课件：癌性疼痛的处理.ppt

癌性疼痛的处理 WHO 3-阶梯镇痛疗法 Management of Cancer Pain WHO 3 Step Analgesic Ladder,Terence L. Gutgsell, MD Hospice of the Bluegrass Lexington, KY,目标 比较，对比感受伤害性的和神经病性的疼痛 了解癌痛镇痛处理的阶梯 了解阿片类镇痛剂给药的其他途径 讲解维持镇痛时阿片类药物间互相转换的技巧 Objectives Compare, contrast nociceptive, neuropathic pain Know steps of analgesic management of cancer pain Know alternative routes for delivery of opioid analgesics Demonstrate ability to convert between opioids while maintaining analgesia,躯体的疼痛Physical Pain,情感的 疼痛 Emotional Pain,社交 障碍 Social Discord,宗教的困扰Spiritual Distress,病痛=总体的疼痛 Suffering = Total Pain,总的原则 多因素对患者反应的影响 环境 心理/社会状态 年龄 性别 多系统疾病和障碍 复合用药 General Principles Influences on patients response to Rx Environment Psycho/social status Age Sex Multi-system disease and disorders Polypharmacy,普遍原则 “拇指原则” 诊断可能的机制,个体化治疗 ATC和PRN用药,保持简单 反复评价,注意细节 General Principles “Rules of Thumb” Diagnose underlying mechanism Individualize treatment ATC and PRN medications Keep it simple, Reassess Attention to Detail,疼痛的病理生理学 急性疼痛 已明确的原因，缓解时间：数日到数周 通常是感受伤害性的 慢性疼痛 原因常不易确定，多因素的 持续时间不确定 感受伤害性的和/或神经病理性的 Pain pathophysiology Acute pain Identified event, resolves daysweeks Usually nociceptive Chronic pain Cause often not easily identified, multifactorial Indeterminate duration Nociceptive and / or neuropathic,感受伤害性的疼痛 对健全的伤害感受器的直接刺激 沿正常神经传递 锐痛，酸痛，搏动性疼痛 本体性的 -易于描述和定位 内脏性的 -难以描述和定位 Nociceptive pain Direct stimulation of intact nociceptors Transmission along normal nerves Sharp, aching, throbbing Somatic - Easy to describe, localize Visceral - Difficult to describe, localize,感受伤害性疼痛 组织损伤明显 治疗 阿片类药物 辅助药物/联合镇痛剂 Nociceptive pain Tissue injury apparent Management Opioids Adjuvant / coanalgesics,神经病性疼痛 外周或中枢神经的功能障碍 压迫，横断，浸润，缺血，代谢性损伤 不同类型 外周的 传入神经阻滞 交感神经介导的 Neuropathic pain Disordered peripheral or central nerves Compression, transection, infiltration, ischemia, metabolic injury Varied types Peripheral deafferentation sympathetically mediated,神经病性疼痛 疼痛可能不仅只由可见的损伤引起 描述为烧灼感，麻刺感，射痛，刺痛，电击样疼痛 治疗 阿片类药物 常需要辅助药物/联合镇痛剂 Neuropathic pain Pain may exceed observable injury Described as burning, tingling, shooting, stabbing, electrical Management Opioids Adjuvant / coanalgesics often required,WHO 3- 阶梯疗法 WHO 3-step Ladder,1 mild (1 3/10),2 moderate (4 6/10),3 severe (7 - 10/10),Morphine吗啡 Hydromorphone氢吗啡酮 Oxycodone羟考酮 Fentanyl芬太尼 Methadone美沙酮 Adjuvants,A/Codeine可待因 A/Hydrocodone氢可酮 A/Oxycodone羟考酮 Tramadol曲马多 Adjuvants,ASA Acetaminophen扑热息痛 NSAIDs Adjuvants,WHO 3-阶梯疗法,1 轻度 (1 3/10),阿斯匹林 扑热息痛 NSAIDs 辅助药物,2 中度 (4 6/10),A/可待因 A/氢可酮 A/羟考酮 曲马多 辅助药物,3 重度 (7 - 10/10),吗啡 氢吗啡酮 羟考酮 芬太尼 美沙酮 辅助药物,阿片类的药理学 在肝脏结合 通过肾脏排泄（90%-95%） 一级动力学 Opioid pharmacology Conjugated in liver Excreted via kidney (90%95%) First-order kinetics,Plasma Concentration,0,Half-life (t1/2),Time,IV,po / pr,SC,Cmax,阿片类的药理学 4-5个半衰期后呈稳定状态 1天（24小时）后呈稳定状态 “即释”剂型作用的持续时间 每4小时 PO/PR 非肠道的冲击剂量持续时间更短 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,常规口服剂量 即释剂型 吗啡，氢可酮，羟考酮，氢吗啡酮，（芬太尼） 剂量 q 4 h 每天调整剂量 - 轻度/中度疼痛 25%50% - 重度/难以控制的疼痛 50%100% 对于严重的难以控制的疼痛需要较快地调整剂量 Routine oral dosing immediate-release preparations Morphine, hydrocodone, oxycodone hydromorphone, (fentanyl) Dose q 4 h Adjust dose daily - mild / moderate pain 25%50% - severe / uncontrolled pain 50%100% Adjust more quickly for severe uncontrolled pain,2019/8/5,17,可编辑,常规口服剂量 缓释剂型 增加依从性与合作性 按 q8,12,或24h给予药物 不要压碎或咀嚼药片 可以通过鼻饲管将缓释颗粒注入 每2-3天调整剂量 Routine oral dosing extended-release preparations Improve compliance, adherence Dose q 8, 12, or 24 h Dont crush or chew tablets May flush time-release granules down feeding tubes Adjust dose q 2 3 days,突破性剂量 使用即释阿片类 应用24小时总量的10%-15% 在达最高浓度后使用 PO q 1 h SC q 30 min IV q 1015 min 不要使用缓（控）释阿片类 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,对阿片类反应欠佳的疼痛 如果剂量增加不良反应 需要更复杂的疗法来拮抗不良反应 替代方法 - 给药途径 - 阿片类轮换 联合镇痛剂 使用非药物方法 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,给药的替代途径 Alternative routes of administration,Enteral feeding tubes 置管喂饲 Transmucosal 经粘膜 Rectal经直肠,Transdermal 经皮 Parenteral 胃肠外 Intraspinal 脊柱内 Epidural 硬膜外 Intrathecal 鞘内,更换阿片类药物 交叉耐受 按已公认的等效剂量原则，从相应剂量的50%-75%开始使用 如果疼痛不能控制，追加剂量 如果不良反应明显，减少剂量 Changing opioids Cross-tolerance Start with 50%75% of published equianalgesic dose More if pain not controlled less if adverse effects prominent,阿片类镇痛剂的等效剂量 Equianalgesic doses of opioid analgesics,po / pr (mg) Analgesic SC / IV (mg) 30 Morphine吗啡 10 30 Hydrocodone氢可酮 - 20 Oxycodone羟考酮 - 7.5 Hydromorphone氢吗啡酮 1.5 ( 300 Meperidine度冷丁 75 ) ( 200 Codeine可待因 120 ),阿片类镇痛剂的等效剂量 透皮芬太尼 25 mg/张 50 mg PO 吗啡 / 24 h. 50 mg/张 100 mg PO 吗啡/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 . . .,阿片类镇痛剂的受体亲和力 Receptor Affinity of Opioid Analgesics,Receptor Type 受体类型 mu kappa delta NMDA _ Morphine吗啡 A - - - Fentanyl芬太尼 A - - - Hydromorphone氢吗啡酮 A - - - Oxycodone羟考酮 A(?) A(?) - - Methadone美沙酮 A - A Ant A = strong agonist强激动剂 Ant = strong antagonist强拮抗剂 - = negligible activity 低活性 Twycross R et al. Palliative Care Formulary. 1998.,药代动力学概况 Pharmacokinetic Profile,Peak onset Duration Potency Analgesic of Action of Effect Ratio _镇痛剂_峰值作用时间_ 作用持续时间_效能比_ morphine 吗啡 30 - 60 m 3 - 4 h and 8 - 12 h - oxycodone羟考酮 30 - 60 m 3 - 4 h and 8 - 12 h 1:1 methadone美沙酮 30 - 60 m 8 - 12 h 5 - 20:1 hydromorphone氢吗啡酮 45 m 4 - 5 h 4:1 fentanyl TTS芬太尼 16 - 24 h 48 - 72 h 100:1,美沙酮转换指南 Methadone conversion guidelines Istituto Nazionale dei Tumori Milan, Italy,24小时吗啡总量 与吗啡的对比率 Dose of morphine q 24 h Ratio to Morphine 300 mg 12:1 Ripamonti C. Cancer Pain and Palliative Care. IASP, 1999.,药理学 半衰期范围为10-60小时 达稳态时间从2-10天不等 等效镇痛剂量难以预测 连续使用美沙酮可能造成的蓄积是个体化的 Pharmacology Half life ranges from 10 - 60 hours Time to steady state varies from 2 - 10 days Equianalgesia very difficult to predict Accumulation with continued use may occur of methadone must be individualised,美沙酮初始剂量的计算 第一步：停用吗啡（或其他强阿片类药物） 第二步：给予美沙酮的固定剂量，即当口服吗啡24小时总量300mg时,固定剂量应该是30mg。 第三步：必要时给予口服的固定剂量，但给药频数不能超过q3h。 Calculating the starting dose of methadone 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. Pain Reviews. 1998.,美沙酮起始剂量的计算 第四步：第六天，计算前两天美沙酮的平均口服用量，并转换为定时的q12h用量（和q3h prn） 第五步：如果持续需要临时给药，每4-6天一次增加1/2-1/3的美沙酮用量（即，10mg bid 变为15mg bid;30mg bid变为40mg 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). Morley JS, Mak