Pharm - Prog2 - Anticoag And Thrombolytics

Front 1

What kind of clot does an arterial thrombus arise from? What pathologies does it cause?

Back 1

White clot: platelets and fibrin
MIs and CVA (stroke)

Front 2

What kind of clot does a venous thrombus arise from? What pathologies does it cause?

Back 2

Red clot: fibrin, platelets, RBC, other cellular elements
Pulmonary embolism, DVT
Classically described by Virchow's Triad:
Blood stasis, Endothelial injury, Hypercoagulability

Front 3

What are the intrinsic and extrinsic pathways and where do they meet?

Back 3

Both clot formation pathways to link platelets with fibrin to make clot.
Intrinsic: Factor 12 -> 11, 9, 8, evaluate by PTT = Partial Thromboplastin Time
Extrinsic: Factor 7, evaluate by PT = Prothrombin Time
Final Common pathway: 10 -> 5, 2, Prothrombin, fibrinogen, fibrin clot...

Front 4

What is the MOA of unfractionated heparin (UFH)?

Back 4

Accelerates antithrombin III activity (anticoagulant) -- breaks down thrombin and inactivates tissue factors
Interferes with platelet aggregation at HIGH doses

Also: inc lipoprotein lipase activity, inhibit smooth cell proliferation

Front 5

What are the uses of heparin (UFH)?

Back 5

Venous thrombosis, PE, early in unstable angina and acute MI
Prophylaxis (surgery): prevent post-op DVT and PE
Prophylaxis: clotting in blood transfusions, dialysis, blood samples

DOC in PREGNANCY: does NOT cross placenta

Front 6

How is heparin (UFH) administered?

Back 6

ONLY IV, subQ (immed/ short delay)
Half-life depends on dose

Front 7

How should you monitor heparin (UFH)?

Back 7

APTT = Activated Partial Thromboplastin Time, dose adjust

Monitor skin lesions, thrombotic complications, UFH/platelets (HIT toxicity)

Front 8

What are the toxicities of heparin?

Back 8

MC bleeding, dose dep (GP IIb/IIIa antagonism)
THROMBOCYTOPENIA: heparin associated/induced = HAT (benign, 2 days), HIT (serious, 1 wk)
results from autoimmune rxn to UFH, thrombosis
Also, LIVER tox, OSTEOPOROSIS (heparin binds osteoblasts, activate osteoclasts)

Front 9

Where is heparin (UFH) CI?

Back 9

Severe thrombocytopenia (bleeding!)

Front 10

What drug interactions does heparin (UFH) involve?

Back 10

Digoxin, tetracycline, nicotine, antihistamine DECREASE effect
Anticoags, NSAIDs, ASA, dipyridamole, Plavix, direct thrombin inhibitors INCREASE effect

OD! use ANTAGONIST Protamine sulfate to bind heparin and neutralize

Front 11

What are the 3 Low Molecular Weight Heparins (LMWH)?

Back 11

Dalteparin, Enoxaparin, Tinzaparin

Front 12

What is the MOA of LMWHs?

Back 12

Bind and inactivate ONLY factor Xa

Front 13

What are the uses of LMWHs?

Back 13

Similar to heparin
Special: Renal failure, obesity, PREGNANCY
DVT, PE, unstable angina and MI, surgery, hemodialysis

Front 14

How are LMWHs administered?

Back 14

Subq
Also, must continue drug to continue effects

Front 15

How is LMWH monitored?

Back 15

Does NOT need monitoring

Front 16

What are the toxicites of LMWH?

Back 16

Bleeding! (esp at injection site)
Thrombocytopenia (HIT)
Osteoporosis

Advantages: less side effects!!! Less HIT, less osteoporosis, minor bleeding

Front 17

What are the direct thrombin inhibitors?

Back 17

Hirudin
Lepirudin - IRREV binds thrombin, kidneys
Argatroban - REV binds, liver
Bivalirudin - REV binds, kidneys

ALL given IV

Front 18

What is the MOA of direct thrombin inhibitors?

Back 18

Interacts directly with thrombin -- inhibits both CIRCULATING and CLOT-BOUND thrombin

Front 19

What is the use of direct thrombin inhibitors?

Back 19

Alternative to heparin in pts with HIT!

Front 20

What is the side effect of direct thrombin inhibitors?

Back 20

Bleeding!! high incidence

Front 21

What is the direct Xa inhibitor and its MOA?

Back 21

Fondaparinux - REV binds Xa to accelerate antithrombin III

Front 22

What is the use of Fondaparinux? How is it administered?

Back 22

Alternative to pts with HIT!
Subq, kidney

Front 23

What is the MOA of warfarin (coumadin)?

Back 23

Inhibits hepatic synthesis of vitamin K-dependent CLOTTING FACTORS
Interferes with synthesis of anticoagulants, protein C & S

Front 24

What are the uses of warfarin (coumadin) as an anti-coagulant?

Back 24

Prophylaxis/tx of venous thrombosis and PE
Cardiac dz, Atrial fib, prosthetic heart valve, rheumatic dz

Front 25

What are the kinetics of warfarin (coumadin)? When should you administer it?

Back 25

Oral, good absorption
Takes time to see full effect (months)
Start within 24 hours of heparin, tx overlap

Front 26

What should you avoid when taking warfarin (coumadin)?

Back 26

Food high in vit K (leafy greens)!! don't binge.
Herbals increase anticoag effects: ginkgo, ginger, garlic, vit E, St Johns wart

LOTS of drug interactions

Front 27

What kinds of toxicities does warfarin (coumadin) have?

Back 27

BLEEDING!
Coumadin-induced SKIN NECROSIS

Antidote: Frozen plasma (replaces clotting factors)

Front 28

Where is the use of warfarin (coumadin) CI?

Back 28

PREGNANCY (crosses placenta)
Uncontrolled bleeding and GI ulcers

Front 29

How do you monitor the use of warfarin (coumadin)?

Back 29

PT, expressed in INR = PTpt/PTnormal
INR ~2-3

Front 30

What is the MOA of aspirin? What happens if you increase the dose of aspirin?

Back 30

Irrev inhibits COX, prevents synthesis of thromboxane A2 -->inhibits platelet aggregation and vasoconstriction

IRREV - lasts life of platelet, 7-10 days

Increased dose does NOT incr efficacy, INC BLEEDING TOX

Front 31

What is the MOA of dipyridamole?

Back 31

Inhibits phosphodiesterase --> increase in cAMP in platelets which reduces aggregation
Stimulates prostacyclin, anti-platelet effects

Front 32

What is the use of dipyridamole?

Back 32

Prevent embolization from heart valves (with Warfarin)
Reduce thrombosis in thrombotic dz (with Aspirin)

Front 33

What is the MOA of ticlopidine?

Back 33

IRREV inhibits platelet ADP receptor, impairs activation of glycoprotein IIb/IIIa

Front 34

What are the toxicities of ticlopidine?

Back 34

SEVERE NEUTROPENIA: monitor CBC closely

Front 35

What is the MOA of clopidogrel? What is the toxicity of clopidogrel?

Back 35

IRREV inhibits platelet ADP receptor, impairs activation of glycoprotein IIb/IIIa

Well tolerated versus ticlopidine

Front 36

What is the MOA of prasugrel? What is the toxicity of prasugrel?

Back 36

IRREV inhibits platelet ADP receptor, impairs activation of glycoprotein IIb/IIIa

Tox: Similar to clopidogrel
BLACK BOX warning!! life-threatening bleeding risk in 1.3% pts

Front 37

What are the Glycoprotein IIb/IIIa receptor antagonists?

Back 37

Eptifibatide, Tirofiban, ABCIXIMAB

Directly bind receptor, no platelet cross linking

Front 38

What is the use of Glycoprotein IIb/IIIa receptor antagonists? What are the toxicities of these drugs?

Back 38

Acute coronary syndrome at high risk for further MI, ischemia

Bleeding and Thrombocytopenia (less than Heparin)

Front 39

What are the thrombolytics? What is their MOA?

Back 39

Streptokinase, Urokinase, Alteplase, Anistreplase, Reteplase

Converts plasminogen to plasmin, which digests fibrin (all are tPA = tissue plasminogen activators except streptokinase)

Front 40

What is the use of thrombolytics?

Back 40

Dissolve FORMED clot (also direct thrombin inhibitors do this)

Front 41

What are the CIs of thrombolytics?

Back 41

Bleeding risks: recent surgery, Serious GI BLEED within past 3 months, disorder
Cardiac: aortic dissection, acute pericarditis
Previous stroke, intracranial problems
Hx HTN (predisposed to have hypertensive brain bleeds)