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

304 transient or may respond to adjustment of dosage or administration system. For example, selective antagonists of β 1
receptors
block most actions of epinephrine and NE on the
of the drug with meals. Other drugs that have been utilized include
tricyclic antidepressants, antipsychotic agents, and clonidine. A sustained
release formulation of guanfacine (INTUNIV), an α 2A
heart, while having less effect on β 2
receptors in
receptor
bronchial smooth muscle and no effect on responses
agonist, has recently been approved for use in children (ages 6-17 years)
in treating ADHD.
mediated by α 1
or α 2
receptors. Detailed knowledge of
the autonomic nervous system and the sites of action of
drugs that act on adrenergic receptors is essential for
Adrenergic Receptor
understanding the pharmacological properties and
therapeutic uses of this important class of drugs.
Antagonists
Additional background material is presented in
Chapter 8. Agents that block DA receptors are considered
in Chapter 13.
SECTION II
NEUROPHARMACOLOGY
Many types of drugs interfere with the function of the
sympathetic nervous system and thus have profound
effects on the physiology of sympathetically innervated
organs. Several of these drugs are important in clinical
medicine, particularly for the treatment of cardiovascular
diseases.
The remainder of this chapter focuses on the
pharmacology of adrenergic receptor antagonists, drugs
that inhibit the interaction of NE, epinephrine, and other
sympathomimetic drugs with α and β receptors
(Figure 12–5). Almost all of these agents are competitive
antagonists; an important exception is phenoxybenzamine,
an irreversible antagonist that binds covalently
to α receptors. There are important structural differences
among the various types of adrenergic receptors
(Chapter 8). Since compounds have been developed
that have different affinities for the various receptors,
it is possible to interfere selectively with responses that
result from stimulation of the sympathetic nervous
α ADRENERGIC RECEPTOR
ANTAGONISTS
The α adrenergic receptors mediate many of the important
actions of endogenous catecholamines. Responses
of particular clinical relevance include α 1
receptor–
mediated contraction of arterial, venous and visceral
smooth muscle. The α 2
receptors are involved in suppressing
sympathetic output, increasing vagal tone,
facilitating platelet aggregation, inhibiting the release
of NE and ACh from nerve endings, and regulating
metabolic effects. These effects include suppression of
insulin secretion and inhibition of lipolysis. The α 2
receptors also mediate contraction of some arteries
and veins.
α receptor antagonists have a wide spectrum
of pharmacological specificities and are chemically
Adrenergic Receptor Antagonists
Alpha Receptor Antagonists
Beta Receptor Antagonists
Non-selective
α 1 -selective
α 2 -selective
Non-selective
(First Generation)
β 1 -selective
(Second Generation)
Non-selective
(Third Generation)
β 1 -selective
(Third Generation)
phenoxybenzamine prazosin yohimbine nadolol acebutolol
phentolamine
penbutolol
pindolol
propranolol
timolol
atenolol
bisoprolol
esmolol
metoprolol
terazosin
doxazosin
alfuzosin
tamsulosin
indoramin
urapidil
bunazosin
carteolol
carvedilol*
bucindolol
labetalol*
betaxolol
celiprolol
nebivolol
sotalol
levobunolol
metipranolol
Figure 12–5. Classification of adrenergic receptor antagonists. Drugs marked by an asterisk (*) also block α 1
receptors.