Anti Thrombotic Flashcards
3 classes of anti thrombotic drugs
Ani platelet — inhibit platelet aggregation
Anti coagulants — coagulation factors, white to red thrombus formation
Fibrinolytics — fibrinolysis. Fibrin dissolution of red thrombus
What class of anti thrombotic is aspirin
Anti platelet
Mechanism of aspirin
Irreversible cox inhibitor, block txa2 more than pgi2 synthesis as takes 1-2weeks to make new platelets while endothelial cells take 304h to recover to restore inhibition of aggregation
Side effects of aspirin
Peptide ulcer, GI bleeding, allergy
What class of anti thrombotic is clopidogrel
Antiplatelet
What is the mechanism of clopidogrel
Prodrug
Irreversible antagonist at p2y12 —> block decrease in adenylyl cyclase activity and [cAMP], block sustained aggregation
Inhibit lifespan of platelet
Side effect of clopidogrel
Hemorrhage, dypsnea, dizziness, nausea, headache
What class of anti thrombotic is ticlopidine
Predecessor to clopidogrel, anti platelet
Side effects of ticlopidine
Neutropenia, thrombotic thrombocytopenic purpura. Need to monitor WBC for first 3 months
Compare prasugrel and clopidogrel
Both are prodrugs
Prasugrel fast onset while clopidogrel slow onset
Both are irreversible antagonists
Compare Ticagrelor and clopidogrel
Ticagrelor is an active drug while clopidogrel is a prodrug
Ticagrelor is reversible while clopidogrel is irreversible
What class of anti thrombotic is abcixmab
Anti platelet
Mechanism of abcixmab
Fibrinogen receptor antagonist. Blocks fibrinogen binding to prevent platelet aggregation
Reduces ischemic complications and restenosis. Used in high risk patients undergoing angioplasty
What combination of drugs given to patient undergoing angioplasty
Aspirin, heparin, abciximab
Side effects of abciximab
Bleeding, thrombocytopenia
What class of anti thrombotic is heparin
Anti coagulant
How is heparin administered
Iv, subcutaneous
Chemical structure of heparin
Polysaccharide with pentasaccharide
Mechanism of heparin
Bind and activate plasma protease inhibitor anti thrombin 3, induce conformational change of at3
Enhance interaction of at3 with clotting factors 2a, 9a, 10a to form an inactive complex, inhibiting coagulation pathway
Stimulate tissue factor pathway inhibitor from endothelium, blocking conversion of factor 10 to 10a
What is heparin used for
Treatment and prophylaxis of venous thromboembolism, eg Dvt pulmonary
Induce anticoagulant therapy followed by oral anticoagulant
Arterial thrombosis
Pregnant woman at risk of thrombosis because does not cross placenta
Can heparin be used in pregnant women
Yes, does not cross the placenta
Side effects of heparin
Narrow therapeutic window Bleeding Allergy (discontinue use and use Argatroban or synthetic analogue)allergy can result in heparin induced thrombocytopenia and paradoxical thromboembolism
Long term side effects include osteoporosis, reversible transient alopecia, mineralcorticoid deficiency
LMW heparin vs normal heparin
LMW heparin inhibits factor 10a more than 2a
LMW heparin causes less thrombocytopenia and osteoporosis
What class of anti thrombotic is warfarin
Anticoagulant
How is warfarin administered
Orally
Warfarin is a racemic mixture. Compare a and r warfarin
S warfarin is 4x more potent but more rapidly metabolised by hepatic microsomal enzyme
Mechanism of warfarin
Inhibit production of coagulation factor 2, 7, 9, 10 [slower onset than heparin because inhibit synthesis rather than activity]
This is done by inhibiting vitamin k epoxidase reductase, depleting vitamin K. Cannot carboxylate to form coagulation factor 2, 7, 9, 10
Can warfarin be used in pregnancy
No as it crosses the placenta (unlike heparin)
Teratogenic — bone/cns defect, hemorrhagic, fetus, abortion
Side effects of warfarin
Narrow therapeutic window
Bleeding
Teratogenic
Cutaneous necrosis (infarction of breast, buttock, extremities) because warfarin decreases synthesis of protein c which inhibits thrombosis at these tissues
Which drugs enhance anticoagulant effect of warfarin
Metronidazole, fluconazole, cimetidine, aspirin
What conditions enhance anti coagulant effect of warfarin
Hyperthyroidism, hepatic disease
What deceases anti coagulant effect of warfarin
Barbiturates, vitamin k1, vit k epoxied reductase mutation, hypothyroidism
Antidote for heparin overdose
Protamine sulfate, a highly basic peptide which forms stable complex with heparin
Antidote for warfarin overfose
Vitamin k1 aka phytonadione to reestablish normal activity of clotting factors
How are fibrinolytics administered
Iv
Mechanism of fibrinolytics
Activate conversion of plasminogen to plasmin which cleaves clot
Tpa vs streptokinase
Tpa cleaves clot faster than streptokinase
