Anticoagulants Flashcards
Thrombus
clot adheres to vessel wall
Embolus
Intravascular clot that floats in vessel
Virchow’s triad
- Injury to blood vessel
- Altered blood flow
- Abnormal coagulability of blood
Intrinsic Coagulation cascade
XII>XIIa>XIa>IXa>VIIIa> Xa> Xa+Va> conversion of prothrombin to thrombin> fibrinogen and platelets to site of injury
Extrinsic coagulation cascade
Tissue factor+ VIIa>Xa> intrinsic pathway combination
Main event in coagulation
Conversion of soluble fibrinogen to insoluble fibrin
MOA that maintains resting state of platelet
Endothelium release prostacyclin> synthesis of cAMP> stabilizes inactive GIIb/IIIa receptor and inhibits release of granules
Platelets after injury
Adhere to collagen on subendothelial surface> release ADP, thromboxane A2 and serotonin> platelets recruited to platelet plug> Increase levels of Ca2+> Release of granules, activation of thromboxane A2 synthesis and activation of GIIb/IIIa receptors
Anticoagulants
- Heparin
- LMWH
- Warfarin
- Antithrombin III-independent anticoagulants
MOA of Heparin
- Activate antithrombin III and accelerated its action by 1000 fold. Which inhibits thrombin (IIa) and factor Xa
Onset duration of heparin
IV: immediate
Subcutaneous: 60min delay
* LMWH: longer half life
- LMWH: does not need to be monitored- predictable effects
Heparin side effects
-Haemorrhage
- Thrombocytopenia
- Hyperaldosteronism
- Hypersensitivity reactions
MO of warfarin (oral)
Inhibits vitamin K epoxide reductase> Interferes with post translational y-carboxylation of glutamic acid residues on clotting factors II, VII, IX and X> in turn reduces synthesis of vitamin K dependent coagulation factors
Drugs that reduce effect of warfarin
- Vitamin K
- Rifampicin
- Cholestyramine
Drugs that potentiate effects of warfarin
- Amiodarone
- Aspirin
- Chloral hydrate
Warfarin side effects
- Haemorrhage
- Purple toe
- induced skin necrosis
Reversing effects of warfarin
- Vitamin K
- Oral activated charcoal
- Frozen plasma
- Oral cholestyramine
antithrombin III independent hirudins
- Derived from medical leech
-Lepirudin> irreersibly bind to fibrin-binding & thrombin catalytic sites - Bivalirudin> aspirin+clopidogrel
Antithrombin III independent drugs excluding hirudins
- Dabigatran etexilate
- Rivaroxaban
- Apixaban
Antithrombin III independent drug adverse effects
- bleeding
- nausea
- anaemia
Antiplatelet drugs
- Aspirin
- Dipyridamole
- Adenosine receptor antagonist
- Glycoprotein IIb/IIIa receptor antagonist
MOA of aspirin
Irreversibly acetylates COX-I> inhibits platelet thromboxane 2 synthesis, preventing platelet aggregtion
Chronic use of aspirin
- combine with proton pump inhibitor
- Decreased reabsorption in the stomach
MOA of dipyridamole
Blocks adenosine uptake into RBC> inhibits phosphodiesterase and thromboxane A2 synthesis> inhibits platelet activation. also increases activity of aspirin.
Adenosine receptor antagonist drugs and their MOA
- Thienopyridine
- prasugrel, clopidogrel (combinations with aspirin)
- irreversible adenosine receptor antagonist> inhibit platelet aggregation
GPIIa/IIIb receptor antagonist drugs
- Abciximab
- Tirofiban
- Eptifibatide
Fibrinolytic system
Plasminogen activators> cleave plasminogen to release plasmin> plasmin fibrin and fibrinogen> fibrin degradation products (FDP)
Fibrinolytic classes and their drugs
- tPA: alteplase, retaplase
- Streptokinases: anistreplase
- Urokinase
MOA of fibrinolytics
Activate conversion of plasminogen> breaks cross-links between fibrin> dissolves clots> reopen occluded arteries
