Common side effects of opioids

From the December ACP Observer, copyright © 2004 by the American College of Physicians.

You need to carefully watch patients on long-term opioids for potential side effects, and use the necessary means to counteract them. Patients can develop intolerable side effects to an individual opioid. In some cases, another opioid will not cause side effects to the same extent, making switching to an alternative opioid a reasonable option.

Keep in mind that opioid-naive patients are more susceptible to respiratory depression than patients receiving long-term opioids. You therefore need to provide careful follow-up when initiating opioids in those who are opioid-naive.

Constipation is an almost inevitable side effect of chronic opioid therapy and should be anticipated. Constipation can be prevented or minimized with regularly scheduled doses of stool softeners and agents to increase motility.

A constipation prevention regimen could include:

• docusate;

• bisacodyl or senna concentrate; and

• a hyperosmotic agent such as milk of magnesia or lactulose.

Treat opioid-related nausea and vomiting with a phenothiazine antiemetic, transdermal scopolamine or hydroxyzine. Some patients will experience less nausea if the opioid blood level remains constant throughout the day rather than with period peaks.

Changing the dosing interval of an immediate release preparation from every four hours to a smaller dose every three hours may stabilize the blood level and reduce nausea and vomiting. Changing to a sustained release opioid or the transdermal route will also produce more constant opioid blood levels and may be helpful.

Adding a stimulant can sometimes successfully treat sedation. Stimulants include caffeine, dextroamphetamine and methylphenidate.

You need to prescribe an antihistamine for opioid-related itching and urticaria due to the release of histamine. Oxymorphone and fentanyl are two opioids that do not release histamine, so consider switching to one of those.

Patients quickly develop tolerance to an opioid's respiratory-depressant effects, and respiratory depression is rare in patients on chronic opioid therapy.

High-risk patients are those who are opioid-naive and require high doses to treat acute pain. In some circumstances, careful and close observation and physical stimulation to keep the patient awake may be all that is needed until the opiate level declines, generally within three to four hours.

When rapid reversal of opiate depression is indicated, you can administer naloxone in small increments to improve respiratory function without totally reversing analgesia. Until an episode of respiratory depression resolves, all patients require careful monitoring.

Meperidine and mixed agonist-antagonist analgesics

After repeated doses of meperidine, the toxic metabolite normeperidine accumulates and can produce anxiety, tremors, myoclonus and seizures. Because the kidneys excrete the metabolite, patients with renal insufficiency are at particularly high risk for this complication.

Meperidine should not be dosed beyond 48 hours and is not indicated in the management of chronic pain. The use of meperidine in biliary disease is over-rated and offers no proven advantage over morphine.

And in treating pain, mixed agonist-antagonist drugs offer no advantages over morphine-like drugs and can precipitate opioid withdrawal symptoms when given to patients taking chronic morphine-like opioids.

Special issues in opioid treatment of chronic non-malignant pain

• Establish that nonopioid therapy does not control the pain.

• Explain the potential benefits and pitfalls of long-term opioid therapy.

• Establish agreed-upon treatment goals.

• Consider a written plan that specifies both physician and patient responsibilities.

• Ensure careful follow-up.

• Use adjuvant pharmacologic and nonpharmacologic therapy whenever possible.

• Monitor for signs of opioid abuse.

• Consider weaning and discontinuing opioid therapy if treatment goals are not met, or if you see evidence of addiction or noncompliance.

• Avoid meperidine after 48 hours of dosing or for chronic pain management.

• Avoid drugs with mixed agonist-antagonist properties.

For more information, see "Suggested protocol for opioid therapy."

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When should you consider consultation?

• Refer patients for invasive procedures when noninvasive measures provide inadequate relief or produce intolerable side effects.

• Refer patients with difficult-to-manage chronic pain syndromes to multidisciplinary pain treatment groups.

• Consult specialists with expertise in both pain and addiction management for patients with current or past history of substance abuse or addiction.

• Consider nondrug interventions for all patients with significant, persistent or recurrent pain.

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Treating older patients

When treating older patients with opioids, you should apply the same general principles as in care for younger adults. However, you need to consider age-related factors and specific dosing recommendations. Those include:

Slowly and carefully titrate opioids, having specific subjective and objective end points in mind, such as 50% of usual adult starting dose.

For patients with severely debilitating pain, titrate the opioid rapidly and consider hospital admission for diagnosis, aggressive treatment and close monitoring.

Simplify drug regimens as much as possible and adjust them to meet individual needs, lifestyle and care settings.

Be aware of common economic barriers, including limited Medicare reimbursement for outpatient oral medications, restricted formularies and delays from mail order pharmacies in some managed care plans. One noteworthy exception: The Medicare Hospice Benefit covers the cost of all medications associated with the diagnosis that prompted hospice admission.

Do not prescribe propoxyphene or meperidine for older patients. Neuroexcitatory side effects may be more likely in this population because of central sensitivity and subclinical renal insufficiency.

Use methadone very cautiously because its long and variable half-life makes it especially problematic in older patients. Adverse effects from drug accumulation may arise several days after regular dosing begins.

If the patient drives, consider restricting driving until doses are stable and cognitive capacity is reassessed.

For patients with borderline mobility capabilities and a propensity for falls, monitor carefully for increased gait and balance disturbances.

Warn patients that chewing or crushing continuous release tablets destroys their controlled release properties and causes rapid absorption of the entire dose, which may result in overdose.

Adapted with permission from Fine PG and Portenoy RK: A Clinical Guide to Opioid Analgesia, 2004. ©2004, by The McGraw-Hill Companies Inc.

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