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

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Agents decreasing O 2 demand
β Adrenergic antagonists
Some Ca 2+ entry blockers
Organic nitrates
Ca 2+ entry blockers
Heart rate
Contractility
Preload
Afterload
O 2 Demand
BALANCE
=
>
ISCHEMIA
O 2 Supply
Coronary
blood flow
Regional
myocardial
blood flow
Agents increasing O 2 Supply
Vasodilators
(esp. Ca 2+ entry blockers)
Also statins,
anti-thrombotics
Figure 27–1. Pharmacological modification of the major determinants of myocardial O 2
supply. When myocardial O 2
requirements
exceed O 2
supply, an ischemic episode results. This figure shows the primary hemodynamic sites of actions of pharmacological agents
that can reduce O 2
demand (left side) or enhance O 2
supply (right side). Some classes of agents have multiple effects. Stents, angioplasty,
and coronary bypass surgery are mechanical interventions that increase O 2
supply. Both pharmacotherapy and mechanotherapy
attempt to restore a dynamic balance between O 2
demand and O 2
supply.
SECTION III
MODULATION OF CARDIOVASCULAR FUNCTION
receptor antagonists appear to be more effective than the
Ca 2+ channel blockers in the prevention of episodes.
Therapy directed at abolishing all silent ischemia has
not been shown to be of additional benefit over conventional
therapy.
This section describes the principal pharmacological
agents used in the treatment of angina. The major
drugs are nitrovasodilators, β adrenergic receptor antagonists
(see Chapter 12), and Ca 2+ channel antagonists.
These anti-anginal agents improve the balance of myocardial
O 2
supply and O 2
demand, increasing supply by dilating
the coronary vasculature and/or decreasing demand
by reducing cardiac work (Figure 27–1).
Other drugs also have efficacy in treatment of both
stable and unstable angina, including antiplatelet agents
(see Chapters 30) as well as statins (HMG CoA-reductase
inhibitors) (see Chapter 31), which may have a role
in stabilizing the vulnerable plaque. A new class of medications
that appears to be effective in treatment of
angina is exemplified by ranolazine (RANEXA) (Wilson
et al., 2009), which has been approved for treatment of
chronic angina. The mechanisms whereby ranolazine
exerts its anti-anginal effect are incompletely understood,
but the drug appears to exert direct effects on cardiac
myocyte Na + channels (Hasenfuss and Maier 2008; Nash
and Nash 2008).
Increasing the cardiac extraction of O 2
from the
blood has not been a practical therapeutic goal. Drugs
used in typical angina function principally by reducing
myocardial O 2
demand by decreasing heart rate,
myocardial contractility, and/or ventricular wall stress.
By contrast, the principal therapeutic goal in unstable
angina is to increase myocardial blood flow; strategies
include the use of antiplatelet agents and heparin to
reduce intracoronary thrombosis, often accompanied
by efforts to restore flow by mechanical means, including
percutaneous coronary interventions using coronary
stents, or (less commonly) emergency coronary
bypass surgery. The principal therapeutic aim in variant
or Prinzmetal angina is to prevent coronary
vasospasm.
Anti-anginal agents may provide prophylactic or
symptomatic treatment, but β adrenergic receptor antagonists
also reduce mortality apparently by decreasing
the incidence of sudden cardiac death associated with
myocardial ischemia and infarction. The chronic use of
organic nitrate vasodilators, which are highly efficacious
in treatment of angina, is not associated with improvements
in cardiac mortality, and some investigators have
suggested that chronic use of nitroglycerin may have
adverse cardiovascular effects (Parker, 2004). It is
unclear whether the new anti-anginal agent ranolazine
may have beneficial effects on cardiovascular mortality,
but this drug does appear to have salutary effects on glucose
metabolism (Morrow et al., 2009).
The treatment of cardiac risk factors can reduce the
progression or even lead to the regression of atherosclerosis.
Aspirin is used routinely in patients with myocardial
ischemia, and daily aspirin use reduces the incidence
of clinical events (Gibbons et al., 2003). Other
antiplatelet agents such as oral clopidogrel and intravenous
anti-integrin drugs such as abciximab, tirofiban,
and eptifibatide have been shown to reduce morbidity in
patients with angina who undergo coronary artery stenting
(Yeghizarians et al., 2000). Lipid-lowering drugs such
as the statins reduce mortality in patients with hypercholesterolemia
with or without known coronary artery disease
(Libby et al., 2002). Angiotensin-converting enzyme