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1、末期病人疼痛處置概論,Woei-Yau Kao, MD, PhD Tri-Service General Hospital National Defense Medical Center,Outline,General guidelines (Pharmacology, titration) Transdermal fentanyl patch Opioid tolerance, Hyperanalgesia, Withdrawal symptoms Opioid rotation Addition of a second opioid Combination of opioid agonis
2、ts and antagonists Renal/hepatic failure, old man Summary,疼痛用藥原則,經口服藥 按時用藥 階梯步驟 個人化原則 加入輔助用藥 注意細節 最大效果與最小副作用,癌症疼痛的評估-1,疼痛是主觀感覺 所以止痛，要以顧客滿意度為最重要考量,癌症疼痛的評估-3,癌症病人的疼痛，絕大部分與癌症本身有關，可以用止痛藥緩解。 但是病人也有可能出現別的疾病，此時一定要先仔細評估，才不會遺漏： 腸穿孔、急性闌尾炎、心肌梗塞 病理性骨折 也就是要先排除急症的可能性,Mantyh PW et al. Nature reviews cancer 2002,Ad
3、apted from WHO. Cancer Pain Relief, with a Guide to Opioid Availability. 1996.,Ultracet,(7-10),(4-6),(1-3),Choice of Opioid Analgesic,Recommendation from AHCPR Cancer Pain Guidelines Panel: “The simplest dosage schedules and least invasive pain management modalities should be used first” (Panel Cons
4、ensus),重度疼痛,快速生效之短效嗎啡，使用腸胃蠕動劑 止吐藥 合併使用止痛藥物 敎育病人 心理支持,(1/6),Around the clock,非鴉片類止痛用藥,NSAID or Cox-2 具抗發炎效果，通常用於骨轉移和軟組織疼痛。 選擇半衰其較短的藥物，調整較富彈性。 通常止痛效果越強者，副作用較多。 一般以建議量之最小量開始使用，注意其極限效應（Ceilings effect）。 可與Opioid併用。,Classical type of opioid receptor: m, k, d,Actions of Opioids,Gourlay GK Support Care Can
5、cer 2005;13:153-9,Opioid binding affinities,常見鴉片類止痛劑的副作用,鎮靜、呼吸抑制、噁心/嘔吐、便秘*、皮膚癢、口乾*、小便困難/滯留、睡眠異常、幻覺、耐藥性*、依賴性*、情緒改變*、肌肉陣攣* * 經長期使用仍可能持續,弱效鴉片類止痛藥,Codeine Tramadol Ultracet Proxyphene (Depain X) 避免長期使用 Meperidine,Tramadol,中樞及周邊的非成癮性止痛劑 低度結合鴉片類受體，活化脊髓內鴉片類受體 抑制 Serotonin 及 Noradrenaline 的再吸收。 口服劑量 Ceiling
6、 effect (+) 起始：100 mg/q12h 或 50 mg /q6h 一般：200 mg/q12h 或 100 mg/q6h 衛生署合格通過為非成癮性管制用藥之鴉片類止痛藥。 副作用：噁心、嘔吐、暈眩。,ULTRACET,Body System (% of Patients) Preferred Term N = 142 Gastrointestinal System Constipation6 Diarrhea3 Nausea3 Dry Mouth2 Psychiatric Disorders Somnolence6 Anorexia3 Insomnia2 Central chi(
7、2): 0.73). Use of tramadol produced higher rates of adverse events than codeine and hydrocodone: vomiting, dizziness, loss of appetite, and weakness (p 0.05).,Rodriguez et al., J Palliat Med. 2007 Feb;10(1):56-60,IV, SC, rectal route, oral: Short acting vs long acting Dose conversion: PRN dose Compl
8、ications,強效鴉片類止痛藥,作用與副作用均類似 單純的 agonist opioids 無極限藥量限制（No Ceiling Effect），藥量增大則止痛效果持續加強，但副作用亦隨之增加,強效鴉片類止痛藥,Morphine Fentanyl transdermal patch Temgesic (Buprenorphine hydrochloride) SL Butaro (butorphanol tartrate) nasal spray,Morphine Pharmacology 7(3):462-8,Opioid Dose Titration for Severe Cancer
9、 Pain,Regardless of the regimen, the majority of patients had their pain relieved within 24 hrs (level III-D) The onset to analgesia is fastest for parenteral dosing schedules (level III-A) No difference between SR and IR oral opiates for acute pain (level III-A),Davis MP et al., J Palliat Med2004;7
10、(3):462-8,Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: a randomized, double-blind trial,Starting dose 60 mg/day (oral) A fixed titration schedule (60-90-120-180-270-360 mg) Morfin (IR) vs Kapanol (SR) Mean time needed for titration: IR 2.1d (
11、1.4-2.7) vs SR 1.7 d (1.1-2.3) A simplified titration using SR morphine is equally as IR morphine,Klepstad P et al., Pain 2003;101:193-8,Recognition, diagnosis 8 Suppl 1:S8-13. Payne R 2007;8 Suppl 1:S3-7.,Inadequate pain management Difficult pain problem,Mixed pattern,Mercadante S et al. Cancer 200
12、2,Differentiation of episodic pain,Mercadante S et al. Cancer 2002,Algorithm for treatment of breakthrough pain,Mercadante S et al. Cancer 2002,Algorithm for treatment of neuropathic breakthrough pain,Mercadante S et al. Cancer 2002,Rescue dose,Individualized: Opioid-nave vs opioid-taking IV, SC (on
13、set delay 30 min) or short-acting oral form Dosing 50%-200% of daily IV opioid dose as needed q15 min (NCCN guideline),Nelson KA et al., J Pain Symptom Manage 1997,Breakthrough Dosing,Donnelly S et al. Support Care Cancer 2002,50% of hourly dose,Dose conversion,IV : Oral = 1:3 for low doses = 1:2 fo
14、r high doses,Hanks GW et al. BMJ 1996 Mercadante S et al. Cancer 2002,Donnelly S et al. Support Care Cancer 2002,如何換算Durogesic 的劑量?,Durogesic Oral morphine 25(g) 60 (30 90) mg 50 120 (90 150) 75 180 (150 210) 100 240 (210 240) 125 300 (270 330),For every additional 60 mg, increase Durogesic 25 mcg/h
15、rs,Muijers RBR et al, Drugs 2001;61:2289-2307,Fentanyl TTS (Durogesic),強效鴉片類止痛劑 作用： 活化(supraspinal)與(intraspinal)接受器。 抑制 spinothalamic tract 侵害性訊息的傳導。 代謝 主要經肝臟代謝 (hepatic dealkylation) 75% 經尿液排泄 老年人、腎臟清除率較差者謹慎使用,Durogesic 貼片,12 H,Fentanyl transdermal patch,以簡單、非侵入性的方式提供穩定的Fentanyl 血中濃度，發揮止痛效果。 Fenta
16、nyl transdermal patch：25、50 ug/hr 每72小時換一次，少數人需48小時換一次。,Fentanyl TTS v.s. 口服Morphine,同樣提供良好的疼痛控制效果 便秘、噁心、嘔吐、皮膚癢比率較少發生 白天嗜睡等常困擾病患的鴉片類副作用較低 呼吸抑制：比率和嗎啡一樣低。 過敏作用：和黏貼劑有關，可以用 antihistamine 處理。,Withdrawal symptoms during therapy with transdermal fentanyl,Despite good pain control, severe abdominal withdrawal symptoms (diarrhea, headache, abdominal cramps, nausea, sweating, freezing, shivering and restless) Fentanyl dosages toward the upper end of c
