1,急慢性中重度疼痛口服药物规范治疗探讨,南京军区南京总医院 麻醉科 徐建国 教授,2,背景资料,1,泰勒宁的药理药代基础 2,泰勒宁的特点 3,国外中重度疼痛治疗的概况A,急性疼痛B,慢性疼痛,3,参考一,泰勒宁的药理药代基础,4,羟 考 酮,OXYCODONEINN阿片类药物：可待因的衍生物,5,化 学 结 构,6,药 效 学,镇痛（主要应用） 镇咳（次要应用） 镇静 肠蠕动减少（止泻，便秘） 呼吸抑制（大剂量的毒性反应）,7,镇 痛 作 用 机 制,受体激动剂，主要作用在脊髓 与曲马多（双重受体作用机制）不同 与吗啡有协同作用，无交叉耐受现象 与喷他佐辛（部分激动剂）不同；与喷他佐辛有拮抗作用,8,激 动 受 体 的 效 应,亚型 效 应 痛 呼吸 心率 血压 瞳孔 精神情绪 - - 欣快，成瘾 镇静 ? 欣快 幻觉，谵妄 欣快,9,吗啡，可待因，羟考酮 止痛作用及成瘾性比较,10,参考二,泰勒宁的特点,11,胶囊：盐酸羟考酮 5mg对乙酰氨基酚 500mg片剂：盐酸羟考酮 5mg对乙酰氨基酚 325mg,泰勒宁- 氨酚羟考酮,12,1 受体结合饱和度不同羟考酮 用于中到重度疼痛吗 啡 用于重度疼痛 2 口服生物利用度不同羟考酮 60%80%吗 啡 15%64%3 副作用羟考酮几乎没有致幻作用（hallucination）其它副作用弱于吗啡,羟考酮与吗啡的主要差别,13,泰勒宁（氨酚羟考酮）镇痛机理,盐酸羟考酮中枢+外周对乙酰氨基酚中枢+外周,14,泰勒宁与临床常用阿片类镇痛药比较,吗啡，泰勒宁,度冷丁,度冷丁,吗啡,泰勒宁,成瘾性,镇痛效果,曲马多,曲马多,15,羟考酮1、口服10-15分钟起效2、镇痛效果持续4-6小时对乙酰氨基酚1、口服起效15-30分钟2、镇痛效果持续6-8小时,泰勒宁氨酚羟考酮,16,主要副作用,不良反应轻微，一般无严重不良反应头晕、嗜 睡 便秘 胃部不适、恶心、呕吐 肝脏损害,17,临床应用（FDA）,限成人用 关节痛：可与NSAID合用，效良 背痛（持续性）：效良 癌痛：中、重度痛，效佳 牙痛：效佳 神经痛：效良 术后痛：效佳,18,临床应用 （复方：羟考酮+对乙酰氨基酚）,骨关节炎：优于单独用NSAID 术后痛： 优于单独应用羟考酮或对乙酰氨基酚 牙痛：优于单独应用羟考酮或对乙酰氨基酚 术后痛：优于单独应用羟考酮或对乙酰氨基酚 优点：有10%的患者用可待因无效（不能转化为吗啡），用羟考酮有效,19,参考三,国外中重度疼痛治疗的概况,20,慢性疼痛-癌痛,90 to 95 percent of all cancer pain can be well controlled using a special set of guidelines . - World Health Organization committee on cancer pain(These guidelines separate pain into levels of intensity and suggest tailoring the strength and potency of prescribed pain-relieving medications to the intensity. Not all cancer pain requires strong narcotics. But strong pain requires strong medications,21,cancer pain guideline,moderate pain be treated with a combination of NSAIDs and weak narcotics such as codeine (Tylenol with codeine), hydrocodone (Vicodin or Lortab), Percocet, Percodan or propoxyphene (Darvon), and severe pain be treated with strong opioids such as morphine, Demerol, Dilaudid, fentanyl (duragesic patches) or methadone in combination with an NSAID. The guidelines also suggest adding an adjuvant medication to these narcotic and nonnarcotic medications when appropriate. These medications-which include steroids, bone-forming, antidepressant and anticonvulsant medications, antihistamines and sedatives-are often useful in treating opioid-resistant pain. For whatever reason, they do relieve pain, although they are not usually labeled as pain relievers. NCCN GUIDELINE,22,American Pain Society Releases New Clinical Guideline For Treatment Of Arthritis Pain,Among the major recommendations in the APS Arthritis Pain Management Guideline are: All treatment for arthritis should begin with a comprehensive assessment of pain and function For mild to moderate arthritis pain, acetaminophen is the drug of choice for its mild side effects, over-the-counter availability and low cost For moderate to severe pain from both osteoarthritis and rheumatoid arthritis, COX-2 non-steroidal anti-inflammatory drugs (NSAIDS), such as Celebrex and Vioxx, are the drugs of choice for their pain-relieving potency and absence of gastrointestinal side effects. Use of non-selective NSAIDs should only be considered if the patient is non-responsive to acetaminophen and COX-2 drugs and is not at risk for NSAID-induced GI side effects. Due to the high cost of the COX-2 agents, some patients might benefit from taking non-specific NSAIDS and a medication to moderate GI distress. Opioid medications, such as oxycodone and morphine, are recommended for treating severe arthritis pain for which COX-2 drugs and non-specific NSAIDs do not provide substantial relief. Unless there are medical contraindications, most people with arthritis, including the obese and elderly, should be referred for surgical treatment when drug therapy is ineffective and function is severely impaired to prevent minimal physical activity. It is advised that surgery be recommended before the onset of severe deformity and advanced muscular deterioration.,23,Acute Pain Management: Operative or Medical Procedures and Trauma. Clinical Practice Guideline.,Half of all patients given conventional therapy for their painmost of the 23 million surgical cases each yeardo not get adequate relief. These patients continue to feel moderate to severe pain. Giving patients pain medicine only “as needed“ can result in prolonged delays because patients may delay asking for help. Aggressive prevention of pain is better than treatment because, once established, pain is more difficult to suppress. Patients have a right to treatment that includes prevention of or adequate relief from pain. Physicians need to develop pain control plans before surgery and inform the patient what to expect in terms of pain during and after surgery. Fears of postsurgical addiction to opioids are generally groundless. Patient-controlled medication via infusion pumps is safe In February 1992, AHCPR released a clinical practice guideline .The guideline was developed by an 18-member private-sector panel of pain experts. The multidisciplinary panel reviewed the research literature on pain management to develop the scientific base for the guideline. (After analyzing the results of more than 7,000 published studies, the panel concluded the following),