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109 Cards in this Set
- Front
- Back
What are the 3 classes of Anticlotting Drugs?
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- Anticoagulants
- Thrombolytics - Antiplatelet Drugs |
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What are the 3 classes of Proclotting Drugs?
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- Replacement Factors
- Vitamin K - Antiplasmin Drugs |
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What are the 3 main types of Anticoagulants?
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1.) Heparins
2.) Direct Thrombin Inhibitors 3.) Warfarin |
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What are the 2 Thrombolytic drugs?
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1.) t-PA Derivatives
2.) Streptokinase |
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What are the 4 Antiplatelet drugs?
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1.) Aspirin
2.) Glyocoprotein IIb/IIIa Inhibitors 3.) ADP inhibitors (clopidogrel) 4.) PDE/adenosine uptake inhibitors |
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What are the 3 classes of Anticlotting Drugs?
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- Anticoagulants
- Thrombolytics - Antiplatelet Drugs |
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What are the 3 classes of Proclotting Drugs?
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- Replacement Factors
- Vitamin K - Antiplasmin Drugs |
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What are the 3 main types of Anticoagulants?
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1.) Heparins
2.) Direct Thrombin Inhibitors 3.) Warfarin |
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What are the 2 Thrombolytic drugs?
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1.) t-PA Derivatives
2.) Streptokinase |
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What are the 4 Antiplatelet drugs?
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1.) Aspirin
2.) Glyocoprotein IIb/IIIa Inhibitors 3.) ADP inhibitors (clopidogrel) 4.) PDE/adenosine uptake inhibitors |
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What can you use to neutralize the acidity of Heparin
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Protamine
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How is Heparin administered and why?
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i.v. or s.c.
to avoid the risk of hematoma associated with intramuscular |
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What is Enoxaparin?
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Low molecular weight fractions of heparin
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Why are LMW Heparins better?
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They have a greater biovailability + longer durations of action than unfractionated heparin
Can be given less frequently throughout the day, like 1-2 times daily. |
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What is Fondaparinux?
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A small syntetic drug that is biologically active pentasaccharide present in unfractionated and LMW heparins.
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MOA of Heparin
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Binds to Antithrombin III, making it proteolyze Thrombin and Xa 1000-times faster
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What is Antithrombin III?
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An endogenous anticlotting protein that irreversibly inactivates thrombin and factor Xa. Its enxymatic action is markedly accelerated by Heparins
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How long does it take for heparin to take effect?
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Immediately
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How do you monitor the actio nof Heparin?
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aPTT
activated partial thromboplastin time |
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What is the difference in MOA between LMW heparins/fondaparinux and unfractionated heparin?
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LMW's bind to ATIII, with the same effect on Xa, but do not affect thrombin.
Therefore, aPTT tests aren't as reliable in measuring their anticoagulant effect. Esp. in renal failure, b/c clearance is decreased. |
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Clinical Use of Heparins
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- DVT's
- Pulmonary Embolism - Acute MI - w/ thrombolytics for revascularization - w/ glycoprotein IIb/IIIa inhibitors during angioplasty and placing stents |
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What is Heparin the DOC for?
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Pregnant ppl who need an anticoagant
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SE of Heparin
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- XS bleeding
- Hemorrhagic stroke - Transient/severe thrombocytopenia (unfractionated; HIT) - Osteoporosis (longterm use) |
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Describe the effect that Protamine has on the different kinds of heparin
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Used on UNfractionated heparin the most
Only partially works on LMW Heparins No effect on Fondaparinux |
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What are the 4 kinds of Direct Thrombin Inhibitors?
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Lepirudin
Desirudin Bivalirudin Argatroban |
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Where are direct thrombin inhibitors extracted from?
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proteins made by Hirudo medicinalis, the medicinal Leech.
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What is the difference between Lepirudin and Desirudin & Bivalirudin?
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Lepirudin is the recombinant form of the leech protein Hirudin
Desirudin&Bivalirudin are modified forms of hirudin. |
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MOA of Lepirudin, Desirudin, and Bivalrudin
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Bind simultaneously to the active site of Thrombin and Thrombin substrates.
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MOA of Argatroban
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Binds solely to the active site of thrombin
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How are Direct Thrombin Inhibitors different from Heparins
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DTI's inhibit both the soluble thrombin and the thrombin enmeshed within developing clots
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Which DTI also inhibits platelet activation?
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Bivalrudin
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Clinical use of DTI's
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In pts with Heparin-induced thrombocytopenia, as an alternative to heparin
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This drug is also used with aspirin during percutaneous coronary angioplasty
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Bivalirudin
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How do you monitor the used of DTI's?
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aPTT
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SE of DTI's
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- Bleeding
- No reversal agent exists. - Prolonged Lepirudin --> anaphylactic rxns |
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Describe the metabolism of Warfarin
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Binds to plasma proteins > 99% and its eliminated by P450
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MOA of Warfarin
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Interferes with the posttranslational modification of clotting factors in the liver.
Takes much longer to take effect b/c the clotting factors have a t1/2 of 8-60 h, takes longer to get rid of them |
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Clinical Use of Warfarin
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Chronic anticoag & everything heparin's uesd for
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Warfarin is Contraindicated in
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Pregnancy
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SE of Warfarin
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- Bleeding
- Hypercoagulability early in does, due to Protein C deficiency. Protein C has a shorter halfl-life - Bone defects and hemorrhage in fetus |
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Drug interactions of Warfarin
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P450 INDUCERS: carbamazepine, pheyntoin, rifampin, barbiturates
* Increase Warfarin's CLEARANCE * * Reduce anticoag. effect * P450 INHIBITORS: amiodarone, SSRI's, cimetidine * Reduce Warfarin's Clearance * * Increase the anticoag effect * |
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What are the 2 kinds of Thrombolytic drugs?
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1.) forms of t-PA (alteplase, tenecteplase, reteplase)
2.) Streptokinase |
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What is plasmin?
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A Fibrinolytic enzyme that degrades clots by splitting fibrin into fragments.
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How do thrombolytic enzymes work?
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Catalyze the conversion of Plasminogen to Plasmin
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MOA of t-PA
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- Directly converts plasminogen to plasmin
- Has selectivity for plasminogen already bound to fibrin (i.e. in a clot) |
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What is alteplase?
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Normal human plasminogen activator
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What is reteplase?
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- a mutated form of human t-PA
- w/ similar effects but a slightly faster onset of action and longer duration of action |
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What is tenecteplase?
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Another mutated form of t-PA wtih lonfer half life
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MOA of Streptokinase
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- Not an enzyme itself, but forms a complex w/ endogenous plasminogen.
- the Plasminogen in the complex changes conformation to convert free plasminogen to plasmin - no selectivity for fibrin-bound plasminogen |
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Clinical Uses of Thrombolytics agents
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- An alternative to percutaneous coronary angioplasty in emergency coronary artery thrombosis(w/in 6h)
- Very prompt use (w/in 3h) is good for ppl with ischemic stroke - Pulmonary Emolism |
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What should you make sure before you adminster t-PA?
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Cerebral hemorrhage should be ruled out
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SE of thrombolytic agents, t-PA and streptokinase
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- Bleeding
- Cerebral Hemorrhage (most serious) - Severe Allergies in pts who had strepp infection and take streptokinase |
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Platelet aggregation is especialy important in which circulation
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Arterial
Esp Coronary and cerebral |
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What are some triggers of platelet aggregation?
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- Thromboxane
- ADP - Thrombin - Fibrin |
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What are some inhibitors of platelet aggregation?
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Things that increased intracellular cAMP:
- prostacyclin - adenosine |
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What are abciximab, tirofiban, adn eptifibatide
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Glycoprotein IIb/IIIa receptor inhibitors
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What are clopidogrel and ticlopidine?
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Antagonists of ADP receptors
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What are dipyridamole and cilostazol?
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Inhibitors of phosphodiesterase 3
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What is Thromboxane A2?
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A potent STIMULATOR of Platelet aggregation
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MOA of Aspirin
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Irreversibly Inhibits COX, which is used to form Thromboxane, so inhibits platelet aggregation.
Lasts long, b/c platelets can't make their own proteins. |
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MOA of Abciximab
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Monoclonal Antibody
Reversibly inhibits the Fibrin binding to Glycoprotein IIb/IIIa receptor on the platelet |
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What is the Glycoprotein IIb/IIIa receptor
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A cell surface protein involved in platelet cross-linking
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MOA of eptifibatide and tirofiban
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Reversibly block the glycoprotein IIb/IIIa
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MOA of Clopidogrel and Ticlopidine
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Irreversibly inhibits Platelet ADP receptor
Thus prevents ADP-mediated platelet aggregation |
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MOA of Dipyridamole and Cilostazol
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1.) Phosphediesterase 3 degrades cAMP. These drugs inhibit phosphodiesterase, thus increasing levels of cAMP which inhibits platelet aggregation.
2.) Inhibit the uptake of adenosine by endothelial cells adn RBCs, thus increasing plasma [adenosine]. Adenosine increases platelet cAMP via platelet adenosine A2 recetors |
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Clinical Use of Aspirin
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- to Prevent further infarcts in pts wtih 1 or more MI's/prevent first MI
- to Prevent TIAs, ischemic stroke, and thrombotic events |
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Clinical Use of Glycoprotein IIb/IIIa receptors inhibitors
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- Prevent restenosis after Coronary angioplasty
- Acute coronary syndomes: unstable angina & non-Q-wave Acute MI |
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Clinical Use of Clopidogrel and Ticlopidine
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- Preventing TIA's and ischemic strokes (esp in pts intolerant of Aspirin)
- Clopidogrel usu used to prevent thrombosis after CA stent |
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Clinical use of Dipyridamole and Cilostazol
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- Intermittent Claudication
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SE of Aspirin
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- GI and CNS effects
- Enhance the effects of other anticlotting agents |
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SE of Glycoprotein IIb/IIIa receptor inhibitors
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- Bleeding
- Thrombocytopenia (chronic use) |
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SE of Ticlopidine
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*Rarely used*
- Bleeding in 5% of pts. - Neutropenia 1% - Thrombotic thrombocytopenic purpura (TTP) |
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SE of Dipyradimole & Cilostazol
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- Headaches
- Palpations |
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How do you treat thrombocytopenia
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Administration of Platelets or Oprelvekin
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What is Oprelvekin
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The recombinant form of megakaryocyte growth factor IL-11
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How do you treat Vitamin K deficiency?
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Phytonadione (Vitamin K1)
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Clinical uses of Phytonadione
(Vitamin K1) |
- Vitamin K Deficiency
- All newborns - To reverse the anticoag effect of XS warfarin |
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What agents do you use to treat Hemophilia?
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- Fresh plasma
- Factor VIII (Hemophilia A) - Factor IX (Hemophilia B) |
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What do you used to prepare pts w/ von Willebrand disease and Hemophilia A for eective surgery? Why?
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Desmopressin acetate
Its a V2 agonist, and increases plasma conc. of vWF and VIII |
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What the three Antiplasmin agents?
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- Aminocaproic acid
- Tranexamic acid - Aprotinin |
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MOA of Aminocaproic acid and tranexamic acid
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Inhibit plasminogen activation
So inhibits fibrinolysis |
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MOA of Aprotinin
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Serine protease inhibitor
So inhibits fibrinolysis by plasmin and by the plasmin-streptokinase |
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Clinical Use of Aprotinin
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Pts undergoing Coronary artery bypass grafting who are at risk of bleeding
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SE of Aprotinin
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Increased risk of MI, Stroke, Renal damage
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* Vitamin K dependent anticoagulant
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* Warfarin (PT)
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* Warfarin is contraindicated in
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* Pregnancy
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* Anticoagulant of choice for Pregnancy
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* Heparin
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* Heparin (PTT) increases activity of
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* Antithrombin 3
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* Route of administration of warfarin
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* Oral
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* Routes of adminstration of heparin
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* i.v. and i.m. (only LMW)
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* SE of both warfarin and heparin
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* Bleeding
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* SE of Heparin
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* Heparin Induced thrombocytopenia
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* Alternative anticoagulant used if HIT develops
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* Lepirudin
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* Antidote to reverse actions of Warfarin
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* Vitamin K or Fresh Frozen Plasma
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* Antidote used to reverse actions of Heparin
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* Protamine sulfate
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* MOA of aspirin
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* Irreversibly blocks COX
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* Agent used to treat MI and to reduce incidence of subsequent MI
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* Aspirin, Metoprolol
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* SE of Aspirin
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* GI Bleeding
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* Antiplatelet drug reserved for pts allergic to Aspirin
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* Ticlopidine
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* SE of Ticlopidine
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* Neutropenia and agranulocytosis
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* Effective in preventing TIA's
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* Clopidogrel and ticlopidine
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* Prevents thrombosis in pts with artificial heart valve
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* Dipyridamole
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* Blocks glycoprotein IIb/IIIa involved in platelet cross linking
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* Abciximab, tirofiban, eptifibatide
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* MOA of thrombolytics
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* Degradation of fibrin clots and are administered IV
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* Thrombolytics are used for
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* Pulmonary Embolism and DVT
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* Thrombolytic that can cause an allergic reaction
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* Streptokinase
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* Thrombolytic used for acute MI and ischemic (non-hemorrhagic) CVA
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* Tissue plasmin activator (t-PA)
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* SE of t-PA
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* Cerebral Hemorrhage
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* Antidote for thrombolytics
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* Aminocaproic acid
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