Anti Thrombotic

Question 1

3 classes of anti thrombotic drugs

Answer 1

Ani platelet — inhibit platelet aggregation

Anti coagulants — coagulation factors, white to red thrombus formation

Fibrinolytics — fibrinolysis. Fibrin dissolution of red thrombus

Question 2

What class of anti thrombotic is aspirin

Answer 2

Anti platelet

Question 3

Mechanism of aspirin

Answer 3

Irreversible cox inhibitor, block txa2 more than pgi2 synthesis as takes 1-2weeks to make new platelets while endothelial cells take 304h to recover to restore inhibition of aggregation

Question 4

Side effects of aspirin

Answer 4

Peptide ulcer, GI bleeding, allergy

Question 5

What class of anti thrombotic is clopidogrel

Answer 5

Antiplatelet

Question 6

What is the mechanism of clopidogrel

Answer 6

Prodrug

Irreversible antagonist at p2y12 —> block decrease in adenylyl cyclase activity and [cAMP], block sustained aggregation

Inhibit lifespan of platelet

Question 7

Side effect of clopidogrel

Answer 7

Hemorrhage, dypsnea, dizziness, nausea, headache

Question 8

What class of anti thrombotic is ticlopidine

Answer 8

Predecessor to clopidogrel, anti platelet

Question 9

Side effects of ticlopidine

Answer 9

Neutropenia, thrombotic thrombocytopenic purpura. Need to monitor WBC for first 3 months

Question 10

Compare prasugrel and clopidogrel

Answer 10

Both are prodrugs

Prasugrel fast onset while clopidogrel slow onset

Both are irreversible antagonists

Question 11

Compare Ticagrelor and clopidogrel

Answer 11

Ticagrelor is an active drug while clopidogrel is a prodrug

Ticagrelor is reversible while clopidogrel is irreversible

Question 12

What class of anti thrombotic is abcixmab

Answer 12

Anti platelet

Question 13

Mechanism of abcixmab

Answer 13

Fibrinogen receptor antagonist. Blocks fibrinogen binding to prevent platelet aggregation

Reduces ischemic complications and restenosis. Used in high risk patients undergoing angioplasty

Question 14

What combination of drugs given to patient undergoing angioplasty

Answer 14

Aspirin, heparin, abciximab

Question 15

Side effects of abciximab

Answer 15

Bleeding, thrombocytopenia

Question 16

What class of anti thrombotic is heparin

Answer 16

Anti coagulant

Question 17

How is heparin administered

Answer 17

Iv, subcutaneous

Question 18

Chemical structure of heparin

Answer 18

Polysaccharide with pentasaccharide

Question 19

Mechanism of heparin

Answer 19

Bind and activate plasma protease inhibitor anti thrombin 3, induce conformational change of at3
Enhance interaction of at3 with clotting factors 2a, 9a, 10a to form an inactive complex, inhibiting coagulation pathway

Stimulate tissue factor pathway inhibitor from endothelium, blocking conversion of factor 10 to 10a

Question 20

What is heparin used for

Answer 20

Treatment and prophylaxis of venous thromboembolism, eg Dvt pulmonary

Induce anticoagulant therapy followed by oral anticoagulant

Arterial thrombosis

Pregnant woman at risk of thrombosis because does not cross placenta

Question 21

Can heparin be used in pregnant women

Answer 21

Yes, does not cross the placenta

Question 22

Side effects of heparin

Answer 22

Narrow therapeutic window
Bleeding
Allergy (discontinue use and use Argatroban or synthetic analogue)allergy can result in heparin induced thrombocytopenia and paradoxical thromboembolism 

Long term side effects include osteoporosis, reversible transient alopecia, mineralcorticoid deficiency

Question 23

LMW heparin vs normal heparin

Answer 23

LMW heparin inhibits factor 10a more than 2a

LMW heparin causes less thrombocytopenia and osteoporosis

Question 24

What class of anti thrombotic is warfarin

Answer 24

Anticoagulant

Question 25

How is warfarin administered

Answer 25

Orally

Question 26

Warfarin is a racemic mixture. Compare a and r warfarin

Answer 26

S warfarin is 4x more potent but more rapidly metabolised by hepatic microsomal enzyme

Question 27

Mechanism of warfarin

Answer 27

Inhibit production of coagulation factor 2, 7, 9, 10 [slower onset than heparin because inhibit synthesis rather than activity]

This is done by inhibiting vitamin k epoxidase reductase, depleting vitamin K. Cannot carboxylate to form coagulation factor 2, 7, 9, 10

Question 28

Can warfarin be used in pregnancy

Answer 28

No as it crosses the placenta (unlike heparin)

Teratogenic — bone/cns defect, hemorrhagic, fetus, abortion

Question 29

Side effects of warfarin

Answer 29

Narrow therapeutic window
Bleeding
Teratogenic
Cutaneous necrosis (infarction of breast, buttock, extremities) because warfarin decreases synthesis of protein c which inhibits thrombosis at these tissues

Question 30

Which drugs enhance anticoagulant effect of warfarin

Answer 30

Metronidazole, fluconazole, cimetidine, aspirin

Question 31

What conditions enhance anti coagulant effect of warfarin

Answer 31

Hyperthyroidism, hepatic disease

Question 32

What deceases anti coagulant effect of warfarin

Answer 32

Barbiturates, vitamin k1, vit k epoxied reductase mutation, hypothyroidism

Question 33

Antidote for heparin overdose

Answer 33

Protamine sulfate, a highly basic peptide which forms stable complex with heparin

Question 34

Antidote for warfarin overfose

Answer 34

Vitamin k1 aka phytonadione to reestablish normal activity of clotting factors

Question 35

How are fibrinolytics administered

Answer 35

Iv

Question 36

Mechanism of fibrinolytics

Answer 36

Activate conversion of plasminogen to plasmin which cleaves clot

Question 37

Tpa vs streptokinase

Answer 37

Tpa cleaves clot faster than streptokinase