DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

while they may be physically dependent, are not
“addicts” even though they may need large doses on a
regular basis. Physical dependence is not equivalent to
addiction (Chapter 24).
Most clinicians who are experienced in the management
of chronic pain associated with malignant disease
or terminal illness recommend that a baseline
long-acting opioid be administered around the clock so
that pain is continually under control and patients do
not dread its return (Foley, 1993). For breakthrough
pain episodes, a fast-onset, short-acting opioid can be
administered. Less drug is needed to prevent the recurrence
of pain than to relieve it initially. Morphine
remains the opioid of choice in most of these situations,
and the route and dose should be adjusted to the needs
of the individual patient. Oral morphine is adequate in
most situations. Sustained-release preparations of oral
morphine and oxycodone are available that can be
administered at 8-, 12-, or 24-hour intervals (morphine)
or 8- to 12-hour intervals (oxycodone); thus, superior
control of pain often can be achieved with fewer side
effects using the same daily dose; a decrease in the fluctuation
of plasma concentrations of morphine may be
partially responsible.
Constipation is an exceedingly common problem
when opioids are used, and the use of stool softeners
and laxatives should be initiated early; newer modalities
include the use of peripheral opiate antagonists such as
methylnaltrexone. Amphetamines have demonstrable
mood-elevating and analgesic effects, enhance opioidinduced
analgesia, and can reverse opioid induced sedation.
However, not all terminal patients require the
euphoriant effects of amphetamine, and some experience
side effects, such as anorexia. Controlled studies
demonstrate no superiority of oral heroin over oral morphine.
Similarly, after adjustment is made for potency,
parenteral heroin is not superior to morphine in terms of
analgesia, effects on mood, or side effects (Sawynok,
1986). Although tolerance does develop to oral opioids,
many patients obtain relief from the same dosage for
weeks or months. In cases where one opioid loses effectiveness,
switching to another may provide better pain
relief. “Cross-tolerance” among opioids exists, but clinically
and experimentally, cross-tolerance among
related receptor agonists is not complete. The reasons
for this are not clear but may relate to differences
between agonists in receptor-binding characteristics
and subsequent cellular signaling interactions.
When oral opioids and other analgesics are no
longer satisfactory, subcutaneous or intravenous opioids,
nerve blocks, or neurolysis may be required if the
nature of the disease permits. Epidural or intrathecal
administration of opioids may be useful when administration
of opioids by usual routes no longer yields adequate
relief of pain.
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CHAPTER 18
OPIOIDS, ANALGESIA, AND PAIN MANAGEMENT