Drugs Affecting Coagulation (Regulate Hemostasis)

Front 1

what does the bleeding time lab test identify?

Back 1

platelet function, adhesion, aggregation and release

Front 2

what does the prothrombin time lab test identify?

Back 2

Factor 7 from the extrinsic pathway and factors 1, 2, 5 and 10 from the common pathway

Front 3

what does the partial thromboplastin time lab test identify?

Back 3

factors 8, 9, 11, and 12 from the intrinsic pathway and factors 1, 2, 5 and 10 from the common pathway

Front 4

What does the thrombin time lab test identify?

Back 4

identifies fibrinogen and inhibitors of thrombin-fibrinogen interaction

Front 5

anticoagulant drugs

Back 5

heparin, enoxaparin, tinzaparin, fondaparinux, pentosan, antithrombin III, warfarin, lepirudin, argatroban, bivslirudin

Front 6

platelet inhibitor drugs (antiplatelet drugs)

Back 6

aspirin, dipyridamole, ticlopidine, abciximab, eptifibatide, tirofiban, clopidagrel, prasugrel, cilostazol, dabigatran

Front 7

thrombolytic agents

Back 7

tPA, anistreplase, streptokinase, urokinase, tenecteplase

Front 8

what is the mechanism of action of heparin?

Back 8

heparin acts indirectly through its effects on antithrombin III, the plasma protein that neutrilizes the activated forms of factors 9,10, 11, and 12. Heparin activates the neutrilizing activity of antithrombin by a factor of 1000 and the effect is immediate.

Front 9

how is heparin administered?

Back 9

parenterally (IV or subcutaneous)

Front 10

what test is used to monitor heparin therapy?

Back 10

APTT/PTT

Front 11

what is protamine sulfate?

Back 11

it is a protein isolated from fish sperm that complexes w/ heparin and is used to reverse heparin anticoagulation effects when immediate reversal is required (i.e. following cardiac surgery, heparin overdose, to neutrilize heparin during extracorporeal circulation following dialysis, and arterial or cardiac surgery)

Front 12

can heparin be used during pregnancy?

Back 12

yes, b/c it doesn't cross the placenta

Front 13

what are the effects of heparin toxicity?

Back 13

bleeding, thrombocytopenia (platelets <100,000) and frequent abnormalities in hepatic function tests

Front 14

Lepirudin

Back 14

Lepirudin
Anticoagulant; recombiant form of the natural anticoagulant found in leeches called hirudin. First drug approved in the US for anticoagulation in patients with heparin induced thrombocytopenia and is a thrombin antiagonist

Front 15

Bivalirudin

Back 15

Bivalirudin
anticoagulant used to treat heparin induced thrombocytopenia. Analog of the thrombin inhibitor hirudin. Indicated for treatment of unstable angina (MI prophylaxis) for pts undergoing PTCA. Also for the tx of acute MI in hospitalized pts. Substitute for heparin in pts undergoing angioplasty who have a hx of heparin induced thrombocytopenia.

Front 16

Ancrod

Back 16

Ancrod
derived from the venom of pit vipers. under investigation as an alternative to heparin in pts with heparin induced thrombocytopenia and in the treatment of ischemic stroke

Front 17

Low molecular weight heparin drugs

Back 17

Enoxaparin, Dalteparin, Danaproid, Tinzaparin, Fondaparinux
Used in the prevention of DVT in pats undergoing hip replacement surgery

Front 18

Mechanism of actin of low molecular weight heparins

Back 18

inhibit activated factor 10 but have much less effect on antithrombin III (less effect on coagulation in general). They produce a more predictable response than heparin w/ a better bioavailabillity and longer half life. Has a dose independant clearance

Front 19

Fondaparinux

Back 19

Fondaparinux; anticoagulant used in the prevention of DVT and pulmonary embolism in pts undergoing hip fractur, hip replacement and knee replacement surgery. First to inhibit a single step in the coagulation cascade (Xa). Does not inhibit thrombin

Front 20

Antithrombin III

Back 20

Antithrombin III; aka heparin cofactor I. A natural anticoagulant made in the liver found in plasma and is necessary for heparin to exert it's anticoagulant activity. Inhibits thrombin, factors 9a, 10a, 11a, and 12a, and plasmin. Used in pts with an AT III deficiency (i.e. DIC) b/c they are predisposed to a venous thromboembolic event.

Front 21

Pentosan

Back 21

Pentosan; a weak oral anticoagulant derived from plants (heparin is derived from animals). Used to eleviate pain associated with interstitial cystitis

Front 22

Dabigatran

Back 22

Dabigatran; An oral anticoagulant that directly inhibits thrombin. Currently under investigation for the short-term prevention of venous thromboembolism after orthopedic surgery. Also under investigation as a prophylaxis to venous thromboembolism, stroke, and atrial fibrillation.May help reduce frequent monitoring and substitute heparins with an oral drug

Front 23

Warfarin (coumadin)

Back 23

Warfarin; An oral indirect anticoagulant that inhibits the synthesis of vitamin K dependant factors of the coagulation cascade (factors 2,7,9,10). Treatment does not result in rapid anticoagulation and therapy should be monitored closely when first done checking for hypocalemia. Main drug used in anticoagulant therapy. Factor 7 is the most effected by warfarin b/c it has the shortest half life so warfarin therepy can be monitored using PT time (extrinsic pthwy). Takes a few days before hemostasis returns to normal after taken off therapy.

Front 24

Methods for warfarin reversal

Back 24

1) vitamin K administration (planned reversal)
2) transfusion w/ fresh frozen plasma (rapid reversal)
solvent/detergent treated plasma can be used as an alternative to FFP

Front 25

drug interactions with warfarin

Back 25

pts cannot take NSAIDS, barbituates, anti-TB meds, and anabolic steroids. These drugs either 1) alter the hepatic metabolic rate or 2) displace the warfarin from albumin

Front 26

Aspirin

Back 26

Aspirin; Irreversibly inhibits cyclooxygenase therfore inhibiting the production of prostaglndin and thromboxane A2. Used prophylacticly for the tx of cerebral ischemia and in MI. Could cause hemorrhagic shock, GI bleeding, conchonism (ear ringing, blurred vision, dizziness low BP) and renal toxicity

Front 27

Ticlopidine

Back 27

Ticlopidine; antiplatelet drug that blocks platelet aggregation by inhibiting the ADP pthwy so platelets can't bind to fibrinogen or each other. Used to decrease the incidence of thromolytic stroke and prevents ischemic attacks for pts that are intolerant to aspirin. Could cause GI upset, bleeding and leukopenia/neutropenia

Front 28

Dipyridamole

Back 28

Dipyridamole; antiplatelet and coronary vasodilator drug used phrophylactically for angina. It inhibits phosphodiesterase thus keeping cAMP levels high which inhibits thromboxane A2 synthesis. Inhibits embolization in pts w/ prosthetic heart valves when used in combination with warfarin.

Front 29

Abciximab

Back 29

Abciximab; antiplatelet drug that is a monoclonal antibody that targets Gp2a/3b receptors on platelet surface so they can't bind to fibrin. Used in pts undergoing angioplasty and atherectomy. Assists in incresing the effectiveness of heparin when used in combination

Front 30

Eptifibatide

Back 30

Epifibatide; antiplatelet drug that bins to Gp2a/3b receptors. rapidly cleared from plasma due to their small structure

Front 31

Clopidogrel

Back 31

Clopidogrel; analogue of antiplatelet drug Ticlopidine that inhibits the ADP pthwy so platelets can't bind to fibrinogen or each other. Does not cause neutropenia like ticlopidine does

Front 32

Prasugrel

Back 32

Prasugrel; antiplatelet drug that works similar to Clopidogrel and Ticlopidine. The difference being that this drug showed greater reduction in cardiovascular death, non-fatal heart attacks, nonfatal stroke, MI, stent thrombosis,. The disadvantage being an increase in bleeding frequency.

Front 33

cliostazol

Back 33

cliostazol; antiplatelet drug that reversibly inhibits platelet aggregation by inhibiting PDE III (increases cAMP levels) and also has vasodilating activity (antithrombic, antiplatelet and vasodilatory). Inhibits aggregation caused by ADP, arachadonic acid, collagen, epinephrine, thrombin, and shear stress.

Front 34

Alteplase, t-PA

Back 34

Alteplase, t-PA; finbrinolytic protease that converts plasminogen to plasmin. Binds selectively to the fibrin on the clot and causes thrombolysis. Requires the presence of fibrin. Activates only plsminogen that is bound to the clot (not free floating). Used for DVT, pulmonary embolism, MI and peripheral arterial thrombosis

Front 35

Streptokinase

Back 35

Streptokinase; fibrinolytic protein taken from group C beta-hemolytic streptococci. Does not have enzymatic activity but indirectly activated plasminogen to plasmin. A loading dose is required to inactivate plasma streptococci derived antobodies. Not specific for clot found antobodies (t-PA is). Used for acute pulmonary embolism

Front 36

Anistreplase

Back 36

Anistreplase; fibrinolytic agent that is composed of streptokinase and recombiant human plasminogen. Semi-selective to the clot site

Front 37

Tenecteplase

Back 37

Tenecteplase; fibrinolytic agent that is a modified form of t-PA that binds to fibrin and converts plasminogen to plasmin but has a longer half-life, increased specificity, and increased resistance to plasminogen-activator inhibitor-1. Used in treatment of acute MI and administered as a rapid IV bolus

Front 38

What two natural products can be used as antiplatelet and anticoagulants through the inhibition of the synthesis of thromboxane?

Back 38

garlic and ginger