癌性疼痛的處理ppt課件

1、癌性疼痛的處理WHO 3-階梯鎮(zhèn)痛療法Management of Cancer PainWHO 3 Step Analgesic Ladder,Terence L. Gutgsell, MD Hospice of the Bluegrass Lexington, KY,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 Objectives Compare, contrast nociceptive, neuropathic pain Know steps of analgesic management

2、 of cancer pain Know alternative routes for delivery of opioid analgesics Demonstrate ability to convert between opioids while maintaining analgesia,軀體的疼痛Physical Pain,情感的 疼痛 Emotional Pain,社交 障礙 Social Discord,宗教的困擾Spiritual Distress,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

3、 多系統(tǒng)疾病和障礙 復(fù)合用藥 General Principles Influences on patients response to Rx Environment Psycho/social status Age Sex Multi-system disease and disorders Polypharmacy,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 treatmen

4、t 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 pathophysiology Acute pain Identified event, resolves daysweeks Usually nociceptive Chronic pain Cause often not easily identified, multifac

5、torial 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 pain Direct stimulation of intact nociceptors Transmission along normal nerves Sharp, aching, throbbing Somatic - Easy to describe, localize Visceral - D

6、ifficult 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 pain Tissue injury apparent Management 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 pain Disordered peripheral or central nerves Compression, transection, infilt

7、ration, ischemia, metabolic injury Varied types Peripheral deafferentation sympathetically mediated,神經(jīng)病性疼痛 疼痛可能不僅只由可見(jiàn)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 pain Pain may exceed observable injury Described as burning, tingling, shooting, stabbing, electrical Management Opioid

8、s Adjuvant / coanalgesics often required,WHO 3- 階梯療法WHO 3-step Ladder,1 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 Adjuvants,A/Codeine可待因 A/Hydrocodone氫可酮 A/Oxycodone羥考酮 Tramadol曲馬多 Adjuvants,ASA Acetaminophen撲熱息痛 NSAIDs

9、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(guò)腎臟排泄（90%-95%） 一級(jí)動(dòng)力學(xué) Opioid pharmacology Conjugated in liver Excreted via kidney (90%95%) First-order kinetics,Plasma Concentration,0,Half-life (

10、t1/2),Time,IV,po / pr,SC,Cmax,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 pharmacology Steady state after 4 5 half-lives Steady state after 1 day (24 hours) Duration of effect of “immediate-release” formulations 4 hours PO / PR Shorter with parenteral bolus,常規(guī)

11、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 preparations Morphine, hydrocodone, oxycodone hydromorphone, (fentanyl) Dose q 4 h Adjust dose daily - mild / moderate pain 25%50% - severe / uncontrolled

12、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(guò)鼻飼管將緩釋顆粒注入 每2-3天調(diào)整劑量 Routine oral dosingextended-release preparations Improve compliance, adherence Dose q 8, 12, or 24 h Dont crush or chew tablets May flush time-release granules down

13、 feeding tubes Adjust 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 dosing Use immediate-release opioids 10% 15% of 24-h dose Offer after Cmax reached PO q 1 h SC q 30 min IV q 1015 min DO NOT use extended-release opioids,對(duì)阿片類反應(yīng)

14、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(lái)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 opioids If dose escalation adverse effects More sophisticated therapy to counteract adverse effect Alternative - route of administration - opioid rotation Coanalgesic Use a non-pharmacologic approach,給藥的替代途徑

15、Alternative routes of administration,Enteral 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(kāi)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 opioids Cross-tolerance Start with 50%75% of published

16、equianalgesic dose More 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 analgesics,po / pr (mg)AnalgesicSC / IV (mg) 30Morphine嗎啡10 30Hydrocodone氫可酮- 20Oxycodone羥考酮- 7.5 Hydromorphone氫嗎啡酮1.5 ( 300Meperidine度冷丁75 ) ( 200Codeine可待因120 ),阿片類鎮(zhèn)痛劑的等效劑量 透皮芬

17、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 analgesics Transdermal fentanyl 25 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 Analgesics,Receptor Type 受體類型 mu kappa delta NMDA _ Mor

18、phine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 = 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

19、 Analgesic 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 gu

20、idelines Istituto 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 Pharmacology Half life ranges from 10 - 60 hours Time to

21、steady state varies from 2 - 10 days Equianalgesia very difficult to predict Accumulation 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(guò)q3h。 Calculating the starting dose of met

22、hadone Step #1: Stop morphine (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. Pai

23、n Reviews. 1998.,美沙酮起始劑量的計(jì)算 第四步：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 methadone Step #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). Morl