization) as signaling efficacy wanes, and over time there is fewer opioid receptors on the cell surface (down-regulation) due to internalization. The combination means the same dose produces less analgesia, so higher doses are often needed for the same pain relief. It’s important to separate tolerance from dependence: tolerance can occur without withdrawal, and dependence involves withdrawal symptoms on cessation or antagonism. The other statements don’t fit because tolerance does not increase analgesic efficacy, does not always accompany physical dependence, and is not the same as dependence.

Repeated opioid exposure causes pharmacodynamic changes that blunt the drug’s effect. Receptors become less responsive (desensitization) as signaling efficacy wanes, and over time there is fewer opioid receptors on the cell surface (down-regulation) due to internalization. The combination means the same dose produces less analgesia, so higher doses are often needed for the same pain relief. It’s important to separate tolerance from dependence: tolerance can occur without withdrawal, and dependence involves withdrawal symptoms on cessation or antagonism. The other statements don’t fit because tolerance does not increase analgesic efficacy, does not always accompany physical dependence, and is not the same as dependence.