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P A R T 8
Drugs acting on the cardiovascular system
A
ntianginal agents are used to help restore the appropri-
ate supply-and-demand ratio in oxygen delivery to the
myocardium. An imbalance in this ratio, manifested by
pain, is most commonly due to
coronary artery disease
(CAD)
.
CAD has, for many years, been a leading cause of
death in Australia and New Zealand and most Western
nations. Despite great strides in understanding the con-
tributing causes of this disease and ways to prevent it,
CAD claims more lives than any other disease. The
drugs discussed in this chapter are used to prevent myo-
cardial cell death when the coronary vessels are already
seriously damaged and are having trouble maintaining
the blood flow to the heart muscle. Chapters 47 and 48
discuss drugs that are used to prevent the blocking of
the coronary arteries before they become narrowed and
damaged or to restore blood flow through narrowed
vessels.
CORONARY ARTERY DISEASE
The myocardium must receive a constant supply of blood
to have the oxygen and nutrients needed to maintain a
constant pumping action. The myocardium receives all
of its blood from two coronary arteries that exit the
sinuses of Valsalva at the base of the aorta. These vessels
divide and subdivide to form the capillaries that deliver
oxygen to heart muscle fibres.
Unlike other tissues in the body, the heart muscle
receives its blood supply during diastole, while it is at
rest. This is important because when the heart muscle
contracts, it becomes tight and clamps the blood vessels
closed, rendering them unable to receive blood during
systole, which is when all other tissues receive fresh
blood. The openings in the sinuses of Valsalva, which
are the beginnings of the coronary arteries, are posi-
tioned so that they can be filled when the blood flows
back against the aortic valve when the heart is at rest.
The pressure that fills these vessels is the
pulse pressure
(the systolic pressure minus the diastolic pressure)—the
pressure of the column of blood falling back onto the
closed aortic valve. The heart has just finished contract-
ing and using energy and oxygen. The acid and carbon
dioxide built up in the muscle cause a local vasodilation,
and the blood flows freely through the coronary arteries
and into the muscle cells.
In CAD, the lumen of the blood vessels becomes
narrowed so that blood is no longer able to flow freely to
the muscle cells. The narrowing of the vessels is caused
by the development of
atheromas
, or fatty tumours in
the intima of the vessels, in a process called
atheroscle-
rosis
(Figure 46.1A). These deposits cause damage to
ANTIANGINAL AGENTS
Nitrates
glyceryl trinitrate
isosorbide dinitrate
isosorbide mononitrate
Beta-blockers
metoprolol
propranolol
Calcium channel blockers
amlodipine
diltiazem
nifedipine
perhexiline
verapamil
Potassium channel opener
nicorandil
Artery
Intima
Atheroma
A
FIGURE 46.1
A.
Schematic illustration of atheromatous plaque.
B.
Thrombosis of atherosclerotic plaque. It may partially or completely occlude
the lumen of the vessel.
Plaque
B
Thrombus
