Routes of Administration

Opioids are the mainstay for pain management and are available in oral, neuraxial, rectal, transdermal, and intravenous forms for delivery. Oral administration is an easy, relatively inexpensive, and effective method for delivery of opioids. Despite significant first-pass effect with some oral opioids (e.g., oral morphine only has 25% of total dose available), the vast majority of patients are able to use oral dosing to provide for their analgesic needs. Concerns over incomplete bioavailability, peak levels, and analgesic onset are overcome with proper scheduling and dosing adjustments. Duration of action can be increased with sustained release preparations.

Intravenous opioid administration is practical for treatment of acute pain following surgery or trauma. Intravenous delivery provides a quicker onset of analgesic activity, but offers no difference in potency, despite popular belief. Intravenous patient-controlled analgesia is commonly used to treat acute pain postoperatively and allows the patient to self-administer analgesics. Hourly limits and lock-out intervals add to the safety profile of this device. Chronic pain patients, for various reasons, occasionally need intravenous administration of opioids. The major disadvantage of this route is the need of continuous intravenous access. Indwelling central or peripheral catheters incur significant cost with placement and maintenance. Additionally, they serve as an entry point for infection. Frequently, home health services are needed to administer the opioid intravenous infusion and maintenance care for the access catheter.

Intraoperatively, the primary intravenous agents used are morphine or a member of the phenylpiperidine family (fentanyl, sufentanil, or remifentanil). Sufentanil is the most powerful opioid mu-receptor agonist available for human clinical use and has been used for many years by cardiac anesthesiologists. Additionally, it has gained popularity in the intensive care unit. Critical care patients under mechanical ventilation require medications to enhance comfort and control noxious stimuli. Sufentanil provides fewer adverse respiratory effects than traditional opioids and enables quicker awakening than standard sedation medications for patients requiring frequent neurological evaluations (Giorgio et al. 2004, Conti et al. 2005).

Hydromorphone, morphine, and oxymorphone are available in rectal suppositories. Some of these preparations provide a more controlled release rate and higher bioavailability than oral preparations. Slow release morphine tablets have been given rectally when the oral route is not tolerable. Insertion of the suppository directly above the anal sphincter minimizes first-pass metabolism. The inferior and middle rectal veins do not drain into the portal circulation. However, higher placement of the suppository in the rectal vault can lead to drainage into the superior rectal vein and first-pass effect.

Another option for patients unable to take oral medications is the transdermal route. It is a noninvasive, avoids many of the gastrointestinal side effects, and, overall, is an effective manner for opioid delivery. Presently, fentanyl (Duragesic patch®, Janssen Pharmaceutica, Titusville, NJ) is the only medication available in this form. The delivery system includes a fentanyl reservoir, which contains a 3-day supply of fentanyl, and a controlling membrane. The medication is delivered through passive diffusion. The transdermal patches take up to 12 h to reach maximal blood levels and provide analgesia for 72 h (Giorgio et al. 2004). The major disadvantage of this route is the inability to rapidly increase or decrease blood levels. Transient and mild skin irritation can occur with transdermal patches. Rotation of skin sites has helped minimize this issue. Overall, this delivery system is well tolerated by chronic pain patients on chronic opioid doses.

Epidural and intrathecal administration of opioids is frequently used for management of postoperative pain. It is utilized by chronic pain physicians when other routes of administration are unable to provide adequate analgesia or when they are causing significant side effects. When placed neuraxially, small opioid doses provide profound analgesia. Fentanyl and morphine are the two most common opioids delivered by this route. The most worrisome side effect is delayed respiratory depression, which can occur up to 12 h after intrathecal administration. Because morphine is hydrophilic, it spreads rostrally and is a more common offender in causing delayed respiratory depression (Gupta et al. 1992).

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