How would you explain the mechanism of tolerance in a 63-year-old patient?

When a patient becomes tolerant to a certain dose of morphine, this means that they will have a decreased morphine receptor density. The most common mechanism of pharmacodynamic tolerance is a receptor down-regulation, which is a decrease receptor density. Other mechanisms can be homeostatic adaptive changes of the organism that counteract the drug effect.

Tolerance due to increased metabolism of the drug is called pharmacokinetic tolerance. Increased affinity of receptors to morphine and decreased binding of morphine to plasma proteins would have increased, not decreased, the effects of morphine.

Pharmacodynamic tolerance refers to a decrease in time of the effect of a drug whose concentration at the site of action remains the same, so decreased concentration of morphine in the brain would not explain the mechanism of tolerance.