Hemostasis Drugs

Question 1

What are examples of anticoagulants?

Answer 1

Heparin, Low Molecular Weight Heparin (enoxaprin), Warfarin

Question 2

What are examples antiplatelet agents?

Answer 2

Aspirin, Abciximab

Question 3

What are examples of ADP (P2Y12) receptor anatogonist?

Answer 3

Clopidigrel, Ticagrelor, Prasugrel

Question 4

What are examples of PDE inhibitors?

Answer 4

Dipyridamole, Cilostazol

Question 5

What are examples of thrombin receptor antagonist?

Answer 5

Vorapaxar

Question 6

Whare example of thrombin inhibitors?

Answer 6

Bivalirudin, Hirudin, lepirudin, dabigatran, argatraban

Question 7

What examples of 10a inhibitors?

Answer 7

Rivaroxiban, Fondaparinux, Apixaban

Question 8

What are examples of Fibrinolytics?

Answer 8

rTPA

Question 9

What are fibrinolytic inhibitors?

Answer 9

Tranexamic acid, Aminocaproic acid

Question 10

Aspirin

Answer 10

MOA - blocks cyclooxygenase therby lowering TXA2 levels, inhibits platelet aggregation

Clincial Use - Early MI, Ischemis Stroke

Advese Effects - Bleeding, GI upset

Question 11

Abciximab

Answer 11

MOA - blocks fibrinogen receptor (GPIIb/IIIa, nocompetitively) on activated platelets, blocks platelet aggregation

Clinical Use - Unstable Angina, Percutaneous coronary intervention

Advese Effects - Bleeding, Thrombocytopenia (rare)

Question 12

Tricagrelor, Clopidogrel, Prasugrel

Answer 12

MOA - blocks ADP (P2Y12) recpetors, prevents expression of GIIb/IIIa on platelet surface,

Clinical Use - Acute coranry syndrome, coronary stenting, decrese recurrence of thrombotic stroke,

Adverse Effects - Bleeding, Thrombocytopenia (rare)

Question 13

Cilostazol and Dipyridamole

Answer 13

MOA - Phasphodeiesterase inhibitors; increase cAMP inmplatelets, resulting in inhibiton of platelet aggregation; vasodilators

Clincial Use - Intermittent claduciation, coronary vasodilation, thrombotic stroke prevention or TIA (aspirin combo),

Adverse Effects - Bleeding, Nausea, headche, hypotension and abdominal pain

Question 14

Warfarin

Answer 14

MOA - Interferes with gamma carboxylation of vitamin K dependent clotting factors (II, VII, IX, X, protein C and S), increases PT (prothrombin time)

Clinical Use - Oral, chronic anticoagulant (takes days for full effect), i.e., Venous thrombosis, prevent stroke atrial fibrillation

Question 15

What are adverse effects of warfarin?

Answer 15

Bleeding increases with age, renal failure, recent trauma or surgery, prior history of GI or intracerebral bleed, hypertension, idiopathic thrombocytopenic purpura (ITP), or leukemia; eclampsia or preeclampsia, Teratogenic (can cross the placenta), skin necrosis (rare) seen when not started with heparin or direct thrombin inhibitors in patients with low protein C and S, drug interactions - polymorphism in VK epoxide recuctase gene

Question 16

How are the effects of warfarin refersed?

Answer 16

Give Vitamin K, for rapid reversal - give fresh frozen plasma or PCC (Prothrombin Complex Concentrate)

Question 17

What increases warfarin effect?

Answer 17

Cytochrome P-450 inhibitors increase warfarin effect

Question 18

Heparin

Answer 18

MOA - Binds to endothelial surface and accelerates antithrombin III to inhibit 2a, 10a, increases PTT - has short half life, injection only

Clinical Use - Intermediate anticoagulant- pulmonary emoblism, acute cornary syndrome, MI, DVT, can be use during pregnancy

Question 19

What are the adverse effects of heparin?

Answer 19

Bleeding, thrombocytopenia (HIT), osteoporosis, Hyperkalemia (high potassium)

Question 20

What is the rapid reversal for Heparin?

Answer 20

For rapid reversal (antidote), use protamine sulfate (positively charged moleculed that binds negatively charge heparin)

Question 21

Problems with Heparin

Answer 21

Question 22

Low-molecular-weight heparins

Answer 22

act predominatly on factor Xa. Fondaprinux acts only on factor Xa. Have better bioavailability and 2-4x longer half life thant unfractioned heparin; can be administered subcutaneoulsy and without laboratory monitoring, not easily reversible

Question 23

Herparin vs Warfarin

Answer 23

Question 24

Heparin-induced thrombocytopenia (HIT)

Answer 24

Development of IgG antibodies against heparin-bound platelet factor (PF4). Antibody-heparin-PF4 complex activates platelets >> thrombosis and thrombocytopenia

Question 25

How is HIT managed?

Answer 25

Stop all heparin, give an alternative anticoagulant, such as argatroban, bivalirudin, or fondaparinux, do not give platelet transfusions, evaluate for thrombosis, particulary deep vein thrombosis

Question 26

Bivalirudin, argatroban, dabigatran (just this one is given oral)

Answer 26

**MOA** - directly inhibits (both free and clot associated thrombin), binds to active thrombin site (competitive), related to anticoag. Mechanism of medicinal leech, **Clinical Use** - Venous thrombosis, prevent stroke in atrial fibrilation, can be used in HIT, when heparin is BAD for the patient, does not require lab monitoring **Adverse effects** - Bleeding; can reverse dabigatran with idarucizumab.

Question 27

Fondaparinux, Rivaroxiban, Apixaban

Answer 27

**MOA** - Rivaroxiban and apixaban directly inhibts factor 10a by binding to 10a (oral), Fondaprinux inactivates 10a indirectly by accelerating ATIII (injection) **Clinica Use** - prophylaxis for DVT, PE and stroke associated with atrial fibrilation, no lab monitoring for oral angents, Fondaprinux has no issues with HIT becasue no anitobdy generated to PF-4 has a long half life **Adverse effects** - Bleeding (andexanet alfa)

Question 28

Alteplase (tPA), reteplase (rTPA), tenecteplase (TNK-tPA)

Answer 28

**MOA** - plasminogen activators, directly or indirectly aid the conversion of plasminogen to plasmin which then cleaves thrombin and fibrin clots, does not affect platelet count **Clinical Use** - Early MI and early ischemic stroke, directy thrombolysis of severe PE **Adverse Effects** - Bleeding (avoid in patients with history of intracranial bleed, recent surgery, severe hypertension, reverse with antifibrinolytics (tranexamic acid or aminocaproic acid), platelet transfusion or FFP or PCC