Kaplan Section 7 - Anticoagulants
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| What happens to fibrinogen in the coagulation process? | soluble fibrinogen is transformed into insoluble fibrinogen
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| What are anticoagulants? | Drugs that decrease the formation of fibrin clots
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| What does warfarin do? | Oral anti-coagulant. Inhibit the hepatic SYNTHESIS of clotting factors 2, 7, 9, and 10
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| What is warfarin? | derivative of vitamin K
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| What does heparin do? | IV anti-coagulant. Activation of anti-thrombin III --> Inhibit the ACTIVITY of ACTIVATED clotting factors (esp 2a and 10a)
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| Which are the endogenous anticoagulants? | Protein C and S
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| What do the endogenous anti-coagulants do? | cause proteolysis of factors 5a and 8a
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| Heparin and Warfarin: which is a large polysaccharide, and which is a small molecule? | large polysaccharide = heparin; small molecule = warfarin
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| Heparin and Warfarin: which is lipid soluble, and which is water soluble? | water soluble = heparin; lipid soluble = warfarin
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| Heparin and Warfarin: which is a vitamin K derivative? | Warfarin
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| Heparin and Warfarin: which is given orally and which is given parenterally? | Hep = IV/subQ, Warfarin = PO
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| Heparin and Warfarin: which is metabolized in the liver? | Warfarin
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| Heparin and Warfarin: which has hepatic and reticuloendothelial elimination? | Heparin
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| Heparin and Warfarin: which is 98% protein bound? | Warfarin
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| Heparin and Warfarin: which has a longer half life? What are the half lives? | Warfarin = 30+ hours (this is why you can take it orally at home); Heparin = 2 hr (this is why it's IV in the hosp)
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| Heparin and Warfarin: which can cross the placenta? | Heparin can't. Warfarin can and is teratogenic! Pregnant people can't be on warfarin!
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| What is the mechanism of heparin? | Binds to antithrombin III --> increases its inhibition of factors 12a, 11a, 9a, 10a, and 2a.
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| What is the mechanism of warfarin? | Prevent gamma-carboxylation --> decrease hepatic synthesis of the vitaminK-dependent factors (2,7,9,10)
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| What are the vitaminK-dependent factors in the coagulation cascade? | 2,7,9,10, protein C & S
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| What should you note about the onset of warfarin? | it has no effect on the vitaminK-dependent factors already present - it only inhibits synthesis of new factors that are vitK-dependent, so onset takes longer because the ones present have to die off!
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| How to monitor warfarin? | PT/INR
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| How to monitor heparin? | PTT
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| How to antagnize warfarin? | Use protamine sulfate - fast onset
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| How to antagnize warfarin? | Slow - give Vitamin K; fast - give fresh frozen plasma that should already have a supply of the vitaminK-dependent factors used in the coag cascade
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| Heparin and Warfarin: which to use for rapid anticoagulation for thromboses? | Heparin
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| Heparin and Warfarin: which to use for longer-term anticoagulation for thromboses? | Warfarin
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| Heparin and Warfarin: which to use for unstable angina? | Heparin
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| Heparin and Warfarin: which to use for DIC? | Heparin
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| Heparin and Warfarin: which to use for post-MI? | Warfarin
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| Heparin and Warfarin: which to use for atrial arrhythmias? | Warfarin
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| Heparin and Warfarin: which to use for heart valve damage? | Warfarin
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| Heparin and Warfarin: which to use for open heart surgery? | Heparin
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| What is a dangerous adverse effect of heparin? | Heparin-induced thrombocytopenia (HIT) - low platelet count due to the administration of heparin; thrombosis is a complication (clots).
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| Heparin and Warfarin: which can cause osteoporosis? | Heparin
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| Heparin and Warfarin: which can cause skin necrosis if low protein C? | Warfarin
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| Heparin and Warfarin: which causes more drug interactions? | Warfarin (metabolized by CYP450)
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| Heparin and Warfarin: which is more likely to cause hypersensitivity? | Heparin
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| What is the advantage of low MW heparin vs. regular heparin? | 1. longer 1/2 life, 2. less thrombocytopenia, 3. enhanced activity against factor 10a
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| What is danaparoid? | heparin of a different structure -- safer in pts who have hypersensitivity rxn to heparin
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| How do bile acid sequestrants affect the oral absorption of warfarin? | decreases oral absorption of heparin
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| Is warfarin an acidic or basic molecule? | acidic
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| If warfarin is used in conjunction with other drugs that also bind plasma proteins, what will happen? | It binds plasma proteins weakly, but extensively. If other drugs displace warfarin's binding to plasma proteins --> inc free fraction of warfarin --> increase anti-coag effect!
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| What happens to warfarin if used in conjunction with ASA/cimetidine/metronidazole/phenytoin/sulfonamides? | warfarin's actions increased
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| What happens to warfarin if used in conjunction with barbiturates/carbamazepine/cholestyramine/rifampin/thiazides/vitamin K? | warfarin's actions decreased!
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| What is the role of protein C and protein S? | Endogenous anti-cogulants; they block the cofactors 5 and 8
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| What happens when a person does not have protein C? | hypercoagulation state
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| Put these coagulation factors in increasing order of half life duration: 2a, 7a, 9a, 10a, protein C | 7 sees "C's" 9 and 10, too "2"!: 7a (8hr = 1/3 day) < protein C (14 hr = 1/2 day) < 9a (24 hr = 1 day) < 10a (40 hr ~ 2 days) < 2a (60 hr ~ 3 days)
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| When treating with warfarin, what factors are depleted first? | 7 and protein C because they have the shortest half lives. Therefore, with warfarin, the extrinsic pathway is inactivated, while the intrinsic remains active for a few days longer.
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| What is the consequence of initial warfarin treatment? | Since protein C is depleted --> hypercoagulability --> dermal vascular thrombosis and skin necrosis
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| What are fibrinolytics? | drugs that lyse thrombi by catalyzing plasminogen --> plasmin
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| Name some fibrinolytics | tissue plasminogen activator (tPA), streptokinase (antibacterial)
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| When would you use thrombolytics? | 1. coronary thromboses in MI, 2. deep venous thromboses, 3. pulmonary embolism, and 4. ischemic stroke (tPA)
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| What thrombolytic would you use for ischemic stroke? | tPA
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| What does plasmin do? | degrades blood clots
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| What activates the conversion of plasminogen to plasmin? | fibrin (factor 1a) as well as tPA
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| How does streptokinase work? | Binds to both bound and free plasminogen (not clot specific) --> depletes circulating fibrinogen, factor 5 and factor 8
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| Why wouldn't you want to use streptokinase as a thrombolytic in someone who's previously had a B-hemolytic streptococci infection? | Streptokinase will bind to antigens that it recognizes, so those with the antigens --> decreased streptokinase activity for thrombolytics
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| What is alteplase? | tPA - clot-specific drug. Acts on plasminogen that is bound to fibrin (fibrin is activating the plasminogen). No allergy problems)
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| What is the most important factor in maximizing the effectiveness of thrombolytics? | Early administration!! (> 60% decrease in mortality post-MI if used within 3 hrs)
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| Thrombolytics + ASA post MI | further decrease in mortality
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| Thrombolytics + adenosine post MI | decreases size of infarction
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| Which thrombolytic can cause hypersensitivity rxns? | streptokinase
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| Which thrombolytic can cause hypotn? | streptokinase
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| What are antidotes to thrombolytics? | If excessive bleeding, can use aminocaproic and tranexamic acids - both are antifibrinolysins
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| What is the difference between thrombolytics and antiplatelet drugs? | One breaks up the clot, while the other keeps the clot from forming in the first place
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| Name compounds that increase platelet aggregation. | 5 ATTa: 5HT, thrombin, TXA2, a2 agonists
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| Name compounds that decrease platelet aggregation. | cAMP PAD goes TIC toc clip CLOP: cAMP, PGI2, ASA, dipyridamole, ticlopidine, clpidogrel
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| Name some anti-platelet drugs | 1. ASA, 2. ticlopidine, 3. clopidogrel, 4. abciximab, 5. eptifibatide, 6. tirofiban
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| What is the mechanism of ASA's antiplatelet action? | Irreversibly inhibits COX in platelets --> decrease platelet aggregation
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| What does low dose ASA do? | prevent MI and recurrence
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| For what is ASA used prophylactically | atrial arrhythmias and TIA's
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| What are toclopidine and clopidogrel? | Antiplatelet drugs.
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| What is the mechanism of toclopidine and clopidogrel? | blocks ADP receptors on platelets --> decrease activation
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| When should you use toclopidine and clopidogrel? | as ASA alternatives for: 1. TIA's, 2. post-MI, 3. unstable angina
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| What are some adverse effects of toclopidine and clopidogrel? | 1. hemorrhage, 2. leukopenia, 3. thrombocutopenic purpura
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| What are abciximab, epitifibatide, and tirofiban? | Antiplatelet drugs.
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| What is the mechanism of abciximab, epitifibatide, and tirofiban? | antagonists that bind to glycoprotein 2b/3a receptors --> decrease aggregation by preventing the cross-linking rxn
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| When to use abciximab, epitifibatide, and tirofiban? | 1. acute coronary syndromes, 2. post-angioplasty
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| What is enoxaparin? | LMW heparin derivative
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