DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Adrenergic Agonists and
Antagonists
Thomas C. Westfall
and David P. Westfall
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 α 1
, terbutaline for β 2
) or may have no
or minimal selectivity and act on several receptor types
(e.g., epinephrine for α 1
, α 2
, β 1
, β 2
, and β 3
receptors;
norepinephrine for α 1
, α 2
, and β 1
receptors). Indirectacting
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 (MAO) (e.g., pargyline) or catechol-Omethyltransferase
(COMT) (e.g., entacapone)