Page 161 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 9 Adrenoceptor Agonists & Sympathomimetic Drugs 147

80 100

HR
bpm

0 0

BP
mm Hg 100 100

Phe Phe
75 µg 7.5 µg

0 0
Intact Ganglionic blockade

FIGURE 9–7 Effects of ganglionic blockade on the response to phenylephrine (Phe) in a human subject. Left: The cardiovascular effect of
the selective α agonist phenylephrine when given as an intravenous bolus to a subject with intact autonomic baroreflex function. Note that the
increase in blood pressure (BP) is associated with a baroreflex-mediated compensatory decrease in heart rate (HR). Right: The response in the
same subject after autonomic reflexes were abolished by the ganglionic blocker trimethaphan. Note that resting blood pressure is decreased
and heart rate is increased by trimethaphan because of sympathetic and parasympathetic withdrawal (HR scale is different). In the absence of
baroreflex buffering, approximately a 10-fold lower dose of phenylephrine is required to produce a similar increase in blood pressure. Note also
the lack of compensatory decrease in heart rate.

stimulation in the atrioventricular node increases conduction to improve perfusion to the kidney in situations of oliguria
velocity (positive dromotropic effect) and decreases the refrac- (abnormally low urinary output). The activation of presynaptic
tory period. Beta activation also increases intrinsic myocardial D receptors suppresses norepinephrine release, but it is unclear
2
contractility (positive inotropic effect) and accelerates relaxation. if this contributes to cardiovascular effects of dopamine. In addi-
In the presence of normal autonomic reflex activity, the direct tion, dopamine activates β receptors in the heart. At low doses,
1
effects on heart rate may be masked by a reflex response to blood peripheral resistance may decrease. At higher rates of infusion,
pressure changes (with sympathetic withdrawal and parasympa- dopamine activates vascular α receptors, leading to vasocon-
thetic activation, which lower heart rate). These direct effects are striction, including in the renal vascular bed. Consequently,
easily demonstrated in the absence of reflexes evoked by changes high rates of infusion of dopamine may mimic the actions of
in blood pressure, eg, in isolated myocardial preparations and in epinephrine.
patients with ganglionic blockade. Physiologic stimulation of the
heart by catecholamines tends to increase coronary blood flow.
adrenoreceptors has been detected in the human Noncardiac Effects of Sympathomimetics
Expression of β 3
heart and may be upregulated in disease states; its relevance is Adrenoceptors are distributed in virtually all organ systems.
under investigation. This section focuses on the activation of adrenoceptors that are
responsible for the therapeutic effects of sympathomimetics or
D. Effects of Dopamine-Receptor Activation that explain their adverse effects. A more detailed description of
Intravenous administration of dopamine promotes vasodila- the therapeutic use of sympathomimetics is given later in this
tion of renal, splanchnic, coronary, cerebral, and perhaps other chapter.
resistance vessels, via activation of D receptors. Activation of Activation of β receptors in bronchial smooth muscle leads
2
1
the D receptors in the renal vasculature may also induce natri- to bronchodilation, and β agonists are important in the treat-
2
1
uresis. The renal effects of dopamine have been used clinically ment of asthma (see Chapter 20 and Table 9–3).