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Opioid Pain Management

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Balancing the risks and benefits
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  46   DRUG TOPICS   September 2011 DrugTopics.com Continuing Education  I n the United States today, pain is the single most com-mon reason for seeking medical care. An estimated 9% of American adults report moderate to severe noncancer pain — the focus of this article — and many of these patients report suboptimal pain management. 1  Thirty-five percent of Americans suffer from chronic pain and more than 50 mil-lion Americans are partly or totally disabled by chronic pain. In addition, 50 million workdays are lost per year, and the estimated annual cost in lost productivity, medical costs, and lost income is $560 billion to $635 billion. 2,3  Yet 40% to 50% of patients in routine practice settings fail to achieve adequate pain relief. 4  This establishes that much more needs to be done to educate healthcare professionals in the safe and proper use of the most effective class of pain medications, the opioids. It is hoped that this educational activity will contribute to the achievement of that goal.  Barriers to the use of opioid therapies Although opioids provide effective pain relief, there are several potential barriers to their use. These include poor communication between healthcare provider and patient, fear of disciplinary action or prosecution on the part of the provider, concern for potential abuse, inadequate training, patient factors (including fear of addiction and side effects), socioeconomic and psychological factors associated with tak-ing opioids on a chronic basis, lack of knowledge on the part of the patient, and possibly reimbursement issues, depending on the situation. At the same time, there are clear data to show that pa-tients are undertreated for pain. 5-7  Prescribers are often un-willing to treat pain sufficiently or aggressively, and in some cases they fail to take it seriously or they place it low on their AN ONGOING CE PROGRAM OF THE UNIVERSITY OF CONNECTICUT SCHOOL OF PHARMACY AND DRUG TOPICS Jeffrey Fudin, BS, PharmD, FCCP ADJUNCT ASSOCIATE PROFESSOR, PHARMACY PRACTICEALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCESALBANY, N.Y. Opioid pain management: Balancing risks and benefits    G   E   T   T   Y   I   M   A   G   E   S   /   O   J   O   I   M   A   G   E   S   /   T   O   M    M   E   R   T   O   N Faculty : Jeffrey Fudin, BS, PharmD, FCCP . Dr. Fudin is a clinical pharmacy specialist at the Stratton Veterans Administration Medical Center in Albany, NY. He is also a Diplomate to the American Academy of Pain Management, founder and CEO of NovaPain Associates, and adjunct associate professor of Pharmacy Practice at Albany College of Pharmacy & Health Sciences. Faculty Disclosure : Dr Fudin has received fees for non-CME services from PriCara and Cumberland Pharmaceuticals Inc. Disclosure of Discussions of Off-Label and Investigational Uses of Drugs:  This activity may contain discussion of unlabeled/unap-proved use of drugs for pain management. The content and views presented in this educational program are those of the faculty and do not necessarily represent those of Drug Topics or University of Connecticut School of Pharmacy. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.  Abstract   Pain has a high prevalence in medical practice, yet nearly half of all patients do not receive adequate treatment for pain. Al-though a wide variety of opioids provide effective pain relief, barriers to their use often result in undertreatment, especially  for chronic pain. Extended-release products are most useful in treating chronic pain, while rapid-release products are most useful in controlling acute and breakthrough pain. Opioids work as agonists and/or antagonists at endogenous delta, kappa, and mu opioid receptors and mostly belong to one of  four chemical categories: phenanthrenes, benzomorphans,  phenylpiperidines, or diphenylheptanes. Patients’ adverse re-actions to the members of one class are often a predictor of how they will react to other members of that class. Opioids such as methadone that block NMDA receptors may be particularly effective in treating neuropathic pain, but the long half-life and polymorphic differences associated with methadone re-quire careful dosing strategies as well as a specific method for calculating dosing equivalencies when patients transition to methadone from other opioids. Bone pain, connective tissue  pain, and neuropathic pain usually require adjuvant thera- pies with NSAIDs, anti-inflammatories, or anticonvulsants, although these medications may increase the risk of undesir-able side effects, especially in elderly patients. Risks of opioid therapy include gastrointestinal disorders, hyperalgesia, and addiction/abuse. New “abuse-deterrent” formulations have become available, and FDA’s new Risk Evaluation and Miti- gation Strategy (REMS) program is currently focused on edu-cating healthcare providers about the risks and appropriate use of extended-release and rapid-onset opioids.  September 2011   DRUG TOPICS   47 DrugTopics.com   EDUCATIONAL OBJECTIVES EARN CE CREDIT FOR THIS ACTIVITY AT WWW.DRUGTOPICS.COM   CREDIT: 2.0 Goal:  To assist pharmacists and pharmacy technicians with pain management issues related to risks and ben-efits of opioid use in their practice settings. After participating in this activity, pharmacists should be able to: Describe the risks and benefits of opioid and nonopioid agents available for pain relief.   Describe the techniques for minimizing multiple dosing and overdosing, and calculate opioid equivalencies.   Respond appropriately to patients’ allergic reactions to opioids. Select the optimal opioid agent(s) for treatment of patients with specific comorbidities.After participating in this activity, pharmacy technicians should be able to: Describe the risks and benefits of opioid and nonopioid agents available for pain relief.   Identify the techniques for minimizing multiple dosing and overdosing.   Recognize appropriate responses to patients’ allergic reactions to opioids.  The University of Connecticut School of Pharmacy is ac-credited by the Accreditation Council for Pharmacy Edu-cation as a provider of continuing pharmacy education. Pharmacists are eligible to participate in both the knowledge-based and application-based activities, and will receive up to 0.2 CEUs (2 contact hours) for completing the activity/activities, passing the quiz/quizzes with a grade of 70% or better, and com-pleting an online evaluation. Statements of credit are available via the online system. Pharmacy technicians are eligible to participate in the knowl-edge-based activity and will receive 0.1 CEU (1 contact hour) for completing the activity, passing the quiz with a grade of 70% or better, and completing the online evaluation. Statements of credit are available via the online system.   ACPE # 0009-9999-11-024-H01-P/T  ACPE # 0009-9999-11-025-H01-P  To obtain immediate CPE credit, take the test online at www.drugtopics.com/cpe . Just click on the link you find ( CPE Activi- ties: Free CPE ), which will take you to the CPE site. For first-time users, please complete the registration page. For those already registered, log in, find, and click on this lesson. Test results will be displayed immediately and you will receive a printable state-ment of credit by e-mail, showing your earned CPE credit. For questions concerning the online CPE activities,e-mail cpehelp@advanstar.com. Initial release date: 9/1/2011Expiration date: 9/1/2013 Grant Funding:  Funding for this activity was provided by: Cephalon; Endo Pharmaceuticals, Inc.; Purdue Pharma L.P. Activity Fee:  There is no fee for these activities.  48   DRUG TOPICS   September 2011 DrugTopics.com Continuing Education OPIOID PAIN MANAGEMENT priority list of medical problems to address. Among prescribers there is lack of knowledge about pain, fear of tolerance and addiction to opioids, and fear of regulatory agencies. 8 Regulatory issues vary by state. Most states have “prescrip-tion monitoring programs” that track controlled substance pre-scriptions, while others, unfortunately, do not. But that is now changing. Figure 1  is a schematic of various states and their position with regard to prescription monitoring. 9 Acute vs. chronic pain Acute pain typically has a clearly identifiable cause. 10-11 We know what the issues are; most acute pain is readily treat-able; and the pain will subside within an expected period of time. Chronic pain, on the other hand, is defined as pain that has been present for 3 months or longer, and it does not necessarily have an identifiable pathology. 12  It often involves sleep deprivation as well as a host of other behavioral health issues, such as anxiety and depression. 13  Often, chronic pain cannot be measured as readily as acute pain. Sedation for acute pain may be desirable in situations where the patient is anxious about the pain; for example, when someone has an acute debilitating injury requiring sur-gery, sedation may be appropriate. Sedation is generally not desirable in the treatment of chronic pain. There may be some end-of-life situations, however, in which the patient may be so distressed that sedation would be an appropriate palliation. 14 As with any chronic disorder, patients with chronic pain need to be on a regular dosing schedule, and PRN should be used only for breakthrough pain. If a patient is receiving a PRN prescription every 30 days, the pharmacist should contact the prescriber and suggest that the patient be switched to an extended-release product, because it is no longer a PRN situ-ation. Meanwhile, the patient is being exposed to peaks and troughs, which could adversely affect both mood and toxicity. The Clinical Treatment Guidelines from the American Pain Society (APS) and the American Academy of Pain WAORCANVUT  AZ AK GU TX LANMCOWY IDMT NDSDNEKSOK  ARMOIAMNWIILINOHWY  VANCSCGA ALMSFLPANY ME VT NHMARICT NJDEMDDCMIKY HI Figure 1. Status of prescription drug monitoring programs (PDMPs) as of May 2011 Operational PDMPsEnacted PDMP legislation, but program not yet operationalLegislation pending  Research is current as of May 16, 2011Source: Ref 9   September 2011   DRUG TOPICS   49 DrugTopics.com  CONTINUING EDUCATION Management (AAPM) for noncancer pain include defini-tions of “monitoring use” and “therapeutic goals.” 12 How opioids work 15 Agonists are those medications that have a binding affinity to the opiate receptors. Agonists cause analgesic activity and respiratory depression, decrease gastrointestinal (GI) activ-ity, and have a number of other effects, depending on their association with receptor type(s) and the binding affinities. Opioids work as agonists, antagonists, or mixed agonist/an-tagonists at various endogenous opioid receptors. The vari-ous opioid receptors include delta, kappa, and mu. Mu-1 plays the largest role in analgesia. 16 The antagonists have a higher affinity for those same opi-ate receptors, but they do not have analgesic activity. Using the metaphor of the lock and key, the opiate represents the key, the receptor represents the corresponding keyhole, and they are both magnetized. In this case, the antagonist key may be a stron-ger magnet, but it cannot turn the lock. Mu and kappa opioid receptors cause analgesia. 16  Mu-1 receptor ago-nists that have some degree of kappa activity are the most useful for anal-gesia. 16  Mu-1 receptor subtypes have  been isolated, indicating that genetic polymorphism is an important consid-eration in therapeutic response. 16  Mu-2 receptors, on the other hand, are most often associated with bothersome opioid side effects rather than analgesia. 16  Delta receptors have been studied, but thus far none has been approved for human use. 16   Choosing a specific opioid As shown in Figure 2  (page 50), there are four categories of opioids, plus a fifth category of “hybrids.” It is important to remember that if a patient cannot tolerate one member of a certain class, that patient is less likely to tolerate another medication from the same category. On the other hand, the patient may be able to tolerate an opioid that belongs to a different chemical class. 17 It is important to know, as Figure 2  makes clear, that certain medications in the phenanthrene class are missing a hydroxyl group, while others are not. The ones lacking the 6-hydroxyl group are marked with an asterisk ( Figure 2 ). In the author’s experience, these medications tend to be better tolerated than the phenanthrenes with that hydroxyl group. 18  For example, if a patient can tolerate hydrocodone but needs an extended-release product, then the patient will tolerate oxymorphone or oxycodone, because those two medications lack the 6-hydroxyl group just as does hydrocodone. The pa-tient who cannot tolerate codeine is very unlikely to tolerate morphine, because codeine is metabolized to morphine, and they are both hydroxylated. 18 If a patient is able to tolerate meperidine, then that patient also will be likely to tolerate fentanyl, because fentanyl and me-peridine are in the same chemical class. Figure 2  is organized so that the risk of cross-allergenicity decreases as one moves from left to right on the chart. Although true allergic reactions to opioids are relatively rare, a patient with a true allergy to oxy-codone also will be allergic to all the other medications in that class. 18  As will be discussed later, morphine is not a good medi-cation to use in a patient with compromised renal function. For patients who are not tolerant of the drowsiness associated with opioids, oxycodone might be a useful option, because it often causes wakefulness, agitation, and insomnia. 19  The benzomor-phans are generally not used for pain management, but they are used to decrease motility for patients with diarrhea. The next group of medications is the phenylpiperidines, which includes the fentanyl family as well as meperidine. Fentanyl and its chemical relatives (alfentanil, sufent-anil, and remifetanil) have the least his-tamine reactivity compared to all other opioids, and therefore are among the most well tolerated. 20 If transdermal fentanyl is most de-sirable and a patient regularly experi-ences breakthrough pain prior to the scheduled 72-hour-interval change, the manufacturer recommends either re-ducing the dosing interval to 48 hours or increasing the dosage while keeping the interval constant. 21  The author rec-ommends reducing the dosing interval as the preferred strategy, since a higher-dose patch will deliver more medication than the patient actually requires. 22  If a rash develops beneath the patch, consideration could be given to using triamcinolone in the form of aerosol spray on the area just before placement. Providers occasionally prescribe oral inhaled steroids, otherwise intended for administration with handheld devices, to prevent skin irritation, but this has not been studied and is not FDA approved for this purpose. Also, it is far more expensive and certain inhalers have built-in spacers that would preclude ex-ternal application applicability. Topical creams, ointments, or gels are not options because they would compromise patch adhesion. Finally, if patch adherence is a problem, an occlusive dressing may be placed over the fentanyl patch. Meperidine is one of the most toxic opioids, and it has a very high incidence of neurotoxicity (including escalated seizure risk) due to its desmethyl-meperidine (also known as nor-meperi-dine) metabolite. Caution should be exercised if meperidine is dispensed with other medications that reduce seizure threshold, such as theophylline, phenothiazines, SSRIs, and SNRIs. Both fentanyl and hydromorphone offer viable alternatives for paren-terally administered patient-controlled analgesia (PCA) in patients who are unable to tolerate morphine. 23 Most opioids may be used in the presence of hepatic dys-function if use is started at low doses and carefully escalated, as  There are four categories of opioids, plus a fifth category of “hybrids.” It is important to remember that if a patient cannot tolerate one member of a certain class, that patient is less likely to tolerate another medication from that category.
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