Overview Anticoagulants decrease the formation of fibrin clots heparin warfarin (coumadin) bivalirudin Heparin Mechanism catalyzes the binding of antithrombin III to multiple clotting factors inactivates several factors IIa (thrombin) Xa IXa XIa XIIa Clinical use immediate anticoagulation pulmonary embolism acute coronary syndrome stroke MI DVT DIC cardiovascular surgery during pregnancy does not cross placenta Toxicity bleeding osteoporosis heparin-induced thrombocytopenia (HIT) heparin binds to platelet factor IV antibodies bind to and activate platelets leads to hypercoagulable state and thrombocytopenia hypersensitivity Pharmacology IV delivery only for therapeutic anticoagulation short half-life (2h) large, water-soluble polysaccharide low-molecular-weight heparins (e.g. enoxaparin) have advantages of longer half-lives (2-4x) less thrombocytopenia enhanced activity against factor Xa administered subcutaneously without laboratory (PTT) monitoring not easily reversible Monitoring partial thromboplastin time (PTT) Antagonist protamine sulfate positively charged to bind negatively charged heparin Warfarin (Coumadin) Mechanism ↓ hepatic synthesis of vitamin K-dependent clotting factors prevents the reduction of vitamin K, a necessary step in the synthesis of clotting factors vitamin K epoxide reductase is inhibited γ-carboxylation of clotting factors cannot occur affected clotting factors include II VII IX X protein C protein S no effect on clotting factors already present affects the extrinsic pathway Clinical use chronic anticoagulation DVT prophylaxis post-STEMI heart valve damage atrial arrhythmias Toxicity transient hypercoagulability transient protein C deficiency when beginning warfarin treatment due to short half life of protein C coagulation factors have relatively long half lives can lead to skin necrosis and dermal vascular thrombosis give heparin as you begin warfarin treatment bleeding teratogenic bone dysmorphogenesis not used in pregnancy drug interactions P450 metabolism inhibitors → ↑ PT decrease in P450 degrades less warfarin and levels rise mnemonics SICKFACES.COM Sodium valproate Isoniazid Cimetidine Ketoconazole Fluconazole Alcohol (binge drinking) Chloramphenicol Erythromycin Sulfonamides Ciprofloxacin Omeprazole Metronidazole inducers → ↓ PT increase in P450 degrades more warfarin and levels fall mnemonics BS CRAP GPS "induces" rage Barbiturates St John's Wort Carbamazepine Rifampin Alcohol (chronic) Phenytoin Griseofulvin Phenobarbital Sulfonylureas ASA, sulfonamides, and phenytoin displace warfarin from plasma proteins, leading to increased free fraction → ↑ PT cholestyramine ↓ oral absorption due to low pKa Pharmacology oral long half life (>30 hr) small, lipid-soluble Monitoring prothrombin time (PT) INR (tested PT / reference PT)^(calibration value) Antagonist vitamin K (slow onset) fresh frozen plasma (fast onset) prothrombin complex concentrates (fast onset, low volume) Lepirudin and Bivalirudin Mechanism direct inhibtors of thrombin (IIa) Clinical use alternative to heparin during heparin-induced thrombocytopenia unstable angina during percutaneous transluminal coronary angioplasty Direct Factor Xa Inhibitors (Apixaban, Rivaroxaban, Edoxaban, and Betrixaban) Mechanism noncompetitive inhibitors of factor Xa Clinical use treatment and prophylaxis for deep venous thrombosis and pulmonary embolism stroke prophylaxis for patients with atrial fibrillation Monitoring PT and PTT are not reliable Chromogenic anti-Xa assay Antagonist andexanet alfa
QUESTIONS 1 of 11 1 2 3 4 5 6 7 8 9 10 11 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.HE.13.18) A 58-year-old Caucasian male with a history of peripheral vascular disease is admitted to the hospital with a painful, pulseless foot. He is prescribed antiplatelet and anticoagulant drugs. Which of the following matches a drug with its correct characteristic? Tested Concept QID: 100534 Type & Select Correct Answer 1 Warfarin: directly inhibits thrombin 6% (16/248) 2 Heparin: activates antithrombin 3 56% (138/248) 3 Aspirin: reversibly inhibits COX-1 8% (20/248) 4 Clopidogrel: antagonizes ADP receptors on endothelial cells 26% (64/248) 5 Prasugrel: reduced risk of bleeding compared to other drugs in its class 3% (8/248) M 1 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review tested concept Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.HE.12.28) A 66-year-old male with a history of deep venous thrombosis is admitted to the hospital with shortness of breath and pleuritic chest pain. He is treated with an anticoagulant, but he develops significant hematochezia. His BP is now 105/60 and HR is 117; both were within normal limits on admission. The effects of the anticoagulant are virtually completely reversed with the administration of protamine. Which of the following was the anticoagulant most likely administered to this patient? Tested Concept QID: 101338 Type & Select Correct Answer 1 Warfarin 8% (6/76) 2 Enoxaparin 3% (2/76) 3 Heparin 88% (67/76) 4 Bivalirudin 0% (0/76) 5 Dabigatran 1% (1/76) M 3 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Review tested concept (M1.HE.12.60) A 48-year-old woman is admitted to the hospital and requires anticoagulation. She is administered a drug that binds tightly to antithrombin III. Which of the following drugs was administered? Tested Concept QID: 101370 Type & Select Correct Answer 1 Aspirin 2% (3/156) 2 Warfarin 10% (15/156) 3 Dabigatran 17% (27/156) 4 Rivaroxaban 4% (6/156) 5 Enoxaparin 67% (104/156) M 1 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review tested concept