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31 Cards in this Set

  • Front
  • Back
Coagulation cascade
Injured tissue and platelets -- formation of thrombin (factor II) -- converts fibrinogen to fibrin -- fibrin incorporates into plug
Fibrin lysis
Plasminogen converted to plasmin by plasminogen activators -- lyses fibrin
Platelet activation
Opposing: high prostacyclin level, low thrombin and thromboxane levels

Promoting: Decreased prostacyclin level, exposed collagen, increased synthesis of thromboxanes
Acts on antithrombin III which neutralizes activated forms of factors XII, XI, X, IX, and II.

Large particle, crosses membranes poorly, not absorbed through intestine

Half life 1-4 hours, metabolized in liver
How is heparin monitored?
aPTT/PTT, therapeutic if twice normal (normal 25-35).
Heparin reversal agent?
Protamine sulfate
Heparin side effects
Heparin induced toxicity: bleeding, heparin induced thrombocytopenia (HIT), hepatic function test abnormalities
Lepirudin (Refludan)
Recombinant form of hirudin (natural anticoagulant)

Substitute for heparin (including patients with heparin induced thrombocytopenia)
Argatroban (Acova)
Substitute for heparin after Lepirudin (Refludan) (including patients with heparin induced thrombocytopenia).

Eliminated through liver, may be used in End Stage Renal Disease
Bivalirudin (Angiomax)
Analog of thrombin inhibitor hirudin

Treatment of unstable angina (MI prophylaxis) in patients undergoing percutaneous transluminal coronary angioplasty, and treatment of acute MI in patients with history of HIT
Low Molecular Weight Heparin
Enoxiparin (Lovenox)
Dalteparin (Fragmin)
Danaproid (Orgaran)
Tinzaparin (Innohep)
Fondaparinux (Arixtra)

Inhibit activated factor X

DVT prophylaxis
Fondaparinux (Arixtra)
DVT and Pulmonary embolism prevention

Inhibits factor Xa, does not inhibit thrombin
Antithrombin III (Thrombate III, Atnativ)
Heparin cofactor I, factor in plasma necessary for heparin to work

Used in patients with congenital AT III deficiency (or acquired, e.g. DIC)
Pentosan (Elminron)
Weak anticoagulant, 1/15 of heparin, indicated for relief of pain associated with interstitial cystitis in US
Dabigatram (Pradaxa, only in Europe)
Oral direct thrombin (factor IIa, FIIa) inhibitor

Under investigation (venous thromboembolism, stroke prophylaxis in patients with atrial fib., and acute VTE treatment)

To substitute heparin
Warfarin (Coumadin)
Teratogenic, (rat poison)

Inhibits hepatic synthesis of vitamin K dependent clotting factors (II, VII, IX, X)

Competitively antagonizes vitamin K

Slow onset, monitored through PT/INR (therapeutic if 1.5-2.5 notmal level), half life 37 hours

Drug interactions: NSAIDs, barbiturates, anabolic sterioids, anti-tuberculosis medications
Warfarin (Coumadin) reversal?
Vitamin K administration - several hours

Fresh frozen plasma (FFP) - immediate
Antiplatelet, irreversibly inhibits cyclooxigenase, lasts 7-10 days

Prophylaxis of transient cerebral ischemia and MI

SE: GI bleeding, hemorrhagic shock, cinchonism (tinitus, dizziness, blurred vision), renal toxicity
Ticlopidine (Ticlid)
Antiplatelet, inhibits ADP pathway

TIA prophylaxis, patients who do not tolerate aspirin

SE: GI upset, bleeding, leukopenia,
Dipyridamol (Persantine)
Coronary vasodilator, in combination with ASA, prophylactic for angina

Inhibits cyclic nucleotide phosphodiesterase, keeping intracellular cAMP high, which inhibits thromboxane A2 synthesis.
Abciximab (Reopro)
mouse/human chimeric monoclinal agent against platelet IIb/IIa receptors

Reduced MI in combination with heparin
Eptifibatide (Integrilin)
Tirofiban (Aggrastat)

Cromafiban, Lamifiban, and Sibrafiban (under investigation)
Similar to Abciximab (Reopro)
Clopidogrel (Plavix)
Analogue to ticlopidine, blocks ADP binding to platelets, inhibits platelet aggregation

Metabolized in lever/kidney, may increase drug concentration of other agents because of CPY I phase reactions inhibition
Prasugrel (Effient)
Blocks ADP binding to platelets, similar to ticlopidine and clopidogrel

Benefit of reduction in thrombotic events but bleeding seen more frequently
Cilostazol (Pletal)
Platelet aggregation inhibitor with vasodilating activity
Altepase, t-PA (Activase, Cathflo)
Reteplase (Retavase, r-PA)
Converts plasminogen to plasmin, only activates plasminogen in clot

Complication: bleeding, cerebral hemorrhage
Streptokinase (Kabikinase, Streptase)
Indirectly activates plasminogen, loading dose required to inactivate streptococci derived antibodies, non-specific for clot bound fibrin
Anistreplase (anysolated plasminogen streptokinase activator complex, APSAC, Eminase)
Streptokinase plus reconvinant human plasminogen
Urokinase (Abbokinase, Open-Cath)
Suruplase (prourokinase)
Human enzyme synthesized in kidney, degrades fibrin and fibrinogen, does not depress plasminogen levels
Tenecteplase (TNK-tPA, TNKase)

Amediplase, Lanoteplase, Saruplase, etc. under investigation
Single, rapid IV bolus for MI, binds to fibrin and converts plasminogen to plasmin
Garlic, allium sativum

Ginger, zingiber officinale
Garlic: Inhibits platelet fuction

Ginger: Inhibits thromboxane synthesis