pre-IC3 Flashcards
How do anti-platelets work?
Block platelet aggregation & primary haemostasis
4 key steps in haemostasis & thrombosis
- Vasoconstriction
- Primary haemostasis (recruitment of platelets & clotting factors)
- Secondary haemostasis (thrombin activation & fibrin polymerisation)
- Clot stabilisation
How do anti-coagulants work?
Block activation of fibrin polymerisation & secondary haemostasis
When does extrinsic pathway occur
Tissue damage
When does intrinsic pathway occur
Surface contact (e.g. with glass, collagen, or subendothelium)
MOA for warfarin
Vit K antagonist; Inhibits vitamin K reductase enzyme that reactivates oxidised vitamin K
Should vit K be active or inactive to achieve anti-coagulation? Hence should it be reduced or oxidised form?
Inactive form (oxidised); because the active form drives activation of clotting factors
Warfarin is primarily metabolised in the liver by _______
CYP2C9
What causes variability in warfarin response?
Genetic polymorphisms in CYP2C9 and vit K reductase complex subunit 1 (VKORC1)
Adverse effects of warfarin
- Haemorrhage/ bleeding
- Hepatitis
- Cutaneous necrosis
Contraindication for warfarin
- Active bleeding
- Severe or malignant HTN
- Severe renal/ hepatic disease
- Pregnancy
Reversal agent for warfarin
Vit K
Reversal agent for dabigatran
Idacizumab
MOA for dabigatran
Antagonist of thrombin (factor IIa)
*Competitive & reversible
MOA for rivaroxaban
Antagonist of activated factor Xa; competitive & reversible
Reversal agent for rivaroxaban & how it works
Andexanet alfa; acts as recombinant factor Xa
Which drug reduce dabigatran level?
Rifampin
Which kind of drug reduce rivaroxaban level?
P-glycoptn & CYP3A4 inducers
Adverse effects: rivaroxaban
bleeding
Adverse effects: dabigatran
bleeding, GI symptoms
Example of LMWH
Enoxaparin
LMWH is more selective for factor ______ than ____
Xa; IIa
MOA for heparin
Active heparin binds to anti-thrombin III -> inactivates thrombin (factor IIa) and factor Xa
Which factor is thrombin?
factor IIa
Reversal agent for heparin
Protamine sulfate (derived from salmon sperm)
Reversal agent for LMWH
Protamine sulfate (but not complete reversal)
Can heparin/ LMWH be used in pregnancy?
Yes
Why is LMWH preferred over heparin?
- Longer t1/2
- Higher bioavailability
- Lower risk of thrombocytopenia
How does heparin induce thrombocytopenia?
- Heparin binds to platelet factor 4 (PF4) on activated platelet surface
- IgG antibody is produced against heparin-PF4 complex
MOA for dipyridamole
Adenosine reuptake & PDE3 inhibitor -> incr cAMP within platelets -> inhibits platelet activation & aggregation
What kind of preparation is dipyridamole often given as?
Modified-release preparation
Adverse effects: dipyridamole
- Headache
- Hypotension
When to avoid dipyridamole
Hypotension/ severe coronary artery disease
MOA of aspirin
Irreversible COX inhibitor (COX-1 > COX-2) -> inhibits platelet production of thromboxane A2
Examples of antiplatelets
- Dipyridamole
- Aspirin
- Clopidogrel, Ticagrelor
Is aspirin more effective at high/ low dose as an antiplatelet?
Low dose
Adverse effects: aspirin
- Upper GI events e.g. gastric ulcer, bleeding
- Incr risk of bruising/ bleeding
Variation in onset of clopidogrel action is due to ____
CYP2C19-mediated metabolism of clopidogrel (prodrug) into active form
MOA: clopidogrel / ticagrelor
P2Y12 inhibitor -> prevents activation of glycoptn receptors -> prevents platelet recruitment & aggregation
Clopidogrel: Irreversible or reversible P2Y12 inhibitor?
Irreversible
Ticagrelor: Irreversible or reversible P2Y12 inhibitor?
Reversible
Adverse effects: Clopidogrel/ ticagrelor
- Bleeding (incl intracranial bleeding)
- Easy bruising
- Dyspepsia
- Rashes
- Bronchospasm
- Dyspnea
- Hypotension
Adverse effects: ticagrelor
- Bleeding (incl intracranial bleeding)
- Easy bruising
- Bradycardia
- Cough
Role of fibrinolytic (thrombolytic)
Breaks down fibrin crosslinking to reverse clot stabilisation
MOA: alteplase
Recombinant tissue-type plasminogen activators (t-PA); binds preferentially to clot-associated plasminogen, activating plasmin at the clot -> fibrinolysis
Adverse effects: alteplase
- Haemorrhage/bleeding
- Ventricular arrhythmias, hypotension, oedema
- Cholesterol embolization, venous thromboembolism
- Hypersensitivity and anaphylaxis
Reversal agents for fibrinolytics and how they work
Tranexamic acid / aminocaproic acid;
Compete for lysine binding sites on plasminogen and plasmin-> block fibrinolytic’s interaction with fibrin
Which drug reduces alteplase level?
Nitroglycerin
