Morphine
Morphine remains the standard
by which other anal-gesic drugs are compared. The predominant effects of
morphine are at the μ-opioid receptor, although it in-teracts with other opioid
receptors as well. Morphine is indicated for the treatment of moderate to
severe and chronic pain. It is useful preoperatively for sedation, anxiolytic
effects, and to reduce the dose of anesthetics. Morphine is the drug of choice
for the treatment of myocardial infarction because of its bradycardiac and
vasodilatory effects. In addition, morphine is the most commonly used drug for
the treatment of dyspnea-associated pulmonary edema. It is thought that mor-phine
reduces the anxiety associated with shortness of breath in these patients along
with the cardiac preload and afterload.
The use of morphine via the
oral route has draw-backs because of its first-pass effect; however, oral
mor-phine has been recommended for use in cancer patients for its ease of
administration. In particular, the long-acting preparations of morphine, such
as MS-Contin and Ora-Morph, are described as the cornerstone of pain treatment in
cancer patients, either alone or in combination with nonopioids.
Morphine is the most commonly
used analgesic drug administered via the epidural route because it is potent,
efficacious, and hydrophilic. The more hydrophilic the drug, the slower the
onset and the longer the duration of action following epidural administration.
Single-dose or continuous infusion of morphine is used to provide pain relief
in thoracic and abdominal surgical patients and in cancer patients at high risk
for developing side effects associated with systemic opioids. Since morphine
does not produce anesthesia via the epidural route, the patient is able to move
about normally; motor function is preserved. The drawback to epidural use of
morphine is that certain types of pain are relatively unresponsive, such as
that associated with visceral stimuli, as in pan-creatitis, and neuropathic
pain from nerve deafferenta-tion. In addition, patients can develop respiratory
de-pression and nausea from the rostral flow of the drug to medullary centers,
although the effects are much less se-vere than those observed following the
systemic admin-istration of the drug, and can be alleviated by elevation of the
head of the patient at a 30-degree angle. Patients may also itch because of
histamine release.
Patient-controlled analgesia
(PCA) is an alternative method of administration of morphine. The use of an
in-dwelling catheter allows the patient to administer the drug at frequent
intervals for pain relief. PCA systems allow patients the freedom to assess the
need for their own analgesia and to titrate a dose tailored to their needs.
Dependence is rarely observed in patients using PCA for acute pain management.
The opioids generally have a
high level of safety when used in therapeutic dosages. However, there are several
notable exceptions. Morphine and other opioids are contraindicated in patients
with hypersensitivity reac-tions to the opioids. In addition, morphine should
not be used in patients with acute bronchial asthma and shouldnot be given as
the drug of first choice in patients with pulmonary disease, because it has
antitussive effects that prevent the patient from clearing any buildup of mucus
in the lungs. Opioids with less antitussive effects, such as meperidine, are
better for such situations.
When used via the epidural
route, the site for injec-tion must be free of infection. In addition, the use
of corticosteroids by the patient should be halted for at least 2 weeks prior
to the insertion of the catheter to prevent infection, since morphine increases
the im-munosuppressive effects of the steroids.
Opioids are contraindicated
in head trauma because of the risk of a rise in intracranial pressure from
vasodi-lation and increased cerebrospinal fluid volume. In ad-dition, in such
patients the onset of miosis following opi-oid administration can mask the
pupillary responses used diagnostically for determination of concussion.
The clearance of morphine and
its active metabolite, morphine-6-glucuronide depends on adequate renal
function. The elderly are particularly susceptible to ac-cumulation of the
drugs, hence respiratory depression and sedation. Morphine, like all opioids,
passes through the placenta rapidly and has been associated with pro-longation
of labor in pregnant women and respiratory depression in the newborn.
Morphine and other opioids exhibit intense sedative effects and
increased respiratory depression when com-bined with other sedatives, such as
alcohol or barbitu-rates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic
drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the
anxiolytics, such as diazepam.
Respiratory depression,
miosis, hypotension, and coma are signs of morphine overdose. While the IV
ad-ministration of naloxone reverses the toxic effects of morphine, naloxone
has a short duration of action and must be administered repeatedly at 30- to
45minute in-tervals until morphine is cleared from the body.
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