Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5200_Библиотеки_им_академика_М_И_Перельмана
.pdf
ManagingpaininpatientswithOUDischallengingandcomplex,andtreatmentreliesonassessingrisk
versus benefit and applying the ultimate goal of do no harm. Practitioners should be mindful to not
stigmatizea patientdiagnosedwith OUDasthiscaninterfere witheffectivelymanagingpain.Another
barriertotreatingthispopulationisthatpatientsdiagnosedwithOUDgenerallyhaveahighertoleranceto
opioidsandanincreasedpainsensitivity,makingtheirpainevenmoredifficulttotreat.Twoofthemost
common medications used for bothprevention of withdrawal symptoms and maintenance treatment of
OUDthatcanproficientlymanagepainarebuprenorphineandmethadone;thesetwomedicationsarefirstlinetreatmentoptionsformedication-assistedtreatment(MAT)inOUD.Bothmedicationshaveeffectsat
the mu opioid receptor, alleviating pain while also reducing cravings. In patients in need of
pharmacotherapyfor painmanagementwithahistoryofsubstance abuse notrespondingtonon-opioid
interventions,methadoneorbuprenorphinemaybebeneficial.Also,inpatientswithOUDalreadybeing
treatedwithmethadoneorbuprenorphine,thedosingcanbeadjustedtomaximizetheiranalgesiceffect.
PATHOPHYSIOLOGYBETWEENPAINANDADDICTION
RefertoChapter9andChapter44fortheindividualpathophysiologyofpainandOUD.
Theexperienceofpainoccursvianociception,definedasthetransmissionofpainsignalingthroughthe
central nervous system (CNS). Chronic use of opioids, whether prescribed or misused, alters the
processing of pain stimuli, which leads to increased pain sensitivity and the occurrence of opioid
tolerance.InpatientswithOUD,themesolimbicpathway(rewardpathway)facilitatedbytheactionsof
muopioidagonistsalsoplaysamajorroleinthereinforcingeffectleadingtoitsaddictiveproperties.
FIGURE10–1Rewardandintoxicationcycleinthebrain.(FromKoob,G.F.(2020).Neurobiologyof
opioid addiction: Opponentprocess, hyperkatifeia,andnegative reinforcement.BiologicalPsychiatry,
87(1),44–53.doi:10.1016/j.biopsych.2019.05.023.)
ACC,anteriorcingulatecortex;BNST,bednucleusofthestriaterminalis;dlPFC,dorsolateralprefrontalcortex;DS,dorsalstriatum;GP,
globuspallidus;HPC,hippocampus;NAc,nucleusaccumbens;OFC,orbitofrontalcortex;PAG,periaqueductalgray;vlPFC,ventrolateral
prefrontalcortex;vmPFC,ventromedialprefrontalcortex.
Painprovidesbothapositive andnegativereinforcementofopioiduse.Opioidsproducefeelingsof
pleasure primarilydue toactivationof theventral tegmentalarea andsubsequentrelease ofdopamine
fromthenucleus accumbens.Continuedmisuse ofopioids leads todysregulation oftheneurochemical
systemcausingseveredistressanddiscomfortwhenopioidsarewithdrawnor absent.This dysphoria,
whichmaybefurtherexacerbatedbyconcomitantpain,correlatestonegativereinforcementmotivating
continuedopioid use.Thepositiveandnegativereinforcementofopioidsisdecreased inchronic pain
resultingintheneedforhigherandmorefrequentdoses(Figure10.1).
SCREENINGANDASSESSMENTFORPAIN
Whenassessingpain,patientswithOUDshouldbetreatedlikeanyotherpatient.Athoroughassessment
shouldbeconductedwithtypeandclassofpainidentified(refertoChapter9forclassificationofpain)
using subjective information offered by the patient. In addition, clinical examinationand testing (e.g.,
magnetic resonance imaging, X-ray, etc.) can be performed when applicable. The patient’s ability to
function is critical in the evaluation. After completion of a detailed workup of the patient’s pain
complaints,collateralinformationshouldbeobtained.Thepatient’sconcomitantdiseases,especiallyany
psychological comorbidities, must be taken into consideration when developing a treatment and
monitoring plan. Review all medications (including over-the-counter and herbal medicine) for the
presence of drug interactions and potential side effects. If the patient has been diagnosed with OUD,
determinationofcurrentorpastMATmustbereviewed.Itisalsoimportanttobeawareofresponsesto
anypreviouspain managementtreatments.Lastly, identifyand confirm a strongsupportsystem before
interventionsareinitiated.
SCREENINGANDASSESSMENTOFOPIOIDUSEDISORDER
While all patients should be screened routinely for OUD (and other substance use disorders), it is
essential to perform this assessment before initiating opioid analgesics. Continuously assessing for
potential opioid misuse, as well as monitoring for worsening or continued pain, is recommended.
Differentiate OUD diagnosis from “pseudo-addictive” behavior (refer to Chapter 9 for definition).
Nonjudgmentalandopencommunicationshouldbeappliedwhenassessingthepatient.Patientsareoften
reluctanttodivulgeapresentorpasthistoryofopioidmisuse.Somepatientsmaynotbereadytodisclose
whentheystrugglewithopioiduseduetoconcernoftheirpainbeingleftuntreatedorfearofwithdrawal.
Other patients maynotrealizethatoverutilizationofopioiddosingreflectstoleranceand/oraddiction.
Evaluationand diagnosis ofa substanceuse disorder canbe based on the Diagnostic and Statistical
ManualofMentalDisorders,FifthEditioncriteria(refertoChapter44onsubstanceusedisorder).
Urinedrugscreensmayalsoassistintheassessment;however,false-positiveor-negativeresultscan
anddooccur.Bothquantitativeandqualitativetestsare available toassessforillicitsubstancesinthe
urine.Immunoassaysusedforscreeningarequickandinexpensive butmayproducefalsepositivesand
negativeresults.For example,patientstakinganantipsychoticmedicationmayproduceafalse-positive
result for fentanyl on a urine drug screen assay (Wang et al., 2014). If an immunoassay returns an
unanticipated positive or negative finding, a more precise gas chromatography-mass spectrometry is
advisedforconfirmation.Gaschromatography-massspectrometryismoresensitiveandtestsforspecific
medications(Standridgeetal.,2010).
Referencing a prescription drug monitoring program (PDMP), an electronic database that relays
informationonfilledprescriptionsforcontrolledsubstances,canassistinidentifyingopioidmisuseinan
individualpatient.Thisdatabasedisplaysthemedication,date,andquantity/daysuppliedaswellasthe
name of the prescribing physician and dispensingpharmacy. Early fills, large quantities, andmultiple
pharmaciesandprovidersonapatient’sPDMPprofilealertaprovidertopotentialmisuse.
Ifopioidmisuseissuspectedorconfirmed,referralfortreatmentshouldbeoffered.Atoolthatcanbe
usedtohelpguideapractitioneronwhetherornotanopioidmaybesafelyprescribedistheOpioidRisk
Tool (Webster &Webster,2005). This toolisused onpatientswithchronicpainandisbasedonrisk
factors for OUDincludingfamilyhistoryofsubstance abuse,personal historyofsubstanceabuse,age,
historyofpreadolescentsexualabuse,andpsychologicaldiseases.TheScreenerandOpioidAssessment
forPatientswithPain-Revised(SOAPP®-R)isanalternativeoradjunctivetoolaprescribercanuseto
helpfurtherevaluateriskformisusewithprescribedopioids(Butleretal.,2008).SeeBox10.1foralist
ofriskassessmenttools.
Whenapatientisonbuprenorphineor methadonefor treatmentofOUD,doses shouldbeconfirmed
beforestartinganynewmedications.BuprenorphinedosingcanbeconfirmedbyreferencingaPDMPand
clarifyingwithpharmacyorprovider.Methadonedosingwillneedtobeverifiedbypatient’smethadone
clinic.
Box10.1 RiskAssessmentandMonitoringToolsforOpioidUseDisorder
OPIOIDRISKASSESSMENTS
Screening
•ORT(OpioidRiskTool)
•SOAPP®-R(ScreenerandOpioidAssessmentforPatientswithPain-Revised)
•SISAD(ScreeningInstrumentforSubstanceAbusePotential)
Monitoring
•PDUQ(PrescriptionDrugUseQuestionnaire)
•COMM(CurrentOpioidMisuseMeasure)
•PMQ(PatientMedicationQuestionnaire)
•PADT(PatientAssessmentanddocumentationTool)
•ABC(AddictionBehaviorChecklist)
INITIATINGDRUGTHERAPY
GoalsofDrugTherapy
The goals of treatingpain inpatients withOUDinclude(1) reducingor eliminatingpain andtreating
underlyinginjury/disease,(2)reducingoreliminatingcravings,(3)preventingrelapse,(4)minimizingor
managingsideeffects,and(5)improvingqualityoflife.MedicationsusedinOUDincludebuprenorphine,
methadone,andnaltrexone.Naltrexone,anopioidantagonist,isnotroutinelyusedinthemanagementof
chronicpain(Table10.1).
BuprenorphineandBuprenorphine/Naloxone
Buprenorphine is a partial mu opioid receptor agonist providing analgesic effects similar to full mu
opioid receptor agonists (opioids).Thepartialagonism feature creates a ceiling effect,whichlessens
bothitseuphoriaanditsriskofcausingrespiratorydepression.Partialagonistpropertiesarereflectedin
thedoseresponse,whichplateausasthedoseisincreased.Therefore,higherdosesofbuprenorphinedo
notproducegreatereuphoricorrespiratorydepressiveoutcomes.Theanalgesicimpactofbuprenorphine
doesnotseemtobelimitedbythisceilingeffect.
Antinociceptionandanti-hyperalgesiamayalsobeseenthroughagonizingtheopioidreceptorlike-1,
making buprenorphine an option for the treatment of neuropathic pain (Marquez et al., 2008).
Buprenorphinehasadditionalbenefitsoverothermuagonists.Buprenorphinedoesnotcausespasmofthe
sphincterofOddiandthereforeinduceslessconstipation.Cognitivedysfunctionmaybelessened,making
asafeandeffectivetherapeuticoptionforolderpatientswhencomparedtofullmuopioidagonists.
Buprenorphinehashighbindingaffinitytothemuopioidreceptor.Whengiventoapatientwithrecent
opioid use,buprenorphinewilldisplacethepreviousopioidsfromthereceptorsandprecipitateavery
substantial andexaggeratedwithdrawal.Toavoid this, patientswithrecentopioid useshouldnothave
buprenorphineinitiateduntilobjective symptomsofwithdrawalareseen.Withdrawalsymptomscanbe
assessedusingtheClinicalOpiateWithdrawalScale(Wesson&Ling,2003).
TABLE10.1
DrugsUsedintheTreatmentofOpioidUseDisorderandPain
CNS, central nervous system; DEA, Drug Enforcement Agency; EKG, electrocardiography; GI, gastrointestinal; IM, intramuscular; IV,
intravenous.
Source: Lexicomp Online. (2021). Lexicomp: Evidence-based drug referential solutions. Retrieved from
http://www.wolterskluwercdi.com/lexicomp-online/onDecember27,2019.
Buprenorphineishighlyproteinboundandhasalargevolumeofdistribution.Thedrugisasubstrateof
cytochromeP4503A4(CYP3A4);therefore,CYP3A4inducersandinhibitorswilldecreaseorincrease
buprenorphineconcentrations,respectively.Also,decreaseddosesshouldbeusedinpatientsidentified
as poor metabolizers of CYP3A4. Adverse effects of buprenorphine include precipitated withdrawal
(whengivenconcurrentlyorafterrecentopioiduse)withsubsequentnausea/vomitingandtremors.Other
commonsideeffectsincludeheadache,insomnia,andperipheraledema.Whilebuprenorphinehasadoseceiling effectonrespiratorydepression,riskincreaseswhenusedwithother CNSdepressantssuchas
benzodiazepines.
The dosing of buprenorphine for OUD is generally once a day. Because the analgesic effect of
buprenorphineisshorter(6–8hours)thanitspropertiesrelatedtotreatmentofOUD,thedrugshouldbe
dosedtwicetothricedailytooptimizetheanalgesiceffectwhenusedforpainmanagement(incontrastto
theonce-a-daydosingusedinOUD).Whilebuccalandsublingualformulationsofbuprenorphinearethe
mostcommonly used formulations for OUD, a long-acting implant and extended-release subcutaneous
injection are available for use in patients who have been maintained on transmucosal buprenorphine.
Theseformulationsarelong-actingandconsequentlylessbeneficialintreatingpain.Variousformulations
ofbuprenorphine(suchasSuboxone–)maycontainnaloxone,amuopioidreversalagent.Thepurposeof
theadditionofnal-oxoneistodeter abuse.Whentakenbuccallyorsublingually,theabsorptionofthe
naloxoneisverypoor,renderingitineffective.However,wheninjected,thenaloxonewillantagonizethe
opioidreceptors,therebylesseningtheeuphoriceffects.Theformulationofbuprenorphinewithnaloxone
canbeverybeneficialintheoutpatientsetting.
WhilebuprenorphineformulationsapprovedforOUDcanbeusedoff-labeltotreatpain,formulations
ofbuprenorphineapprovedbytheFoodandDrugAdministration(FDA)areavailablespecificallyforthe
treatmentofpain.Theanalgesiceffectsofbuprenorphineareseenatlowerdosesthanwhatis usedfor
OUD.Sincehigherdosesareneededtopreventopioidcravings,manyofthebuprenorphineformulations
indicatedforthetreatmentofpainarenotasefficaciousforconcomitantlytreatingOUD.Whenbothpain
controlandOUDtreatmentsareneeded,increasedanalgesicbenefitmaybeobtainedbydividingthedose
of formulations indicated for OUD. Formulations are not interchangeable and no current dosing
equivalents among agents are available. Bioavailability of the products must be assessed in order to
determinesafeinterchangeamongproducts(Table10.2).
Buprenorphine isa Schedule 3–controlled medication requiringa DrugEnforcementAgency(DEA)
numberforitsprescribing.InordertoprescribebuprenorphineforOUD,theDrugAddictionTreatment
Act(DATA)requires prescriberstorequestawaiverandcompletespecificrequirementsoftheCenter
forSubstanceAbuseTreatment.Restrictionsonthenumberofpatientsaprescribercantreatatanygiven
time are also included in the DATA prescribing information. However, any prescriber can write
buprenorphinewhenusedasananalgesic(Table10.3).
Patientsshouldbeeducatedonhow toproperlyadministerbuprenorphine.Thesublingualor buccal
tablet/filmshouldbe placedunderthetongueor placedinsidethecheek,respectively, until completely
dissolved. The long-acting implant and extended-release subcutaneous injection formulation require
administrationbyatrainedhealthcareproviderandarenotavailableinretailpharmacies.Buprenorphine
should be used cautiously in patients with respiratory depression as well as preexisting hepatic
impairment.Patientsshouldhaveliverfunctiontestsassessedatbaseline,6months,andthenannually.
TABLE10.2
BioavailabilityofBuprenorphineFormulations
Formulation AverageBioavailability(%)*
Buccalformulation(Belbuca) 55
Transdermalpatch(Butrans) 15
Sublingual—Zubsolv 25
Sublingual—Suboxone 35
Sublingual—Bunavail 5G
*Informationobtainedfromrespectivepackageinserts.
TABLE10.3
DrugAuuiciionireairneniAGIprescribing
BrandName GenericName Formulation Indication
Belbuca Buprenorphine Buccalfilm Pain
Bunavail Buprenorphine/naloxone Buccalfilm Opioiddependence
Buprenex Buprenorphine Solutionforinjection(IV/IM) Pain
Butrans Buprenorphine Transdermalpatch Pain
Probuphine Buprenorphine Intradermalimplant Opioiddependence
Sublocadelate Buprenorphine Solutionforinjection(SQ)or(SC) Opioiddependence
Suboxone Buprenorphine/naloxone Sublingualfilm/tablet Opioiddependence
Subutex Buprenorphine Sublingualtablet Opioiddependence
Zubsolv Buprenorphine/naloxone Sublingualtablet Opioiddependence
IV,intravenous;IM,intramuscular.
Methadone
MethadoneiseffectiveintreatingOUDduetoitsverylonghalf-life,whichreducescravingsanddullsthe
euphoriceffectsofotheropioidagonists.Becauseofitsfullmuopioidagonistproperties,methadoneis
alsoefficaciousinpaincontrolandisthoughttobelesslikelytoproducetoleranceduetoitsantagonistic
effects at the N-methyl-D-aspartate receptor. Methadone is a Schedule 2–controlled substance. When
being used for pain, prescriptions can be filled at a retail pharmacy, usually dispensed in tablet
formulation.WhenbeingusedforOUD,dosingisusuallyonceaday,andthemedicationisonlyavailable
throughfederallyregulatedopioidtreatmentprogramsoftenreferred toasmethadone clinics. Atthese
facilities,theliquidformulationisusuallydispensed,anddosesareprovideddailybytheclinicdirectly
tothepatient.MethadonethatisprovidedtopatientsfromaclinicmaynotdisplayinthePDMPreport.
Similar to buprenorphine, methadone is primarily metabolized by CYP3A4 (also by CYP2B6 and
CYP2D6). Drug interactions should be analyzed and used cautiously in patients who are poor
metabolizers ofthese enzymes.Pharmacokineticsofmethadoneare widelyvariable. Methadone’shalflifecanrangebetween8and59hourswithadurationofeffectlastingapproximately30hours.Unlike
buprenorphine,thereisnoceilingeffectandthereforecarriesagreaterriskofrespiratorydepressionif
dosedinappropriately.
TheFDAblackboxwarningsassociatedwithmethadoneuseemphasizedangerousadverseeffectssuch
as respiratory depression and riskof abuse/dependence. Respiratory rate should be monitored during
initiation and titration of methadone doses. When taken with other medications that cause CNS
depression, the incidence of respiratory depression increases. Also, methadone is associated with an
increasedriskoftorsadesdepointesbyprolongingtheQTcinterval.Electrocardiography(EKG)should
bedonepriortotreatmentinitiation,within30daysofstarting,andthenonceayear.Electrolytessuchas
potassiumandmagnesiumneedtobeinnormalrangetopreventriskofarrhythmias.IftheQTcinterval
exceeds500ms,stoppingorreducingmethadoneisrecommended,andanalternativemedicationshould
beconsidered.Riskisincreasedwhenmethadoneisgivenwithothermedicationsthatalsoprolongthe
QTcinterval(e.g.,antipsychotics,antiarrhythmics).Commonsideeffectsaresimilartootheropioidsand
canincludenausea/vomiting,sedation,andhypotension.
Unfortunately,methadonehasincompletecross-tolerancewithotheropioids,andconversionsare not
bidirectional.Whenconvertingfromhigh-doseopioidstomethadone,ahigherconversionfactorisused
as opposed to switching offmethadone. Tolerancewillnotgenerallydeveloptomethadoneasisseen
withotheropioidssuchasmorphine.Therefore,whenconvertingbetweenmethadoneandotheropioids,
nostandardequivalentanalgesicdoserecommendationsareavailable.Dosingrecommendationssuggest
startinglowandtitratingupgradually.Inthepast,increases indeathswere seenwhenmethadonewas
initiatedfor painwithout a thoroughunderstandingoftheproperties ofthemedication. This prompted
development of guidelines for methadone use in pain, providing direction for initial dosing in both
opioid-naiveand-tolerantpatients(Chouetal.,2014).Whilemethadoneisusuallydosedonceadayfor
OUD,morefrequentdosingisnecessarywhenbeingusedforpain.Ingeneral,higheronce-dailydosesfor
methadone are recommended for OUD compared to lower doses givenmultiple times a day for pain
management.WhenbothacutepainandOUDarepresent,themethadonedosecanbedividedthreetofour
timesdailyinordertoprovideanalgesictreatment.
Non-opioidandMultimodalAnalgesia
Non-opioid analgesics are firstlinefor mild tomoderatepain.Examplesofnon-opioid analgesics are
acetaminophenandnonsteroidalanti-inflammatorydrugs.Thesemedicationsdonothaveaneffectonthe
opioidreceptorsthatmayleadtoabuseandthereforearegoodanalgesicoptionsforpatientswithOUD,
especiallyforacutepaintreatment.Also,theuseofcoanalgesics,eitheraloneorasadjuncttreatment,can
alsobeusedinpatientswithOUD,particularlyifpainischronic.Classesofadjunctivepainmodalities
includeantidepressants,anticonvulsants,cannabinoids,sodiumchannelblockers,antispasmodicskeletal
musclerelaxers,andantispasticagents.Whiletramadolistechnicallynotanopioid,itsweakmureceptor
propertiesmayelicitcravings.Therefore,tramadolisgenerallynotrecommendedinpatientswithOUD
dueto misusepotential (butcanbe considered incertainsituations).Referto Chapter9 for additional
informationoneachclassofnon-opioidagentsindicatedforpain.
Opioids
Opioids arenotgenerallyrecommended forpain inpatientswithdiagnosed or suspectedOUD.There
maybeaplaceforopioidsinacutepainorcancer-relatedpainwhenusedincontrolledsettingsafterthe
potentialrisksandbenefitsof treatment havebeenweighedandotheroptions havebeenexhausted.If
indicated,opioidswithlessrewardingpropertiesshouldbeselectedandtitratedupslowlytoaneffective
dose(avoid supratherapeuticdoses).Recently, someopioidshavebeenreformulatedtodeterabuseby
makingthemedicationmorearduoustotamperwithoncemanipulated.
Dosingis more complicatedbecause ofexistingtolerance. Ifopioids mustbe used in patients with
OUD,activesubstanceabuseshouldnotbepresent.Ifanopioidisaddedtoapatientalreadystabilized
onMAT,higherdosesmayberequiredwithshorterintervalsduetoincreasedpainsensitivityandopioid
tolerance.Patientswillrequire close monitoring, andonly limitedquantitiesshouldbe dispensed ata
time. Urine drug screens can be utilized, but unexpected results should be confirmed due to a high
frequency of false positives/negatives. Refer to Chapter 9 for more information on opioid
pharmacotherapy.
SelectingtheMostAppropriateTherapy
Non-opioidmedicationsarerecommendedforuseinpatientswithOUD.IfapatientisreceivingMAT,
thedosingintervalcanbeadjustedtoallowfullanalgesicpotential.Singledailydosesofmethadoneand
buprenorphineforOUDarenotadequateincontrollingpainduetotheshorter-actinganalgesiceffectsof
bothmedications compared tolonghalflives.For example, methadone’s analgesic effectslastabout 6
hoursalthoughitshalf-lifecanbeupto59hoursinsomepatients.
Arecommendedoutpatientoptionfortreatingpaininapatientestablishedonbuprenorphinetherapyis
Соседние файлы в папке Библиотека им академика М.И. Перельмана