Which mechanism contributes to tolerance?

Which mechanism contributes to tolerance?

• A. Downregulation of receptor availability due to repeated exposure
• B. Increased synthesis of neurotransmitters
• C. Increased breakdown of the drug leading to lower plasma levels
• D. Increased efficacy of the receptor per receptor

Answer: (A)

Tolerance happens when the body adapts to repeated drug exposure and the same dose produces a weaker effect. A primary way this happens is downregulation of receptor availability: the target cells decrease the number of receptors on their surface (or receptors become less responsive) through internalization and related changes. With fewer receptors available, the drug’s signaling diminishes, so you need a larger dose to achieve the same effect. Increasing neurotransmitter synthesis would typically boost signaling rather than reduce it, so it doesn’t explain the diminishing response. Increased breakdown of the drug lowers its plasma levels, which is a pharmacokinetic change, not a change in receptor responsiveness. And increasing efficacy per receptor would enhance, not reduce, the response. So the mechanism of receptor downregulation best accounts for tolerance.

Tolerance happens when the body adapts to repeated drug exposure and the same dose produces a weaker effect. A primary way this happens is downregulation of receptor availability: the target cells decrease the number of receptors on their surface (or receptors become less responsive) through internalization and related changes. With fewer receptors available, the drug’s signaling diminishes, so you need a larger dose to achieve the same effect.

Increasing neurotransmitter synthesis would typically boost signaling rather than reduce it, so it doesn’t explain the diminishing response. Increased breakdown of the drug lowers its plasma levels, which is a pharmacokinetic change, not a change in receptor responsiveness. And increasing efficacy per receptor would enhance, not reduce, the response. So the mechanism of receptor downregulation best accounts for tolerance.