C H A P T E R 4 6
Antianginal agents
715
the intimal lining of the vessels, attracting platelets and
immune factors and causing swelling and the develop
ment of a larger deposit. Over time, these deposits
severely decrease the size of the vessel. While the vessel
is being narrowed by the deposits in the intima, it is
also losing its natural elasticity and becoming unable to
respond to the normal stimuli to dilate or constrict
to meet the needs of the tissues.
The person with atherosclerosis has a classic supply-
and-demand problem. The heart may function without
a problem until increases in activity or other stresses
place a demand on it to beat faster or harder. Normally,
the heart would stimulate the vessels to deliver more
blood when this occurs, but the narrowed vessels are
not able to respond and cannot supply the blood needed
by the working heart (Figure 46.1B). The heart muscle
then becomes hypoxic. This imbalance between oxygen
supply and demand is manifested as pain, or
angina
pectoris
, which literally means “suffocation of the
chest”.
Angina
The body’s response to a lack of oxygen in the heart
muscle is pain, called angina. Although the heart muscle
does not have any pain fibres, a chemical mediator called
factor P is released from ischaemic myocardial cells, and
pain is felt wherever factor P reacts with a pain receptor.
For many people this is the chest, for some it is the left
arm, while others have pain in the jaw and teeth. The
basic response to this type of pain is to stop whatever
one is doing and to wait for the pain to go away. In cases
of minor limitations to the blood flow through vessels,
stopping activity may bring the supply and demand for
blood back into balance. This predictable condition is
called
stable angina
. There is no damage to heart muscle
and the basic reflexes surrounding the pain restore blood
flow to the heart muscle. This process can go on for a
long time with no resultant myocardial infarction. This
is also called chronic angina, and can severely limit a
person’s activities and quality of life.
If the narrowing of the coronary arteries becomes
more pronounced, the heart may experience unpredict-
able episodes of ischaemia even when the person is at
rest. This condition is called
unstable angina
or pre-in-
farction angina. Although no damage to heart muscle
occurs, the person is at increased risk of a complete
blockage of blood supply to the heart muscle if the heart
needs to work harder or the oxygen demand increases.
Variant angina
(also known as
Prinzmetal
angina
or
vasospastic
angina) is an unusual form of angina
because it seems to be caused by spasm of the coronary
blood vessels and not just by vessel narrowing. The
person with this type of angina has angina at rest, often
at the same time each day and usually with an associ-
ated electrocardiogram (ECG) pattern change.
Acute myocardial infarction
If a coronary vessel becomes completely occluded and is
unable to deliver blood to the cardiac muscle, the area of
muscle that depends on that vessel for oxygen becomes
ischaemic and then necrotic. This is called a
myocardial
infarction (MI)
.
The pain associated with this event can
be excruciating. Nausea and a severe sympathetic stress
reaction may also be present. A serious danger of an MI
is that arrhythmias can develop in nearby tissue that is
ischaemic and very irritable. Most of the deaths caused
by MI occur as a result of fatal arrhythmias. If the heart
muscle has a chance to heal, within 6 to 10 weeks, scar
tissue will form in the necrotic area and the muscle will
compensate for the injury. If the area of the muscle that
is damaged is very large, however, the muscle may not
be able to compensate for the loss, and heart failure and
even cardiogenic shock may occur. These conditions
can be fatal or can leave a person severely limited by the
weakened heart muscle.
■■
CAD involves changes in the coronary vessels that
promote atheromas (tumours), which narrow the
coronary arteries and decrease their elasticity and
responsiveness to normal stimuli.
■■
Angina pectoris occurs when the narrowed vessels
cannot accommodate the myocardial demand for
oxygen.
■■
Stable angina occurs when the heart muscle is
perfused adequately except during exertion or
increased demand.
■■
Unstable or pre-infarction angina occurs when the
vessels are so narrow that the myocardial cells are
deprived of sufficient oxygen even at rest.
■■
Variant angina is a spasm of a coronary vessel that
decreases the flow of blood through the narrowed
lumen.
■■
When a coronary vessel is completely occluded, the
cells that depend on that vessel for oxygen become
ischaemic, then necrotic and die. The result is known
as an MI.
ANTIANGINAL AGENTS
Antianginal drugs (Table 46.1) are used to help restore
the appropriate supply-and-demand ratio in oxygen
delivery to the myocardium when rest is not enough.
These drugs can work to improve blood delivery to the
heart muscle in one of two ways: (1) by dilating blood
vessels (i.e. increasing the supply of oxygen) or (2) by
decreasing the work of the heart (i.e. decreasing the
demand for oxygen). Nitrates, beta-adrenergic blockers
KEY POINTS
