Managing Chronic Pain: An Analysis of the Use of Opioids Melinda Jean Throm, PharmD, BCPS Jeffrey !

"din, BS, PharmD, #Ph, DAAPM $ James A% D% Otis, MD Published Online: J"ly &, '(() * &':((:(( AM +CDT, Brought to you through an educational grant from Janssen Ortho-McNeil Primary Care Behavioral Objectives After completing this continuing education article, the pharmacist should be able to: &% Explain the epidemiology, pathophysiology, and clinical presentation of nociceptive pain; '% Discuss safe and appropriate equianalgesic dosing and administration of opioid analgesics in chronic pain management; -% Assess potential adverse drug events occurring with the use of opioid analgesics; .% Define the importance of route of administration and controlled-release delivery systems in the management of chronic pain with opioid analgesics; )% Explain the definitions of physical dependence, addiction, pseudoaddiction, tolerance, and cross-tolerance, and discuss their significance with respect to opioid therapy in chronic pain; /% Analy e substance abuse issues in relationship to pain management and opioids; 0% Describe the controversies and concerns regarding the use of opioids for chronic nonmalignant pain and the recommended guidelines for use; 1% Define the role of the pharmacist in chronic pain management! Program Note "his continuing education article was written directly from the transcripts of the continuing education symposium, #$hronic %ain and &pioids: "he 'ise of %harmaceutical $are,#that was presented at the American %harmacists Association meeting on (unday, April ), *++,, in &rlando, -la! "he clinical application of equianalgesic tables when rotating opioids is also reviewed! %ortions of the information included in this article are represented in the published literature, while the remainder reflects opinions of the presenting faculty, based on their clinical experience! Background 2Pain is 3hate4er the e5periencing person says it is, e5isting 3hene4er he says it does%2& The 6nternational Association of the St"dy of Pain defines pain as 2an "npleasant sensory and emotional e5perience associated 3ith act"al or potential tiss"e damage, or descri7ed in terms of s"ch damage%2' O78ecti4e parameters to diagnose and meas"re pain do not e5ist% Th"s, pain is s"78ecti4e and m"st 7e 7ased on the indi4id"al9s perception of, reaction to, and tolerance to pain% Epidemiology Appro5imately )( million Americans:& in ) people:s"ffer from pain% Unfort"nately, this n"m7er is e5pected to rise o4er the ne5t ' decades% The ma8ority of chronic pain s"fferers ha4e 7een li4ing 3ith their pain for o4er ) years% Ann"al health care costs associated 3ith

pain a4erage ;&(( 7illion, and pain contri7"tes to )( million lost 3or< days% Chronic pain ca"ses more disa7ility than cancer and heart disease com7ined%- A 8oint statement from '& health organi=ations remar<ed, 2Undertreatment of pain is a serio"s pro7lem%%%% >ffecti4e pain management is an integral and important aspect of ?"ality medical care, and pain sho"ld 7e treated aggressi4ely%2. Consequences of nrelieved Pain Minority, female, cogniti4ely impaired, and geriatric patients are significantly less li<ely to recei4e appropriate pain medication and, conse?"ently, more li<ely to s"ffer from inade?"ate pain relief%),/ Unrelie4ed pain affects not only the ?"ality of life and economic sec"rity of the person 3ith pain, 7"t also his or her family% 0 Ta7le & s"mmari=es the negati4e conse?"ences of "nrelie4ed pain%1

Characteristics of !cute and Chronic Pain An "nderstanding of the pathophysiology of pain is re?"ired to ade?"ately control pain% .ociception refers to the process 7y 3hich information a7o"t tiss"e damage is con4eyed to the central ner4o"s system%@ Tiss"e damage stim"lates the ascending transmission of pain thro"gh the spinal cord to the 7rain% The 7rain mod"lates pain imp"lses 7y the release of endogeno"s opioids, s"ch as endorphin, that descend to inhi7it pain% These opioids 7ind to m", <appa, or delta receptors to decrease transmission of the pain% >5ogeno"s opioids 3or< at the same m", <appa, or delta andAor other opioid receptors% Contin"o"s acti4ation of .* methyl*D*aspartate +BMDA, receptors can decrease m" receptors9 response to opioids%-,@,&( Ac"te pain is a normal response after tiss"e in8"ry and typically s"7sides once healing has occ"rred%&& $hronic pain is defined as 2pain that persists for longer than the e5pected time frame for healing or pain associated 3ith progressi4e, nonmalignant disease%20 Ta7le ' s"mmari=es similarities and differences 7et3een ac"te and chronic non*cancer*related pain characteristics%0 Chronic nonmalignant pain 3ill 7e the foc"s of this contin"ing ed"cation article%

Pain is s"78ecti4e therefore, a comprehensi4e assessment of the pain:ie, the patient9s perception of pain, emotional state and somatic preocc"pation, f"nctional stat"s at home and at 3or<, and "se of analgesic medications: is 4ital%&' The goals of chronic pain therapy are to decrease pain, increase f"nction, and impro4e o4erall ?"ality of life% "reatment of Chronic Pain Both nonpharmacologic and pharmacologic treatment strategies are effecti4e in achie4ing ade?"ate pain relief 3hen "sed appropriately% Bonpharmacologic treatment options incl"de e5ercise, ac"p"nct"re, massage, transc"taneo"s electrical ner4e stim"lation, hydrotherapy, manip"lation, g"ided feed7ac<, hypnotherapy, 7iofeed7ac<, and treatment of concomitant mood disorders% Certain patients may re?"ire the addition of pharmacologic treatment to achie4e ade?"ate pain relief% Acetaminophen, nonsteroidal antiinflammatory dr"gs +BSA6Ds,:incl"ding cycloo5ygenase type ' +COC*', selecti4e agents:m"scle rela5ants, anticon4"lsants, antidepressants, stim"lants, sleeping pills, sleep medications, an5iolytics, gl"cocorticoids, anesthetics, topical analgesics, and opioids may help in ade?"ately controlling chronic pain% Opioid !nalgesics The Dorld Eealth Organi=ation9s +DEO, -*Step Analgesic Fadder +!ig"re &, s"pports opioids as the cornerstone of analgesic therapy for patients 3ith moderate*to*se4ere cancer pain%&-,&. 6n clinical practice, the DEO Fadder is commonly e5trapolated for patients 3ith non*cancer*related pain%

B"mero"s 7arriers to effecti4e pain management 3ith opioid analgesics ha4e 7een identified% !ail"re to ro"tinely assess pain and pain relief is the most common reason for "nrelie4ed pain% The Joint Commission on Accreditation of Eealthcare Organi=ations recogni=es pain as the fifth 4ital sign and enco"rages ro"tine assessment%&) Eealth*pro4ider 7arriers incl"de mis"nderstanding of the pathophysiology of pain, lac< of <no3ledge of opioid analgesic pharmacotherapy, lac< of acco"nta7ility of pain control among health care pro4iders, ins"fficient s"pplies of opioids in pharmacies, and legal and reg"latory iss"es go4erning opioid "se and a7"se% Patients often "nderreport pain for fear of addiction, fear of disappointing or annoying friends and family, and to a4oid ad4erse dr"g e4ents +AD>s,%-,.,&/*'( Common Opioid !#Es #ecall that e5ogeno"s opioids 7ind to certain opiate receptors in the 7rain and spinal cord to inhi7it the transmission of pain% Acti4ation of these receptors also ca"ses the common AD>s associated 3ith opioid analgesics +Ta7le -,%'&*-'

6t is 7elie4ed 7y many that common AD>s of opioids are allergic reactions% A tr"e opioid allergy is rare +G&H,, ho3e4er, and is a reaction in 3hich the 7ody9s imm"ne system responds in an o4erstated 3ay +s<in rash, facial s3elling, or asthma, to a foreign s"7stance% 6n the case of a tr"e opioid allergy, the offending opioid sho"ld 7e discontin"ed and replaced 3ith another opioid from a different analog"e class% The theory is to change the chemical str"ct"re eno"gh to a4oid anti7ody recognition% Cross*reacti4ity to another analog"e class is rare +Ta7le .,%--*-0

!dvantages of $ong%!cting Opioids Patients 3ith contin"o"s or fre?"ent pain sho"ld 7e gi4en a fi5ed sched"led dose of a long* acting opioid to pre4ent the pain from rec"rring and to pro4ide contin"o"s relief%'' Fong*acting opioids may 7e more fa4ora7le than short*acting opioids for the follo3ing reasons-1,-@:

More sta7le pain relief Fong d"ration of pain relief

Fess e"phoria Fess a7"se potential Fess fre?"ent dosing re?"ired 6mpro4ed sleep patterns

Choice of long*acting opioid may 7e limited 7y renal and hepatic f"nction, ho3e4er% Meta7olites or acti4e dr"g may acc"m"late in the presence of renal dysf"nction +Ta7le ), and hepatic dysf"nction +Ta7le /,%

&oute of !dministration Fong*acting agents are a4aila7le in a 4ariety of deli4ery systems +Ta7le 0,%.( Oral administration is the most common and preferred ro"te 7y patients% Most oral form"lations last less than '. ho"rs and re?"ire m"ltiple daily dosing% 6f the oral ro"te is not feasi7le, nonin4asi4e ro"tes s"ch as transdermal or rectal are alternati4es% Transdermal deli4ery allo3s for enhanced compliance +application "s"ally e4ery 0' ho"rs for fentanyl, altho"gh e4ery*.1* ho"r changes are accepta7le if re?"ired,% #ectal administration is not accepta7le to many patients% 6n4asi4e parenteral ro"tes are reser4ed for later "se% 6ntram"sc"lar administration of pain medications is not recommended, as this ro"te of administration is painf"l, yields 3ide fl"ct"ation in a7sorption, has "p to a /(*min"te lag time for analgesic effect, has a rapid falloff, and may ca"se sterile a7scesses and fi7rosis of m"scle and soft tiss"e%),.&

'orphine Morphine is the gold standard to 3hich all other opioids are compared% Se4eral oral e5tended* release form"lations are a4aila7le% Controlled*release +C#, morphine s"lfate may 7e administered e4ery 1 to &' ho"rs%.' S"stained*release +S#, morphine s"lfate may 7e administered e4ery &' to '. ho"rs%.-,.. C# or S# morphine form"lations sho"ld not 7e cr"shed, as the inherent release property is o7literated, and the patient recei4es the e?"i4alent of an immediate*acting morphine dose% A sprin<le*dose form"lation of morphine s"lfate once daily is no3 a4aila7le%.) The caps"les can 7e opened and sprin<led on soft food in patients 3ho ha4e diffic"lty s3allo3ing or 3ho re?"ire administration 4ia nasogastric, perc"taneo"s esophageal gastric, or 8e8"nal t"7es% Morphine e5tended*release prod"cts are not appro4ed for "se in children% D"e to morphine9s histamine*releasing acti4ity, it may ca"se more na"sea and pr"rit"s than other opioids% O(ycodone O5ycodone may ca"se less na"sea and pr"rit"s than morphine% 6t is also more potent than morphine% To pre4ent o4erdose especially in opioidna:4e patients, o5ycodone C# sho"ld not 7e cr"shed%./ O5ycodone C# is not !DA*appro4ed for "se in children% )ydromorphone Eydromorphone is appro5imately ) to &( times more potent than morphine% Eydromorphone C# ta7lets are no3 a4aila7le and sho"ld not 7e cr"shed%.0 Eydromorphone C# is not !DA* appro4ed for "se in children% 'ethadone*+%,-

#ecall that BMDA receptors can decrease m" receptors9response to opioids% Methadone is an m"*receptor agonist and a BMDA*receptor antagonist% Therefore, it may 7e especially "sef"l d"ring opioid rotation% The concept of opioid rotation is disc"ssed 7elo3% Methadone ta7lets may 7e cr"shed, 7eca"se methadone e5hi7its long*acting properties d"e to its long half*life +not dr"g form"lation,% An oral sol"tion is also a4aila7le% Methadone is an alternati4e in patients 3ith tr"e morphine allergy it is ine5pensi4e it does not re?"ire renal dose ad8"stment it is relati4ely safe in sta7le, chronic li4er disease and it may 7e gi4en once or t3ice daily% Methadone9s "ni?"e properties incl"de high oral 7ioa4aila7ility long, highly 4aria7le half*life +"p to &@( ho"rs, and high lipophilicity +creates a depot effect 7y slo3ing releasing of dr"g from the tiss"e into the 7loodstream,% These "ni?"e properties increase the ris< of delayed to5icity s"ch as sedation, respiratory depression, and +rarely, coma% Parado5ically, 3hen con4erting to methadone, higher doses of the chronically ta<en opioid 3ill res"lt in a relati4ely more potent methadone response% >?"ianalgesic ta7les fail to consider these "ni?"e properties of methadone, and dose con4ersions 7ased on these ratios may res"lt in drastic o4erdose% Dhen con4erting to methadone, some references recommend red"cing the calc"lated e?"ianalgesic dose of methadone 7y 0)H to @(H to achie4e a 3ell* tolerated and efficacio"s con4ersion +Ta7le 1,%.& Other so"rces recommend more acc"rately dosing in a triphasic fashion s"ch that the con4ersion ratio changes as the total daily dose of morphine +or its e?"i4alent, increases% !or e5ample, 3hen doses of morphine are lo3 +G@( mgAday,, the ratio is appro5imately .:& +morphine:methadone,% Dhen doses of morphine are high +I-(( mgAday,, the ratio of oral morphine to oral methadone approaches &':&% !or doses in the middle, a ratio of 1:& has 7een st"died%)' Methadone may 7e "sed in children%

.entanyl "ransdermal /ystem

A fentanyl transdermal system +!TS, is comprised of a protecti4e liner +remo4ed prior to application, and . f"nctional layers)-: &% '% -% .% contact adhesi4e rate*controlling mem7rane dr"g reser4oir of fentanyl and alcohol 7ac<ing

C"tting this patch renders the system "n"sa7le% Jeneric !TS has a protecti4e liner +remo4ed prior to application, and ' f"nctional layers).: &% fentanyl*containing adhesi4e '% 7ac<ing Some generic transdermal fentanyl patches do not ha4e a rate*controlling mem7rane% These patches are a matri5type system, "nli<e the compartmental deli4ery system seen 3ith the D"ragesic Transdermal System and similar mechanically and generically e?"i4alent alternati4es% 6n the case of the matri5 system, dr"g a7sorption is li<ely more dependent on patient specific characteristics +s<in thic<ness,% C"tting this patch may lead to mis"se% Both !TSs sho"ld 7e disposed of properly% An !TS may 7e "sed in children older than ' years of age% An !TS sho"ld 7e reser4ed for those patients 3ith chronic, sta7le pain and analgesic needs 3hose pain cannot 7e maintained on oral opioids, 7eca"se the patient is "na7le to s3allo3, has a dysf"nctional gastrointestinal tract, or is intolerant of other opioids d"e to allergy or AD>s%)-,). Consideration of dosage, initiation, dose ad8"stments, and discontin"ation of an !TS re?"ires <no3ledge of the dr"g deli4ery system% Dose Calculation and Conversion to Transdermal Fentanyl5 !5" &% Calc"late total opioid "se in the past '. ho"rs% '% Con4ert to oral or intra4eno"s e?"i4alents of morphine "sing the information in Ta7le 1% -% Use Ta7le @ to determine the appro5imate e?"i4alent topical dose to 7e gi4en e4ery 0' ho"rs +some patients may re?"ire e4ery*.1*ho"r dosing,% .% After application of the patch, it ta<es &' to &/ ho"rs to see a s"7stantial therape"tic effect and .1 ho"rs to achie4e steady*state 7lood concentrations% 0f no /& opioid prior to conversion: Apply the patch% To manage 7rea<thro"gh pain, the patient may "se short*acting opioids% 0f receiving /& opioid prior to conversion: Dith the application of the first patch, the patient recei4es the last ta7let of S# morphine preparation, allo3ing s"fficient opioid ser"m le4els "ntil fentanyl concentration 7egins to increase%)) )% Do not "se for 7rea<thro"gh pain% /% Do not c"t patches%

Dose #d$ustments5 !5" &% The initial dosage may 7e increased after - days 7ased on the s"pplemental dose of the resc"e short*acting opioid +') mcgAhr increase in fentanyl patch K @( mg oral morphine per '. ho"rs,% '% S"7se?"ent dose ad8"stments sho"ld not occ"r more fre?"ently than e4ery / days, 7eca"se this amo"nt of time is re?"ired for the patient to reach a ne3 steady state%

Discontinuation of Transdermal Fentanyl5 !5" &% Calc"late the e?"ianalgesic dose of the opioid "sing Ta7les 1 and @% '% #emo4e the fentanyl patch, and initiate treatment 3ith half of the e?"ianalgesic S# dose &' to &1 ho"rs later% 6t ta<es I&0 ho"rs for fentanyl ser"m concentration to fall 7y )(H after patch remo4al% 6n s"mmary, long*acting opioids may increase 4itality, social f"nctioning, and mental health 7y pro4iding e5tended periods of pain relief and fe3er AD>s, compared 3ith short*acting opioids%-@ Dosing and prod"ct selection m"st 7e patient*specific% Bo single medication is perfect for e4ery patient, and some patients may re?"ire the "se of ' long*acting opioids%)/ >4al"ation of treatment o"tcomes associated 3ith opioid analgesics in chronic pain may 7e s"mmari=ed 7y the . As: analgesia, acti4ities of daily li4ing, AD>s, and a7errant dr"g*related 7eha4iors%)0 "erminology 6nconsistent "se of terms related to pain often res"lts in mis"nderstandings 7et3een reg"lators, health care pro4iders, patients, and the general p"7lic regarding the "se of opioids for the treatment of pain%)1 The esta7lishment of "niform definitions promotes enhanced patient care in patients recei4ing opioid therapy% 6t is 4ital to recogni=e that physical dependence, tolerance, cross-tolerance, addiction, and pseudoaddiction are all distinct terms% Physical De%endence %hysical dependence is defined as 2a state of adaptation that is manifested 7y a dr"g*class* specific 3ithdra3al syndrome that can 7e prod"ced 7y a7r"pt cessation, rapid dose red"ction, decreasing 7lood le4el of the dr"gs, andAor administration of an antagonist%2)1 Dithdra3al symptoms incl"de irrita7ility, chills, na"sea, 4omiting, diarrhea, a7dominal pain, s3eating, r"nny nose, and insomnia% Dithdra3al symptoms are not e4idence of addiction:they also occ"r 3ith many nonnarcotic medications +antihypertensi4es and antidepressants,% These symptoms do not occ"r if the patient contin"es to ta<e the opioid +a4oids a7stinence,% Physical dependence is a pharmacologic property of the opioid and is common in patients recei4ing opioid therapy I) days%) Tolerance 2Tolerance is a state of adaptation in 3hich e5pos"re to a dr"g ind"ces changes that res"lt in a dimin"tion of & or more of the dr"g9s effects o4er time%2)1 Patients 3ith tolerance to opioid therapy re?"ire higher than normal doses to achie4e the same le4el of analgesic effect% Tolerance to pain relief is "ncommon% #apid increases in pain or in opioid dose may represent disease progression and not tolerance% Tolerance can also de4elop to common opioid AD>s% Dhen tolerance de4elops to a partic"lar opioid, cross*tolerance to other opioids concomitantly de4elops, altho"gh s"ch tolerance may 7e incomplete% Cross-Tolerance Cross*tolerance may 7e tho"ght of as the a7ility of one dr"g to s"ppress the manifestations of physical 3ithdra3al prod"ced 7y another dr"g and to maintain the physically dependent state% Ca"tion m"st 7e "sed 3hen s3itching to an alternati4e opioid dr"g this is also termed opioid

rotation or sequential opioid trials%.&,)@ Dhen rotating opioids, 2the degree of tolerance to opioid effects, 7oth analgesic and nonanalgesic, does not f"lly transfer to the ne3 dr"g, leading to a greater potency of the ne3 dr"g than e5pected%2.& >?"ianalgesic ta7les do not ta<e into consideration cross*tolerance +Ta7le 1,% Th"s, it is commonly recommended to decrease the dose of the ne3 opioid 7y -(H to )(H 3hen initiating a different opioid%.& Dhen <eeping the same opioid, 7"t con4erting to a different ro"te, ad8"stments for cross*tolerance do not ha4e to 7e made% #ddiction Altho"gh physical dependence is common, addiction is rare in patients treated 3ith prolonged opioid therapy%)0,/( Addiction is defined as 2a maladapti4e pattern of s"7stance "se leading to clinically significant impairment or distress%2/& Addiction is a psychological property of the patient% Addicti4e 7eha4iors are psychological in nat"re and incl"de a dysf"nctional and comp"lsi4e pattern of "se in 3hich cra4ing, o7taining, and "sing a dr"g constit"te the principal foc"s of the "ser9s life in addition, "se is contin"ed despite harm% Addiction is diagnosed 7y the o7ser4ation of a7errant dr"g*related 7eha4ior +Ta7le &(,%)/,)0

Clinicians can recogni=e addiction 7y noting the follo3ing 7eha4iors)/,)0:

Demands end*of*office*ho"r appointments or arri4es 8"st after close +r"nning late, Beeds immediate action #ef"ses physical e5amination or tests Prohi7its release of medical records Cannot or 3ill not pro4ide past pro4iders Uses e5c"ses of 4isiting from o"t of to3n and lost or stolen prescriptions Bo medical 7asis for allergies to nonopioids Un"s"al <no3ledge of controlled s"7stances

Eistory of pre4io"s s"7stance a7"se 7y the patient andAor family are strong indicators of the li<elihood of contin"ed a7"se%)/,)0 Appropriate medical "se of opioids is not generally tho"ght to 7e associated 3ith addiction% Pseudoaddiction

Pse"doaddiction is commonly seen in patients 3ith se4ere, "nrelie4ed pain% Patients 7ecome preocc"pied 3ith finding opioids% Their "nderlying foc"s, ho3e4er, is on finding relief for their pain% Pse"doaddiction may 7e differentiated from tr"e addiction 7eca"se dr"g*see<ing 7eha4iors typically resol4e 3hen pain is ade?"ately controlled%)1,/' Opioids and #rug !buse The US Department of Eealth and E"man Ser4ices sponsors the Dr"g A7"se Darning Bet3or< +DADB,%/- DADB reports the fre?"ency of emergency department +>D, dr"g a7"se* related 4isits and the total dr"g mentions for nonmedical p"rposes% 6nformation 3as gathered from a representati4e sample of '& metropolitan >Ds +.-0 hospitals participated in '((',% 6n '((', there 3ere appro5imately /0(,((( 4isits to the >D that 3ere related to dr"g a7"se%)0 The 4isits 3ere categori=ed, and 0 categories acco"nted for more than 1(H of all dr"g mentions: alcohol in com7ination, cocaine, heroin, mari8"ana, 7en=odia=epines, antidepressants, and analgesics% A7o"t &(H +&&@,&1), of dr"g mentions in4ol4ed narcotic analgesics% Trends in opioid a7"se ha4e changed o4er time +Ta7le &&,%/. !ig"re ' sho3s the li<elihood of dr"g a7"se 7et3een short*acting and long*acting opioid analgesics%/-

Opioid se in Clinical Practice 6n &@@1, the !ederation of State Medical Boards created model g"idelines for the "se of controlled s"7stances for the treatment of pain%/) 6n May '((., these 3ere adopted as policy%// As opioids are the standard of care for chronic pain, clinicians sho"ld perform thoro"gh patient e4al"ations, o7tain informed consent for an appropriate opioid treatment plan, periodically assess for opioid efficacy and AD>s, and maintain ade?"ate doc"mentation% Clinicians may follo3 se4eral practical pointers to differentiate 7et3een dr"g*see<ing

7eha4ior and medical necessity of opioid "se% Maintenance of archi4ed, complete medical records is 4ital% 6n addition, an agreement 7et3een the clinician and patient may c"rtail dr"g* see<ing 7eha4ior s"ch a doc"ment might incl"de an agreement to see< ser4ices only from & doctor and & pharmacy, reasona7le treatment goals, no early refills or changes in therapy 3itho"t an office 4isit, no illicit dr"g "se, and as*needed "rine dr"g screens or ser"m monitoring%&0,)/ Lno3ledge of federal and state reg"lations restricting opioid "se is also f"ndamental% A la3f"l prescription for a controlled s"7stance m"st 7e iss"ed for a legitimate medical p"rpose 7y an indi4id"al practitioner acting in the "s"al co"rse of his or her professional practice and m"st 7e doc"mented in the medical records% !ederal la3 does not precl"de the "se of opioids as analgesics for legitimate medical p"rposes, incl"ding treating chronic pain and treating pain in addicts% Eo3e4er, federal la3 does prohi7it the "se of opioids to maintain an addicted state 3itho"t special registration% Pharmacist1s &ole in Chronic Pain 'anagement Pharmacists are <ey mem7ers of the interdisciplinary approach to the management of chronic pain%0 Beca"se of their <no3ledge of opioid medications, pharmacists can pro4ide 4al"a7le information on the most appropriate opioid for pain management and perform a comprehensi4e re4ie3 of past and c"rrent pharmacologic inter4entions%0,/0 To alle4iate concerns a7o"t addiction, pharmacists can ed"cate patients a7o"t the principles of tolerance, dependence, addiction, and pse"doaddiction% Pharmacists play a 4ital role in the safe deli4ery of pain medications 7y pro4iding pain medication ed"cation and 2clinical pearls2 maintaining "pdated and easily accessi7le e?"ianalgesic con4ersion ta7les assisting in the con4ersion 7et3een changes in medications and ro"tes of opioid therapy and assisting in the monitoring of opioid therapy for safety and efficacy%/0,/1 Conclusion Fong*acting opioids are safe and effecti4e 3hen "sed appropriately for the management of chronic pain and may 7e rotated to gain 7etter pain control 7y "sing e?"ianalgesic ta7les% Treatment*ind"ced addiction are rare% Doc"mentation and <no3ledge of reg"lations regarding opioid "se are essential% The 7est analgesic res"lts are o7tained 3hen a therape"tic alliance 7et3een the patient and health care professional is formed% /elinda 0ean "hrom, %harmD, 1$%(: Assistant %rofessor, Department of %harmacy %ractice, $ollege of %harmacy - 2lendale, /idwestern 3niversity; 0effrey -udin, 1(, %harmD, '%h, DAA%/: $linical %harmacy (pecialist in %ain /anagement, (tratton 4A /edical $enter; Ad5unct Associate %rofessor of %harmacy %ractice, Albany $ollege of %harmacy; 6 0ames A! D! &tis, /D: Director, %ain /anagement 2roup, 1oston /edical $enter; Director of .eurology 'esidency "raining, 1oston 3niversity -or a list of references, send a stamped, self-addressed envelope to: 'eferences Department, Attn! A! (tahl, %harmacy "imes, *78 -orsgate Drive, 0amesburg, .0 +99)8; or send an email request to: astahl:ascendmedia!com!

CE ABSD># !O#M 6BST#UCT6OBS "E/"0N2 !N# 2&!#0N2 P&OCE# &E/

34 >ach participant achie4ing a passing grade of 0(H or higher on any e5amination 3ill recei4e a statement of credit gi4ing the n"m7er of C> credits earned% This form sho"ld 7e safeg"arded and may 7e "sed as doc"mentation of credits earned% -4 Participants recei4ing a failing grade on any e5am 3ill 7e notified and permitted to ta<e & ree5amination at no e5tra cost% 54 All ans3ers sho"ld 7e recorded on the ans3er form attached% !or each ?"estion, decide 3hich choice is the 7est ans3er, and circle the letter of the response representing yo"r choice% *4 Mail yo"r completed e5am form to the follo3ing address: Pharmacy Times, .() Jlenn Dri4e, S"ite ., Sterling, MA '(&/.* ..-'% NE6 /CO&0N2 OP"0ON/ 34 Mail -4 !a5: 0(-*.(.*&1(& 54 This lesson is .&EE on*line recei4e instant grading, as 3ell as do3nload yo"r certificate: www!pharmacytimes!com! Please print clearly:certificate 3ill 7e iss"ed from information gi4en% Please mail completed forms to: Pharmacy "imes CE #epartment7 *8, 2lenn #rive7 /uite *7 /terling7 9! -83:*%**5-

CE #>M6>D NU>ST6OBS This educational lesson &ill 'e availa'le to %harmacists on-line at &&&(%harmacytimes(com( ;1ased on the article starting on page 99< $hoose the 8 most correct answer! 34 The 6nternational Association for the St"dy of Pain defines pain as an "npleasant sensory and emotional e5perience: a% 7% c% d% Associated 3ith act"al tiss"e damage% Associated 3ith potential tiss"e damage% Associated 3ith either act"al or potential tiss"e damage% That has no relationship to tiss"e damage%

-4 Unrelie4ed pain affects the patient9s ?"ality of life and also may affect: a% 7% c% d% The cardio4asc"lar system% The gastrointestinal system% The imm"ne system% All of the a7o4e%

54 Barriers to effecti4e pain management incl"de all of the follo3ing except: a% 7% c% d% 6ns"fficient s"pplies of opioids in pharmacies% Patients reporting pain% Fegal and reg"latory iss"es go4erning opioid "se and a7"se% 6nade?"ate <no3ledge of opioid analgesic pharmacotherapy%

*4 Patients 3ith chronic pain recei4ing opioids de4elop tolerance to all of the follo3ing opioid*ind"ced ad4erse dr"g e4ents except: a% 7% c% d% #espiratory depression% Constipation% Ba"sea and 4omiting% Sedation%

,4 A cancer patient reports an allergy to morphine +throat s3ollen sh"t,% The most appropriate alternati4e opioid in this patient is: a% 7% c% d% Codeine% Eydromorphone% !entanyl% O5ycodone%

:4 Ad4antages of long*acting opioids incl"de: a% 7% c% d% More sta7le pain relief% Fong d"ration of pain relief% Fess a7"se potential% All of the a7o4e%

;4 Dhich of the follo3ing opioids is most appropriate for ac"te pain management in a 0-* year*old 3oman 3ith sei="re disorder and end*stage renal disease on dialysis: a% 7% c% d% Meperidine Propo5yphene Morphine controlled release Eydromorphone

+4 Dhich of the follo3ing opioids is most appropriate for chronic pain management in a ))* year*old man 3ith chronic, sta7le end*stage alcoholic li4er disease: a% 7% c% d% Meperidine O5ycodoneAacetaminophen O5ycodone immediate release, 3itho"t acetaminophen Methadone

<4 #ecommended ro"tes of administration for chronic opioid "se incl"de all of the follo3ing except: a% Oral%

7% 6ntra4eno"s% c% 6ntram"sc"lar% d% Transdermal% 384 A patient is to ha4e all medications cr"shed and administered thro"gh the nasogastric t"7e% The patient reports an allergy to fentanyl transdermal patches +erythemato"s rash 3ith 7listers,% The most appropriate long*acting opioid is: a% 7% c% d% Methadone ta7lets% Morphine s"lfate controlled*release% O5ycodone controlled*release% !entanyl transdermal system%

334 All of the follo3ing are "ni?"e properties of or considerations regarding methadone except: a% 7% c% d% Fong, highly 4aria7le half*life% Fipophilic% Does not re?"ire renal or hepatic dose ad8"stment% #ed"ce the calc"lated e?"ianalgesic dose 7y at least -(H to )(H 3hen changing to methadone%

3-4 All of the follo3ing are indications for the fentanyl transdermal system except: a% 7% c% d% Chronic, sta7le pain and analgesic needs% Tolerating oral opioids and responding 3ell 3itho"t intolera7le side effects% Being "na7le to s3allo3% Ea4ing a dysf"nctional gastrointestinal tract%

354 Eo3 do the potencies of morphine and fentanyl compare: a% 7% c% d% !entanyl is &(( times more potent than morphine% Morphine is &(( times more potent than fentanyl% !entanyl is &( times more potent than morphine% Morphine and fentanyl are appro5imately e?"i4alent%

3*4 Dhich of the follo3ing statements is incorrect regarding physical dependence: a% 7% c% d% A7r"pt cessation of the chronic opioid may ca"se 3ithdra3al symptoms% 6t is common d"ring chronic opioid "se% 6t is a physical property of the dr"g% 6t is a psychological property of the person%

3,4 Dhich of the follo3ing statements is incorrect regarding addiction: a% 7% c% d% Addicti4e 7eha4iors incl"de dr"gsee<ing 7eha4ior% 6t is rare d"ring chronic opioid "se% 6t is a physical property of the dr"g% 6t is a psychological property of the person%

3:4 >?"ianalgesic ta7les do not ta<e into consideration cross*tolerance% Dhen changing from oral morphine to oral hydromorphone, it is most appropriate to: a% 7% c% d% #ed"ce the calc"lated e?"ianalgesic dose 7y at least -(H to )(H% 6ncrease the calc"lated e?"ianalgesic dose 7y at least -(H to )(H% #ed"ce the calc"lated e?"ianalgesic dose 7y at least 0)H% 6nitiate the calc"lated e?"ianalgesic dose 3itho"t a dose red"ction%

3;4 Dr"g*related 7eha4iors predicti4e of addiction incl"de: a% 7% c% d% Prohi7iting release of medical records% !re?"ent prescription 2losing%2 Demanding end*of*office*ho"r appointments% All of the a7o4e%

3+4 Dhich of the follo3ing sho"ld 7e "sed in the management of patients 3hen they are recei4ing a narcotic for chronic pain: a% 7% c% d% The patient agrees that only one medical practice 3ill prescri7e for them% Only one pharmacy refills prescriptions for the patient% There are no refills after ho"rs or on 3ee<ends% All of the a7o4e%

3<4 Beca"se of federal and state la3s go4erning the prescri7ing and dispensing of Sched"le 66 narcotics, clinicians sho"ld: a% 7% c% d% Be4er prescri7e opioids% Prescri7e opioid narcotics for legitimate medical p"rposes% A4oid maintaining "p*to*date medical records% >nco"rage patients to see n"mero"s doctors%

-84 Dhich of the follo3ing roles may a pharmacist play in chronic pain management: a% Pharmacists may pro4ide 4al"a7le information on the most appropriate opioid% 7% To alle4iate concerns of addiction, the pharmacist can ed"cate the patient on the differences 7et3een addiction and dependence% c% Pharmacists can maintain "pdated and easily accessi7le e?"ianalgesic ta7les% d% All of the a7o4e%