Proactively addressing potential opioid-related side effects and knowing the factors that can affect how opioids are metabolized can lead to more effective treatment.
At the 2012 annual meeting of the American Society of Interventional Pain Physicians (ASIPP), Andrea Trescot, MD, director of the Trescot Pain Fellowship at the Algone Pain Center in Wasilla, AK, described opioids as “extremely useful but potentially dangerous broad spectrum analgesics” that are associated with a range of potentially severe side effects that can reduce patient adherence and clinical efficacy if not recognized and managed. Trescot said that “understanding the pharmacology, metabolism, and genetics of opioids may help predict effectiveness and potential side effects.”
Side effects commonly associated with opioids include constipation, nausea, vomiting, sedation, and respiratory depression. Patients may forego the option of opioid therapy “even in the face of significant pain” to avoid some of the more severe side effects, Trescot said. Constipation, the most common opioid side effect, occurs in 40-95% of patients. Trescot recommended that clinicians treat opioid-induced constipation prophylactically with bulk laxatives, hyperosmotics, promotility agents, lubricants, stool softeners, and opioid antagonists. She said that clinicians should try several approaches to ensure success.
Another common side effect associated with opioids is nausea and vomiting, which can affect up to 25% of patients. Treatment options include promethazine (available in several formulations), scopolamine, metoclopramide (which also helps treat constipation), and ondansetron. Up to 10% of patients on opioid therapy also develop pruritis, which results from “a direct release of histamine, and is not usually an antigen/antibody reaction,” said Trescot. Treatment options include antihistamines such as diphenhydramine and cyproheptadine.
Sedation occurs in 20-60% of patients, is associated with initiation of opioid therapy or an increase in dosage, and is usually transient. This can be exacerbated by infection, dehydration, metabolic abnormality, or benzodiazepines, which Trescot strongly suggested that clinicians not prescribe to patients on opioid therapy. She said that opioid-induced respiratory depression is rare, and is “less of a problem with oral opioid medications.” However, she did note that “a significant portion of patients taking long-term, opioids develop central apnea during sleep, and advised clinicians to “test your obese patients for sleep apnea.”
Opioids can also produce endocrine effects in patients. For example, Trescot noted that one study found that amenorrhea developed in 52% of female patients treated with opioids for chronic pain. Another study found subnormal testosterone levels in 74% of males treated with sustained-release oral opioids. Osteoporosis, another side effect associated with chronic opioid use, may be due to endocrine effects. Because this is often not diagnosed until after patients suffer a fracture. Trescot advised clinicians to include bone density testing as part of routine screening in this patient group.
Trescot also discussed the phenomenon of opioid-induced hyperalgia (OIH) and potential treatment options for it. She said that OIH (defined as pain sensitization from chronic opioid treatment), “is often overlooked as a potential complication of opioid therapy,” and should be suspected when “opioid treatment effectiveness seems to wane in the absence of disease progression,” especially if found in the context of unexplained pain, if the patient “reports diffuse allodynia not associated with the original pain,” or the patient reports increased levels of pain despite increased opioid dosing.
OIH can be treated by:
According to Trescot, it is also important to consider several genetic and metabolic factors that can alter the analgesic effect of opioids. She said that many opioids “are potentially prodrugs that require metabolism to a more active compound,” for example oxycodone is metabolized to oxymorphone, and many opioids are metabolized through the cytochrome P450 2D6 (CYP2D6) pathway, so that anything that interferes with this pathway can have a significant impact on the drug’s effect and concentration in the system. Some antidepressants (such as fluoxetine) and other drugs can inhibit the CYP2D6 pathway, and a sizeable percentage of the population has some form of genetic abnormality that affects CYP2D6 metabolism (some are poor CYP2D6 metabolizers, soe are “ultrarapid” metabolizers). These metabolism effects can be particularly important to consider when deciphering urine drug test results showing the unexpected presence or absence of opioid metabolites.
In closing, Trescot reminded the audience that opioids are not always effective analgesics, and that understanding why the drugs they have prescribed to a patient may not be having the desired effect requires clinicians to consider the possible genetic and drug-drug interactions that may be affecting the patient’s ability to metabolize the prescribed opioids. She advised the audience to evaluate their patients’ medication lists, consider genetic testing in the face of potential abnormal metabolic effects, to be vigilant for OIH, and monitor for endocrine effects.