| Flap 1 |
 |
|
| Flap 2 |
|
|
| What happens to fibrinogen in the coagulation process? |
soluble fibrinogen is transformed into insoluble fibrinogen |
| What are anticoagulants? |
Drugs that decrease the formation of fibrin clots |
| What does warfarin do? |
Oral anti-coagulant. Inhibit the hepatic SYNTHESIS of clotting factors 2, 7, 9, and 10 |
| What is warfarin? |
derivative of vitamin K |
| What does heparin do? |
IV anti-coagulant. Activation of anti-thrombin III --> Inhibit the ACTIVITY of ACTIVATED clotting factors (esp 2a and 10a) |
| Which are the endogenous anticoagulants? |
Protein C and S |
| What do the endogenous anti-coagulants do? |
cause proteolysis of factors 5a and 8a |
| Heparin and Warfarin: which is a large polysaccharide, and which is a small molecule? |
large polysaccharide = heparin; small molecule = warfarin |
| Heparin and Warfarin: which is lipid soluble, and which is water soluble? |
water soluble = heparin; lipid soluble = warfarin |
| Heparin and Warfarin: which is a vitamin K derivative? |
Warfarin |
| Heparin and Warfarin: which is given orally and which is given parenterally? |
Hep = IV/subQ, Warfarin = PO |
| Heparin and Warfarin: which is metabolized in the liver? |
Warfarin |
| Heparin and Warfarin: which has hepatic and reticuloendothelial elimination? |
Heparin |
| Heparin and Warfarin: which is 98% protein bound? |
Warfarin |
| 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) |
| Heparin and Warfarin: which can cross the placenta? |
Heparin can't. Warfarin can and is teratogenic! Pregnant people can't be on warfarin! |
| What is the mechanism of heparin? |
Binds to antithrombin III --> increases its inhibition of factors 12a, 11a, 9a, 10a, and 2a. |
| What is the mechanism of warfarin? |
Prevent gamma-carboxylation --> decrease hepatic synthesis of the vitaminK-dependent factors (2,7,9,10) |
| What are the vitaminK-dependent factors in the coagulation cascade? |
2,7,9,10, protein C & S |
| 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! |
| How to monitor warfarin? |
PT/INR |
| How to monitor heparin? |
PTT |
| How to antagnize warfarin? |
Use protamine sulfate - fast onset |
| 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 |
| Heparin and Warfarin: which to use for rapid anticoagulation for thromboses? |
Heparin |
| Heparin and Warfarin: which to use for longer-term anticoagulation for thromboses? |
Warfarin |
| Heparin and Warfarin: which to use for unstable angina? |
Heparin |
| Heparin and Warfarin: which to use for DIC? |
Heparin |
| Heparin and Warfarin: which to use for post-MI? |
Warfarin |
| Heparin and Warfarin: which to use for atrial arrhythmias? |
Warfarin |
| Heparin and Warfarin: which to use for heart valve damage? |
Warfarin |
| Heparin and Warfarin: which to use for open heart surgery? |
Heparin |
| 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). |
| Heparin and Warfarin: which can cause osteoporosis? |
Heparin |
| Heparin and Warfarin: which can cause skin necrosis if low protein C? |
Warfarin |
| Heparin and Warfarin: which causes more drug interactions? |
Warfarin (metabolized by CYP450) |
| Heparin and Warfarin: which is more likely to cause hypersensitivity? |
Heparin |
| 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 |
| What is danaparoid? |
heparin of a different structure -- safer in pts who have hypersensitivity rxn to heparin |
| How do bile acid sequestrants affect the oral absorption of warfarin? |
decreases oral absorption of heparin |
| Is warfarin an acidic or basic molecule? |
acidic |
| 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! |
| What happens to warfarin if used in conjunction with ASA/cimetidine/metronidazole/phenytoin/sulfonamides? |
warfarin's actions increased |
| What happens to warfarin if used in conjunction with barbiturates/carbamazepine/cholestyramine/rifampin/thiazides/vitamin K? |
warfarin's actions decreased! |
| What is the role of protein C and protein S? |
Endogenous anti-cogulants; they block the cofactors 5 and 8 |
| What happens when a person does not have protein C? |
hypercoagulation state |
| 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) |
| 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. |
| What is the consequence of initial warfarin treatment? |
Since protein C is depleted --> hypercoagulability --> dermal vascular thrombosis and skin necrosis |
| What are fibrinolytics? |
drugs that lyse thrombi by catalyzing plasminogen --> plasmin |
| Name some fibrinolytics |
tissue plasminogen activator (tPA), streptokinase (antibacterial) |
| When would you use thrombolytics? |
1. coronary thromboses in MI, 2. deep venous thromboses, 3. pulmonary embolism, and 4. ischemic stroke (tPA) |
| What thrombolytic would you use for ischemic stroke? |
tPA |
| What does plasmin do? |
degrades blood clots |
| What activates the conversion of plasminogen to plasmin? |
fibrin (factor 1a) as well as tPA |
| How does streptokinase work? |
Binds to both bound and free plasminogen (not clot specific) --> depletes circulating fibrinogen, factor 5 and factor 8 |
| 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 |
| What is alteplase? |
tPA - clot-specific drug. Acts on plasminogen that is bound to fibrin (fibrin is activating the plasminogen). No allergy problems) |
| 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) |
| Thrombolytics + ASA post MI |
further decrease in mortality |
| Thrombolytics + adenosine post MI |
decreases size of infarction |
| Which thrombolytic can cause hypersensitivity rxns? |
streptokinase |
| Which thrombolytic can cause hypotn? |
streptokinase |
| What are antidotes to thrombolytics? |
If excessive bleeding, can use aminocaproic and tranexamic acids - both are antifibrinolysins |
| 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 |
| Name compounds that increase platelet aggregation. |
5 ATTa: 5HT, thrombin, TXA2, a2 agonists |
| Name compounds that decrease platelet aggregation. |
cAMP PAD goes TIC toc clip CLOP: cAMP, PGI2, ASA, dipyridamole, ticlopidine, clpidogrel |
| Name some anti-platelet drugs |
1. ASA, 2. ticlopidine, 3. clopidogrel, 4. abciximab, 5. eptifibatide, 6. tirofiban |
| What is the mechanism of ASA's antiplatelet action? |
Irreversibly inhibits COX in platelets --> decrease platelet aggregation |
| What does low dose ASA do? |
prevent MI and recurrence |
| For what is ASA used prophylactically |
atrial arrhythmias and TIA's |
| What are toclopidine and clopidogrel? |
Antiplatelet drugs. |
| What is the mechanism of toclopidine and clopidogrel? |
blocks ADP receptors on platelets --> decrease activation |
| When should you use toclopidine and clopidogrel? |
as ASA alternatives for: 1. TIA's, 2. post-MI, 3. unstable angina |
| What are some adverse effects of toclopidine and clopidogrel? |
1. hemorrhage, 2. leukopenia, 3. thrombocutopenic purpura |
| What are abciximab, epitifibatide, and tirofiban? |
Antiplatelet drugs. |
| 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 |
| When to use abciximab, epitifibatide, and tirofiban? |
1. acute coronary syndromes, 2. post-angioplasty |
| What is enoxaparin? |
LMW heparin derivative |
