癌性疼痛的處理

WHO

3-階梯鎮(zhèn)痛療法

ManagementofCancerPain

WHO3–StepAnalgesicLadderTerenceL.Gutgsell,MDHospiceoftheBluegrassLexington,KY軀體的疼痛PhysicalPain情感的疼痛EmotionalPain社交障礙SocialDiscord宗教的困擾SpiritualDistress病痛=總體的疼痛Suffering=TotalPain普遍原則“拇指原則”診斷可能的機制,個體化治療

ATC和PRN用藥,保持簡單反復評價,注意細節(jié)GeneralPrinciples“RulesofThumb”DiagnoseunderlyingmechanismIndividualizetreatmentATCandPRNmedicationsKeepitsimple,ReassessAttentiontoDetail疼痛的病理生理學急性疼痛已明確的原因，緩解時間：數(shù)日到數(shù)周

通常是感受傷害性的慢性疼痛原因常不易確定，多因素的持續(xù)時間不確定

感受傷害性的和/或神經(jīng)病理性的PainpathophysiologyAcutepainIdentifiedevent,resolvesdays–weeks

UsuallynociceptiveChronicpainCauseoftennoteasilyidentified,multifactorialIndeterminateduration

Nociceptiveand/orneuropathic感受傷害性的疼痛對健全的傷害感受器的直接刺激沿正常神經(jīng)傳遞銳痛，酸痛，搏動性疼痛本體性的-易于描述和定位內(nèi)臟性的-難以描述和定位NociceptivepainDirectstimulationofintactnociceptorsTransmissionalongnormalnervesSharp,aching,throbbingSomatic-Easytodescribe,localizeVisceral-Difficulttodescribe,localize感受傷害性疼痛組織損傷明顯治療阿片類藥物輔助藥物/聯(lián)合鎮(zhèn)痛劑NociceptivepainTissueinjuryapparentManagementOpioidsAdjuvant/coanalgesics神經(jīng)病性疼痛外周或中樞神經(jīng)的功能障礙壓迫，橫斷，浸潤，缺血，代謝性損傷不同類型外周的傳入神經(jīng)阻滯交感神經(jīng)介導的NeuropathicpainDisorderedperipheralorcentralnervesCompression,transection,infiltration,ischemia,metabolicinjuryVariedtypesPeripheraldeafferentationsympatheticallymediated神經(jīng)病性疼痛疼痛可能不僅只由可見的損傷引起描述為燒灼感，麻刺感，射痛，刺痛，電擊樣疼痛治療

阿片類藥物

常需要輔助藥物/聯(lián)合鎮(zhèn)痛劑NeuropathicpainPainmayexceedobservableinjuryDescribedasburning,tingling,shooting,stabbing,electricalManagementOpioids

Adjuvant/coanalgesicsoftenrequiredWHO3-階梯療法

WHO3-stepLadder1mild(1–3/10)2

moderate(4–6/10)3severe(7-10/10)Morphine嗎啡Hydromorphone氫嗎啡酮Oxycodone羥考酮Fentanyl芬太尼Methadone美沙酮±AdjuvantsA/Codeine可待因A/Hydrocodone氫可酮A/Oxycodone羥考酮Tramadol曲馬多±AdjuvantsASAAcetaminophen撲熱息痛NSAIDs±AdjuvantsWHO3-階梯療法

1輕度

(1–3/10)阿斯匹林撲熱息痛NSAIDs±輔助藥物2

中度

(4–6/10)A/可待因A/氫可酮A/羥考酮曲馬多±輔助藥物3重度

(7-10/10)嗎啡氫嗎啡酮羥考酮芬太尼美沙酮±輔助藥物阿片類的藥理學在肝臟結合通過腎臟排泄（90%-95%）一級動力學OpioidpharmacologyConjugatedinliverExcretedviakidney

(90%–95%)First-orderkineticsPlasmaConcentration0Half-life(t1/2)TimeIVpo/prSCCmax常規(guī)口服劑量即釋劑型嗎啡，氫可酮，羥考酮，氫嗎啡酮，（芬太尼）劑量q4h

每天調(diào)整劑量

-輕度/中度疼痛

25%–50%

-重度/難以控制的疼痛

50%–100%對于嚴重的難以控制的疼痛需要較快地調(diào)整劑量Routineoraldosing

immediate-releasepreparationsMorphine,hydrocodone,oxycodone

hydromorphone,(fentanyl)Doseq4h

Adjustdosedaily-mild/moderatepain

25%–50%-severe/uncontrolledpain

50%–100%

Adjustmorequicklyforsevereuncontrolledpain常規(guī)口服劑量緩釋劑型增加依從性與合作性按q8,12,或24h給予藥物

不要壓碎或咀嚼藥片可以通過鼻飼管將緩釋顆粒注入每2-3天調(diào)整劑量Routineoraldosing

extended-releasepreparationsImprovecompliance,adherenceDoseq8,12,or24hDon’tcrushorchewtabletsMayflushtime-releasegranulesdownfeedingtubesAdjustdoseq2–3days給藥的替代途徑

AlternativeroutesofadministrationEnteralfeedingtubes置管喂飼Transmucosal

經(jīng)粘膜Rectal經(jīng)直腸Transdermal經(jīng)皮Parenteral胃腸外Intraspinal脊柱內(nèi)Epidural硬膜外Intrathecal鞘內(nèi)更換阿片類藥物交叉耐受按已公認的等效劑量原則，從相應劑量的50%-75%開始使用

如果疼痛不能控制，追加劑量如果不良反應明顯，減少劑量ChangingopioidsCross-toleranceStartwith50%–75%ofpublishedequianalgesicdoseMoreifpainnotcontrolledlessifadverseeffectsprominent阿片類鎮(zhèn)痛劑的等效劑量

Equianalgesicdosesofopioidanalgesics

po/pr(mg) Analgesic SC/IV(mg) 30 Morphine嗎啡 10 30 Hydrocodone氫可酮 - 20 Oxycodone羥考酮 - 7.5 Hydromorphone氫嗎啡酮 1.5

(300 Meperidine度冷丁 75) (200 Codeine可待因 120)阿片類鎮(zhèn)痛劑的等效劑量透皮芬太尼

25mg/張≈50mgPO嗎啡/24h.

50mg/張≈100mgPO嗎啡/24h.

EquianalgesicdosesofopioidanalgesicsTransdermalfentanyl25mgpatch~50mgPOmorphine/24h.

50mgpatch~100mgPOmorphine/24h.

etc...阿片類鎮(zhèn)痛劑的受體親和力

ReceptorAffinityofOpioidAnalgesicsReceptorType

受體類型 mukappadeltaNMDA

______________________________________________________________________Morphine嗎啡 A - - -Fentanyl芬太尼 A - - -Hydromorphone氫嗎啡酮

A - - -Oxycodone羥考酮 A(?)A(?) - -Methadone美沙酮 A - A Ant A=strongagonist強激動劑Ant=strongantagonist強拮抗劑-=negligibleactivity

低活性 TwycrossRetal.PalliativeCareFormulary.1998.

藥代動力學概況

PharmacokineticProfile

Peakonset Duration PotencyAnalgesic ofAction ofEffect Ratio____鎮(zhèn)痛劑__________峰值作用時間___作用持續(xù)時間________效能比___morphine 嗎啡 30-60m 3-4hand8-12h-

oxycodone羥考酮30-60m 3-4hand8-12h 1:1methadone美沙酮30-60m 8-12h 5-20:1hydromorphone氫嗎啡酮45m4-5h 4:1 fentanylTTS芬太尼16-24h 48-72h 100:1美沙酮轉(zhuǎn)換指南

Methadoneconversionguidelines

IstitutoNazionaledeiTumori

Milan,Italy24小時嗎啡總量與嗎啡的對比率 Doseofmorphineq24h

RatiotoMorphine <100mg 4:1 101mgto299mg 8:1

>300mg 12:1

RipamontiC.CancerPainandPalliativeCare.IASP,1999.美沙酮初始劑量的計算第一步：停用嗎啡（或其他強阿片類藥物）第二步：給予美沙酮的固定劑量，即當口服嗎啡24小時總量<300mg時，給予24小時口服嗎啡總量的1/10，或24小時嗎啡用量>300mg時,固定劑量應該是30mg。第三步：必要時給予口服的固定劑量，但給藥頻數(shù)不能超過q3h。CalculatingthestartingdoseofmethadoneStep#1:Stopmorphine(orotherstrongopioid)Step#2:Giveafixeddoseofmethadonethatis1/10ofthe24horalmorphinedosewhen24hdoseis<300mg.,OR

whenthe24hmorphinedoseis>300mg.,thefixeddoseshouldbe30mg.Step#3:ThefixeddoseistakenPOprnbutnotmorefrequentlythanq3h.bMorleyJS,MakinMK.PainReviews.1998.美沙酮起始劑量的計算第四步：第六天，計算前兩天美沙酮的平均口服用量，并轉(zhuǎn)換為定時的q12h用量（和q3hprn）第五步：如果持續(xù)需要臨時給藥，每4-6天一次增加1/2-1/3的美沙酮用量（即，10mgbid變?yōu)?5mgbid;30mgbid變?yōu)?0mgbid)CalculatingthestartingdoseofmethadoneStep#4:Onday6,theamountofmethadonetakenovertheprevious2daysisaveragedandconvertedintoaregularq12dose(andq3hp