[曲马多药理学]。
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李志刚，李志刚
[曲马多药理学]。
药物，1997;53增刊2:18-24。
- PubMed ID
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9190321 (PubMed视图］
- 摘要
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(+/-)-曲马多是可待因的一种合成的4-苯基哌啶类似物。它是一种对阿片受体具有低亲和力的中枢镇痛药。它对mu受体的选择性最近已被证明，曲马多的M1代谢物，由肝脏o去甲基化产生，比母体药物对阿片受体表现出更高的亲和力。这种M1衍生物(o -去甲基曲马多)的生产速率受debrisoqui型的多态同工酶，细胞色素P450 2D6 (CYP2D6)的影响。然而，这种对中枢神经系统的mu受体的亲和力仍然很低，比吗啡低6000倍。此外，与其他阿片类药物相比，曲马多的镇痛作用仅被阿片类拮抗剂纳洛酮部分抑制，这表明存在另一种作用机制。发现了一种单胺能活性，可以抑制去甲肾上腺素(去甲肾上腺素)和血清素(5-羟色胺;5-HT)的再摄取，通过阻断脊髓水平的痛觉冲动，对镇痛作用做出了重大贡献。(+/-)-曲马多是两种对映体的外消旋混合物，每一种对不同的受体显示不同的亲和力。(+/-)-曲马多是mu受体的选择性激动剂，优先抑制血清素的再摄取，而(-)-曲马多主要抑制去甲肾上腺素的再摄取。 The action of these 2 enantiomers is both complementary and synergistic and results in the analgesic effect of (+/-)-tramadol. After oral administration, tramadol demonstrates 68% bioavailability, with peak serum concentrations reached within 2 hours. The elimination kinetics can be described as 2-compartmental, with a half-life of 5.1 hours for tramadol and 9 hours for the M1 derivative after a single oral dose of 100mg. This explains the approximately 2-fold accumulation of the parent drug and its M1 derivative that is observed during multiple dose treatment with tramadol. The recommended daily dose of tramadol is between 50 and 100mg every 4 to 6 hours, with a maximum dose of 400 mg/day; the duration of the analgesic effect after a single oral dose of tramadol 100mg is about 6 hours. Adverse effects, and nausea in particular, are dose-dependent and therefore considerably more likely to appear if the loading dose is high. The reduction of this dose during the first days of treatment is an important factor in improving tolerability. Other adverse effects are generally similar to those of opioids, although they are usually less severe, and can include respiratory depression, dysphoria and constipation. Tramadol can be administered concomitantly with other analgesics, particularly those with peripheral action, while drugs that depress CNS function may enhance the sedative effect of tramadol. Tramadol should not be administered to patients receiving monoamine oxidase inhibitors, and administration with tricyclic antidepressant drugs should also be avoided. Tramadol has pharmacodynamic and pharmacokinetic properties that are highly unlikely to lead to dependence. This was confirmed by various controlled studies and postmarketing surveillance studies, which reported an extremely small number of patients developing tolerance or instances of tramadol abuse. Tramadol is a central acting analgesic which has been shown to be effective and well tolerated, and likely to be of value for treating several pain conditions (step II of the World Health Organization ladder) where treatment with strong opioids is not required.
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