癌性疼痛處理

1、癌性疼痛處理目標(biāo)比較，對(duì)比感受傷害性的和神經(jīng)病性的疼痛了解癌痛鎮(zhèn)痛處理的階梯了解阿片類鎮(zhèn)痛劑給藥的其他途徑講解維持鎮(zhèn)痛時(shí)阿片類藥物間互相轉(zhuǎn)換的技巧ObjectivesCompare, contrast nociceptive, neuropathic painKnow steps of analgesic management of cancer painKnow alternative routes for delivery of opioid analgesicsDemonstrate ability to convert between opioids while maintaining

2、 analgesia軀體的疼痛PhysicalPain情感的疼痛EmotionalPain社交障礙Social Discord宗教的困擾SpiritualDistress病痛=總體的疼痛Suffering = Total Pain總的原則多因素對(duì)患者反應(yīng)的影響 環(huán)境 心理/社會(huì)狀態(tài) 年齡 性別 多系統(tǒng)疾病和障礙 復(fù)合用藥 General PrinciplesInfluences on patients response to Rx Environment Psycho/social status Age Sex Multi-system disease and disorders Polyph

3、armacy普遍原則“拇指原則” 診斷可能的機(jī)制,個(gè)體化治療 ATC和PRN用藥,保持簡(jiǎn)單 反復(fù)評(píng)價(jià),注意細(xì)節(jié)General Principles“Rules of Thumb” Diagnose underlying mechanism Individualize treatment ATC and PRN medications Keep it simple, Reassess Attention to Detail疼痛的病理生理學(xué)急性疼痛 已明確的原因，緩解時(shí)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(shí)間不確定 感受傷害性的和/或神經(jīng)病理性的Pain pa

4、thophysiologyAcute pain Identified event, resolves daysweeks Usually nociceptiveChronic pain Cause often not easily identified, multifactorial Indeterminate duration Nociceptive and / or neuropathic感受傷害性的疼痛對(duì)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(dòng)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Nociceptive painDirect stimulation

5、 of intact nociceptorsTransmission along normal nervesSharp, aching, throbbing Somatic- Easy to describe, localize Visceral- Difficult to describe, 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Nociceptive painTissue injury apparentManagement Opioids Adjuvant / 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(rùn)，缺血，代謝

6、性損傷不同類型 外周的 傳入神經(jīng)阻滯 交感神經(jīng)介導(dǎo)的Neuropathic painDisordered peripheral or central nervesCompression, transection, infiltration, ischemia, metabolic injuryVaried types Peripheral deafferentation sympathetically mediated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Neuropathic painPain may

7、 exceed observable injury Described as burning, tingling, shooting, stabbing, electrical Management Opioids Adjuvant / coanalgesics often requiredWHO 3- 階梯療法WHO 3-step Ladder1 mild (1 3/10)2 moderate (4 6/10)3 severe (7 - 10/10)Morphine嗎啡Hydromorphone氫嗎啡酮 Oxycodone羥考酮Fentanyl芬太尼Methadone美沙酮 Adjuvant

8、sA/Codeine可待因A/Hydrocodone氫可酮A/Oxycodone羥考酮Tramadol曲馬多 AdjuvantsASAAcetaminophen撲熱息痛NSAIDs Adjuvants WHO 3-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(xué)在肝臟結(jié)合通過腎臟排泄（90%-95%）一級(jí)動(dòng)力學(xué)Opioid pharmacologyConjugated in liverExcreted via

9、kidney (90%95%)First-order kineticsPlasma Concentration0Half-life (t1/2)TimeIVpo / prSCCmax阿片類的藥理學(xué)4-5個(gè)半衰期后呈穩(wěn)定狀態(tài) 1天（24小時(shí)）后呈穩(wěn)定狀態(tài)“即釋”劑型作用的持續(xù)時(shí)間 每4小時(shí) PO/PR 非腸道的沖擊劑量持續(xù)時(shí)間更短Opioid pharmacologySteady state after 4 5 half-lives Steady state after 1 day (24 hours)Duration of effect of “immediate-release” formu

10、lations 4 hours PO / PR Shorter with parenteral bolus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 q 4 h 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(duì)于嚴(yán)重的難以控制的疼痛需要較快地調(diào)整劑量Routine oral dosingimmediate-release preparationsMorphine, hydrocodone, oxycodone hydromorphone, (fentanyl) Dose q 4 h Adjust dose daily- mi

11、ld / moderate pain 25%50%- severe / uncontrolled pain 50%100% Adjust more quickly for severe uncontrolled pain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Routine oral dosingextended-release preparationsImprove compliance, adherenceDose q 8, 12, or 24 h Dont crush or chew tab

12、lets May flush time-release granules down feeding tubesAdjust dose q 2 3 days突破性劑量使用即釋阿片類 應(yīng)用24小時(shí)總量的10%-15% 在達(dá)最高濃度后使用 PO q 1 h SC q 30 min IV q 1015 min不要使用緩（控）釋阿片類Breakthrough dosingUse immediate-release opioids 10% 15% of 24-h dose Offer after Cmax reached PO q 1 h SC q 30 min IV q 1015 minDO NOT u

13、se extended-release opioids對(duì)阿片類反應(yīng)欠佳的疼痛如果劑量增加不良反應(yīng) 需要更復(fù)雜的療法來拮抗不良反應(yīng) 替代方法 - 給藥途徑 - 阿片類輪換 聯(lián)合鎮(zhèn)痛劑 使用非藥物方法 Pain poorly responsive to opioidsIf dose escalation adverse effects More sophisticated therapy to counteract adverse effect Alternative- route of administration- opioid rotation Coanalgesic Use a non-p

14、harmacologic approach給藥的替代途徑Alternative routes of administrationEnteral feeding tubes 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(rèn)的等效劑量原則，從相應(yīng)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(yīng)明顯，減少劑量Changing opioidsCross-tolerance Start with 50

15、%75% of published equianalgesic doseMore if pain not controlled less if adverse effects prominent阿片類鎮(zhèn)痛劑的等效劑量Equianalgesic doses of opioid analgesicspo / pr (mg)AnalgesicSC / IV (mg)30Morphine嗎啡1030Hydrocodone氫可酮-20Oxycodone羥考酮-7.5 Hydromorphone氫嗎啡酮( 300Meperidine度冷丁75 )( 200Codeine可待因120 )阿片類鎮(zhèn)痛劑的等效劑

16、量透皮芬太尼 25 mg/張 50 mg PO 嗎啡 / 24 h. 50 mg/張 100 mg PO 嗎啡/24 h. Equianalgesic doses of opioid analgesicsTransdermal fentanyl25 mg patch 50 mg PO morphine / 24 h.50 mg patch 100 mg PO morphine/24 h.etc . . .阿片類鎮(zhèn)痛劑的受體親和力Receptor Affinity of Opioid AnalgesicsReceptor Type 受體類型 mu kappa delta NMDA_Morphin

17、e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 AntA = strong agonist強(qiáng)激動(dòng)劑 Ant = strong antagonist強(qiáng)拮抗劑 - = negligible activity 低活性 Twycross R et al. Palliative Care Formulary. 1998.藥代動(dòng)力學(xué)概況Pharmacokinetic Profile Peak onset Duration Potency Analgesic

18、 of Action of Effect Ratio_鎮(zhèn)痛劑_峰值作用時(shí)間_ 作用持續(xù)時(shí)間_效能比_ morphine嗎啡 30 - 60 m3 - 4 h and 8 - 12 h - oxycodone羥考酮 30 - 60 m3 - 4 h and 8 - 12 h 1:1 methadone美沙酮 30 - 60 m 8 - 12 h 5 - 20:1 hydromorphone氫嗎啡酮 45 m 4 - 5 h 4:1 fentanyl TTS芬太尼 16 - 24 h 48 - 72 h 100:1美沙酮轉(zhuǎn)換指南Methadone conversion guidelines Ist

19、ituto Nazionale dei TumoriMilan, Italy 24小時(shí)嗎啡總量 與嗎啡的對(duì)比率Dose of morphine q 24 h Ratio to Morphine 300 mg 12:1 Ripamonti C. Cancer Pain and Palliative Care. IASP, 1999.藥理學(xué)半衰期范圍為10-60小時(shí)達(dá)穩(wěn)態(tài)時(shí)間從2-10天不等等效鎮(zhèn)痛劑量難以預(yù)測(cè)連續(xù)使用美沙酮可能造成的蓄積是個(gè)體化的PharmacologyHalf life ranges from 10 - 60 hoursTime to steady state varies f

20、rom 2 - 10 daysEquianalgesia very difficult to predictAccumulation with continued use may occur of methadone must be individualised 美沙酮初始劑量的計(jì)算第一步：停用嗎啡（或其他強(qiáng)阿片類藥物）第二步：給予美沙酮的固定劑量，即當(dāng)口服嗎啡24小時(shí)總量300mg時(shí),固定劑量應(yīng)該是30mg。第三步：必要時(shí)給予口服的固定劑量，但給藥頻數(shù)不能超過q3h。Calculating the starting dose of methadoneStep #1: Stop morphin

21、e (or other strong opioid)Step #2: Give a fixed dose of methadone that is 1/10 of the 24 h oral morphine dose when 24 h dose is 300 mg., the fixed dose should be 30 mg.Step #3: The fixed dose is taken PO prn but not more frequently than q 3 h. b Morley JS, Makin MK. Pain Reviews. 1998.美沙酮起始劑量的計(jì)算第四步：

22、第六天，計(jì)算前兩天美沙酮的平均口服用量，并轉(zhuǎn)換為定時(shí)的q12h用量（和q3h prn）第五步：如果持續(xù)需要臨時(shí)給藥，每4-6天一次增加1/2-1/3的美沙酮用量（即，10mg bid 變?yōu)?5mg bid;30mg bid變?yōu)?0mg bid)Calculating the starting dose of methadoneStep #4: On day 6, the amount of methadone taken over the previous 2 days is averaged and converted into a regular q 12 dose (and q 3 h pr n).Step #5: If prn medication continues to be needed, increase the dose of methadone 1/2-1/3 every 4-6 days (i.e., 10 mg bid to 15 mg bid; 30 mg bid to 40 mg bid).Morley JS, Makin MK. Pain Revi