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

Table 28–3
Vasodilator Drugs Used to Treat Heart Failure
MECHANISM OF PRELOAD AFTERLOAD
DRUG CLASS EXAMPLES VASODILATING ACTION REDUCTION REDUCTION
Organic nitrates Nitroglycerin, NO-mediated vasodilation +++ +
isosorbide dinitrate
NO donors Nitroprusside NO-mediated vasodilation +++ +++
ACE inhibitors Captopril, enalapril, Inhibition of AngII ++ ++
lisinopril
generation, b BK
degradation
Ang II Losartan, candesartan AT 1
receptors blockade ++ ++
receptor
blockers
PDE inhibitors Milrinone, inamrinone Inhibition of cyclic AMP ++ ++
degradation
K + channel Hydralazine Unknown + +++
agonist Minoxidil Hyperpolarization + +++
of vascular smooth
muscle cells
α 1
antagonists Doxazosin, prazosin Selective α 1
adrenergic +++ ++
receptor blockade
Nonselective Phentolamine Nonselective α adrenergic +++ +++
α antagonists
receptor blockade
β/α 1
antagonists Carvedilol, labetalol Selective α 1
adrenergic ++ ++
receptor blockade
Ca 2+ channel Amlodipine, nifedipine, Inhibition of L-type Ca 2+ + +++
blockers felodipine channels
β agonists Isoproterenol Stimulation of vascular + ++
β 2
adrenergic receptors
Ang II, angiotensin II; AT 1
, type 1 angiotensin II receptor; NO, nitric oxide; ACE, angiotensin converting enzyme; PDE, cyclic nucleotide phosphodiesterase;
BK, bradykinin.
reduction, particularly at higher doses, and epicardial
coronary artery vasodilation for which systolic and
diastolic ventricular function is enhanced by increased
coronary blood flow. Collectively, these beneficial
physiologic effects translate into improved exercise
capacity and CHF- symptom reduction. However, these
drugs do not substantially influence systemic vascular
resistance, and pharmacologic tolerance greatly limits
their utility over time. For these reasons and others,
organic nitrates are not commonly used alone; rather, a
number of trials have shown that when used together,
selected organic nitrates increase the clinical effectiveness
of other vasodilators, such as hydralazine, resulting
in a sustained improvement in hemodynamics.
Nitrate tolerance. Nitrate tolerance may limit the longterm
effectiveness of these drugs in the treatment of
CHF. Blood nitrate levels may be permitted to fall to
negligible levels for at least 6-8 hours each day (see
Chapter 27). The timing of nitrate withdrawal symptoms,
if present, may be useful, however, for developing
an appropriate drug- dosing schedule. Patients with
recurrent orthopnea or paroxysmal nocturnal dyspnea,
e.g., might benefit from nighttime nitrate use. Likewise,
co- treatment with hydralazine (e.g., isosorbide dinitrate
and hydralazine [BIDIL]) may decrease nitrate tolerance
by an antioxidant effect that attenuates superoxide formation,
thereby increasing the bioavailable NO levels
(Münzel et al., 1996).
Parenteral Vasodilators
Sodium Nitroprusside. Sodium nitroprusside (NITRO-
PRESS, others) is a direct NO donor and potent vasodilator
that is effective in reducing both ventricular filling
pressure and systemic vascular resistance. The downstream
beneficial physiologic effects of afterload reduction
in CHF are outlined in Figure 28–4. Onset to