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P A R T 8
Drugs acting on the cardiovascular system
C
ardiotonic agents are drugs used to increase the con
tractility of the heart muscle of people experiencing
heart failure.
Heart failure (HF)
is a condition in which
the heart fails to pump blood around the body effect
ively. Because the cardiac cycle normally involves a tight
balance between the pumping of the right and left sides
of the heart, any failure of the muscle to pump blood out
of either side of the heart can result in a backup of blood.
If this happens, the blood vessels become congested;
eventually, the body’s cells are deprived of oxygen and
nutrients, and waste products build up in the tissues.
The primary treatment for HF involves helping the heart
muscle to contract more efficiently to restore system
balance.
HEART FAILURE
HF, a condition that was once called “dropsy”, or
decompensation, is a syndrome that usually involves
dysfunction of the cardiac muscle, of which the sar
comere is the basic unit. The sarcomere contains two
contractile proteins, actin and myosin, which are highly
reactive with each other but at rest are kept apart by
the chemical troponin. When a cardiac muscle cell
is stimulated, calcium enters the cell and inactivates
the troponin, allowing the actin and myosin to form
actomyosin bridges. The formation of these bridges
allows the muscle fibres to slide together or contract
(Figure 44.1). The formation of these bridges and
subsequent contraction require a constant supply of
oxygen, glucose and calcium. (See Chapter 42 for a
review of heart muscle contraction processes.)
Heart failure can occur with any of the disorders
that damage or overwork the heart muscle:
• Coronary artery disease (CAD) is the leading cause
of HF, accounting for approximately 95% of the
cases diagnosed (see Chapter 47 for a discussion of
CAD). CAD results in an insufficient supply of blood
to meet the oxygen demands of the myocardium.
Consequently, the muscles become hypoxic and can
no longer function efficiently. When CAD evolves into
a myocardial infarction (MI), muscle cells die or are
damaged, leading to an inefficient pumping effort.
•
Cardiomyopathy
is a disease of the heart muscle that
leads to an enlarged heart and eventually to complete
muscle failure and death. It can occur as a result of a
viral infection, alcoholism, anabolic steroid abuse or
a collagen disorder. It causes muscle alterations and
ineffective contraction and pumping.
• Hypertension eventually leads to an enlarged cardiac
muscle because the heart must work harder than
normal to pump against the high pressure in the
arteries. Hypertension puts constant, increased
demands for oxygen on the system because the heart
is pumping so forcibly.
• Valvular heart disease leads to an overload of the
ventricles because the valves do not close tightly,
which allows blood to leak backwards into the
ventricles. This overloading leads to muscle stretching
Troponin-calcium
Troponin
Troponin
SARCOMERE Troponin keeps actin
and myosin from reacting
Troponin
released
from
Ca
Na
+
rushes in
Na, calcium pumped out of cell
0
1 2
3
4
Action potential—cell is stimulated
Na pumped out of cell
Calcium enters cell
Calcium
binds troponin
Myosin
Actin
Actinomyosin bridges
form and sarcomere slides
together— “contraction”
Actinomyosin bridges
separate—sarcomere slides
apart— “relaxation”
FIGURE 44.1
The sliding filaments
of myocardial muscles. Calcium
entering the cell deactivates troponin
and allows actin and myosin to
react, causing contraction. Calcium
pumped out of the cell frees troponin
to separate actin and myosin; the
sarcomere filament slides apart, and
the cell relaxes.
