Anticoagulants + Antiplatelets Flashcards by Minhee Kim

When are anticoagulants used

Why

Venous thrombosis treatment and prevention

Venous thrombus consist more of fibrin than platelets due to slow flow

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What is Thrombosis

Formation of solid mass of blood within circulatory system during life

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What causes thrombosis

Virchows triad:
Abnormal blood flow (stagnation in venous)
Abnormal vessel wall (atheroma in arteries)
Abnormal blood components (post-op)

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When are antiplatelets used

Why

Arterial thrombosis

Arterial thrombus consists of platelets>fibrin due to high flow

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What are the types of anticoagulants

Warfarin
Heparin
Selective FXa inhibitor
Direct thrombin inhibitor 
NOACs

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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)

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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

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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)

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How is warfarin administered

Oral - good bioavailability

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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

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What effects does warfarin crossing the placenta have

Teratogenicity in 1st trimester

Brain haemorrhage in 3rd trimester

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What drug interactions occur with warfarin

CYP450 enzyme inducers/inhibitors

Heavily protein bound drugs

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What monitoring is required for warfarin

INR: international normalised ratio

To adjust dose

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What is INR

PT/APTT

Measure of time take for blood to clot compared to average for age+gender

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What types of interactions can occur with warfarin

Potentiating: Increased anticoagulatory effect
Inhibiting: decreased anticoagulatory effect

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What causes potentiating DIs

CYP450 inhibitors: amiodarone, quinolone, metronidazole, acute alcohol binge, cimetidine
Heavily protein bound drugs: NSAIDs

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What causes inhibiting DIs

CYP450 inducers: antiepileptics, rifampicin, St Johns wort, chronic alcohol

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What are side effects of warfarin

Bleeding: epistaxis, GI bleed (unexplained anaemia), intracranial haemorrhage
Teratogenicity

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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)