神经病性疼痛和辅助镇痛剂的意义.ppt
神经病性疼痛和辅助镇痛剂的意义Neuropathic pain and the meaning of adjuvant analgesics,Dr.Z.ZyliczHospice in the WealdPembury,Tunbridge WellsKent,UK,“自然”疼痛的两种类型适应性疼痛-“正常”的疼痛，疼痛有助于维护躯体的整合（自闭，总是准备，“急性疼痛”大部分与A-纤维相关）疼痛促进康复：“不要移动你断了的腿”，炎性疼痛，“慢性疼痛”大部分与C纤维有关Two types of“natural”painAdaptation pain“normal pain”,The pain helps to preserve bodys integrity(withdrawal,always ready,“fast pain”mostly A delta fibres）The pain promotes recovery:“do not move your broken leg”,inflammatory pain,“slow pain”mostly C fibres,感受伤害性的疼痛Nociceptive pain,炎性疼痛Inflammatory pain,痛觉过敏,“病理性疼痛”与适应性无关“病理性疼痛”，“没有目的的疼痛”常常是神经病性源性对经典镇痛剂没有或部分敏感对辅助镇痛剂常常敏感“pathologic pain”has nothing to do with adaptation“pathologic pain”,“pain without purpose”frequently of neuropathic origin,not or only partially sensitive to classical analgesicsfrequently sensitive to adjuvant analgesics,神经病性疼痛Neuropathic pain,痛觉过敏,神经病性疼痛的2种类型Two types of neuropathic pain,Neurogenic pain 神经源性疼痛pressure on the nerve 神经受压迫peripheral sensitization 外周神经敏化Reversible可逆转性distal to the damage 末稍损伤partially sensitive to analgesics 对镇痛剂部分敏感responds to local anaethetics 对局部麻醉剂有反应nerve entrapment 神经的压迫性损害,True neuropathic pain 真性神经病性疼痛damage irreversible 不可逆损伤central sensitization(spinal cord,brain)中枢神经敏化（脊索，脑）classical analgesics and anesthetics frequently ineffective普通镇痛剂和麻醉剂常常无效adjuvant analgesics like TCA are effective 辅助镇痛剂有效，如TCA类nerve section 神经切除,背角的初级传入纤维的正常终端神经损伤以后，C纤维终端萎缩而A纤维终端长入后角表层,“辅助性镇痛剂”所有的药物，包括尚未被许可用于治疗疼痛，但对于改善镇痛质量有用的药物。这些药物可能有经典镇痛剂的内在镇痛活性或潜在活性，或减低经典镇痛剂的毒性作用。“Adjuvant analgesics”All drugs,not licensed as such for the treatment of pain,but useful to improve the quality of analgesia.They may have an intrinsic analgesic activity or may potentiate the activity of classical analgesics or diminish their toxic effects.,我们将讨论哪些药物？About which drugs we are talking about?,Antidepressants 抗抑郁剂Anxiolytics 抗焦虑剂Anticonvulsants 抗惊厥药物NMDA inhibitors N-甲基-D-天冬氨酸抑制 剂类 Muscle relaxants 肌肉松弛剂Psychostimulants 精神兴奋剂Neuroleptics 精神抑制剂Corticosteroids 糖皮质激素,抗抑郁剂Antidepressants,amitriptylline(Tryptizol)阿米替林imipramine(Tofranil)丙咪嗪Venlafaxine(Efexor)文拉法辛Paroxetine(Seroxat)帕罗西汀 Mirtazapine(Remeron)米氮平,阿米替林与安慰剂amitryptylline versus placebo,HJ McQuay 1999,抗焦虑剂（咪达唑仑）低剂量时与阿片类药物的协同作用抗焦虑作用的辅助镇痛作用高剂量时的过度镇静作用与抗惊厥药物同用时，其代谢机制不同吗啡与咪达唑仑同用时,其剂量明显减少内在抗惊厥活性（作为盖巴喷丁的替代药物是有用的）Anxiolytics(Midazolam)in low dose synergistic with opioidsanxiolytic effect useful in analgesiain high dose sedativesmetabolism is variable in presence of anticonvulsant drugsmorphine dose significantly lower when used with midazolamintrinsic anticonvulsant activity(useful as replacement of gabapentin）.,抗惊厥药物Anticonvulsants,carbamazepin(Tegretol)卡马西平phenytoin(Difantoine)苯妥英valporoic acid(Depakine)丙戊酸clonazepam(Rivotril)氯硝安定lamotrigine(Lamictal)拉莫三嗪gabapentin(Neurontin)盖巴喷丁pregabalin(Lyrica)普瑞巴林,N-甲基-D-天冬氨酸抑制剂类NMDA inhibitors,ketamine(S en R)(Ketalar)氯胺酮(左旋和右旋异构体，即外消旋物)ketamine S(Ketanest)左旋氯胺酮dextromethorphan(Dampo),(Morfidex)右甲啡烷D-methadone 右旋-美沙酮magnesium(MgSO4+)镁,肌肉松弛剂巴氯芬（鞘内）Lind G.等。鞘内巴氯芬用作辅助性治疗以增强在神经病性疼痛中对脊髓的刺激作用。Eur J Pain 2004;8:377-83 Muscle relaxantsBaclofen(intrathecal)Lind G.et al.Intrathecal baclofen as adjuvant therapy to enhance the effect of spinal cord stimulation in neuropathic pain.Eur J Pain 2004;8:377-83,精神兴奋剂利他林Challman TD,Lipsky JJ.利他林：其药理学和使用。Mayo Clin Proc 2000 Jul;75(7):711-21Corey PJ,Heck AM,Weathermon RA.苯丙胺用于对抗阿片类引起的镇静作用Ann Pharmacother 1999 Dec;33(12):1362-6 PsychostimulantsMethylphenidate(Ritalin)Challman TD,Lipsky JJ.Methylphenidate:its pharmacology and uses.Mayo Clin Proc 2000 Jul;75(7):711-21Corey PJ,Heck AM,Weathermon RA.Amphetamines to counteract opioid-induced sedation.Ann Pharmacother 1999 Dec;33(12):1362-6,精神兴奋剂利他林5+5 mg(08.00 和 12.00点)如果必要，可增加至10+10 mg,时间与上相同PsychostimulantsMethylphenidate(Ritalin):5+5 mg(08.00 and 12.00)Increase if necessary to 10+10 mg,same time.,精神抑制剂左美丙嗪（甲氧异丁嗪）内在镇痛作用 优良的广谱止吐作用 良好的镇静作用 长期使用有毒性反应 产生耐受性NeurolepticsLevomepromazine(Nozinan)-intrinsic analgesic effect-excellent wide spectrum antiemetic-good as sedative-toxic in longer use-development of tolerance,非典型精神抑制剂奥氮平(Zyprexa)-疼痛治疗的优良辅助药物-优良的止吐剂-良好的谵妄和精神病的治疗作用Atypic neurolepticsOlanzapine(Zyprexa)excellent adjuvant in pain treatmentexcellent antiemeticgood in the treatment of delirium and psychosis,最佳方案：用于神经源性疼痛的一线药物扑热息痛，弱阿片类，非甾体类抗炎药物酌情考虑放疗TENS（经皮电神经刺激）或者针灸可能有帮助神经毁损：例如腹腔神经丛阻滞强阿片类滴定至可耐受的最大剂量地塞米松（8-12mg)以减轻神经受压迫The best strategy:1st line in neurogenic painparacetamol,weak opioids,NSAIDsconsider radiotherapyTENS or acupuncture may be helpfulNeurodestruction:a.o.coeliac blockstrong opioids titrated to maximum tolerable dosedexamethasone(8-12 mg)to decrease pressure on the nerve,最佳方案：用于真性神经病性疼痛如果没有禁忌症，阿米替林25 mg q.n.，使用一周，必要时增加剂量文拉法辛，37.5 mg b.i.d.,必要时增加剂量盖巴喷丁或普瑞巴林，滴定至有效剂量The best strategy:in true neuropathic painAmitriptyline 25 mg a.n.if no contraindications,trial for 1 week,increase the dose if necessaryVenlafaxine,37.5 mg b.d.,increase the dosegabapentin or pregabalin,titrate to effective dose,总 结辅助性镇痛剂对于控制症状是重要的这些药物拓宽了镇痛活性谱减少镇痛剂的不良反应增加镇痛剂的特异性ConclusionAdjuvant analgesics are important in symptom controlThey widen the spectrum of analgesic activityDecrease the adverse effects of analgesicsIncrease specificity of analgesics,
