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Antithrombotic drugs - Coggle Diagram

- - - - Mechanism: NSAID
        
        irreversible acetalytion of COX enzyme x-> blocking TXA2 synthesis by platelet & it’s release —> prevent platelet aggregation & vasoconstriction
        
        Complete inactivation of platelets occurs w/ 75mg of aspirin given daily.
        
        Resulting suppression of platelet aggregation last for the life of the platelet, which is approx. 7 to 10 days (irreversible inhibitor)
      - Uses:
        
        Prophylaxis in transient cerebral ischemia
        
        Reduce incidence of recurrent MI
      - Adverse effects:
        bleeding time prolonged, cause complications, eg. Inc incidence of hemorrhagic stroke & GI bleeding esp. at higher doses
  - - - Mechanism:
        inhibit binding of ADP to receptors on platelets (ADP blockers) so inhibit activation of GP IIb/IIIa receptors req. for platelets to bind to fibrinogen & each other
      - Uses:
        
        Prevention of atherosclerotic events
        2.Prophylaxis of thrombotic events in acute coronary syndromes
        
        Percutaneous coronary intervention (PCI) w/ or w/o coronary stenting
      - Pharmacokinetics
        
        Clopidogrel
        
        Prodrug that require CYP 2C19 to give its active metabolite
        CI in Patient w/ genetic polymorphism of CYP 2C19 “poor metabolizers”
        or receive drugs that inhibit CYP 2C19 such as omeprazole & esomeprazole
      - Adverse effects:
        
        Prolonged bleeding for which there is no antidote
        
        Ticlopidine associated w/ severe hematologist reactions that limit its use eg. Neutropenia. CBC every 2 weeks from 2nd week to 3rd month of treatment, & any time they develop an infection.
        
        Clopidrogel causes fewer adverse reactions, and the incidence of neutropenia is lower.
  - - - Mechanism:
        
        Abciximab: a monoclonal antibody to GP IIb/IIIa that blocks the binding of fibrinogen so blocks final pathway of platelet aggregation.
        intravenously, along w/ heparin & aspirin, as an adjunct to percutaneous coronary interventions for prevention of cardiac ischemic complications.
      - Adverse effects:
        
        Bleeding esp. if used w/ anticoagulant
  - - - Mechanism: dipyridamole is a coronary vasodilator, inhibits phosphodiesterase enzyme —> inhibit degradation of cAMP level—>decrease release of arachidonic acid (precursor of TXA2) from membrane phospholipids—> dec. TXA2 synthesis.
        Prostacyclin induces adenylate Cyclades and therefore inc. synthesis of cAMP, elevated levels of intracellular cAMP , dec. intracell. Calcium—> dec. platelet adhesion to thrombogenic surfaces & inhibit platelet aggregation by inhibiting release of mediators of aggregation
      - Uses: Stroke prevention, usually w/aspirin
      - Adverse effects:
        
        Headache & orthostatic hypotension esp. if administered w/ IV
    - - Inhibit phosphodiesterase type III —> inc. cAMP level in platelets & vascular tissues —> dec. TXA2 synthesis prevent platelet aggregation & promotes vasodilation of BVs
      - Adverse effects: Headache & GI side effects (dyspepsia, diarrhea, abdominal pain)
- - - - Mechanism: interacts w/ anti-thrombin III alters its mol. configuration —> activates antithrombin III (AT-III) 1000-4000 times more potent —> rapid inactivation of coagulation factors: thrombin & factor Xa
      - Uses:
        
        Treat thromboembolic diseases, deep vein thrombosis, pulmonary embolism
        
        Prophylaxis of postoperative venous thrombosis in patients undergoing surgery (ie. Hip replacement) & those w/acute MI
        
        Prophylactically prevent clotting in arterial & heart surgery, during blood transfusions & in renal dialysis & blood sample collection
        
        Anticoagulants of choice for treating pregnant women, because they do not cross placenta due to their large size & negative charge.
      - Adverse effects:
        
        Bleeding
        
        Heparin induced thrombocytopenia due to heparin platelet factor 4 complex
        
        Osteoporosis
        
        Alopecia
        
        Hypersensitivity
      - Facts:
        
        naturally occurring sulfates monosaccharides in mast cells, basophils, vascular endothelium.
        
        Mix of polymers of varying weights
        
        for use obtained from porcine intestine/ bovine lung
        water soluble
        
        Given parenterally (IV, SC), not IM or oral because degraded by gastric acid/ painful hematoma
    - - Pharmacokinetics:
        
        Formed from Heparin that undergo chemical/ enzymatic degradation
        
        longer half life (once daily), less thrombocytopenia
        
        same as heparin but it’s complex with ATxIII has less affinity for thrombin ; mainly factor Xa
        
        Typically administered SC injection
        
        More predictable dose response relationship, 2-4 times longer plasma half life & improved bioavailability after SC administration compared to UFH, due to red. binding to plasma proteins macrophages & endothelial cell.
    - - Pharmacokinetics
        
        Synthetic pentasaccharide that binds ATIII w/ high specific activity, resulting in efficient inactivation of FXa only.
        
        Drug well absorbed from SC route w/ predictable pharmacokinetic profile & therefore req. less monitoring than heparin
        long half life, so given once daily
  - - - Dabigatran
        
        Given w/ Idaruxizumab monoclonal antibody to counteract bleeding caused by it
    - - Argatroban
      - Bivalirudin & Desirudin
  - - - Oral inhibitors of factor Xa, bind to its active site, preventing its ability to convert prothrombin to thrombin
  - - - Mechanism: inhibits the hepatic synthesis of coagulation factors II, VII, IX & X, whose carboxylation is dependent on a reduced form of Vitamin K- dependent factors
        Warfarin inhibits Vit. K epoxide reductase —> blocks reduction of oxidized vitamin k x-: prevent vit. K depend. carboxylation of clotting factors
      - Pharmacokinetics:
        
        Narrow therapeutic index
        
        Warfarin has delayed onset of action (72-96 hours) time to deplete pool of circulating clotting factors after synthesis is inhibited
      - Uses: 1. Prevention & treatment of DVT & PE
        
        Stroke prevention in setting of atrial fibrillation and/ or prosthetic heart valves & antiphospholipid syndrome
        
        prevention of DVT during orthopedic or gynecology surgery
      - Adverse effects:
        
        Hemorrhage
        
        skin lesions & necrosis
        
        Purple toe syndrome
        
        Warfarin is tetratogenic & should never be used during pregnancy
        
        fetal warfarin syndrome: malformations result from antagonism of vitamin K dependent maturation of bone proteins during process in which these proteins are carboxylated in same manner as clotting factors —> cause bone deformities & various birth defects
      - Facts: coumarin compound, small molecule, lipid soluble deriv. Of Vit. K,oral anticoagulant, cross placental barrier, dietary Vit. K can affect warfarin activity
        anything that dec. availability of Vit. K eg. Antibiotics, Vit. E, fish oils, enhance its affects
      - CI: in surgery, patients on long term warfarin temporarily discontinued & short term direct anticoagulant is used