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Objective 4: Understand the routes of administration available for opioids, and know the major advantages and disadvantages for each.

A. Oral Administration
B. Transdermal
C. Other GI Routes
D. Parenteral Administration

A. Oral Administration is best for most patients. It is the preferred route of administration because of increased patient convenience, lower cost, and reduced invasiveness. "Simpler is better."

B. Transdermal administration is also a good choice for many patients.  It is a useful alternative for patients who cannot take oral medication.  It is helpful not only when nausea and vomiting prevent oral use but also in patients who are reluctant to take medication. Finally, it can be great for those in “marginal” care-giving situations, where getting oral medication on a regular schedule may be an issue.

Continuous absorption has significant potential advantages: avoiding fluctuations in serum levels can reduce peak-related side effects and minimize breakthrough pain at the trough.

C. Other GI Routes [back to top]

1. Rectal administration is commonly used though not well studied.  Both regular and sustained release opioids can be given rectally.  This may be a useful alternative for patients who cannot take oral medication, especially in the active dying phase. The dosing is 1:1 with the oral medication used previously.  Absorption and effect may vary according to how high the suppository is placed -  the lower area is drained by veins that do not enter the hepatic venous system and thus avoid the first-pass effect.  This consideration is not usually of clinical significance.

Be sensitive to the discomfort that family members may feel about administering medication by this route, and the fact that few patients find it acceptable  on an ongoing basis. 

2. Transmucosal (sublingual/buccal) administration of morphine is commonly used although not well-studied. It is an additional useful alternative route for delivering opioids to patients who cannot swallow. Either elixir or crushed tablets can be used; the solution allows for finer titration. Many experts believe that this route actually works by slow swallowing of the medication over a period of time.

Fast Fact: Sublingual morphine

Fentanyl is also available in transmucosal/buccal preparations that are well-studied. This form of dosing provides a more rapid onset of analgesia than other oral opioids—more useful for sudden and intense breakthrough pain. It is also far more expensive. Like the transdermal form, transmucosal or buccal fentanyl should never be used by opioid-naïve patients.

D. Parenteral Administration [back to top]

1. Subcutaneous (SQ) administration is an excellent alternative for patients who cannot take oral medication and in whom intravenous access is not desirable or is difficult. Dosing is 1:1 with IV / IM medication.  The drugs may be given as repeated intermittent bolus or continuous infusion (see below). 

This technique is safe and simple enough for home use.  The patient can be mobile, and typically finds this route more comfortable than repeated IV placement.  A 25 or 27 gauge butterfly (needle with stabilizing side wings along with short tubing and a cap) can be inserted subcutaneously, covered by a transparent dressing (e.g. Opsite) and left in place for extended periods.   Special subcutaneous “buttons” (very short needles with a firm flat top) are also available for ongoing subcutaneous administration.

Fast Fact: Subcutaneous Infusions

2. Intramuscular (IM) administration is not recommended.  it is not only more painful but it also provides slower and more erratic absorption than subcutaneous administration.

3. Intravenous (IV) administration is the standard route in the hospital setting, and it has the advantage of rapid onset of action.  However, it is often difficult to maintain IV access over extended periods of time.  The exception is the patient who has a port inserted for chemotherapy or a midline catheter placement for other treatments, where ready IV access is available.

4. Continuous infusions may be IV or SQ.  This requires a pump and a highly concentrated solution of opioid (mainly morphine or hydromorphone – both are highly soluble so the total volume being administered can be kept relatively low, [an important consideration for subcutaneous administration of higher doses].  

Most pumps available in the US can be programmed to include a patient-controlled analgesia (PCA) mode to include bolus therapy controlled by the patient at a predetermined dose and interval. The safety of such self-management has been demonstrated clearly, and most studies show that patients actually use less total opioid when they have a PCA.

5. Epidural administration is clearly beneficial to occasional patients (such as those with severe side-effects from systemic medication or those with severe lower body pain only).  However, it is difficult to identify prospectively the patients who will benefit.  No randomized trials have demonstrated superiority of epidural administration over oral therapy in either pain relief or side-effects in unselected populations.  Disadvantages of the epidural route include site maintenance and changing, technical assistance needed, negative psychological associations for patients or families, low but definite risks of infection or catheter migration, and expense.

Fast Fact: Epidural Analgesia

Next: Examples of Changing Routes of Administration

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