C H A P T E R 4 4
Cardiotonic agents
685
thereby decreasing preload of the heart and helping
to improve function (see Chapter 43 for a discussion
of ACE inhibitors and Chapter 46 for a discussion
of nitrates). Diuretics decrease blood volume, which
decreases venous return and blood pressure, resulting
in decreased afterload, preload and cardiac workload.
(See Chapter 51 for additional information.)
• Beta-adrenergic agonists stimulate the beta receptors
in the sympathetic nervous system, increasing calcium
flow into the myocardial cells and causing increased
contraction, a positive inotropic effect. Other
sympathetic stimulation effects can cause increased
HF because the heart’s workload is increased by most
sympathetic activity. (See Chapter 30 for additional
information.)
• Human B-type natriuretic peptides are normally
produced by myocardial cells as a compensatory
response to increased cardiac workload and
increased stimulation by the stress hormones. They
bind to endothelial cells, leading to dilation and
resulting in decreased venous return, peripheral
resistance and cardiac workload. They also suppress
the body’s response to the stress hormones, leading
to increased fluid loss and further decrease in cardiac
workload.
■■
In HF, the heart pumps blood so ineffectively
that blood builds up, causing congestion in the
cardiovascular system.
■■
HF can result from damage to the heart muscle
combined with an increased workload related to
CAD, hypertension, cardiomyopathy, valvular disease
or congenital heart abnormalities. As the heart
pump fails, the muscle cells can no longer work to
move calcium into the cell, and cardiac contractions
become weak and ineffective.
■■
Signs and symptoms of HF result from the backup
of blood in the vascular system and the loss of fluid
in the tissues. Right-sided HF is characterised by
oedema, liver congestion, elevated jugular venous
pressure and nocturia, whereas left-sided failure
is marked by tachypnoea, dyspnoea, orthopnoea,
haemoptysis, anxiety and poor oxygenation of the
blood.
■■
Treatment agents include vasodilators (to lighten
the heart’s workload); diuretics (to reduce blood
volume and workload); beta-blockers (to decrease the
heart’s workload by activating sympathetic reaction);
human B-type natriuretic peptides (to decrease the
heart’s workload by vasodilation and suppression
of the response to the sympathetic reaction); and
cardiotonic (inotropic) agents (to stimulate more
effective muscle contractions).
KEY POINTS
CARDIOTONIC AGENTS
Cardiotonic (inotropic) drugs affect the intracellular
calcium levels in the heart muscle, leading to increased
contractility. This increase in contraction strength leads
to increased cardiac output, which causes increased
renal blood flow and increased urine production.
Increased renal blood flow decreases renin release, and
hence reduces the effects of the renin–angiotensin–
aldosterone system, increasing urine output, and leading
to decreased blood volume. The result is a decrease in the
heart’s workload and relief of HF. Two types of cardio
tonic drugs are used: the classic cardiac glycosides,
which have been used for hundreds of years, and the
newer phosphodiesterase inhibitors. Table 44.1 presents
a complete list of these agents. Box 44.1 summarises the
use of cardiotonic drugs in different age groups.
C
ardiac glycosides
The cardiac glycosides were originally derived from the
foxglove or digitalis plant. These plants were once ground
up to make digitalis leaf. Today, digoxin (
Lanoxin,
Sigmaxin
) is the drug most often used to treat HF.
Therapeutic actions and indications
Digoxin increases intracellular calcium and allows more
calcium to enter myocardial cells during depolarisation
(Figure 44.4), causing the following effects:
• Increased force of myocardial contraction (a positive
inotropic effect).
• Increased cardiac output and renal perfusion (which
has a diuretic effect, increasing urine output and
decreasing blood volume while decreasing renin
release and activation of the renin–angiotensin–
aldosterone system).
• Slowed heart rate, owing to slowing of the rate of
cellular repolarisation (a negative chronotropic effect).
• Decreased conduction velocity through the
atrioventricular node.
The overall effect is a decrease in the myocardial
workload and relief of HF. Digoxin is indicated for the
treatment of HF, atrial flutter, atrial fibrillation and par
oxysmal atrial tachycardia (see Table 44.1). Digoxin has
a very
narrow margin of safety
(meaning that the thera
peutic dose is very close to the toxic dose), so extreme
care must be taken when using this drug (see Adverse
effects and Box 44.3 for information on digoxin
antidote).
Pharmacokinetics
Digoxin is available for oral and parenteral adminis
tration. The drug has a rapid onset of action and rapid
absorption (30 to 120 minutes when taken orally, 5 to
