Department of Internal Medicine, University of Pisa, Pisa, Italy.
Am J Cardiovasc Drugs. 2011;11(1):13-20. doi: 10.2165/11586670-000000000-00000.
Control of cardiovascular (CV) risk factors, particularly hypertension, is still unsatisfactory, resulting in excess CV morbidity and mortality worldwide. CV risk is linearly associated with an increase in blood pressure (BP) values, and clinical studies have clearly demonstrated that BP lowering represents the most effective means of preventing CV events. However, while BP reduction is a fairly easy target, BP normalization is much more difficult to achieve, and adequate BP control (<140/90 mmHg) is attained only in a small percentage of the hypertensive population. One of the main reasons for the lack of efficacy of antihypertensive pharmacological treatment is that very often drugs are not administered at the correct dosage. In this review, we discuss the importance of using clinical pharmacology to guide treatment of hypertension. Controlled clinical trials, including HOPE, EUROPA, and CONSENSUS, are used to guide prescribing decisions. Unfortunately, the results obtained in pivotal studies such as these have been obtained using drug dosages much higher than those usually used in clinical practice. The prescription of a drug for the treatment of hypertension should take into consideration the potency of the drug, i.e. the degree of BP reduction required, and the duration of action of the drug, i.e. the need to cover the dosing interval (possibly 24 hours) in a homogeneous way. This is especially the case for angiotensin-converting enzyme (ACE) inhibitors, compounds characterized by a flat dose-response curve. The significance of this flat dose-response curve is that a low dose of an ACE inhibitor has the same potency as a high dose but a shorter duration of action. If a low dosage is administered to a hypertensive patient it causes BP fluctuations, which have been associated with negative CV outcomes. In contrast, other drug classes, including calcium channel antagonists, diuretics, and β-adrenoceptor antagonists, can be used at different dosages in order to modulate their hemodynamic effects. Thus, it is important to be aware of the clinical pharmacology of antihypertensive drugs in order to choose not only the class or the molecule best suited to the clinical characteristics of the patient, but also the correct dosages to ensure effective and homogeneous 24-hour BP reduction.
控制心血管（CV）风险因素，特别是高血压，仍然不尽如人意，导致全球 CV 发病率和死亡率过高。CV 风险与血压（BP）值的升高呈线性相关，临床研究清楚地表明，降低血压是预防 CV 事件最有效的手段。然而，虽然降低血压是一个相当容易的目标，但要实现血压正常化要困难得多，只有一小部分高血压患者能够达到足够的血压控制（<140/90mmHg）。降压药物治疗效果不佳的主要原因之一是，药物通常没有按正确剂量使用。在这篇综述中，我们讨论了使用临床药理学指导高血压治疗的重要性。使用 HOPE、EUROPA 和 CONSENSUS 等对照临床试验来指导处方决策。不幸的是，这些关键研究中获得的结果是使用比临床实践中通常使用的剂量高得多的药物剂量获得的。治疗高血压的药物处方应考虑药物的效力，即需要降低的血压程度，以及药物的作用持续时间，即需要以均匀的方式覆盖给药间隔（可能 24 小时）。对于血管紧张素转换酶（ACE）抑制剂等药物尤其如此，这些化合物的特点是剂量反应曲线平坦。这种平坦的剂量反应曲线的意义在于，ACE 抑制剂的低剂量与高剂量具有相同的效力，但作用持续时间较短。如果给高血压患者服用低剂量，会导致血压波动，这与 CV 不良结局有关。相比之下，其他药物类别，包括钙通道拮抗剂、利尿剂和β-肾上腺素受体拮抗剂，可以在不同剂量下使用，以调节其血液动力学效应。因此，了解抗高血压药物的临床药理学非常重要，以便不仅选择最适合患者临床特征的类别或分子，还选择正确的剂量，以确保有效且均匀的 24 小时血压降低。
