Chapter 12: Adrenergic Agonists and Antagonists

INTRODUCTION

Catecholamines and Sympathomimetic Drugs

Most of the actions of catecholamines and sympathomimetic agents can be classified into seven broad types:

1. A peripheral excitatory action on certain types of smooth muscle, such as those in blood vessels supplying skin, kidney, and mucous membranes; and on gland cells, such as those in salivary and sweat glands.

2. A peripheral inhibitory action on certain other types of smooth muscle, such as those in the wall of the gut, in the bronchial tree, and in blood vessels supplying skeletal muscle.

3. A cardiac excitatory action that increases heart rate and force of contraction.

4. Metabolic actions, such as an increase in the rate of glycogenolysis in liver and muscle and liberation of free fatty acids from adipose tissue.

5. Endocrine actions, such as modulation (increasing or decreasing) of the secretion of insulin, renin, and pituitary hormones.

6. Actions in the central nervous system (CNS), such as respiratory stimulation, an increase in wakefulness and psychomotor activity, and a reduction in appetite.

7. Prejunctional actions that either inhibit or facilitate the release of neurotransmitters, the inhibitory action being physiologically more important.

Many of these actions and the receptors that mediate them are summarized in Tables 8–1 and 8–8. Not all sympathomimetic drugs show each of the above types of action to the same degree; however, many of the differences in their effects are only quantitative. The pharmacological properties of these drugs as a class are described in detail for the prototypical agent, epinephrine.

Appreciation of the pharmacological properties of the drugs described in this chapter depends on an understanding of the classification, distribution, and mechanism of action of α and β adrenergic receptors (Chapter 8).

CLASSIFICATION OF SYMPATHOMIMETIC DRUGS

Catecholamines and sympathomimetic drugs are classified as direct-acting, indirect-acting, or mixed-acting sympathomimetics (Figure 12–1). Direct-acting sympathomimetic drugs act directly on one or more of the adrenergic receptors. These agents may exhibit considerable selectivity for a specific receptor subtype (e.g., phenylephrine for α₁, terbutaline for β₂) or may have no or minimal selectivity and act on several receptor types (e.g., epinephrine for α₁, α₂, β₁, β₂, and β₃ receptors; norepinephrine for α₁, α₂, and β₁ receptors). Indirect-acting drugs increase the availability of norepinephrine (NE) or epinephrine to stimulate adrenergic receptors. This can be accomplished in several ways:

• by releasing or displacing NE from sympathetic nerve varicosities

• by blocking the transport of NE into sympathetic neurons (e.g., cocaine)

• by blocking the metabolizing enzymes, monoamine oxidase ...