Mspa 2017 - Anticoagulant

Front 1

What are the key steps in vascular repair following vessel wall injury?

Back 1

Platelet activation and aggregation

Front 2

When doest Platelet Activation occur?

Back 2

Rupture of atheromatous plaque exposes circulating platelets to:

ADP, TxA2, epinephrine, thrombin, Collagen tissue factor

Front 3

What is the potent stimulant for platelet activation?

Back 3

Thrombin

Front 4

When does Platelet aggregation occur?

Back 4

1) Platelet activation leads to expression of GP on platelet surface.

2) GP receptors lead to binding of fibrinogen between adjacent platelets

3) Leads to platelet aggregation

Front 5

What is the VW factor?

Back 5

protein found on the vessel wall and plasma

Front 6

Process of activation and aggregation are ______

Back 6

Progressive and overlapping event

1) Platelets changes shape

2) Develop pseudopods

Front 7

A central element in the coagulation pathway is ________

Back 7

Thrombin - factor II (Soluble protein)

Front 8

Describe the thrombotic process

Back 8

Tissue factor VII on diseased endothelium activates the factor Xa (part of prothrombinase complex) which converts prothrombin to thrombin

Front 9

What is the direct role of thrombin?

Back 9

Convert fibrinogen to fibrin

Front 10

What are the secondary effects of thrombin?

Back 10

1) Promoting tissue factor production

2) Expression of adhesive molecules in endothelial cells

3) Smooth muscle cell proliferation

4) Leukocyte activation

5) Platelet aggregation

Front 11

Thrombin may also enhance _________

Back 11

activity of protein S, thereby actually exerting an anti thrombotic effect

Front 12

Describe the process of Clot formation

Back 12

1) Endothelial damage

2) Activation of intrinsic pathway which involves fibrin growth and maintenance

3) ADP stimulates platelet aggregation

4) Tissue factor activates the extrinsic pathway which initiates fibrin formation

5) Common pathway activates Factor X

Front 13

What are the predisposing conditions for clot formation?

Back 13

1) Immobilization

2) Surgery & immediate post-op period

3) Trauma to lower limb

4) Pregnancy & Contraceptives

5) Heredity

6) CHF, MI, A Fib

7) Clotting factors deficiencies

Front 14

What are the indications for anticoagulant therapy?

Back 14

1) Pulmonary embolism

2) DVT

3) A Fib

4) Heart valve prosthesis

5) Acute MI

6) TIA/Stoke

7) Hip fracture - for prevention (temporarily)

Front 15

What are the characteristics of Heparin?

Back 15

Unfractionated

1) Mucopolysaccharides

2) Unfractionated (pig mucosa or bovine lung)

3) Low molecular weight

4) IV or SQ (NOT IM)

Front 16

What is the mechanism of action of Heparin?

Back 16

binds to Antithrombin III and inactivates factor Xa, XIa and XIIa

Front 17

Heparin dosing

Back 17

Loading dose (70 - 100 units/kg) is much higher than maintenance dose (18 units/kg)

Front 18

What is the adjustment of Heparin dose based on?

Back 18

aPTT

1) test done every 6 hours

2) always wait 6 hours before testing again after a change in dose

Front 19

What are the adverse effects of Heparin?

Back 19

1) Hemorrhage

2) Thrombocytopenia (HIP)

3) Paradoxical thrombosis

Front 20

What is Paradoxical thrombosis?

Back 20

Condition in which arterial or venous clots may develop after a period of heparin therapy

- caused by production of antiplatelet antibodies that induce clotting

Front 21

What should be done in case of Heparin overdose?

Back 21

Should use

1) Protamine - a specific antidote

2) Whole blood transfusion

3) Fresh frozen plasma transfusion

Front 22

Name the Low molecular weight heparins

Back 22

1) Enoxaparin (Lovenox)

2) Dalteparin (Fragmin)

3) Ardeparin (Normiflo)

4) Tinzaparin (Innohep)

Front 23

Fondaparinux (Arixtra) is ____________

Back 23

Synthetic pentasaccharide

Leads to efficient inactivation of factor Xa

1) Heparinoid

2) Works the same way as haparin - however doesn't cause HIT

Indication of use is VTE

Front 24

Low molecular weight heparin has less chances of _____ compared to heparin

Back 24

Less chances of HIT

Front 25

What are the indications of Low molecular weight heparin?

Back 25

1) DVT and PE treatment

2) May be used in out patient therapy as well

Front 26

What are the contraindication Heparin?

Back 26

1) Low renal function

2) Overweight or underweight

Front 27

What are the contraindication of Fondaparinux?

Back 27

if creatinine clearance < 30 mL/min

Front 28

What are the types of Direct Thrombin inhibitors (DTI)?

Back 28

1) Divalent

2) Univalent

Front 29

Name the Divalent DTIs

Back 29

1) Hirudin

2) Lepirudin (Refludan)

3) Bivalirudin (Angiomax)

Front 30

What are the characteristics/MOA of Lepirudin (Refludan)?

Back 30

1) Derivative of Hirudin

2) Alternative to Heparin

3) Works in the presence of HIT

4) Less monitoring

5) IV preparation

6) Need to monitor PTT (less frequently)

Front 31

What are the adverse effects Lepirudin (Refludan)?

Back 31

1) Hemorrhage

2) Renal impairment???

Front 32

What are the characteristics/MOA of Bivalirudin (Angiomax)?

Back 32

1) IV

2) Quick onset

3) Short half-life

4) Indication: Cath procedures

Front 33

Name the Univalent DTIs

Back 33

1) Argatroban

2) Dabigatran (Pradaxa)

Front 34

What is the mechanism of action of Argatroban?

Back 34

1) Small molecule thrombin inhibitor

2) Used in patients with HIP

Front 35

Dabigatran (Pradaxa) is _________

Back 35

1) First PO DTI

Front 36

Dabigatran (Pradaxa) absorption is ________

Back 36

1) Rapid absorption

2) Bioavailability: 3-7%

- remains relatively static under fast and fed conditions

Front 37

How is Dabigatran distributed?

Back 37

1) Plasma concentration peaks within 1 hour

- delayed 2 hours by food consumption

2) Half life elimination = 12-17 hours

Front 38

How is Dabigatran metabolized?

Back 38

1) Metabolized by microsomal carboxylesterases in the liver

2) Does not affect CYP activity

Front 39

How is Dabigatran excreted?

Back 39

1) Urine (7% as unchanged drug)

2) Feces (86% of total dose)

Front 40

What are the drug interactions of Dabigatran?

Back 40

1) P-glycoprotein inducer

- Avoid taking it with Rifampin

--- can make dabigatran less effective

2) Drug food interaction

- Food has no effect on bioavailability

- However delays the time to peak by 2 hours

Front 41

What are the adverse effects of Dabigatran?

Back 41

1) Dyspepsia

2) Fatigue

3) Dizziness

4) Dyspnea

5) Peripheral edema

7) Diarrhea

8) GI bleed

9) MI

10) Potential for accumulation in presence of renal dysfunction

Front 42

What are the monitoring parameters of Dabigatran?

Back 42

1) Monitor aPTT

- value > 2.5x control may indicate over-anticoagulation

2) Ecarin clotting test (ECT) (if available)

3) Prothrombin time (PT)

4) CBC w/ diff

5) Bleeding

Front 43

What is the dosing for Dabigatran?

Back 43

1) 150mg PO BID

2) In case of renal impairment:

- Cr Cl 15-30: 75mg PO BID

- Cr Cl , 15: no recommendation

3) In case of hepatic impairment:

- No adjustment required

Front 44

Dibigatran vs. Warfarin

Back 44

1) Patients w/ A Fib - dabigatran given at dose of 110mg BID (same effectiveness)

- however, lower rates of major hemorrhage

2) Dabigatran administered at a dose of 150mg BID as compared with warfarin (superior effect)

- lowers the rates of stroke and systemic embolism

- however, similar rates of major hemorrhage

Front 45

Should dabigatran be used based on the trial?

Back 45

1) Same effectiveness with lower hemorrhage risks at 110mg BID

2) Superior effectiveness at lower risk for stroke or embolism at 150mg BID - w/ same hemorrhage risk

3) Wide therapeutic window - safety and efficacy depends on drug compliance

4) BID dose may increase non adherence to tx

5) No specific antidote yet

6) Renal/hepatic impairment

7) High risk of bleeding

Front 46

Name the Direct factor Xa inhibitors

Back 46

1) Rivaroxaban (Xarelto)

2) Apixaban (Eliquis)

Front 47

What are the characteristics of Rivaroxaban (Xarelto) (PO)?

Back 47

1) Predictable pharmacology

2) High bioavailability

3) Low risk of drug-drug interaction

4) Fixed dose

5) No requirements for monitoring

6) Similar efficacy as enoxaparin (Lovenox)

7) No diff in major bleeding btwn rivaroxaban and enoxaparin

8) Wide therapeutic window

Front 48

What is the mechanism of action of Rivaroxaban?

Back 48

1) Specific, competitive, direct Xa inhibitor

2) Inhibits free and clot-associated FXa activity and prothrombinase activity

3) Inhibits thrombin generation via inhibition of FXa activity

- prolongs time to thrombin generation

- inhibits peak thrombin generation

- reduces the total amount of thrombin generated

4) Has a potent effect on aPTT & PT

5) Does not require a cofactor

Front 49

What are the indications for Rivaroxaban (Xarelto)?

Back 49

1) Treatment

2) Secondary Prevention of VTE

Front 50

What are the Vitamin K dependent factors?

Back 50

1) Factor VII

2) Factor IX

3) Factor X

4) Factor II

Front 51

What is the mechanism of action Vitamin K?

Back 51

1) Plays a major role in blood clotting

2) When given too much - reverses the effects of blood thinning medications such as (warfarin)

Front 52

What is the mechanism of action of Warfarin?

Back 52

1) Antagonizes Vitamin K

2) Depletes Vitamin K dependent factors (II, VIII, IX, X, protein C, protein S)

3) Onset of action 1-2 days

4) "True" anticoagulation in 2-7 days

Front 53

What are the characteristics of Warfarin?

Back 53

1) Well absorbed

2) Highly protein bound

3) Metabolized by the liver

4) Should always be monitored via INR (2-3)

Therapeutic goal = 1:2

Front 54

What are the Warfarin Dosing strategies?

Back 54

1) Do not load!

2) a Therapeutic PT does not mean "True" anticoagulation

3) Continue heparin therapy even along with warfarin until INR at therapeutic goal

4) Start one day after initiating heparin

5) Starting dose: 5mg-7.5mg / day

Front 55

What are the adverse effects of Warfarin?

Back 55

1) Bleeding

2) Thrombocytopenia

Front 56

What are the Drug-interactions of Warfarin?

Back 56

1) Enzyme inducers (antiepileptics)

2) Enzyme inhibitors (cimetidine, antibiotics)

3) Protein displacement (digoxin)

Front 57

What are Enzyme inducers?

Back 57

e.g. Antiepileptics

1) Enzyme inducer leads to fast metabolism and excretion of warfarin

2) Making it less effective

3) Causing more clotting

Front 58

What are Enzyme inhibitors?

Back 58

e.g. 1) Cimetidine

2) Antibiotics

1) Enzyme inhibitor will prevent the metabolism of warfarin

2) Leads to warfarin in circulation for longer duration - Increasing the effects of warfarin

3) Causing more bleeding

Front 59

Protein displacement

Back 59

e.g. Digoxin

1) Digoxin has higher protein affinity hence binds to the protein resulting in more free warfarin

2) Free warfarin (active)

3) Increasing the effects of warfarin

4) Causing more bleeding

Front 60

What are the signs of Warfarin Overdosage?

Back 60

Any unusual bleeding

1) Blood in stool or urine

2 )Excessive menstrual bleeding

3) Bruising

4) Excessive nose bleeds/ bleeding gums

5) Persistent oozing from superficial injuries

6) Bleeding from tumor ulcer or other lesions

Front 61

What are the Food-drug & other interactions of Warfarin?

Back 61

1) Vitamin K containing foods

- Ok to continue the regular portion however important to inform the Dr. (how much)

- Also important to inform the Dr. if any changes made in the intake (decreased or increased)

2) Antacids

3) Smoking

Front 62

What should be done in case of Warfarin - Bleeding?

Back 62

1) Fresh Frozen Plasma transfusion

- Contains all the clotting factors

2) Start the patient on Vitamin K

- If INR > 6

***Higher INR = Over anticoagulation

*** Important to control bleeding

Front 63

What is effective patient education?

Back 63

1) Teach basic concepts of safe, effective anticoagulation

2) Discus importance of regular INR monitoring

3) Counsel on use of other medications, alcohol

4) Develop creative strategies for improving compliance

5) Tell patients to take the warfarin right before dinner (for compliance)

Front 64

What are the Peri-Procedural management?

Back 64

1) Stop warfarin 5-7 days prior to procedure

2) Start enoxaprin at treatment dose (1mg/Kg SQ every 12 hours)

3) Last dose of enoxaparin 24 hours prior to procedure

4) Restart enoxaprin and warfarin (at previously stable dose) the evening following procedure

5) Continue until INR at therapeutic goal

Front 65

Name the Antiplatelet agents

Back 65

1) Ticlopidine (Ticlid)

- Slow in producing anti platelet activity

- Limited use

2) Clopidogrel (Plavix)

- More active than ticlopidine

- Better side effects profile

3) Prasugerel (Effient)

- Similar to Clopidogrel

4) Ticagrelor (Brilinta) (IV)

Front 66

What is the mechanism of action of Antiplatelet agents?

Back 66

Inhibits ADP-dependent activation of GP IIb/IIIa complex

Front 67

What are the indications for Antiplatelet agents?

Back 67

1) ACS

2) Post strokes

3) Stroke Prevention

Front 68

What are the indications for Ticlopidicine (Ticlid)?

Back 68

1) Used when Aspirin is contraindicated

2) Use has been limited due to unacceptable side effect profile

Front 69

What are the benefits of using Clopidogrel (Plavix) compared to Ticlopidicine?

Back 69

1) 6 times more active compared to Ticlopidicine

2) Better side effect profile

Front 70

Ticlopidicine and Clopidogrel are used for prophylactic therapy in _______

Back 70

High risk percutaneous coronary interventions

Front 71

Name the Antiplatelet agent monoclonal antibody

Back 71

Abciximab

Front 72

Name the Natural Antiplatelet agent

Back 72

Disintegrin family: RGD containing proteins

** from viper venom **

Front 73

Name the Non peptide antiplatelet agents

Back 73

1) Tirofiban

2) Lamifiban

3) Fradafiban

Front 74

Name the Oral antiplatelet agents

Back 74

1) Xemilofiban

2) Orofiban

3) Lefradafiban

4) Sibrafiban

5) Roxifiban

Front 75

What are the Antiplatelet agents herbal interactions?

Back 75

Decreases platelet aggregation

Front 76

What is the mechanism of action of Thrombolytics?

Back 76

Thrombolytics are Proteins

Dissolves the clot by

1) acting on plasminogen to form plasmin

2) plasmin cleaves fibrin

Front 77

What are the Indications for thrombolytics?

Back 77

MI patients

- Remarkable improvements in outcomes

- Must be started as soon as diagnosis is made

Front 78

Name the Thromobolytic medications

Back 78

1) Streptokinase (streptase)

2) Urokinase

3) Antistreplase (Eminase)

4) Alteplase (Activase, t-PA)

5) Reteplase (Retavase)

6) Tenecteplase (TNKase)

Front 79

Which are the Thrombolytics that needs to be started early?

Back 79

1) Alteplase (Activase, t-PA)

2) Reteplase (Retavase)

3) Tenecteplase (TNKase)

Front 80

Factor _____ with shortest half life on the intrinsic pathway of the clotting cascade

Back 80

Factor VII

Front 81

LMWH

Back 81

Ending in "parin"

Front 82

Divalent DTIs

Back 82

Ending in "rudin"

Front 83

Direct factor Xa Factor

Back 83

Ending in "xaban"

Front 84

Non Peptide and Oral antiplatelet

Back 84

Ending in "fiban"

Front 85

Thrombolytic medications

Back 85

Ending in "ase"

Front 86

List the Anticoagulants that work againsT factor Xa

Back 86

1) Direct factor Xa inhibitors

2) DTI

3) Fondaparinux (Arixtra)

4) LMWH

5) Unfractionated Heparin

6) Warfarin (Vitamin K antagonist)

Front 87

Heparin indirectly inhibits __________ and LMWH indirectly inhibits __________

Back 87

1) Factor IIa & Xa

2) Factor Xa more than Factor IIa

Front 88

Name the Synthetic peptide

Back 88

Eptifibatide