Anticoagulants

Question 1

Direct Thrombin Inhibitors (DTIs)

Answer 1

MOA: Directly inactivates Factor IIa, impeding the activation of Factor I to fibrin

Question 2

Direct Thrombin Inhibitors

Answer 2

Hirudin
Lepirudin
Bivalirudin
Argatroban
Dabigatran

Question 3

Used for the Mx of HIT (Heparin Induced Thrombocytopenia)

Answer 3

Hirudin - Derived from Hiruda medicinalis (medicinal leeches)
Lepirudin - Recombinant form of Hirudin; less associated with hypersensitivity reactions

Question 4

Toxicity of Hirudin/Lepirudin

Answer 4

Bleeding (monitor with aPTT)
Anaphylactic reactions

Management: Idarucizumab + Activated Charcoal + Aminocaproic Acid

Question 5

Used in the management of acute thrombosis post-angioplasty

Answer 5

Bivalirudin

Parenteral

Question 6

Prophylaxis and treatment of thrombosis in patients with HIT

Answer 6

Argatroban

Question 7

First oral direct thrombin inhibitor

Answer 7

Dabigatran

Question 8

Alternative to Warfarin

Answer 8

Dabigatran
Alternative for
* Stroke prophlaxis, prevention in px with atrial fibrillation
* Management of vascular thromboembolic events
* Deep Vein Thrombosis (DVT)

Question 9

Advantages of Dabigatran

Answer 9

• No PT-INR monitoring required
• No significant drug interaction (drug-food)
• AE: Hemorrhage

Question 10

Indirect Thrombin Inhibitors

Answer 10

Heparin
Unfractionated Heparin (UFH) / Regular Heparin
Low Molecular Weight Heparinm(LMWH)
Warfarin

Question 11

Mixture of sulfated mucopolysaccharides

MW: 5,000 - 30,000

Answer 11

Heparin

ACIDIC, PARENTERAL

Question 12

Clinical Uses of Heparin

Answer 12

Initiating anticoagulation therapy
Management of acute coronary syndrome
Management of Deep Vein Thrombosis, VTE (venous thromboembolism), pulmonary embolism

Question 13

Anticoagulant for Pregnant women

Answer 13

Heparin

Question 14

Monitoring needed for Heparin

Answer 14

Activated Partial Thromboplastin Clotting Time (aPTT)

Question 15

Adverse Effects of Heparin

Answer 15

Bleeding/Hemorrhage (Tx: Protamine sulfate)
HIT (heparin-induced thrombocytopenia)
Alopecia
Osteoporosis with chronic use

CI: Active Bleeding, Thrombocytopenia

Question 16

MOA of Unfractionated Heparin (UFH) / Regular Heparin

Answer 16

Forms an active complex with ATIII by 1000-fold; inactivation of IXa, Xa, XIa, XIIIa

Question 17

Routes of Admin for Unfractionated Heparin

Answer 17

• IV bolus (80M/kgBW) or IV infusion (180 units/kgBW/hr)
  For the management of venous thromboembolism, DVT, embolism
• IV Bolus (50M/kBW) or IV Infusion (12-15mg)
  Management of acute coronary syndome (MI)
• Monitoring for IV infusion:
  aPPT: activated partial prothrombin time
  Goal: 60-85 sec delay!
  <40: underdose
  >40: overdose

Question 18

Low Molecular Weight Heparin (LMWH)

Answer 18

Enoxaparin
Dalteparin
Tinzaparin
Fondaparinux

Question 19

Dalteparin, Enoxaparin

Answer 19

MOA: Inactivates Xa
MW: 2,000 - 9,000
Less affinity to thrombin
Route: SQ
Monitoring: None required

Question 20

Fondaparinux

Answer 20

Selective inhibitor of Xa
Synthetic LMWH
No aPTT

Question 21

MOA of Warfarin

Answer 21

• Inhibits vitamin K epoxide reductase (inactive from of Vitamin K)
• Interferes with production of functional vitamin K-dependent clotting and anticlotting factors (II, VII, IX, X)
• Inhibits Protein C & S (endogenous anticoagulants/anticlotting factors)

Question 22

Effects of Warfarin

Answer 22

Initial: Transient procoagulation Effect
Mx: Add LMW Heparin

Final: ANTICOAGULATION

Question 23

Doses of Warfarin

Answer 23

Dosing for Caucaseans: 5mg daily
Dosing for Asians: 1-2 mg daily
(lower dose because there is less
expression of VKERC)

Question 24

Clinical Use of Warfarin

Answer 24

For chronic anticoagulation
* Chronic atrial fibrillation
* Prosthetic heart valve
* Rheumatic heart disease (RHD)
* DVT, VTE

Question 25

Contraindications for Warfarin

Answer 25

Contraindicated to Pregnants Fetal Warfarin syndrome

Question 26

Monitoring of Warfarin

Answer 26

* PT-INR (prothrombin time - international normalized ratio) * Goal: 2-3 (most patients) * 2.4-3.5 : patients with prosthetic heart valve * > 2: underdose (thrombosis) * > 3.5: overdose (hemorrhage)

Question 27

Adverse Effects of Warfarin

Answer 27

Bleeding/Hemorrhage (tx: Vit K1, Fresh plasma, F IX) Cutaneous Necrosis due to procoagulant effect Purple Toe Syndrome

Question 28

Drug Interactions of Warfarin

Answer 28

Increased PT-INR (Hemorrhage) Warfarin + Cimetidine = Decreased metabolism of Warfarin + Antibiotics Warfarin + Aspirin Warfarin + Hyperthyroidism Decreased PT-INR (Thrombosis) Warfarin + Phenobarbital Warfarin + Green Leafy Vegetables Warfarin + Hypothyroidism

Question 29

Active Factor X Inhibitors | Newer Oral Anticoagulants (NOACs/NOVEL)

Answer 29

Rivaroxaban, Apixaban, Edoxaban Antidote: r-Antidote

Question 30

Anti-Coagulants

Answer 30

Direct Thrombin Inhibitors * Hirudin * Lepirudin * Bivalirudin * Argatroban * Dabigatran (Oral) Indirect Thrombin Inhibitors * Warfarin * Heparin * Unfractionated Heparin * LMWH (Dalterparin, Enoxaparin, Tinzaparin) - SQ, IV * Fondaparinux Newer Oral Anticoagulants * Apixaban * Edoxaban * Rivaroxaban