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Anticoagulants
Summer-Pharm II--PA
| Question | Answer |
|---|---|
| What are the two types of Thrombi? | Arterial- mainly platelets in a white clot sits on atherosclerotic plaque and Venous- Mainly fibrin and RBCs occurs when procoagulant stimuli overwhelm the natural protective mechs |
| What are the 3 components of Virchow's Triad? | 1) Venous stasis (i.e. bed-rest) 2) Hypercoagulable state (i.e. pregnancy) 3) Endothelial damage (i.e. HTN) |
| What do Arterial Thrombi tend to cause? | MI, limb gangrene, CVA |
| What do Venous Thrombi tend to cause? | DVT, PE, Postphlebitic syndrome |
| What are some medical mpatient groups at especially high risk for DVT? | Gen surgery, GYN surgery, Urol. surgery, neuro surgery, stroke, Hip fractures, Hip or knee athroplasty, major trauma, spinal injury, critical care pts |
| What are classes of antithrombic agents? Which is the most indicated? | Most indicated: Anticoagulants Antiplatelet drugs Thromboltic drugs |
| The intrinsic pathway of the clotting cascade involves_____ damage, while the extrinsic pathway involves____damage | surface, tissue |
| Prothrombin Time (PT)is defined as: | Time for blood to clot in presence of thromboplastin and CaCl measures: factors X IX VII II (1972) |
| What does INR do? | Standizes the PT (especially between hospitals) and should not normally be >1.1-1.2 INR = [Patient's measured PT (norm: 10-13s)] _____________________________________\ mean normal PT |
| What is an aPTT? | activated Partial Thromboplastin Time -used to monitor heparin -measures factors XI IX VIII VII of the intrinsic pathway and II V and X of the extrinsic |
| What effects aPTT other than heparin? | Warfarin, Thrombin inhibitors, Liver disease, or factor deficiency |
| What is D-dimer? | -a breakdown product of fibrin -marker of: -fibrinolysis -active inflammation -prothrombotic states (DVT, PE, DIC) |
| What is the normal range for D-dimer? | <0.5μg/mL or <200ng/mL |
| What are the two MC used LMWH? | Enoxaparin & Deltaparin |
| What are differences between UFH and LMWH? | ratio of Xa to IIa equal in hep; 3-4:1 in LMWH Hep less predictable dosing (30-70% bioavailable; LMWH 80-99%) clearence hepatic and renal in heparin, only renal in LMWH |
| What is the MOA of UFH? | Binds ATIII causing confirmational change to make ATIII 1000-100000x more potent to inhibit clotting factors IIa and Xa |
| How many 1/2 lives must go by before a drug is totally eliminated? | 5 1/2 |
| When is IV heparin given? When is SQ given? | to treat a clot; to prevent a clot |
| What is the target aPTT for UFH? | 60-85s for PE, venous thrombus 50-70s for acute coronary |
| What adjustment should be made to LMWH if Cr Clearence <30? | renal adjustment to dose; usu cut in 1/2 |
| What levels are used to monitor a Patient on a LMWH? | -SCr -Anti Xa -platelets |
| What adverse drug reactions occur in only UFH? in both UFH and LMWH? | UFH only: alopecia and osteoporosis UFH and LMWH: Bleeding, HIT, pain at injection site |
| What agent reverses UFH and LMWH? HOW? | Protamine-binds to (-) charged sulfa groups and cleaves at random Xa- 100% neutralized IIa- 32-44% neutralized (reverses up to 60% of LMWH effects) |
| What is Fondaparinux? | A pentassacharide anticoagulant medication that selectively binds Xa with reversible binding |
| What are indications for Fondaparinux? | -hepatic failure -patient compliance (1/2 life = 17-21 hours) -no reports of HIT -favored in orthopedics |
| What are CI of Fondaparinux? | -up-coming surgery -not ideal for renal failure (renal clearence) |
| Why might Fondaparinux be dangerous versus UFH/ LMWH? | Although NovoSeven may have potential at reversal, there is no recognized reversal agent |
| What agent is used as a "bridging therapy", usually after a heparin? | Warfarin |
| What are the Vitamin K-dependent factors? | 1972: X IX VII II |
| How is Vit K involved in clotting? | Reduced Vit K and a Prothrombin precursor interact to form oxidized Vit K and Prothrombin |
| Why does it take about 17 days to get patients to a steady state on Warfarin? | The 1/2 lives of the clotting factors are long (up to 100 hours) |
| What is the target INR for PE? valve replacement? Afib? | Afib and PE: 2-3, Valve replacement: 2.5-3.5 |
| How is Warfarin administered? metabolized? | admin: PO metab:CYP2C9 and CYP1A2 |
| Factors that increase bleeding risk | -intensity of anticoag -concommitant conditions -concommitant meds -quality of management |
| Risk factors for bleeding include? | age >75, treated HTN, ASA/ NSAIDs, Heart disease, female, severe anemia, malignancy, DDI, Risk of falling, Carrier of CYP2C9*3 gene, Hx of stroke, alcoholism or liver disease, DM, anemia |
| How should INR be adjusted if it is <5.0 (no bleeding) | lower &/or omit a dose or no change |
| How should INR be adjusted if it is 5.0-9.0 (no bleeding)? | Vit K hold Warfarin until therapeutic INR |
| How should INR be adjusted if it is >9.0? | hold Warfarin, IV Vit K with fresh plasma or prothrombin complex or recombinant factor VIIa |
| Why shouldn't Vitamin K be given liberally? | Administration of a large dose of Vit K may result in warfarin resistance for up to a week or more |
| What is HIT? | -type I and type II - an immune-mediated adverse reaction to UFH or LMWH |
| How is HIT diagnosed? | -antiP4/ heparin Antibodies -90% have thrombocytopenia |
| Why is HIT still an issue in the absence of thrombocytopenia? | Pts will still have endothelial damage that will predispose them to clots |
| How is thrombocytopenia defined? | Platelets <150,000/mm3 or reduced by 50% from baseline |
| How long are the antibodies present? How long does it take for platelet recovery? | 85-100 days for Antibody circulation 4-14 days for platelet recovery |
| What is rapid-onset HIT? | HIT that occurs d/t a second exposure to heparin/ LMWH within 100 days |
| Why do the thromboembolic complications of HIT contribute to high morb/mortality? | Without appropriate treatment ~1/2 patients will develop a new thrombosis |
| The risk of HIT left untreated, even when platelet counts return to normal is: | Thrombosis |
| The clinical presentation of HIT includes: | -DVT/PE -CVA MI -skin lesions at injection sites -Warfarin-induced venous limb gangrene -acute limb ischemia -acute systemic reactions following IV bolus |
| Diagnostic Tests for HIT include: Why are 100% specific methods not always used? | SRA (C-Serotonin-release assay) -100% specific--time consuming HIPAA (Heparin-induced platelet activation assay)-100% specific--Time consuming ELIZA (enzyme-linked immunosorbancy assay) -80% effective--faster results |
| What non-pharmacological patient care should be implimented? | -Update allergy profile -Stop all Heparin products -Stop all platelet infusions (as they amplify the building of clot complexes) |
| What Direct Thrombin Inhibitors are FDA approved? Which is not, but may be used in treatment? | FDA approved: Argatroban and Lepirudin Non-FDA: Bivalrudin |
| What pentasaccharide may be used in treatment of HIT? What is it indicated for? CI? | Fondaparinux- approved for tx/prophylaxis of thromboembolism (DVT, PE) -often used in orthopedic surgery -Heparin allergy CI-Afib and valve replacement--d/t lack of supportive data |
| What are requirements for the prescription of Warfarin? | -not a monotherapy (or initial therapy) - platelets must recover (to baseline) -aPTT therapeutic (must have 2 therapeutic readings) |
| What are indications for Agatroban? CI? | -prophilaxis/ tx thrombosis in patients with HIT CI: hepatic failure -undergoing PCI (percutaneous coronary intervention/ cath) |
| What are indications for Lepirudin? | -in pts w/ HIT and associated thromboembolic disease to prevent further complications |
| What are indications for Bivilrudin? | Patients at risk of or w/ HIT or HITTS or undergoing PCI (cath) |
| Agatroban: what is it? MOA Onset | Agatroban: what is it? synthetic thrombin inhibitor MOA: Reversible binding to thrombin catalytic site Onset: 1-3 hrs |
| Argatroban: Metabolism & Elimination 1/2 life aPTT indication | Metabolism/ Elimination: CYP450 3A4 metab/ Hepatobiliary elimination 1/2 life-24-50 min aPTT indication- aPTT q 2 hrs, 60-85s, have two therapeutic readings |
| Argatroban: Advantages | -No interaction with Heparin-dependent Ab -Short 1/2 life -Easily monitored -No dosage adjustment in renal failure |
| Argatroban: Disadvantages | -Falsely prolongs INR (scares docs) -needs dosage adjustment in hepatic failure -lack of data for SQ administration (only IV) |
| Lepirudin: What is it? MOA Onset | Lepirudin: What is it? A polypeptide direct thrombin inhibitor MOA: Irreversibly binding to catalytic sites of fibrin and thrombin Onset: 3-4 hrs |
| Lepirudin: 1/2 life elimination aPTT indications | Lepirudin: 1/2 life: 40-120 min elimination:renal aPTT indications-aPTT q 4hrs -titrate 20% -2 therapeutic readings |
| Lepirudin: Advantages | -no interactions with Heparin-dependent Ab -Short 1/2 life -Easily monitored -no dosage adjustment in hepatic failure -may be administered SQ |
| Lepirudin: Disadvantages | -Antihirudin Ab form in patients treated for >5 days (increase anticoagulants) -renally cleared -expensive |
| Bivalrudin: Approved for MOA Clearence 1/2 life | Bivalrudin: Approved for: treatment of HIT patients undergoing PCI MOA: bivalent direct thrombin inhibitor -reversible inhibition -proteolytically cleaved by thrombin Clearence: independent of organ function 1/2 life: 25 minutes |
| Summary of FDA approval: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of FDA approval: Fondaparinux-no Lepirudin-yes Argatroban-yes Bivilrudin-no |
| Summary of direct antithrombin inhibition: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of direct antithrombin inhibition Fondaparinux-no Lepirudin-yes Argatroban-yes Bivilrudin-yes |
| Summary of route of elimination: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of route of elimination Fondaparinux-renal Lepirudin-renal Argatroban-hepatic Bivilrudin-enzyme cleavage |
| Summary of 1/2 life: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of 1/2 life Fondaparinux-17-21 hr Lepirudin-1.3 hr Argatroban-39-51 min Bivilrudin-10-24 min |
| Summary of Antidote Available: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of Antidote Available: all = no |
| Summary of Monitoring: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of Monitoring: Fondaparinux-anti-Xa Lepirudin-aPTT/ ECT Argatroban-aPTT/ ACT Bivilrudin-aPTT/ ACT |
| Summary of {regnancy Category: Fondaparinux Lepirudin Argatroban Bivilrudin | Summary of Pregnancy category: all B |
Created by:
tgodin4
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