Clinical Pharmacology of Angiotensin II Receptor Antagonists

Ten years after the introduction for clinical use of losartan, the first orally active angiotensin II receptor antagonist, seven compounds-the pharmacological characteristics of which are described in this chapter-are registered by the US Food and Drug Administration and can be used in the United States and in various European countries for the treatment of hypertension, heart failure and for the prevention of type-2 diabetic nephropathy. These agents have a common mechani sm of action-selective blockade of the binding of angiotensin 11 to the subtype I receptor-and an excellent tolerability profile, a real advantage as these agents are pre scribed most frequently to asymptomatic patients. Within a rather short period of time, a large number of clinical studies has demonstrated the efficacy of angiotensin II receptor antagonists as antihypertensive agents. In addition, the completion of several large outcome trials have made it possible to define the potential benefits of these drugs to lower morbidity and mortality in various groups of patients, including hypertensive and heart failure patients and patients with type-2 diabetes nephropathy. While pharmacokinetic and pharmacodynamic differences clearly accounted for clinically significant differences, at least in terms of blood pressure control between antagonists, some unresolved questions still remain such as the right dose to use in order to achieve the optimal target organ protection, the role of the AT2 receptors or the potential benefits of a combination with ACE inhibitors. These questions will probably find their answers in the next few years with the results of the ongoing studies