C H A P T E R 4 4
Cardiotonic agents
687
excreted through the kidneys and toxic levels could
develop
; and electrolyte abnormalities (e.g. increased
calcium, decreased potassium, decreased magnesium),
which could alter the action potential and change the
effects of the drug.
Digoxin should be used cautiously in women who
are pregnant or breastfeeding
because of the potential
for adverse effects on the fetus or neonate.
It is not
known whether digoxin causes fetal toxicity; it should
be given during pregnancy only if the benefit to the
mother clearly outweighs the risk to the fetus. Digoxin
does enter breast milk, but it has not been shown to
cause problems for the neonate. Caution should be
used, however, during breastfeeding. Children and older
people are also at higher risk (Box 44.2).
Adverse effects
The adverse effects most frequently seen with the cardiac
glycosides include headache, weakness, drowsiness and
vision changes (a yellow halo around objects is often
reported). Gastrointestinal upset and anorexia also
commonly occur. Arrhythmias may develop because
the glycosides affect the action potential and conduc
tion system of the heart. Digoxin toxicity is a serious
syndrome that can occur when digoxin levels are too
high. The person may present with anorexia, nausea,
vomiting, malaise, depression, irregular heart rhythms
including heart block, atrial arrhythmias and ventricu
lar tachycardia. This can be a life-threatening situation.
A digoxin antidote,
digoxin immune Fab
, has been
developed to rapidly treat digoxin toxicity (Box 44.3).
See the Critical thinking scenario for additional infor-
mation about inadequate digoxin absorption
.
Clinically important drug–drug interactions
There is a risk of increased therapeutic effects and toxic
effects of digoxin if it is taken with verapamil, amiodar
one, quinidine, quinine, erythromycin, tetracycline or
cyclosporin. If digoxin is combined with any of these
drugs, it may be necessary to decrease the digoxin dose
to prevent toxicity. If one of these drugs has been part
of a medical regimen with digoxin and is discontinued,
the digoxin dose may need to be increased. The risk of
cardiac arrhythmias could increase if these drugs are
taken with potassium-losing diuretics. If this combin
ation is used, the person’s potassium levels should be
checked regularly and appropriate replacement done.
Digoxin may be less effective if it is combined with
thyroid hormones, metoclopramide or penicillamine,
and increased digoxin dose may be needed. Absorp
tion of oral digoxin may be decreased if it is taken with
cholestyramine, charcoal, colestipol, antacids, bleomy
cin, cyclophosphamide or methotrexate. If it is used in
combination with any of these agents, the drugs should
Myocardial function or failure
Cardiac output
Blood flow to kidneys
Activation of
renin-angiotensisn
system
+ Inotropic effect
Cardiac output
Aldosterone synthesis and release
Baroreceptor stimulation
Cardiac workload
Nitrate
vasodilators work
here to dilate
vessels and reverse
compensation
Adrenergic blockers
work here to block
sympathetic
compensation
Human B-type natriuretic
works to sensitivity
peptide to stress
response and dilate
blood vessels
Blood volume
H 2 O retention
K + retention
ADH release
Na + retention
Cardiac output
Respirations
Sympathetic activation
BP
BP
P
Inotropic drugs work here;
cardioglycosides increase
Ca + levels and myocardial
contractility
Phosphodiesterase
increases cAMP in cell
and may prolong
sympathetic effects
Diuretics work here
to urine productions
and Na levels
ACE inhibitors
work here to
block
angiotensin II
effects
FIGURE 44.4
Sites of action of drugs used
to treat heart failure (HF).
