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(t,1/2,),Time,IV,po/pr,SC,C,max,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,常规口服剂量,缓释,剂型,增加依从性与合作性,按,q8,12,或24,h,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),AnalgesicSC/IV,(mg),30Morphine,吗啡10,30Hydrocodone,氢可酮-,20Oxycodone,羟考酮-,7.5 Hydromorphone,氢吗啡酮,1.5,(,300Meperidine,度冷丁75),(200Codeine,可待因120),阿片类镇痛剂的等效剂量,透皮芬太尼,25,m,g/,张,50,mg PO,吗啡/24,h.,50 m,g/,张,100,mg PO,吗啡,/24 h.,Equianalgesic doses of opioid analgesics,Transdermal fentanyl,25,m,g patch,50 mg PO morphine/24 h.,50 m,g 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,m3-4 h and 8-12 h -,oxycodone,羟考酮 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,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 TumoriMilan,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300,mg,时,固定剂量应该是30,mg。,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，10,mg bid,变为15,mg 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,Makin MK.,Pain Reviews,.1998.,不推荐,度冷丁,口服吸收少,半衰期短,（2-3小时）,去甲度冷丁（去甲哌替啶）是一种,毒性代谢产物,-长半衰期（6小时），没有镇痛作用,-拟精神病的不良反应，肌阵挛，惊厥/抽搐,-如果以,q3h,给药用于镇痛，去甲哌替啶蓄积增加,-肾功能不全时蓄积增加,Not recommended.,Meperidine,Poor oral absorption,Short half-life,(2-3 hours),Nor-meperidine is a,toxic metabolite,-,Long half-life(6 hours),not analgesic,-Psychotomimetic adverse effects,myoclonus,seizures,-If dosing q 3 h for analgesia,nor-meperidine builds up,-Accumulates with renal insufficiency,不推荐,混合性激动-拮抗剂,喷他佐辛，布托啡诺，纳布啡，地佐辛,-与激动剂竞争,撤药状态,-,镇痛的天花板效应,-喷他佐辛和布托啡诺的,拟精神病性不良反应,的风险高,Not recommended,Mixed agonist-antagonists,Pentazocine,butorphanol,nalbuphine,dezocine,-Compete with agonists,withdrawal,-,Analgesic ceiling effect,-High risk of,psychotomimetic adverse effects,with pentazocine,butorphanol,