20.03.3 Tolerance and Physical Dependence

Tolerance and physical dependence develops to the opioids. Tolerance is a decrease in effectiveness with repeated use of the same dose of a drug. Tolerance occurs to most of the effects of the opioids. Thus, it is necessary to increase dose to maintain the same effect. The possible mechanisms for the development of tolerance include receptor internalization with chronic exposure to the opioids, so that they are no longer activated by the opioid. An alternative mechanism for the tolerance is an altered responsiveness of the cell signaling with chronic exposure to the opioids to give a diminished response.

Physical dependence is a set of changes in the body with chronic exposure leading to a withdrawal syndrome when the drug is stopped due to changed homeostasis. Physical dependence can develop to opioids, for example, when morphine is in chronic use for the pain of cancer. Physical dependence is not drug addiction or abuse. Drug addiction is due to psychological dependence and pleasurable effects causing reinforcement of drug use. Subjects with pain do not usually have these and are not drug addicts. Opioids can be discontinued in physically dependent patients (subjects who have had chronic pain) without subjecting them to withdrawal. Associated with decreasing the dose of opioid by 10 to 20% every other day, and eventually stopping the opioid, there is no withdrawal syndrome.