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75 Cards in this Set

  • Front
  • Back
What is the key event in primary hemostasis?
platelet aggregation
What happens in secondary hemostasis?
activation of cascade converting fibrinogen to fibrin -> stabilize clot
What happens during fibrinolysis?
plasmin activated
breaks down insoluble fibrin
in platelets __ is synthesized from arachidonic acid and causes the degranulation of platelets that is essential for subsequent steps of platelet function?
thromboxane A2 (TXA2)
What do agonists such as ADP do to platelets?
induce glycoprotein IIb/IIIa receptor on surface --> essential for cross-linking of platelets by fibrin
this measures the intrinsic pathway
PTT can be modified to eliminate the variable of contact activation by producing the maximal activation of intrinisic pathway by adding negatively charged surfaces such as kaolin, powdered glass, etc ...this is called ...?
Activated PTT (aPTT)
this measures the extrinsic pathway
what normalizes the variations in PT
this is a heterogenous mixture of negatively charged, sulfated mucopolysaccharides
name three low molecular weight heparins (LMWH)
most active coagulation factors act as ...
serine proteases
to prevent a runaway coagulation cascade normal plasma contains which serine protease inhibitor that binds to thrombin with low affinity?
antithrombin III
antithrombin III (the suicide substrate) can also inhibit which 5 factors?
heparin increases the rate of association between antithrombin and the active coagulation factors by 1000x by which two mechanisms
1. pentasaccharide sequence (also in LMWHs) induces conformational change in antithrombin III exposing the reactive site to protease
2. inhibits factor Xa

after forming protease-antithrombin complexes - heparin is released unchanged
how is heparin administered?
What happens to the half life of heparin with increasing doses
the t1/2 increases
When compared with heparin, LMWHs have __ bioavailability
__ t1/2
__ pharmicokinetics
__ to use
greater bioavailability
longer t1/2
simpler pharmicokinetics
easier to use
can patients give themselves LMWHs
yes- small doses (30-40 mg) come in prefilled syringes they can administer at home
What is first line for prevention and treatement of venous thromboembolism
What two are used to prevent venous embolism in patients after hip replacement or abdominal surgery?
name two other conditions for which LMWHs are recommended
prevention of recurrent angina and MI
Describe the therapy for heparin?
loading dose of 5,000-10,000 units as IV bolus
maintenance dose of 900-1600 U/hr
What is the PTT goal of heparin therapy
about 1.5-2.5 times the control value- (normal is 25-35 secs)
what condition may require larger doses of heparin
acute pulmonary embolism
do you give heparin intramuscularly?
risk of hematoma
what may happen in 25% of patients within 1 or 2 weeks after initiation?
transient thrombocytopenia
does heparin cross the placenta
never give heparin to patients undergoing what three types of surgery
spinal cord
eye surgery
severe heparin induced bleeding can be controlled by careful administration of which antidote
protamine sulfate
what was the first synthetic selective inhibitor of Xa; indicated for prophylaxis of deep vein thrombosis
safer alternative to heparin angioplasty
specific reversible direct inhibitor of thrombin
bivalirudin is related to hirudin...what's that?
the anticoagulant in leech saliva
What is the most frequently used anticoagulant?
what is the major difference between warfarin and other oral anticoagulants?
its pharmacokinetics, especially the half life
Warfarin MOA?
inhibits vitamin K epoxide reduction to its active hydroquinone form --> inhibiting the carboxylation of coagulation factors II, VII, IX, X
How is warfarin administered and what is its bioavailability?
as sodium salt
nearly 100%
99% is albumin bound
warfarin has a variable t1/2 of...
25-60 hrs
what part of warfarins racemic solution is 4x more potent than the other
levorotary S-form 4x more potent than R-form
Do the two enantiomers undergo the same metabolic transformation?
What is the warfarin dosage regimen?
small daily doses of 5-10 mg/day for 2-4 days
followed by 2-10 mg/day as indicated by PT time or INR
What is the aim of warfarin therapy?
PT increased to level of 25% of normal intrinsic activity
--> INR of 2.5-3.5
Name five indications for warfarin
1. acute MI
2. high risk for stroke
3. atrial fibrillation
4. prosthetic heart valves
5. tx and prophylaxis of venous thromboembolism
two drugs that inhibit the metabolic transformation of S-warfarin and displace it from albumin
three drugs that inhibit the metabolic transformation of S-warfarin
three drugs that inhibit the metabolism of both warfarin enantiomers?
(increase effect of warfarin)
What do third generation cephalosporins do?
eliminate bacteria in GI tract that produce vitamin K
(increase effect of warfarin)
How do hepatic disease and hypothyroidism augment the effect of warfarin?
increase the turnover rate of clotting factors
(increase effect of warfarin)
barbituates and rifampin
two drugs induce hepatic enzymes involved in metabolic clearance of racemic warfarin
(decrease effect of warfarin)
What reduces the absorption of warfarin
(decreases its effect)
does vitamin k rich food increase or decrease the effect of warfarin
do diuretics concentrating clotting factors increase or decrease the effect of warfarin?
what do you do at any sign of bleeding
withhold anticoagulant and measure PT
What may long-term warfarin treatment do to elderly women
increase risk of fractures
What is an antidote for warfarin
vitamin K
What forms a stable complex with plasminogen facilitating its conversion to plasmin and is made by streptococci
What is the dosing regimen of streptokinase
IV bolus of 250,000 units to overcome potential neutralizing effect of plasma antibodies
followed by 100,000 units/hr for 24-72 hrs
what enzyme is produced by the human kidney and directly converts plasminogen into plasmin
What is the dosing regimen of urokinase
IV bolus of 300,000 units followed by 300,000 units/hr for 12 hrs
what complex of purified streptokinase and human plasminogen that has been acylated to become sensitive for spontaneous activation by cleavage
what is the administration doses for anistreplase
single IV injection of 30 units over 3-5 minutes
give three names for tissue plasminogen activator
what does t-PA require to activate plasminogen
presence of fibrin
What is the tPA dosage protocol
15 mg IV bolus, followed by .75 mg/kg over 30 minutes and .5 mg/kg for the next hour
Name three clinical indications for thromboyltic drugs
multiple pulmonary emboli
central DVT
acute MI- but only for selected patients! depending on ECG and when symptoms started
Name four contraindications for thromboyltic drugs
GI tract bleeding
active bleeding
How does aspirin irreversibly inhibit platelets
inhibits COX --> inhibits TXA2 --> platelets can't change shape, degranulate or aggregate

lasts for the lifetime of the platelet (7-10 days)
What type of stroke has decreased mortality with aspirin therapy?
ischemic stroke
What is the recommended dose for primary prevention for those at increased risk for CHD?
81 mg (baby aspirin)
what interferes with platelet function by increasing intracellular cAMP concentration
has little to no benefit by itself BUT in combination with aspirin it is significantly more effective than aspirin alone to prevent stroke
(when combined with aspirin = Aggrenox)
what inhibits the ADP-induced changes in glycoprotein IIb/IIIa receptor that is responsible for its binding to fibrin, thrombospondin, etc

has no effect on prostaglandin metabolism

and is used for prevention of thrombosis in cerebral, vascular, and CAD
What is an occasional side effect of clopidogrel
What is more effective than aspirin alone for treating unstable angina?
combining clopidogrel and aspirin
what monoclonal antibody directly blocks the glycoprotein IIb/IIIa receptors
What oligopeptides block the same receptors as abciximab but are less immunogenic and thereby reduce the risk of allergic reactions as well as the risk of MI
and aggrastat