pre-IC3

Question 1

How do anti-platelets work?

Answer 1

Block platelet aggregation & primary haemostasis

Question 2

4 key steps in haemostasis & thrombosis

Answer 2

1. Vasoconstriction
2. Primary haemostasis (recruitment of platelets & clotting factors)
3. Secondary haemostasis (thrombin activation & fibrin polymerisation)
4. Clot stabilisation

Question 3

How do anti-coagulants work?

Answer 3

Block activation of fibrin polymerisation & secondary haemostasis

Question 4

When does extrinsic pathway occur

Answer 4

Tissue damage

Question 5

When does intrinsic pathway occur

Answer 5

Surface contact (e.g. with glass, collagen, or subendothelium)

Question 6

MOA for warfarin

Answer 6

Vit K antagonist; Inhibits vitamin K reductase enzyme that reactivates oxidised vitamin K

Question 7

Should vit K be active or inactive to achieve anti-coagulation? Hence should it be reduced or oxidised form?

Answer 7

Inactive form (oxidised); because the active form drives activation of clotting factors

Question 8

Warfarin is primarily metabolised in the liver by _______

Answer 8

CYP2C9

Question 9

What causes variability in warfarin response?

Answer 9

Genetic polymorphisms in CYP2C9 and vit K reductase complex subunit 1 (VKORC1)

Question 10

Adverse effects of warfarin

Answer 10

• Haemorrhage/ bleeding
• Hepatitis
• Cutaneous necrosis

Question 11

Contraindication for warfarin

Answer 11

• Active bleeding
• Severe or malignant HTN
• Severe renal/ hepatic disease
• Pregnancy

Question 12

Reversal agent for warfarin

Answer 12

Vit K

Question 13

Reversal agent for dabigatran

Answer 13

Idacizumab

Question 14

MOA for dabigatran

Answer 14

Antagonist of thrombin (factor IIa)
*Competitive & reversible

Question 15

MOA for rivaroxaban

Answer 15

Antagonist of activated factor Xa; competitive & reversible

Question 16

Reversal agent for rivaroxaban & how it works

Answer 16

Andexanet alfa; acts as recombinant factor Xa

Question 17

Which drug reduce dabigatran level?

Answer 17

Rifampin

Question 18

Which kind of drug reduce rivaroxaban level?

Answer 18

P-glycoptn & CYP3A4 inducers

Question 19

Adverse effects: rivaroxaban

Answer 19

bleeding

Question 20

Adverse effects: dabigatran

Answer 20

bleeding, GI symptoms

Question 21

Example of LMWH

Answer 21

Enoxaparin

Question 22

LMWH is more selective for factor ______ than ____

Answer 22

Xa; IIa

Question 23

MOA for heparin

Answer 23

Active heparin binds to anti-thrombin III -> inactivates thrombin (factor IIa) and factor Xa

Question 24

Which factor is thrombin?

Answer 24

factor IIa

Question 25

Reversal agent for heparin

Answer 25

Protamine sulfate (derived from salmon sperm)

Question 26

Reversal agent for LMWH

Answer 26

Protamine sulfate (but not complete reversal)

Question 27

Can heparin/ LMWH be used in pregnancy?

Answer 27

Yes

Question 28

Why is LMWH preferred over heparin?

Answer 28

- Longer t1/2 - Higher bioavailability - Lower risk of thrombocytopenia

Question 29

How does heparin induce thrombocytopenia?

Answer 29

1. Heparin binds to platelet factor 4 (PF4) on activated platelet surface 2. IgG antibody is produced against heparin-PF4 complex

Question 30

MOA for dipyridamole

Answer 30

Adenosine reuptake & PDE3 inhibitor -> incr cAMP within platelets -> inhibits platelet activation & aggregation

Question 31

What kind of preparation is dipyridamole often given as?

Answer 31

Modified-release preparation

Question 32

Adverse effects: dipyridamole

Answer 32

- Headache - Hypotension

Question 33

When to avoid dipyridamole

Answer 33

Hypotension/ severe coronary artery disease

Question 34

MOA of aspirin

Answer 34

Irreversible COX inhibitor (COX-1 > COX-2) -> inhibits platelet production of thromboxane A2

Question 35

Examples of antiplatelets

Answer 35

- Dipyridamole - Aspirin - Clopidogrel, Ticagrelor

Question 36

Is aspirin more effective at high/ low dose as an antiplatelet?

Answer 36

Low dose

Question 37

Adverse effects: aspirin

Answer 37

- Upper GI events e.g. gastric ulcer, bleeding - Incr risk of bruising/ bleeding

Question 38

Variation in onset of clopidogrel action is due to ____

Answer 38

CYP2C19-mediated metabolism of clopidogrel (prodrug) into active form

Question 39

MOA: clopidogrel / ticagrelor

Answer 39

P2Y12 inhibitor -> prevents activation of glycoptn receptors -> prevents platelet recruitment & aggregation

Question 40

Clopidogrel: Irreversible or reversible P2Y12 inhibitor?

Answer 40

Irreversible

Question 41

Ticagrelor: Irreversible or reversible P2Y12 inhibitor?

Answer 41

Reversible

Question 42

Adverse effects: Clopidogrel/ ticagrelor

Answer 42

- Bleeding (incl intracranial bleeding) - Easy bruising - Dyspepsia - Rashes - Bronchospasm - Dyspnea - Hypotension

Question 43

Adverse effects: ticagrelor

Answer 43

- Bleeding (incl intracranial bleeding) - Easy bruising - Bradycardia - Cough

Question 44

Role of fibrinolytic (thrombolytic)

Answer 44

Breaks down fibrin crosslinking to reverse clot stabilisation

Question 45

MOA: alteplase

Answer 45

Recombinant tissue-type plasminogen activators (t-PA); binds preferentially to clot-associated plasminogen, activating plasmin at the clot -> fibrinolysis

Question 46

Adverse effects: alteplase

Answer 46

- Haemorrhage/bleeding - Ventricular arrhythmias, hypotension, oedema - Cholesterol embolization, venous thromboembolism - Hypersensitivity and anaphylaxis

Question 47

Reversal agents for fibrinolytics and how they work

Answer 47

Tranexamic acid / aminocaproic acid; Compete for lysine binding sites on plasminogen and plasmin-> block fibrinolytic's interaction with fibrin

Question 48

Which drug reduces alteplase level?

Answer 48

Nitroglycerin