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Palliative Care Perspectives : Chapter 4: Pain Management : Routes of Opioid Administration

Routes of Opioid Administration

I turn now to a more detailed discussion of the use of opioids. As mentioned in the section on pain strategy, having considered specific side effects to be avoid and "two-fers," the route of therapy is usually a key consideration in choosing a particular agent.

Oral Route

Generally, the oral route is the preferred route of administration. It is easy to use, and medications are generally cheaper. The oral route also maximizes patient autonomy. It works poorly if patients have trouble swallowing, are intermittently nauseated, or need rapid onset of analgesia. Patients on oral opioids who have nausea and vomiting may have a particularly difficult time reaching a steady state of opioid blood level, which perpetuates nausea. Confused patients and patients dependent on others for administration may have difficulty complying with oral regimens, especially if short-acting agents are relied upon. Short-acting oral agents, which generally take an hour to reach peak effect, do not work as fast as parenteral agents, which may be a disadvantage if rapid analgesia is desired. This delayed time to peak effect risks slow titration to adequate analgesia or (if additional doses are given prior to peak effect) a "stacking" of multiple doses, resulting in overdosage. On the other hand, use of oral agents, especially long-acting opioids, may avoid possible toxicities associated with rapid increases in blood opioid levels. Some patients may prefer equianalgesic parenteral doses of drugs, believing a shot or injection is more potent. As injections usually take more work on the part of the administrator or nurse, a preference for parenteral injections may reflect a desire for more hands on care. I have noticed this tendency particularly in fearful and isolated dying patients.

Enteral Tubes

Nasogastric (NG), percutaneous endoscopically placed gastrostomy (PEG) tubes, and jejunal (J) tubes, if already present, may also be used for drug delivery. These tubes overcome the inability of patients to swallow. More noxious agents, such as concentrated liquid morphine, which is bitter, can be easily administered. Absorption of some drugs may be limited if the patient is vomiting or has significant intestinal obstruction. Probably the greatest problem associated with tubes is the administration of long-acting opioids. SR opioids, such as SR morphine and SR oxycodone, cannot be crushed, as to do so would release the total drug in a short-acting and excessively strong form. Methadone in liquid form or Kadian (morphine in polymeric bead form, which is expensive) can be used if administration of a long-acting agent by tube is desired.

Transdermal Route

Currently, the only major opioid available by the transdermal route is fentanyl. The transdermal route is useful when the enteral route cannot be used. Nauseated patients, patients with poor compliance, and patients unable to swallow are all potential candidates. It takes at least 12 hours (12 to 22 h) for fentanyl to work by the transdermal route. When removed, serum levels fall, on average, 50% in 17 hours.42 Because of this slow onset and offset of serum levels, fentanyl is useful only for stable, chronic pain and should not be used to treat acute pain. Transdermal fentanyl also works poorly for patients who have very high opioid needs (generally above 500 mcg/h - five 100 mcg/h patches), as patients tend to have difficulty tolerating more than five patches. Transdermal fentanyl is relatively expensive compared to long-acting oral opioid preparations.


Fentanyl is now available as a lozenge that can be administered through the buccal mucosa. Although expensive, this approach allows rapid onset of analgesia (about 20 minutes) without parenteral administration.43


Used primarily in the treatment of dyspnea, opioids administered by a nebulizer can allow rapid peak blood levels, comparable to parenteral administration.44 Bioavailability via this route is a subject of debate. It would be safest to assume a high degree of bioavailability and then titrate the medication up, based on patient response. Only IV preparations are used for aerosols, with similar peak levels to those obtained using IV administration. Morphine is most commonly used. Care must be taken as, morphine can theoretically release histamine locally, causing bronchospasm, although the clinical significance of this is debatable. I have not seen a patient in which this has happened. All patients I have treated via this route tolerated morphine via other routes without pruritus. It may be wise to give patients who have not previously taken morphine a test dose via another route before giving aerosolized morphine.

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Palliative Care Perspectives

James L. Hallenbeck, M.D.

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Copyright 2003 by Oxford University Press, Inc.

The online version of this book is used with permission of the publisher and author on web sites affiliated with the Inter-Institutional Collaborating Network on End-of-life Care (IICN), sponsored by Growth House, Inc.