羟考酮/对乙酰氨基酚的药理机制与临床应用进展

Research progress of pharmacological mechanism and clinical application of oxycodone /paracetamol

含有羟考酮/对乙酰氨基酚两种镇痛药物的复方制剂(氨酚羟考酮)治疗慢性疼痛具有优势:对乙酰氨基酚具有显著的中枢镇痛活性,但无非甾体抗炎药(NSAID)样或阿片样效应;羟考酮是一种半合成的阿片激动剂,羟考酮与对乙酰氨基酚固定剂量复方的口服常释制剂具有协同作用机制,可用于治疗中至重度疼痛,且对单独的NSAID或对乙酰氨基酚治疗无应答者有效。此固定剂量复方具有明显优势:鉴于它们的协同作用机制及阿片类药物的节省效应,可以使用更低剂量的药物,使其具有良好的疗效与耐受性特征。长期临床实践对此固定复方制剂的疗效与安全性进行了评估,患者人群涉及骨关节炎或慢性肌肉骨骼痛(包括伴有神经症状)、老年患者的慢性痛、癌症相关性疼痛、术后痛和神经病理性疼痛。除了神经病理性疼痛通常需要与NSAID或其他药物联用外,对于其他大多数病征,该固定复方制剂均能产生良好疗效,而且可使用更低的个体剂量。氨酚羟考酮可以成为治疗慢性中重度疼痛的一线药物。

The combination of two analgesic agents（oxycodone/paracetamol） offers several advantages in the treatment of chronic pain.Paracetamol（acetaminophen） has central analgesic activity without a nonsteroidal anti-inflammatory drug（NSAID）-like or opioid-like effect.Oxycodone is a semisynthetic opioid agonist.The oral fixed-dose combination of oxycodone and paracetamol immediate-release formulation has a synergistic mechanism of action,which is useful for moderate-to-severe pain and for nonresponders to NSAIDs or paracetamol alone.This fixed-dose combination offers several advantages：lower individual drug doses can be used because of their synergistic mechanisms of action,its opioid-sparing effect,and it has a good efficacy and tolerability profile.Efficacy and safety of this fixed-dose combination were assessed in a wide range of clinical settings：in patients with osteoarthritis or chronic musculoskeletal pain including when complicated by a neuropathic component;for chronic pain in elderly patients;cancer-related pain;postoperative pain;and for neuropathic pain,in the latter case usually given in combination with an NSAID or other drugs.This fixed dose combination may be useful for a large variety of indications,which can be attributed to the pharmacological synergy between oxycodone and paracetamol,and because lower individual drug dosages can be used.Therefore,this combination may be a first-line agent for the treatment of chronic moderate-to-severe pain.