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P A R T 8
Drugs acting on the cardiovascular system
Pharmacokinetics
Heparin is injected IV or subcutaneously (SC) and has
an almost immediate onset of action. It is excreted in
urine. Warfarin, apixaban, dabigatran and rivaroxaban
are used orally. All other drugs in this class (heparin,
antithrombin, fondaparinux and bivalirudin) are given
parenterally. Warfarin is readily absorbed through the
GI tract, metabolised in the liver and excreted in urine
and faeces. Warfarin’s onset of action is about 3 days;
its effects last for 4 to 5 days. Because of the time delay,
warfarin is not the drug of choice in an acute situation,
but it is convenient and useful for prolonged effects.
Because antithrombin is an exogenous form of a
naturally occurring anticoagulant, the body handles
it in the same way that it handles naturally occurring
antithrombin. Fondaparinux is absorbed quickly from
SC sites and metabolised and excreted by the kidneys.
Bivalirudin is given IV and is excreted through the
kidneys.
Contraindications and cautions
The anticoagulants are contraindicated in the presence
of known allergy to the drugs
to avoid hypersensitivity
reactions
. They also should not be used with any condi
tions
that could be compromised by increased bleeding
tendencies
, including haemorrhagic disorders, recent
trauma, spinal puncture, GI ulcers, recent surgery,
intrauterine device placement, tuberculosis, presence of
indwelling catheters and threatened abortion. Warfarin
is contraindicated in pregnancy
because fetal injury
and death have occurred
;
in breastfeeding,
because of
the potential risk to the baby
;
and in renal or hepatic
disease,
which could interfere with the metabolism and
effectiveness of these drugs.
Although some adverse
fetal effects have been reported with its use during
pregnancy, heparin does not enter breast milk, and so
it is the anticoagulant of choice if one is needed during
breastfeeding. Dabigatran is renally cleared and accu
mulates in people with poor renal function. Therefore,
dabigatran must not be given to people with a creatinine
clearance (CrCl) of less than 30 ml/minute.
Caution should be used in people with heart failure
(HF), thyrotoxicosis, senility or psychosis
because of
the potential for unexpected effects
and in individuals
with diarrhoea or fever,
which could alter the normal
clotting process by, respectively, loss of vitamin K from
the intestine or activation of plasminogen
. Caution
should be used in pregnancy with anticoagulants other
than warfarin
because of the potential for adverse
effects
; benefit should outweigh potential risks.
Adverse effects
The most commonly encountered adverse effect of the
anticoagulants is bleeding, ranging from bleeding gums
with tooth brushing to severe internal haemorrhage.
Individuals will need teaching about administra
tion, disposal of the syringes and signs of bleeding to
watch for. Periodic blood tests will be needed to assess
the effects of the drug on the body. Clotting times
should be monitored closely to avoid these problems.
Table 48.2 reviews clotting studies that should be
monitored. The person should also be monitored for
warfarin overdose.
Serious adverse effects may occur when adding or
taking away a drug from the regimen of a person receiv
ing warfarin without careful monitoring and adjustment
of the warfarin dose (see Clinically important drug–
drug interactions). Warfarin has been associated
with alopecia and dermatitis, as well as bone marrow
depression and, less frequently, prolonged and painful
erections. The Focus on safe medication administra
tion discusses treatment of heparin overdose. Nausea,
GI upset, diarrhoea and hepatic dysfunction also may
occur secondary to direct drug toxicity.
Clinically important drug–drug interactions
Increased bleeding can occur if heparin is combined
with oral anticoagulants, salicylates, penicillins or
• Report any of the following to your healthcare provider:
unusual bleeding
(when brushing your teeth, excessive
bleeding from an injury, excessive bruising); black or tarry
stools; cloudy or dark urine; sore throat, fever or chills; severe
headache or dizziness.
• Tell any doctor, nurse or other healthcare provider
involved in your care that you are taking this drug. You
should carry or wear medical identification stating that
you are taking this drug to alert emergency medical
personnel that you are at increased risk for bleeding.
• Avoid situations in which you could be easily injured—
for example, engaging in contact sports or games with
children or using a straight razor.
• Keep this drug, and all medications, out of the reach of
children.
• Avoid the use of over-the-counter medications while
you are taking this drug. If you feel that you need one
of these, consult with your healthcare provider for the
best choice. Many of these drugs can interfere with your
anticoagulant.
• Schedule regular, periodic blood tests while you are
taking this drug to monitor the effects of the drug on
your body and adjust your dose as needed.
