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P A R T 8
Drugs acting on the cardiovascular system
Therapeutic actions and indications
As noted previously, the anticoagulants interfere with
the normal cascade of events involved in the clotting
process. Warfarin causes a decrease in the production
of vitamin K–dependent clotting factors in the liver. The
eventual effect is a depletion of these clotting factors and
a prolongation of clotting times. It is used to maintain a
state of anticoagulation in situations in which the person
is susceptible to potentially dangerous clot formation
(see Table 48.1 for usual indications for warfarin).
See
the Critical thinking scenario for additional care for
people taking warfarin.
Heparin, bivalirudin, apixaban, dabigatran and
rivaroxaban block the formation of thrombin from pro
thrombin. The usual indications for heparin include
acute treatment and prevention of venous thrombosis
and pulmonary embolism; treatment of atrial fibrilla
tion with embolisation; prevention of clotting in blood
samples, and in dialysis and venous tubing; and diagnosis
and treatment of disseminated intravascular coagulation
(DIC) (Box 48.3). Because heparin must be injected,
it is often not the drug of choice for outpatients, who
would be responsible for injecting the drug several times
during the day. Individuals may be started on heparin in
the acute situation and then switched to the oral drug
warfarin. Apixaban, dabigatran and rivaroxaban are
commonly used to prevent thrombosis following total
hip or knee replacement and in individuals with atrial
fibrillation.
Antithrombin interferes with the formation of
thrombin from prothrombin; it is a naturally occur
ring anticoagulant, as mentioned earlier, and a natural
safety feature in the clotting system. Fondaparinux is
the newest of the anticoagulants, approved in 2002. It
inhibits factor Xa and blocks the clotting cascade to
prevent clot formation. It is supplied in prefilled syringes,
making it convenient for people who self-administer the
drug at home.
Disseminated intravascular coagulation (DIC) is a
syndrome in which bleeding and thrombosis are found
together. It can occur as a complication of many
problems, including severe infection with septic shock,
traumatic childbirth or missed abortion, and massive
injuries. In these disorders, local tissue damage causes
the release of coagulation-stimulating substances into
the circulation. These substances then stimulate the
coagulation process, causing fibrin clot formation in
small vessels in the lungs, kidneys, brain and other
organs. This continuing reaction consumes excessive
amounts of fibrinogen, other clotting factors and
platelets. The end result is increased bleeding. In essence,
the person clots too much, resulting in the possibility of
bleeding to death.
The first step in treating this disorder is to control
the problem that initially precipitated it. For example,
treating the infection, performing dilation and curettage
to clear the uterus, or stabilising injuries can help stop
this continuing process. Whole-blood infusions or the
infusion of fibrinogen may be used to buy some time
until the person is stable and can form clotting factors
again. There are associated problems with giving whole
blood (e.g. development of hepatitis or AIDS), and there
is a risk that fibrinogen may set off further intravascular
clotting. Paradoxically, the treatment of choice for DIC
is the anticoagulant heparin. Heparin prevents the
clotting phase from being completed, thus inhibiting
the breakdown of fibrinogen. It may also help avoid
haemorrhage by preventing the body from depleting its
entire store of coagulation factors.
Because heparin is usually administered to
prevent blood clotting, and the adverse effects that
are monitored with heparin therapy include signs of
bleeding, it can be a real challenge for the healthcare
providers to feel comfortable administering heparin to
a person who is bleeding to death. Understanding of the
disease process can help alleviate any doubts about the
treatment.
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BOX 48.3
Understanding disseminated
intravascular coagulation
CRITICAL THINKING SCENARIO
Oral anticoagulant therapy
THE SITUATION
G.R. is a 68-year-old woman with a history of severe mitral
valve disease. For the last several years, she has been able
to manage her condition with digoxin, a diuretic and a
potassium supplement. However, on a recent visit to her
doctor she disclosed that she had been experiencing
periods of breathlessness, palpitations and dizziness.
Tests showed that she was having frequent periods of
atrial fibrillation (AF), with a heart rate of up to 140 beats/
minute. Because of the danger of emboli as a result of her
valve disease and the bouts of AF, warfarin therapy was
begun.
