Dollery C T
Proc R Soc Med. 1965 Nov;58(11 Part 2):983-7. doi: 10.1177/003591576505811P208.
The complex mechanisms that maintain the blood pressure can be interfered with at many points by drugs. A drug acting at one point may be potentiated by another which blocks a compensatory reflex minimizing the effect of the first. Many therapeutically useful drug combinations have a nonspecific mechanism of this kind although drugs that act upon different points in the sympathetic efferent vasomotor pathway have not been proved to have a useful additive effect.It is not easy to prove a synergistic action of two drugs unless it is large. The best supported examples are combinations of either a diuretic or a vasodilator with a sympathetic blocking drug. These combinations are the ones most widely used in treatment of hypertension. They allow the dose of each active substance to be reduced so that unwanted side-effects are decreased without losing the desired action on the blood pressure.Drug combinations have special risks besides their obvious advantages. Patients are more likely to become confused and take the wrong doses if their treatment regime is complicated. Two drugs which are individually nontoxic may have dangers when used together. Oliguria and a mounting blood urea may follow combined use of powerful modern diuretics. Toxic effects may be entirely unrelated to the main therapeutic action of the drug, as with the enhanced diabetogenic effect of diazoxide used with hydrochlorothiazide.Several potent cardiovascular drugs modify the response to drugs which might be given to raise the blood pressure in an emergency. No drug in common therapeutic use seriously reduces the response to injected noradrenaline but some, such as sympathetic blockers and monoamine oxidase inhibitors, greatly increase sensitivity. Pressor amines that act indirectly by noradrenaline release may be ineffective in the presence of drugs which deplete or insulate the stores of the transmitter in adrenergic nerve endings.The advantages and disadvantages of drug interactions deserve more thought and study than they usually receive.
维持血压的复杂机制在很多环节都可能受到药物的干扰。作用于某一环节的药物可能会被另一种药物增强效应，后者会阻断一种代偿性反射，从而使第一种药物的效果降至最低。许多具有治疗作用的药物组合都有这种非特异性机制，尽管作用于交感传出血管运动通路不同环节的药物尚未被证明具有有益的相加作用。除非两种药物的协同作用很显著，否则很难证明其存在。最有证据支持的例子是利尿剂或血管扩张剂与交感神经阻滞剂的组合。这些组合是治疗高血压最广泛使用的药物。它们可以降低每种活性物质的剂量，从而在不丧失对血压预期作用的情况下减少不必要的副作用。
药物组合除了有明显的优势外，也有特殊风险。如果治疗方案复杂，患者更容易混淆并服用错误剂量。两种单独使用无毒的药物一起使用时可能有危险。强效现代利尿剂联合使用可能会导致少尿和血尿素升高。毒性作用可能与药物的主要治疗作用完全无关，比如二氮嗪与氢氯噻嗪合用时会增强致糖尿病作用。几种强效心血管药物会改变对可能在紧急情况下用于升高血压的药物的反应。常见治疗药物中没有一种会严重降低对注射去甲肾上腺素的反应，但有些药物，如交感神经阻滞剂和单胺氧化酶抑制剂，会大大增加敏感性。通过释放去甲肾上腺素间接起作用的升压胺类药物，在存在使肾上腺素能神经末梢递质储存耗竭或隔离的药物时可能无效。
药物相互作用的利弊值得比通常更多的思考和研究。
