药物相互作用的临床意义(英文)

DRUG INTERACTIONS-CLINICAL IMPLICATIONS

阿片类物质已经被证实在临床上能与多种药物发生相互作用,多数是药代动力学上的相互作用,也有部分药物是在药效学方面发生的相互作用。药代动力学上的相互作用包括对肝药酶P450的抑制或诱导。药效学上的相互作用包括对中枢神经系统附加的抑制作用。抑制肝药酶活性的药物能引起血浆中药物浓度的增高,易导致过量或中毒。诱导肝药酶活性的药物能加速药物的代谢,降低血浆中药物浓度和药物有效性;对阿片物质来说,可能导致戒断症状。药效学的相互作用发生在同时使用抑制呼吸的药物(如苯二氮卓艹类药物)和丁丙诺啡或美沙酮的情况下,两者共同滥用可导致死亡。本文还讨论了HIV和阿片治疗之间相互作用的例子,这种相互作用可导致依从性降低以及较差的临床结局。苯二氮卓艹类药物与可加强心血管效应的药物之间的相互作用也需要被考虑到。

Opioids have been shown to have clinically significant interactions occuring through a pharmacokinetic route, but some drugs may with many medications with most interactions also interact at a phannacodynamic level. Pharmacokinetic interactions usually involve the inhibition or induction of hepatic cytochrome P450 （CYP） enzymes. t Pharmacodynamic interactions may involve additive （CNS） depression. The role of eytochrome P450 （CYP） enzymes, is to oxidise endogenous and exogenous compounds, enhancing their water solubility and preparing them for Phase Ⅱ reactions such as glueuronidation and then elimination from the body. The majority of drugs are metabolised in the liver. There are over 40 CYP enzymes in the human body but only six are responsible for 90% of human drug metabolism： CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. CYP3A4 is the most important, metabolising - 50% of drags. CYP2A6, CYP2B6, CYP3A5 are all thought to play clinically relevant but smaller roles.