B Adrenergic and Dopaminergic Agonists

Dopamine and dobutamine are the positive inotropic agents most often used for the shortterm
support of the circulation in advanced heart failure. These drugs act via stimulation of the
cardiac myocyte dopamine D1 and b adrenergic receptors, leading to stimulation of the
Gsadenylyl cyclasecyclic AMPPKA pathway. Isoproterenol, epinephrine, and norepinephrine,
although useful in specific circumstances, have little role in the treatment of heart failure
(see Chapter 10).
DOPAMINE (DA)
DA has limited utility in the treatment of most patients with cardiogenic
circulatory failure. At low doses (2 g/kg lean body mass per minute), DA causes vasodilation by
stimulating dopaminergic receptors on smooth muscle (causing cyclic AMPdependent
relaxation)
and by stimulating presynaptic D2 receptors on sympathetic nerves in the peripheral circulation
(inhibiting NE release and reducing a adrenergic stimulation of vascular smooth muscle); these
receptors are prominent in splanchnic and renal arterial beds. DA infusion at this rate may
increase
renal blood flow and thereby help to maintain the glomerular filtration rate in patients who are
refractory to diuretics. DA also has direct effects on renal tubular epithelial cells that promote
diuresis.
At intermediate infusion rates (25 g/kg/min), DA directly stimulates b receptors on the heart
and vascular sympathetic neurons, enhancing cardiac contractility and neural NE release. At
higher
infusion rates (515 g/kg/min), peripheral arterial and venous constriction occur, mediated by
a adrenergic receptor stimulation (see above). This effect may be desirable for support of a
critically
reduced arterial pressure in selected patients in whom circulatory failure is the result of
vasodilation (e.g., sepsis or anaphylaxis). However, high-dose DA infusion has little role in the
treatment of patients with primary contractile dysfunction; in this setting, increased
vasoconstriction
will lead to increased afterload, further compromising left ventricular stroke volume and forward
cardiac output. Tachycardia, which is more pronounced with DA than with dobutamine, may
provoke ischemia in patients with coronary artery disease.
DOBUTAMINE
Dobutamine (DOBUTREX) is the preferred b agonist for the management of
patients with end-stage systolic dysfunction and CHF. Dobutamine is supplied as a racemic
mixture
that stimulates both b1 and b2 receptor subtypes. In addition, the () enantiomer is an agonist
for a adrenergic receptors, whereas the () enantiomer is a very weak partial agonist. At infusion
rates that have a positive inotropic effect in humans, the b1 adrenergic effect in the myocardium
predominates. In the vasculature, the a adrenergic agonist effect of the () enantiomer appears
to
be negated by the partial agonism of the () enantiomer and the vasodilator effects of b2
receptor
stimulation. Thus, the principal hemodynamic effect of dobutamine is an increase in stroke
volume due to its positive inotropic action. At doses that increase cardiac output, there is
relatively
little increase in heart rate. Dobutamine infusion generally causes a modest decrease in
systemic
resistance and intracardiac filling pressures. Dobutamine does not activate dopaminergic
receptors.
As such, the increase in renal blood flow that occurs in association with dobutamine is
proportional
to the increase in cardiac output.