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

question the accuracy of the diagnosis. Pulmonary edema sometimes
associated with opioid overdosage may be countered by positivepressure
respiration. Tonic-clonic seizures, occasionally seen as part
of the toxic syndrome with meperidine, propoxyphene, and tramadol,
are ameliorated by treatment with naloxone.
The presence of general CNS depressants does not prevent
the salutary effect of naloxone, and in cases of mixed intoxications,
the situation will be improved largely owing to antagonism of the
respiratory-depressant effects of the opioid. However, some evidence
indicates that naloxone and naltrexone also may antagonize some of
the depressant actions of sedative-hypnotics. One need not attempt
to restore the patient to full consciousness. The duration of action of
the available antagonists is shorter than that of many opioids; hence
patients can slip back into coma. This is particularly important when
the overdosage is due to methadone. The depressant effects of these
drugs may persist for 24-72 hours, and fatalities have occurred as a
result of premature discontinuation of naloxone. In cases of overdoses
of these drugs, a continuous infusion of naloxone should be
considered. Toxicity owing to overdose of pentazocine and other
opioids with mixed actions may require higher doses of naloxone.
CLINICAL SUMMARY
Opioid analgesics provide symptomatic relief of pain,
but the underlying disease remains. The clinician must
weigh the benefits of this relief against any potential
risk to the patient, which may be quite different in an
acute compared with a chronic disease.
In acute problems, opioids will reduce the intensity
of pain. However, physical signs (such as abdominal
rigidity with an acute abdomen) generally will
remain. Relief of pain can facilitate history taking and
examination in the emergency room, and the patient’s
ability to tolerate diagnostic procedures. In most cases
analgesics should not be withheld for fear of obscuring
the progression of underlying disease.
The problems that arise in the relief of pain associated
with chronic conditions are more complex.
Repeated daily administration of opioid analgesics
eventually will produce tolerance and some degree of
physical dependence. The degree will depend on the
particular drug, the frequency of administration, the
quantity administered, the genetic predisposition, and
the psychosocial status of the patient. The decision to
control any chronic symptom, especially pain, by the
repeated administration of an opioid must be made
carefully. When pain is due to chronic nonmalignant
disease, conservative measures using non-opioid
drugs should be tried before resorting to the opioids.
Such measures include the use of NSAIDs, local nerve
blocks, antidepressant drugs, electrical stimulation,
acupuncture, hypnosis, and behavioral modification.
Selected subpopulations of chronic nonmalignant
pain patients can clearly be maintained adequately
on opioids for extended periods of time. Careful
patient selection is important before starting chronic
opioid therapy. All patients should have a risk assessment
for drug abuse, diversion, and noncompliance
using a validated assessment questionnaire. Chronic
pain patients at a higher risk of abuse should not necessarily
be denied opioids; however, these patients
will require a higher level of monitoring (i.e., random
urine drug testing, limited supplies, pill counting) and
perhaps referral to a specialist in pain or addiction to
assist with therapy.
In the usual doses, morphine-like drugs relieve
suffering by altering the emotional component of the
painful experience, as well as by producing analgesia.
Control of pain, especially chronic pain, must include
attention to both psychological factors and the social
impact of the illness that sometimes play dominant
roles in determining the suffering experienced by the
patient. The physician must consider the substantial
variabilities in patients’ capacities to tolerate pain and
in their responses to opioids. Some clinicians, out of an
exaggerated concern for the possibility of inducing
addiction, tend to prescribe initial doses of opioids that
are too small or given too infrequently to alleviate pain
and then respond to the patient’s continued complaints
with an even more exaggerated concern about drug
dependence despite the high probability that the request
for more drug is only the expected consequence of the
inadequate dosage initially prescribed. Infants and children
probably are more apt to receive inadequate treatment
for pain than are adults owing to communication
challenges, physician’s lack of familiarity with appropriate
pain assessment methodologies in this population,
and inexperience with the use of strong opioids in
children. If an illness or procedure causes pain for an
adult, there is no reason to assume that it will produce
less pain for a child (Yaster and Deshpande, 1988).
Pain of Terminal Illness and Cancer Pain
Opioids are not indicated in all cases of terminal illness,
but the analgesia, tranquility, and even euphoria afforded
by the use of opioids can make the final days of life far
less distressing for the patient and family. Although physical
dependence and tolerance may develop, this possibility
should not prevent physicians from fulfilling their
primary obligation to ease the patient’s discomfort. The
physician should not wait until the pain becomes agonizing;
no patient should ever wish for death because of a
physician’s reluctance to use adequate amounts of effective
opioids. This sometimes may entail the regular use
of opioid analgesics in substantial doses. Such patients,