Anticoagulants + Antiplatelets Flashcards
When are anticoagulants used
Why
Venous thrombosis treatment and prevention
Venous thrombus consist more of fibrin than platelets due to slow flow
What is Thrombosis
Formation of solid mass of blood within circulatory system during life
What causes thrombosis
Virchows triad:
Abnormal blood flow (stagnation in venous)
Abnormal vessel wall (atheroma in arteries)
Abnormal blood components (post-op)
When are antiplatelets used
Why
Arterial thrombosis
Arterial thrombus consists of platelets>fibrin due to high flow
What are the types of anticoagulants
Warfarin Heparin Selective FXa inhibitor Direct thrombin inhibitor NOACs
What is the mechanism of action of warfarin
Inhibit synthesis of Vitamin K dependent clotting factors: II, VII, IX, X
by competitive antagonism of Vitamin K Reductase
(Inhibit activation of Vitamin K, inhibit carboxylation of glutamate required for CF synthesis)
What are indications of warfarin
INR 2-3
DVT
PE
AF
INR 2.5-4.5
Mechanical heart valve
Thrombosis with inherited thrombophilia
Recurrent thrombosis on warfarin
What are PK properties of warfarin
Good oral bioavailability (oral admin)
Slow onset/offset (heparin cover, stop 3 days)
Hepatic CYP450 metabolism (DIs)
Heavily protein bound (DIs)
Crosses placenta (teratogenic, brain haemorrhage)
How is warfarin administered
Oral - good bioavailability
Why does warfarin have slow onset/offset
How do you manage this
It takes several days for already synthesised CF to break down/new CF to be synthesised
Initial heparin cover
Withdraw 3 days prior to surgery
What effects does warfarin crossing the placenta have
Teratogenicity in 1st trimester
Brain haemorrhage in 3rd trimester
What drug interactions occur with warfarin
CYP450 enzyme inducers/inhibitors
Heavily protein bound drugs
What monitoring is required for warfarin
INR: international normalised ratio
To adjust dose
What is INR
PT/APTT
Measure of time take for blood to clot compared to average for age+gender
What types of interactions can occur with warfarin
Potentiating: Increased anticoagulatory effect
Inhibiting: decreased anticoagulatory effect
What causes potentiating DIs
CYP450 inhibitors: amiodarone, quinolone, metronidazole, acute alcohol binge, cimetidine
Heavily protein bound drugs: NSAIDs
What causes inhibiting DIs
CYP450 inducers: antiepileptics, rifampicin, St Johns wort, chronic alcohol
What are side effects of warfarin
Bleeding: epistaxis, GI bleed (unexplained anaemia), intracranial haemorrhage
Teratogenicity
How do you reverse warfarin
INR 3-6, no bleed: stop warfarin, restart when <5 INR
INR 6-8, minor bleed: IV Vitamin K (slow onset)
Major bleed: give FFP or Prothrombin complex (fast onset)
What is mechanism of action of heparin
Bind + form complex with antithrombin III by binding to pentasacharide sequence
Increase activity of ATIII
Inhibit thrombin and FXa
What are the types of heparin
Unfractionated heparin
Low molecular weight heparin
What is the mechanism of action of UH
Inhibit FXa and thrombin
Can bind to AT III and thrombin simultaneously
What is the mechanism of LMWH
Inhibit FXa only
Cannot bind to thrombin and AT III simultaneously and thrombin requires binding at 2 sites to be inactivated
What are PK properties of UH
Poor GI absorption - IV
Dose-response - non-linear
Oral bioavailability - unpredictable
Monitoring - required, APTT
What are PK properties of LMWH
Poor GI absorption - SC Dose-response - linear Oral bioavailability - predictable Monitoring - not required Metabolism - renal
What are indications of heparin
Prevention of thromboembolism: surgery, immobility Periop warfarin cover Initial warfarin cover:DVT, PE, AF MI, unstable angina Pregnancy (instead of warfarin)
What are side effects of heparin
Haemorrhage: epistaxis, GI bleed, intracranial haemorrhage
Thrombocytopenia:
heparin binds to pF4, complex cause IgG production and to form immune complex, cause platelet aggregation, thrombosis and depletion of platelets
How do you reverse heparin
Stop heparin
Give protamine
What is protamine
Positive-amine containing molecule
Binds to and neutralise sulphate group on heparin (-ve)
Dissociate heparin from at iii
What are selective FXa inhibitors
Synthetic pentasaccharide that bind to AT III with high specificity for FXa
Give examples of selective Fxa inhibitors
Fondaparinux
What are direct thrombin inhibitors
Binds directly to thrombin and inhibits Without binding to AT III
Give examples of direct thrombin inhibitors
Bivalirudin
Desirudin
When are antiplatelets used
Why
Arterial thrombosis
Arterial thrombi consists of platelets >fibrin due to high flow
What are indications of antiplatelets
Prevention and treatment of arterial thrombotic disease:
Acute coronary syndrome
Stroke
(Arterial thrombosis can occur due to atheroma rupture)
What are types of antiplatelets
Aspirin
Glycoprotein IIb/IIIa inhibitors
Platelet ADP receptor antagonist
Dipyridamol
What are NOACs
Why are they preferred
New oral anticoagulants
No monitoring required, rapid onset/offset
Give examples of NOACs
Apixaban - FXa inhibitor
Dabigatran - thrombin inhibitor
Rivaroxaban - FXa inhibitor
Why is LMWH preferred to UH
Lower risk of thrombocytopenia
No monitoring required
Only Single daily dose required (longer T1/2)
What is mechanism of action of aspirin
Irreversible inhibition of COX1
Inhibit Thromboxane A2 synthesis
(binds to TXA2 receptors to cause intracellular Ca increase and activation of GP IIb/IIIa receptors to allow fibrin binding+aggregation)
Inhibit platelet aggregation
What is mechanism of action of GLYcoprotein IIa/IIIb inhibitors
Inhibit platelet aggregation by binding to GLYcoprotein IIa/IIIb receptors on platelets
(Receptors on platelets that binds to fibrinogen for platelet aggregation)
Give examples of GLYcoprotein IIa/IIIb inhibitors
Abciximab
Tirofiban
Eptifibatide
What is mechanism of action of platelet ADP receptor antagonists
Inhibit platelet aggregation by inhibiting adp binding to its receptors on platelets
(ADP binding causes rise in [Ca]i, activation of GP IIa/IIIb, fibrinogen binding, aggregation)
Give examples of platelet adp receptor antagonists
Clopidogrel
Prasugrel
Ticagrelor
What is dipyridamol
What is its mechanism of action
Phosphodiesterase inhibitor
Inhibit platelet aggregation by increasing cAMP levels
(PDE breaks down cAMP. cAMP inhibits rise in intracellular Ca)
