Page 158 - Basic _ Clinical Pharmacology ( PDFDrive )

144 SECTION II Autonomic Drugs

HO

3 2 β α
HO 4 1 CH 2 CH 2 NH 2
5 6
Catechol Phenylethylamine

HO HO
OH OH
HO CH CH 2 NH 2 HO CH CH 2 NH CH 3

Norepinephrine Epinephrine

HO HO
OH CH 3
HO CH CH 2 NH CH HO CH 2 CH 2 NH 2
CH 3
Isoproterenol Dopamine

FIGURE 9–4 Phenylethylamine and some important catecholamines. Catechol is shown for reference.

prolonging the duration of action of these drugs. Alpha-methyl D. Substitution on the Beta Carbon
compounds are also called phenylisopropylamines. In addition Direct-acting agonists typically have a β-hydroxyl group, although
to their resistance to oxidation by MAO, some phenylisopropyl- dopamine does not. In addition to facilitating activation of adre-
amines have an enhanced ability to displace catecholamines from noceptors, this hydroxyl group may be important for storage of
storage sites in noradrenergic nerves (see Chapter 6). Therefore, sympathomimetic amines in neural vesicles.
a portion of their activity is dependent on the presence of nor-
mal norepinephrine stores in the body; they are indirectly acting
sympathomimetics. ORGAN SYSTEM EFFECTS OF
SYMPATHOMIMETIC DRUGS

Cardiovascular System

CH O General outlines of the cellular actions of sympathomimetics are
3
HO presented in Tables 6–3 and 9–3. Sympathomimetics have promi-
CH CH NH 2 nent cardiovascular effects because of widespread distribution of
CH CH 2 NH CH 3 α and β adrenoceptors in the heart, blood vessels, and neural and
OH CH 3 hormonal systems involved in blood pressure regulation.
OH OCH 3 The effects of sympathomimetic drugs on blood pressure can
Phenylephrine Methoxamine
be explained on the basis of their effects on heart rate, myocar-
dial function, peripheral vascular resistance, and venous return
(see Figure 6–7 and Table 9–4). The endogenous catecholamines,
CH CH NH CH 3 CH 2 CH NH 2 norepinephrine and epinephrine, have complex cardiovascular
OH CH 3 CH 3 effects because they activate both α and β receptors. It is easier
Ephedrine Amphetamine to understand these actions by first describing the cardiovas-
cular effect of sympathomimetics that are selective for a given
adrenoreceptor.
FIGURE 9–5 Some examples of noncatecholamine sympatho-
mimetic drugs. The isopropyl group is highlighted in color. Meth- A. Effects of Alpha -Receptor Activation
amphetamine is amphetamine with one of the amine hydrogens 1
replaced by a methyl group. Alpha receptors are widely expressed in vascular beds, and their
1
activation leads to arterial and venous vasoconstriction. Their direct