The Correct Administration of Antihypertensive Drugs According to the Principles of Clinical Pharmacology

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 beta-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.