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Chapter: Modern Pharmacology with Clinical Applications: Opioid and Nonopioid Analgesics

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Opioid Analgesics: Morphine

Morphine remains the standard by which other anal-gesic drugs are compared.

Morphine

Clinical Uses

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.

Adverse Effects and Contraindications

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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