Antiadrenergic Agents

Abstract

The autonomic nervous system is responsible for the homeostasis/regulation of several internal organs, tissues, and metabolic systems. Well-known examples of such targets of the autonomic nerves are the cardiovascular system (heart and blood vessels), the gastrointestinal system (stomach, intestine, biliary duct, etc.), the respiratory tract (lungs and airways), and glucose/lipid metabolism. The autonomic nervous system is subdivided into the sympathetic and parasympathetic systems. The sympathetic or adrenergic system is activated with the purpose of adapting the individual organism for “flight, fright, or fight”—that is, the short-term availability and release of energy and alertness. In contrast, the parasympathetic nervous system facilitates the storage of energy and metabolic components to allow the release of energy in a situation of flight, fright, or fight. As such, the sympathetic and parasympathetic systems counteract each other's activities in a sort of “yin-yang” balance. Activation of the sympathetic nervous system implies the stimulation of the cardiovascular system, thus increasing heart rate, cardiac output, cardiac contractility, and blood pressure. During sympathetic stimulation, the activity of the gastrointestinal system is attenuated. Stimulation of the parasympathetic system implies the activation of the digestive system, particularly the gastrointestinal tract, with the aim of facilitating the storage of energy. During parasympathetic activation, the cardiovascular system's activity is reduced. Both the sympathetic and parasympathetic systems are subject to modulation by the central nervous system, particularly the brainstem. However, higher (cortical) brain centers can also modulate both subgroups of the peripheral autonomic nervous system. Several diseases are associated with dysregulation of either subgroup of the autonomic nervous system. Relevant examples of this pathophysiological involvement particularly concern the sympathetic nervous system, which is known to be overactive in important cardiovascular derangements or diseases, such as hypertension, congestive heart failure, or cardiac tachyarrhythmia. For this reason, a vast body of research has accumulated with the aim of finding drugs that can attenuate the hyperactivity of the sympathetic nervous system. Drugs with such activity are called antiadrenergic agents.