Transcript DRUGS AFFECTING CLOT FORMATION

Blood coagulation is a complex process that
involves vasoconstriction, platelet clumping
or aggregation, and a cascade of clotting
factors produced in the liver that eventually
react to break down fibrinogen (a protein also
produced in the liver) into insoluble fi brin
threads.
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Damaged vessel
endothelium is a
stimulus to circulating
platelets, causing
platelet adhesion. B.
Platelets release
mediators,
and platelet
aggregation results.
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Drugs that affect clot formation include:
- antiplatelet drugs, which alter platelet
aggregation and the formation of the platelet
plug;
- anticoagulants, which interfere with the
clotting cascade and thrombin formation; and
- thrombolytic agents, which break down the
thrombus or clot that has been formed by
stimulating the plasmin system.
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Antiplatelet agents decrease the formation of the platelet
plug by decreasing the responsiveness of the platelets
to stimuli that would cause them to stick and aggregate
on a vessel wall.
Antiplatelet agents available for use Include:
abciximab (ReoPro), anagrelide (Agrylin), aspirin,
cilostazol (Pletal), clopidogrel (Plavix), dipyridamole
(Persantine), eptifibatide (Integrilin), ticlopidine (Ticlid),
ticagrelor (Brilinta), and tirofiban (Aggrastat
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- Abciximab, eptifi batide, and tirofi ban are administered
intravenously (IV).
- Antiplatelet agents that are administered orally include
anagrelide, aspirin, cilostazol, clopidogrel,ticagrelor,
and ticlopidine.
- Dipyridamole is used orally or as an IV agent.
These drugs are generally well absorbed and highly
bound to plasma proteins. They are metabolized in the
liver and excreted in urine, and they tend to enter breast
milk .
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- Antiplatelet agents are contraindicated in the
presence
of allergy to the specific drug.
- Caution should be used in the following
conditions:
the presence of any known bleeding disorder
because of the risk of excessive blood loss;
recent surgery because of the risk of increased
bleeding in unhealed vessels;and closed head
injuries because of the risk of bleeding from
the injured vessels in the brain
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Although there are no adequate studies of these
drugs in pregnancy, they are contraindicated with
pregnancy because of the potential for increased
bleeding (see Adverse Effects); they should be used
during pregnancy only if the benefi ts to the
mother clearly outweigh the
potential risks to the fetus. These drugs are also
contraindicated during lactation because of the
potential adverse effects on the fetus or neonate; if
they are needed by a breast-feeding mother, she
should fi nd another method of feeding the baby.
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Platelet levels should be checked regularly to
monitor for thrombocytopenia if a patient is
on this drug.
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headache, dizziness, and weakness
Nausea and gastrointestinal (GI)
distress may occur because of direct
irritating effects of the oral drug on
the GI tract. Skin rash, another
common effect, may be related to
direct drug effects on the dermis.
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Anticoagulants are drugs that interfere with the
normal
coagulation process by interfering with the clotting
cascade and thrombin formation. Drugs in this
class include:
antithrombin III (Thrombate III), argatroban (Acova),
bivalirudin (Angiomax), desirudin (Iprivask),
fondaparinux (Arixtra), heparin (generic), and
warfarin (Coumadin) and the two newest oral
anticoagulants dabigatran (Pradaxa) and
rivaroxaban (Xarelto).
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Pharmacokinetics
Heparin is injected IV or subcutaneously and
has an
almost immediate onset of action. It is excreted
in urine.
Warfarin, dabigatran, and rivaroxaban are used
orally.
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Warfarin is readily absorbed through the GI
tract, metabolized in the liver, and excreted in
urine and feces. 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.
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The most commonly encountered adverse effect
of the
anticoagulants is bleeding, ranging from
bleeding gums
with tooth brushing to severe internal
hemorrhage.
 Warfarin has been associated with alopecia
and dermatitis, as well as bone marrow
depression.
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- The anticoagulants are contraindicated in the
presence of
known allergy to the drugs.
- They also should not be used with any conditions
that could be compromised by increased bleeding
tendencies,
including hemorrhagic disorders, recent trauma,
spinal puncture, GI ulcers, recent surgery, intrauterine
device placement, tuberculosis, presence of
indwelling
catheters, and threatened abortion.
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- Warfarin is contraindicated in pregnancy
because fetal injury and death have occurred; in
lactation, because of the potential risk to the
baby; and in renal or hepatic disease.
- heparin does not enter breast milk, and so it
is the anticoagulant of choice if one is needed
during lactation.
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Evaluate for therapeutic effects of warfarin—
prothrombin
time (PT) 1.5 to 2.5 times the control value or ratio of
PT to International Normalized Ratio (INR) of 2 to 3—
to evaluate the effectiveness of the drug dose.
■ Evaluate for therapeutic effects of heparin—whole
blood clotting time (WBCT) 2.5 to 3 times control or
activated partial thromboplastin time (APTT) 1.5 to 3
times the control value—to evaluate the effectiveness
of the drug dose.
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■ Evaluate the patient regularly for any sign of blood
loss (petechiae, bleeding gums, bruises, dark-colored
stools, dark-colored urine) .
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■ Establish safety precautions to protect the patient
from injury.
■ Provide safety measures, such as use of an electric
razor and avoidance of contact sports, to decrease the
risk of bleeding.
■ Provide increased precautions against bleeding during
invasive procedures; use pressure dressings; avoid
intramuscular injections; and do not rub subcutaneous
injection sites because the state of anticoagulation
increases the risk of blood loss.
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■ Mark the chart of any patient receiving this drug to
alert the medical staff that there is a potential for
increased bleeding.
■ Maintain antidotes on standby (protamine sulfate
for heparin, vitamin K for warfarin) in case of
overdose.
■ Monitor the patient carefully when any drug is
added
because of the risk of drug–drug interactions that
would change the effectiveness of the anticoagulant.
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THROMBOLYTIC AGENTS
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