CREDIT: 2.0 Continuing Education earn CE CREDIT for this activity AT www.DRUGTOPICS.com An ongoing CE program of The University of connecticut Educational Objectives school of and Drug Topics

Goal: To assist in recognizing common types, triaging acute and , and identifying appropriate medication selection for various pain types. After participating in this activity, pharmacists will be able to: l Describe the prevalence, consequences and costs of pain Pain management l Discuss the emerging role of the as ambassadors for implementing appropriate pain therapeutics for pharmacists: l Define common terms in pain management

l Describe the common types of pain and Concepts and definitions their presentation/symptoms

l Recall the of pain and Natsuki Kubotera, BA, PharmD Candidate 2013 perception Albany College of Pharmacy & Health Sciences, Albany, NY.

l Define dysesthesia, parathesias, , Jeffrey Fudin, BS, PharmD, RPh, DAAPM, FCCP , and Adjunct Associate Professor of Pharmacy Practice, Albany College of Pharmacy & Health Sciences, Albany, NY. l Discuss the ways pharmacists can assess and monitor painful conditions Abstract Pain and related symptom management involve complex polypharmacy, a keen understanding of pharmacotherapeutics, and interdisciplinary collaboration. This is the first in a series of pharmacist continuing education articles dedicated to pain The University of Connecticut School of management. Primary literature from pharmacy, , and recognize Pharmacy is accredited by the Accreditation an inadequate time commitment to pain management and appropriate medication Council for Pharmacy Education as a provider of continuing pharmacy education. . This, coupled with the necessary balance required for chronic therapy, Pharmacists are eligible to participate in the has become a therapeutic, political, and legal conundrum especially for prescribers knowledge-based activities, and will receive up to 0.2 and pharmacists. Epidemiologic and prevalence data for acute and chronic pain are CEUs (2 contact hours) for completing the activity, reviewed along with recent FDA developments and associated regulatory debates. passing the quiz with a grade of 70% or better, and An overview of the pharmacist’s role in pain and and the developing completing an online evaluation. Statements of credit are available via the online system. specialty practice in pain management are chronologically presented. Common medical terminology, pain pathophysiology, and descriptive pain types demarcated ACPE #0009-9999-13-006-H01-P with respect to acute, chronic, nociceptive, visceral, somatic, and neuropathic pain are reviewed. Physical findings such as dysesthesia, parathesia, allodynia, Grant Funding: As of March 11, 2013, funding for hyperalgesia, and hyperpathia are differentiated, and appropriate medications this activity is as follows: by pharmacotherapeutic class are outlined. Opportunities for medication therapy Supported by an educational grant from , L.P. management, responsibilities for the pharmacist provider, and the key role that pharmacists can provide for quality pain management outcomes are identified. Activity Fee: There is no fee for this activity.

Initial release date: 4/10/2013 Faculty: Natsuki Kubotera, BA, PharmD Candidate and Jeffrey Fudin, BS, PharmD, Expiration date: 4/10/2015 RPh, DAAPM, FCCP Ms. Kubotera is a 2013 PharmD candidate, Albany College of Pharmacy & Health Sciences, Albany, NY. To obtain immediate CPE credit, take the test She has accepted a PGY1 position at Providence Health and Services, Providence Portland and online at www.drugtopics.com/cpe. Just click St. Vincent Medical Centers in Portland, OR. Dr. Fudin is adjunct associate professor of pharmacy practice, on the link in the yellow boxy under Free CPE Albany College of Pharmacy & Health Sciences, Albany, NY, and owner and managing editor of PainDr.com. Activities, which will take you to the CPE site. For

Faculty Disclosure: Ms. Kubotera has no actual or potential conflict of interest associated with this article. o first-time users, please complete the registration t

Dr. Fudin is on speakers’ bureaus for Janssen Pharmaceuticals and Purdue Pharma. This commentary ho

page. For those already registered, log in, find, p k

is the opinion of Dr. Fudin alone and does not reflect the opinions of his employers, employee affiliates, c

and click on this lesson. Test results will be o t

and/or pharmaceutical companies that he has consulted for currently or previously. He is a consultant to S displayed immediately. Complete the evaluation i Practical Pain Management in the development of an online opioid calculator. /

form and Drug Topics will be electronically es Disclosure of Discussions of Off-Label and Investigational Uses of Drugs: This activity may contain discussion g

uploading your CPE credit to CPE Monitor via your ma NABP e-profile ID. You should be able to view of unlabeled/unapproved use of drugs. The content and views presented in this educational program are I

your credits earned within a two-week period of those of the faculty and do not necessarily represent those of Drug Topics or University of Connecticut Getty : e completing the evaluation. School of Pharmacy. Please refer to the official prescribing information for each product for discussion g

of approved indications, contraindications, and warnings. ima For questions concerning the online CPE activi- ties, e-mail: [email protected]. 36 Drug topics April 2013 DrugTopics.com continuing education

Pain Management Considerations in Medication Therapy Management CPE Series

Welcome to a new CPE series, Pain Man- Connecticut School of Pharmacy and agement of common pain conditions by agement Considerations in Medication Drug Topics. pharmacists, including , low Therapy Management, which has been This month, the professional devel- , , , strains, designed for pharmacists in all areas of opment activity will cover concepts and contusions, and generalized . practice who need to further their clinical definitions associated with pain manage- The Pain Management series will also and MTM skills in the management of ment. In May and June, the CPE activities be offering application-based activities patients with pain. Beginning this month will include and therapeu- for an additional 2 CPE credits. Online and continuing through August 2013, tics of pain medications. In July, regulatory interactive case-based studies will be pharmacists can earn up to 10 hours and ethical issues in pain management available with 1 hour of CPE credit, start- of CPE credit with 5 monthly knowledge- will be covered. The knowledge-based ac- ing September and continuing in October based activities from the University of tivities will conclude in August with man- 2013.

ain and related symptom manage- $635 billion per year.5 An estimated 20% Aside from the practical therapeutic ment often involves complex poly- of adults (42 million) report that pain or reasons, federal and state governments pharmacy, a keen understanding physical discomfort disrupts their sleep have sought to more closely scrutinize P 5 of pharmacotherapeutics across several several nights per week. and regulate through prescription drug classes, and collaboration with other programs and nonvalidated opi- healthcare disciplines. Undoubtedly the Chronic pain affects oid dose limitations to address increased time commitment to pain management from opioid abuse.11-13 This past education for entry-level graduates within 100 million people January, an FDA hearing took place to schools of pharmacy, medicine, and nurs- discuss the rescheduling of ing is lacking.1 Given that most complex in the U.S. and is combination products. On January 25, pain syndromes and palliative symptom 2013, an FDA advisory panel voted 19 management involve medications such the most common to 10 recommending to the FDA commis- as opioids, gastrointestinal (GI) agents, sioner that rescheduling for hydrocodone , , skeletal reason that patients combinations be changed to C-II status.14 muscle relaxants, and other medication On February 7-8, 2013, FDA held a classes alone or combined for purposes visit healthcare public hearing on the “Impact of Approved of pain management and other comorbid Drug Labeling on Chronic Opioid Thera- conditions, it is incumbent on pharmacists practitioners. py.”15,16 The purpose was to determine to seek professional advancement in pain whether all or part of a recent citizen’s management and secure a comprehensive In 2006, 46 and 35 million inpatient petition that requested label changes to role as interdisciplinary healthcare team and ambulatory , respectively, opioids should be adopted. The proposal members in all practice settings. Perhaps were performed in the U.S.6,7 In a national included the following label changes:16 most compelling is that even with numer- survey sampling 129 hospitalized surgical ous evidence-based pain practice guide- patients, 88% reported moderate, severe, The petition requests 3 changes by lines in place, patients continue to suffer or extreme pain on discharge.8 the FDA to opioid-product labeling: (1) needlessly, outcomes overall are poor, and In 2006, the Multum Lexicon database strike the term “moderate” from the society pays a high price figuratively and began collecting drug data for emergen- of opioid for non- practically through absenteeism, presen- cy rooms, and during that first year the (leaving “severe pain” as teeism (present at work under suboptimal most commonly prescribed drug classes the only indication); (2) add a maximum health conditions), and costs of suboptimal for each visit included opioid analgesics daily opioid dose, equivalent to 100 treatment strategies, resultant and and nonsteroidal anti-inflammatory drugs milligrams of for noncancer emergency department (ED) visits, hospital (NSAIDs) (collectively 36.8%).9 According to pain; and (3) add a maximum duration admissions, and readmissions.1-4 the National Hospital Ambulatory Medical of 90 days for continuous (daily) opioid Chronic pain affects 100 million peo- Care 2009 Emergency Department Sum- use for noncancer pain. ple in the U.S. and is the most common mary from the Centers for Control reason that patients visit healthcare prac- and Prevention (CDC), 5 of the 10 leading These maneuvers require careful bal- titioners, the leading cause of , principal reasons for ED visits included ance and must not project a negative and comes with a price tag of $560 to acute pain.10 impact on opioid availability to legitimate

DrugTopics.com April 2013 Drug topics 37 Continuing Education Pain management for pharmacists

table 1 bility during work.2 It leads to a significant Potential Problems Regarding Practice Issues decrease in productivity at work, incurring Practice issue barriers Potential problems an economic estimate of $150 billion per year in the U.S.21 Adequate treatment of Failure to use multimodal Miss the benefits of physical, behavioral, and psychological chronic noncancer pain is necessary, but approach approaches to help retrain the central nervous system and maximize functional recovery. despite available guidelines, often such al- gorithms are not effectively implemented. Failure to target the mechanism Suboptimal pain management. Table 1 illustrates the potential problems of pain generation (somatic, Avoidable costs when treatment ineffective. that may ensue if acceptable pain manage- inflammatory, neuropathic) ment needs are not adequately achieved.22 Failure to treat neuropathic pain Worsening nervous system hypersensitivity. Because the treatment of certain pain with adjuvant meds Suboptimal pain management. syndromes is complex, it is not uncom- Heavy reliance on short-acting Increased breakthrough pain, disturbed sleep. mon to use rational medication combina- opioids instead of prescribing Development of opioid tolerance. tions that include various pharmacologic long-acting opioids Acetaminophen toxicity (combination drugs). mechanisms in an attempt to achieve Increased risk of addiction in sub-population with potential synergistic or additive benefit while mini- for abuse. mizing medication .23 Elevated Source: Ref 22 (reprinted with permission) doses of monotherapeutic analgesics are more likely to cause adverse effects than pain patients, honest prescribers, or phar- move forward in establishing pain and pal- lower doses of analgesics in combination. macists. Appropriate learning among phar- liative care as a specialty, although future For example, a higher dose of an antide- macists is therefore essential to ensure BPS certification has not been ruled out.18 pressant used as monotherapy may cause necessary monitoring of opioid therapy For now pharmacists can become creden- sedation; a NSAID may induce a gastroin- across diverse practice settings. tialed through the American Academy of testinal bleed; and an may Recognizing that positive and negative Pain Management or American Society of cause sedation and ataxia. Further, the barriers exist, that particular pharmaco- Pain Educators, although neither are recog- use of opioids as monotherapy increase therapy and pharmacokinetic expertise nized by the Joint Commission of Pharmacy the risk of dependence and abuse liability. are essential, and that pain and symptom Practice (JCPP) as a board certification. In management outcomes are best served the spirit of moving forward to encourage Drug overdose by an interdisciplinary group, the Strategic pain education and support the efforts of Planning Summit for Pain and Palliative those continuing to pave the path, this is deaths, the second Care Pharmacy Practice convened in 2009 the first in a UCONN-initiated Drug Topics to “identify strategies to improve the atti- continuing education series to enhance leading cause of tudes, knowledge, and skills of the profes- pain education among pharmacists. sion as a whole...”1 The summit included 79 unintentional participants and 5 professional stakeholder Epidemiology and costs organizations represented by pharmacy, Pain is a primary health problem that can deaths due to medicine, and nursing. Their summary negatively impact outcomes of multiple statement said it well: “The opportunities disease states, significantly decrease the , have been available for pharmacist involvement in the quality of life, delay hospital discharge, care of these patients are plentiful, and the and increase healthcare costs overall.19 steadily increasing time is now for our profession to take the Additionally the majority of chronic pain next steps in increasing pharmacy involve- patients suffer from anguish and mental in the U.S. since ment in the interdisciplinary care of patients health disorders because of pain; this fre- 1970. in pain and at the end of life.”1 quently necessitates a complex codepen- At least in part at the behest of the dent treatment.20 The loss of productivity Drug overdose deaths, currently the summit, the Board of Pharmaceutical Spe- and concentration during work, lost work second leading cause of unintentional cialties (BPS) issued a press release in time, and increased number of hospital deaths due to injury, have been steadily in- June 2011 indicating that role delineation and visits for diagnosis and creasing in the U.S. since 1970.24 Accord- studies in pain and palliative care to estab- treatment all increase healthcare costs.2 ing to CDC 2011 data, the most commonly lish a board certification for pain manage- Presenteeism also contributes to cost reported source for nonprescribed opioids ment pharmacists would move forward.17 and productivity. This occurs when an em- is from friends or relatives at 54.2%. An- A newly appointed Practice Analysis Task ployee reports for work despite having an other 18.1% reported obtaining the medi- Force group had met in April 2011. In May illness or medical condition that prevents cations from a prescriber, whereas only 2012, however, BPS denied the petition to the employee from functioning at full capa- 3.9% bought their medications from a

38 Drug topics April 2013 DrugTopics.com continuing education

drug dealer or stranger.25 Among friends table 2 and family who supplied the medications, Incidence of Chronic Pain 81.6% reported getting the medication Procedure Estimated Estimated incidence Number of 25 from a single prescriber. incidence of of chronic severe surgeries in the Educating healthcare professionals on chronic pain (disabling) pain* United States proper pain medication use and appropri- Amputation 10% 609,000 ate quantities for acute pain issues could aid in decreasing the number of legal pre- Coronary artery bypass 30%-50% 5%-10% 598,000 scriptions that end up in the wrong hands. Inguinal hernia repair 30%-40% 10% Unknown Pharmacist involvement within community Breast surgery 20%-30% 5%-10% 479,000 practice settings, as community educa- (lumpectomy or mastectomy) tors, and on interdisciplinary healthcare Cesarean section 10% 4% 220,000 teams caring for chronic pain patients *More than 5 of 10 pain scores can ease the pressure on prescribers and Source: Ref 9,36,37 help communities and politicians better un- derstand the societal impact of untreated variously employed policy permutations of that was an injury, surgery, or a disease. pain, appropriate medication access, and this, while others have created what some Chronic pain is pain that lasts longer than mitigating opioid-associated risks. consider to be draconian strategies with the expected healing time, is present for 3 Recently there has been an increase in potential adverse outcomes to legitimate months or longer, adversely affects sleep, marketing campaigns and headlines on the patients.28-33 Such policy changes may give and may not have an identifiable pathol- topic of opioid abuse and overdose deaths. the wrong impression to prescribers and ogy.34 The patient may have comorbidities This has increased the pressure on the cause unnecessary in those who associated with the pain, which may have to provide more have chronic pain. a gradual or acute initial onset. Both can- information and educational materials to their cer and chronic noncancer pain can be a consumers. One pharmaceutical company Definition combination of acute and chronic pain as- has launched the “Turn to Help” campaign Pain is defined as “an unpleasant sensory sociated with different etiologies. For most regarding opioid dependence and abuse.26 and emotional experience associated with chronic disorders the pain may be caused Some urban healthcare facilities have seen actual or potential tissue damage, or de- by the disease itself, associated diagnos- new guidelines for opioid prescriptions. For scribed in terms of such damage” by the tic procedures, and/or the treatment. example, New York City’s Mayor Bloomberg International Association for the Study of During the process of treating acute has proposed a restriction to the city’s Pain (IASP).34 Acute pain usually occurs pain, pharmacists play an important role to public hospital EDs precluding a prescription as a “warning” of trauma to the affected ensure medication compliance in terms of for more than a 3-day supply of any opioid tissue and has a sudden onset. It is usu- counseling on expected side effects (e.g., and without an option for extended-release ally temporary and is resolved when the opioid-induced constipation, urinary reten- dosage forms.27 Certain states have cause is eliminated or healed, whether tion, sedation, tolerance; NSAID-induced GI upset, bleed, fluid retention, elevated FIGURE 1 blood pressure) and avoiding or treating associated side effects effectively. It is Population of rx Opioid users is heterogeneous also important to counsel on when to seek medical attention and when to intervene without a medical visit. The patient should understand the risks associated with pain “Self- management and the risk of not treating “Chemical “Recreational Treaters” “Adherent” the acute pain. Chronic pain syndromes users” copers” “Substance abusers” can develop from insufficient acute pain “Substance abusers” “Addicted” treatment from resultant neuroplasticity, (SUD) including remodeling of nerves in the af- “Addicted” (SUD) fected area.35 This can occur after surgery and is most prevalent following amputa- tion, breast surgery, Cesarean section, coronary artery bypass surgery, and hernia Pain Patients Nonmedical Users repair as listed in Table 2.9,36,37 The pain can persist long after the surgical have healed.38 Educating the patient on Abbreviation: SUD, Source: Ref 42 (reprinted with permission) the importance of compliance is therefore

DrugTopics.com April 2013 Drug topics 39 Continuing Education Pain management for pharmacists

table 3 tion that can manifest itself physically or psy- chologically if the medication is discontinued Spectrum of Aberrant Drug-Taking Behavior abruptly. Pseudoaddiction is when the pa- More suggestive of addiction Less suggestive of addiction tient mimics behaviors associated with true ■ Concurrent abuse of alcohol/illicit drugs ■ Aggressive complaining about need for addiction, but the behavior is fueled by inad- medication equate pain management due to the distrust ■ Evidence of deterioration in ability to between the patient and the prescriber and function at work/in family/other social ■ Drug hoarding during periods of reduced activity that appears related to drug use symptoms can be better interpreted as “relief seeking” behavior.43 The patient may self-medicate, ■ Injecting oral formulations ■ O penly acquiring similar drugs from other which is the use of drugs without consult- medical sources ■ Multiple dose escalations/nonadherence to ing a healthcare professional to alleviate therapy despite warnings ■ Repeating specific drugs the stressor or disease in an attempt to 42 ■ O btaining prescription drugs from ■ R eporting psychic effects not intended by treat the undertreated. It is important for nonmedical sources physician pharmacists to understand the differences between all of these terms to create a less- ■ Prescription forgery ■ R esistance to change in therapy biased view on pain management. We owe it associated with tolerance to adverse ■ R epeated resistance to therapy changes to patients who are newly placed on chronic despite clear physical/psychologic effects effects accompanied by expressions of anxiety related to return of severe opioid therapy to have these discussions. ■ Selling prescription drugs symptoms Figure 1 illustrates the broad spectrum of drug-seeking behavior that a healthcare pro- ■ Stealing/borrowing drugs from others ■ Unapproved use of drugs to treat fessional may encounter.42 symptoms ■ Unsanctioned dose escalation or other Pain taxonomy and nonadherence with therapy on 1 or 2 pathophysiology occasions Several types of pain need to be distin- Source: Ref 42 (adapted with permission) guished to understand the optimal medi- cation treatment strategies. Nociceptive a critical role for the community pharma- Addiction is defined as “a primary, pain is typically classified as visceral or cist to incorporate into practice and is not chronic, neurobiologic disease with genetic, somatic. Visceral nociceptive pain arises easily achieved by other healthcare provid- psychosocial, and environmental factors from the internal organs, and somatic pain ers in any other practice setting. influencing its development and manifes- arises from the skin, bones, muscle, joint, Breakthrough pain has been defined tations.”39 The characteristics associated or connective tissues. The characteristics as a “transient or episodic exacerbation with addiction are behaviors that include associated with visceral nociceptive pain of pain that occurs in patients with pain impaired control or compulsive drug use, include deep, achy, poorly localized pain. that is otherwise considered stable but cravings, and continued use despite harm Somatic pain is usually well localized, persistent.”39 The pain can occur with or to oneself.39 There is no definitive technique sharp, throbbing, and constant, and it may without baseline pain and it can be a sud- to determine whether addiction will occur, increase with movement. den onset or gradual increase.40 There is although there are signs such as smoking, There are 5 steps to : trans- no difference between the terms persistent family history of substance abuse, and un- duction and inflammation, conduction, pain and chronic pain; however, the former sanctioned dose escalation, that clinicians transmission, perception, and modula- has become more acceptable among pain can screen to stratify risk (See https:// tion.22 Transduction is the sensation from clinicians in an effort to lessen the negative painedu.org/tools.asp). Intuitive signs of ad- the pain receptors called the . perception often associated with difficult diction are presented in Table 3, although These distinguish between noxious and patients otherwise labeled with a diagno- these could also be indicative of drug mis- non-noxious stimuli that one feels every sis of “chronic pain”. Fibromyalgia seems use, abuse, or diversion.42 Dependence, day and can be stimulated by chemical, particularly more prevalent among those however, is the adaptation associated with mechanical, or thermal impulses. Inflam- who also have chronic fatigue syndrome.41 chronic use due to tolerance of the medica- mation occurs when there is trauma that causes damage to the cells, causing a Pause&Ponder release of inflammatory markers such as potassium ions, bradykinins, prostaglan- dins, , leukotrienes, serotonin, What can I do to inspire rational polypharmacy, avert drug interactions, mitigate medication misuse, and and . The activation of the encourage best therapeutic outcomes for patients in nociceptors transmits the signal via ac- need of pain management? tion potential through the afferent nerve fibers toward the spinal cord; this is called

40 Drug topics April 2013 DrugTopics.com continuing education

conduction. The large, myelinated A-delta figure 2 nerve fibers transmit the signal for sharp, Acute and Chronic Pain Nociception Processes localized pain to the spinal cord, and the small, unmyelinated C fibers transmit sig- ACUTE PAIN PROCESSING: NOCICEPTION CHRONIC PAIN nals for dull, achy, poorly localized pain PERCEPTION MENTAL OVERLOAD that tends to linger on after the stimulus 5 Recognition and reaction in the Possible neurochemical link between is no longer present. Transmission occurs brain: Complex interactions involve pain and memory. High incidence of where the nerve pathways end and the thalamus (master switchboard), the depression, anxiety. Suffering increases neurotransmitters travel across the syn- sensory cortex, limbic system, and perceived pain. reticular activating system. aptic cleft to continue the pathway. This occurs in 3 different locations: the spinal LOSS OF NOCICEPTIVE CONTROL cord at the dorsal horn, between the spi- 4 MODULATION nal cord to the thalamus to the brain stem, Antinociception Neurons Normally innocuous stimuli become originating in brainstem descend painful. Once activated, any and the thalamus to the cerebral cortex. to spinal cord and release movement/deformity of tissues In the dorsal horn, glutamate, substance chemical messengers that inhibit becomes painful. euron P, and calcitonin are the neurotransmitters transmission of painful stimuli. N that are mainly involved in transmission.22 Norepinephrine and dopamine are involved piral Cord Cord piral with the signal transmission in the other 2 S TRANSMISSION SENSITIZATION 3 areas, hence the reason why certain anti- Synaptic transfer and modulation of input Repeated pain signals produce depressants relieve pain more effectively from one neuron to the next using chemical changes in the nervous system than traditional pain medications. messengers (neurotranmitters). called WINDUP. Pain becomes In the synaptic cleft, glutamate re- more painful. leased from the nociceptive neurons stim- ulates the AMPA receptors in the dorsal CONDUCTION DAMAGED NERVE horn. In acute pain, the NMDA receptors 2 Passage of action potentials along euron Damaged sensory nerves may do not respond to the glutamate released N neurons. Na+ and K+ serum levels may send constant pain signals like an due to Mg++ ions preventing the channels affect pain threshold. alarm bell that won’t shut off. ensory ensory from opening. In chronic pain, the Mg++ S ions in the NMDA receptors are displaced TRANSDUCTION due to repeated stimulation from the gluta- Primary Noxious stimuli translated into mate, opening the channels for activation. electrical activity at sensory nerve NEUROGENIC INFLAMMATION Ca++ ions go through the NMDA receptor endings. Increased prostanoid production channels and activate the protein kinase C 1 at site of pain produces allodynia and nitric oxide activation and release. This and hyperalgesia and generates INFLAMMATION spontaneous pain. causes substance-P release and increases Damaged cells release “Ouch” Pain c-fos expression, which may lead to neu- sensitizing chemicals. Autonomic Response Withdrawal Reflex Noxious roplasticity in the area. Unique NMDA stimulus receptor blockade activity by Source: Ref 22 (reprinted with permission) and levophanol may therefore explain their notable efficacy compared to other opioids it causes changes in the neurochemical en- pain signals within the spinal cord.22 This when treating chronic neuropathic pain.22 vironment located in these areas, and may inhibition, if prolonged, can actually produce The last 2 steps to nociception are per- explain why distraction can cause the per- hypersensitivity to pain stimuli called hyper- ception and modulation. Perception occurs ception of pain to subside.22 algesia.22 In chronic pain patients the pro- when the pain signal travels from the thala- Modulation is the adjustment of the pain longed stimulation increases their sensitivity mus, the “switchboard” of the brain, to the intensity we experience, which is performed to pain and increases pain intensity.22 Figure cortex. In the cortex, the signal is routed to by the antinociceptive system. Endogenous 2 explains the acute and chronic nociceptive the regions involved in sensation, autonomic opioids within this milieu involve a complex pathways side by side.22 nervous system, motor responses, emotion, system that is heightened by opioid medica- stress, and behaviors.22 This perception oc- tions to decrease pain. Endogenous opioids Neuropathic pain curs in 3 main areas of the brain: the thala- include enkephalins and endorphins, and Neuropathic pain can be central or periph- mus, limbic system, and the periaqueductal these are expressed in heightened quanti- eral. Central neuropathy, also called auto- gray area. The interaction between these ties following injury to allow continued am- nomic neuropathy, is caused by damage to areas is the reason why anxiety and depres- bulation post injury with stress analgesia, the central nervous system (CNS), such as sion can worsen the pain sensation because when the limbic system temporarily inhibits the spinal cord and vital organs. This may

DrugTopics.com April 2013 Drug topics 41 Continuing Education Pain management for pharmacists

table 4 titioner, because some of these medica- Types of Drug-Induced Neuropathies tions can cause irreversible damage. Drug-induced neuropathy has 3 differ- Cause of Type of damage Drugs and drug types ent causes. The most common is axonal neuropathy type degeneration, which occurs after pro- Axonal Most Common Colchicine longed exposure to the medication, usu- degeneration Dapsone ally weeks to months after initiation, and Occurs over weeks to Disulfiram the neuropathy will cease after discontinu- months after initiation Gangliosides ing the medication.45 The second is cell Gold salts , mostly in the dorsal root ganglion, Damage only occurs at HMG-CoA reductase inhibitors because these cells are the most vulner- the axon Hydralazine Isoniazid able due to the lack of blood-brain barrier. Resolves after Metronidazole Thalidomide, carboplatin, and oxaliplatin all discontinuation of drug Misonidazole cause this type of neural damage, and be- Nitrofurantoin cause it is causing cell death, it is usually Nondepolarizing neuromuscular blocking drugs irreversible and most debilitating.45 The Nucleoside analogues third is demyelinating neuropathy, which Penicillamine is the least common and only occurs with Phenytoin specific agents: amiodarone, interferon al- Pyridoxine pha, chloroquine, tacrolimus, perhexiline, Sulfasalazine and suramin sodium.45 This type of drug-in- Suramin sodium duced neuropathy can mimic Guillain-Barré Tacrolimus syndrome and may be misdiagnosed as Thalidomide such or overlooked as drug induced.45 Paclitaxel Neuropathic pain can manifest in vari- Vidarabine ous neuropathic disorders. Hyperpathia is Vincristine a that is characterized by Cell death Usually occurs at dorsal Cisplatin experiencing increased pain from a stimu- root ganglion Carboplatin lus, especially repetitive stimulus, that is Oxaliplatin often explosive and radiates, and the pa- Irreversible neuronal Suramin sodium tient may not be able to identify the cor- damage Thalidomide rect area from which the pain originates.34 More physically debilitating Hyperalgesia, as mentioned previously, is the increased sensitivity to pain stimu- Demyelinating Less common Amiodarone lation and can be part of hyperpathia. Interferon alpha When nonpainful stimuli transform to Can mimic Guillain-Barré Suramin sodium syndrome with acute onset Perhexiline painful stimuli or painful stimuli escalate, Chloroquine which can be experienced with sunburn, 22,34 Tacrolimus it is called allodynia. Both of these Source: Ref 45 can be classified under dysethesia, which is “an unpleasant abnormal sensation.”34 be caused by CNS disorders, trauma, brain cause idiosyncratic neuropathies include Parathesia is an even broader term, refer- injury, or stroke. Peripheral neuropathies antiretroviral therapy, nitrofurantoin, tha- ring to all abnormal sensations, whether are conditions in which the nerve damage lidomide, sulfa products, statins, and che- it is intentional or not and incorporates is in the extremities, and roughly 30% of motherapy drugs.45,46 Table 4 shows the dysethesia.34 is decreased all peripheral neuropathies are secondary types of drug-induced neuropathies and pain sensation with a painful stimulus. to diabetes.44 Idiopathic pain is a type of the drugs that are known to cause neu- These terms are summarized in Table 5.34 pain with no etiology that usually mani- ropathy.45 Some drug-induced neuropathy When selecting drugs to treat neuro- fests in the pelvic, head, and shoulders is dose dependent and may be the reason pathic pain, it is important to consider the area. Many drugs may cause idiopathic for discontinuation of therapy, especially upramping in both number and activity of the neuropathies, which must always be ruled with antineoplastic chemotherapy medica- sodium channels. It is for this reason that we out prior to adding more drugs for neuropa- tions.46 It is incumbent on the pharmacist find usefulness from drugs affecting sodium thies that incorrectly are labeled as “idio- to identify the potential of such idiosyn- channels. Examples include antidepressants pathic” when a cause could be identified cratic causes and have an open line of that specifically block reuptake of norepi- by current . Common drugs that communication with the prescribing prac- nephrine such as tricyclic antidepressants,

42 Drug topics April 2013 DrugTopics.com continuing education

table 5 tibiotic cream containing lidocaine. Definitions of Pain All of these assessment strategies and The implications of some of the above definitions may be summarized for convenience as follows: the information collected are important to effectively evaluate the pain and encourage Allodynia lowered threshold stimulus and response mode differ accurate follow-up diagnostics to determine Hyperalgesia increased response stimulus and response mode are the same causation. Moreover this information is key Hyperpathia raised threshold: increased response stimulus and response mode may be for the pharmacist to make intelligent sug- the same or different gestions for medication selection. Hypoalgesia raised threshold: lowered response stimulus and response mode are the same Being a part of the healthcare team can Source: Ref 34 elevate positive analgesic outcomes for pa- tients with the appropriate training, didactic serotonin-norepinephrine reuptake inhibitors, no pain and “10” is the worst imaginable learning, and implementation of established and antiarrhythmics such as lidocaine and pain. The Wong-Baker Faces pain rating protocols. Pharmacists can monitor pain in mexiletine. Although several anticonvulsants scale is often used for children or when both community and institutional settings, also have efficacy, the more contemporary there is a language barrier precluding accu- alleviating some of the responsibilities of gabapentinoids that affect voltage-gated cal- rate communication.47 We must of course other healthcare professionals. Activities cium channels by combining with the alpha- always keep in mind that pain is subjective might include evaluating serum levels of 2-delta subunit receptors, have gained favor and that one person’s “5” may be another pain medications, guiding clinicians when due to their relative safety profile. These will person’s “8.” interpreting urine drug screens, evaluating be discussed in greater detail in a subse- for appropriateness of certain drug classes, quent article in this series. recommending appropriate medication op- Pharmacists can tions, assessing the patient’s current medi- Pharmacist role in monitor pain in cation regimen, and monitoring the patient assessing/monitoring pain for any potential side effects associated Throughout this educational series, the both community with the medications. importance of pharmacist involvement to Significant changes are on the hori- positively impact patient care will be high- and institutional zon with regard to the pharmacist’s role lighted. Because the pharmacist is often in medication therapy management. This the first healthcare professional sought settings, alleviating has been driven by cost-efficiency, a clear by patients for minor-to-moderate pain therapeutics expertise involving all of the and sees patients routinely subsequent some of the pharmaceutical sciences coupled with clini- to a provider who prescribes medication, cal training, expansion of complex rational it is essential that we provide adequate responsibilities of polypharmacy associated with potential for triage. This entails asking the right ques- important drug interactions, and best prac- tions with regard to pain. On initial presen- other healthcare tices in terms of combining the knowledge tation, whether the patient is hospitalized and expertise of all healthcare providers to or in an outpatient setting, there are basic professionals. improve analgesic outcomes. important triage questions for appropriate Given these exciting responsibilities and pain evaluation. Patients will often pres- With this information, the pharmacist the recent recognition of pharmacists as ent with unique descriptors such as: it can make recommendations for the next providers, the opportunities for pharmacists feels like “there is a torch on my skin,” step in terms of visiting the appropriate in pain management are limitless. For all of “my head is in a vise,” or “there’s an ice healthcare provider (ED, primary care, or these reasons, we encourage our readers pick in my back.” These descriptors are behavioral health). Especially for acute to embrace the entire sequence of pain helpful to determine if the pain is visceral, new-onset pain, the pharmacist needs management continuing education in this somatic, neuropathic, or a combination. to know what is treatable with over-the- and subsequent Drug Topics issues. • Inquiries specific to pain should include counter medications and topical products time of onset, precipitating factors, loca- versus what needs first aid and immediate tion, activities that make it better or worse, medical attention. For example, headaches For immediate CPE credit,take the test now online at quality (burning, shooting, radiating, dull, immediately following trauma require im- achy), quantity ( 0-10 mediate attention, whereas intermittent or other suitable device), chronicity, and chronic daily headaches or caffeine with- effect on sleep and mood. It is especially drawal headaches could be addressed by important to quantify the pain. The most the pharmacist. A painful, recent laceration www.drugtopics.com/cpe common scale used is the visual analogue not requiring sutures might be well treated Once there, click on the link below scale of 0 to 10, where “0” represents with an oral anti-inflammatory and triple an- Free CPE Activities

DrugTopics.com April 2013 Drug topics 43 Continuing Education Pain management for pharmacists

test questions

1. When considering medication therapy to treat d. Use anticonvulsants to treat neuropathic 14. Which of the following statements is/are chronic pain, which of the following is true? pain true? a. Monotherapy is best to reduce medication 7. according to the International Association a. Inflammation occurs when there is exposure and potential toxicity. for the Study of Pain, which of the following trauma that causes damage to the b. Rational polypharmacy is often indicated definitions is/are true? cells, causing a release of inflammatory to minimize side effects and maximize a. Acute pain usually occurs as a “warning” markers such as potassium ions, efficacy. of trauma to the affected tissue and has bradykinins, , histamines, c. Opioids are never indicated chronically. a sudden onset, is usually temporary, leukotrienes, serotonin, and substance P. d. NSAID or acetaminophen is first-line and is resolvable. b. Large, myelinated A-delta nerve fibers therapy of any pain type. b. Chronic pain lasts longer than the transmit signals for sharp, localized pain 2. Which of the following have potential expected healing time, is present for to the spinal cord. usefulness in the treatment of pain? 3 months or longer, adversely affects c. Small, unmyelinated C fibers transmit a. Antidepressants sleep, and may not have an identifiable signals for dull, achy, poorly localized b. Anticonvulsants pathology. pain that tends to linger on after the c. Skeletal muscle relaxants c. a and b stimulus is no longer present. d. All of the above d. None of the above d. All of the above 3. Presenteeism means: 8. It is especially important for pharmacists 15. Certain medications that block NMDA a. The pharmacist is present for a to counsel patients on the importance of receptors have a net effect to: multidisciplinary pain intervention. keeping their pain levels manageable with a. Increase pain and enhance neuroplasticity b. The pharmacist is NOT present for a prescribed medications and/or other means b. Decrease pain and avoid neuroplasticity multidisciplinary pain intervention. in an effort to avoid the conversion of acute c. Reduce inflammation c. Being present at work under suboptimal pain to chronic pain as a result of: d. All of the above health conditions a. Bad luck b. Necrotitis 16. The last 2 steps to nociception are: d. Being present at work under optimal c. Neuroplasticity d. Urosepsis a. Perception and modulation health conditions 9. Which of the following best describes b. Transmission and activation 4. Which of the following is/are true with regard episodic pain? c. Termination and deactivation to chronic pain? a. Breakthrough pain that occurs d. None of the above a. It affects 100 million U.S. citizens. occasionally on top of otherwise 17. When considering medication to treat b. It is the most common reason that controlled chronic pain neuropathic pain, an important first step for patients visit healthcare practitioners. b. Pain that occurs with certain scary the pharmacist is to: c. It is the leading cause of disability and television episodes a. Try topical agents first comes with a price tag of $5 billion per c. Continuous pain that subsides on rest b. Review all medications for iatrogenic year. d. None of the above causes d. a and b 10. Which of the following terms refers to a c. Initiate an or anticonvulsant 5. The 2009 Strategic Planning Summit for Pain patient exhibiting drug-seeking behavior d. Initiate NSAIDs and Palliative Care Pharmacy Practice had that is likely driven by inappropriately or 18. Drug-induced neuropathy has 3 different important recommendations for pharmacists. undertreated pain? causes, including: With regard to the summit, which of the a. Addiction b. Dependence a. Axonal degeneration, cell death, and following is/are true? c. Pseudoaddiction d. Tolerance demyelination a. Educators need to identify strategies to 11. Which of the following are proof-positive of b. Sunburn, abrasions, and heat improve the attitudes, knowledge, and an addiction disorder? c. Ice, frostbite, and chemical skills of the profession as a whole. a. Aggressive complaining about the need d. All of the above b. The summit consisted of 79 participants for medication 19. When evaluating a patient’s pain, which of and 5 professional stakeholder b. Drug hoarding during periods of reduced the following is/are key questions? organizations represented by pharmacy, symptoms a. What is the level of your pain (scale of medicine, and nursing. c. Openly acquiring similar drugs from other 0-10)? c. Pharmacists should be an integral part medical sources b. Where is your pain located? of the interdisciplinary care of patients in d. None of the above c. What does your pain sensation feel like pain and at the end of life. (sharp, dull, achy, burning)? d. All of the above 12. Transduction is the sensation from the pain receptors called: d. All of the above 6. suboptimal pain management with a. Nociceptors b. Bradykinins 20. since pain is neuropathic, medication is frequent because clinicians: c. Cytokines d. Prostaglandins which of the following opioids could be most a. Fail to target the mechanism of pain useful due to blockade activity at the NMDA generation (somatic, inflammatory, 13. somatic pain arises from: receptor? neuropathic) a. Skin, bones a. b. methadone b. Overprescribe opioids b. Muscle, joint, connective tissues c. morphine d. meperidine c. Use anti-inflammatories to treat somatic c. a and b pain d. Nerves and bones

44 Drug topics April 2013 DrugTopics.com continuing education

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