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MORPHINE: TOLERANCE, PHYSICAL DEPENDENCE AND PSYCHOLOGICAL DEPENDENCE-TOLERANCE

Lack of understanding about tolerance and dependence is a common cause for the under-use of opioid analgesics for cancer-related pain.

• Concerns about tolerance, physical dependence or psychological dependence are never a reason to delay treatment with opioid analgesics if they are indicated.

Tolerance-Tolerance is a normal physiological response to chronic opioid therapy in which increasing doses may be required to produce the same effect.

In practice, patients with cancer show little opioid tolerance and may require only modest increases in dosage over a period of weeks or months. This is in contrast to the rapid development of tolerance seen in intravenous drug users without pain. In patients with cancer the need for increasing doses usually relates to disease progression and not pharmacologic tolerance.

Concern regarding tolerance is not a reason for ‘saving up’ the use of opioid drugs until the terminal phase. Patients may be concerned that there will be 'nothing left' should their pain get worse; doctors may be concerned about a pre-terminal 'crescendo of pain' which occasionally occurs. However, the therapeutic range of morphine is very broad and there is adequate scope to accommodate these problems should they occur. Patients and their families should be reassured of this. Tolerance is not related to the development of psychological dependence.

Cross-tolerance between the various opioid drugs is not complete and an alternative drug can be substituted if the rate of development of tolerance is of concern. If a patient experiences

dose-limiting side effects from one opioid drug, another drug should be substituted, starting at half the equianalgesic dose.

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