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pharm exam 2
antiplatelets, anticoagulants, & fibrinolytics
| Question | Answer |
|---|---|
| thrombin is the link between | tissue injury, coagulation and platelet response |
| thrombin is a | critical mediator in coagulation and elicits multiple responses in platelets and other cells |
| 3 steps a platelet does | adhesion, activation, aggregation |
| when plaque ruptures, | platelets adhere to the site of tissue damage which makes them become activated |
| once platelets are activated, | they change shape and have receptors |
| after platelets are activated, | they aggregate |
| thrombosis is the formation of | a blood clot |
| thrombus | immobile clot, not moving |
| embolus | drifting blood clot, traveling |
| embolism | blockage due to embolus |
| thrombosis can occur in | any artery, vein, heart chamber, heart valve |
| thrombosis can lead to | DVT, PE, MI, CVA, or stroke |
| warfarin interferes mostly with | vitamin K dependent factors - 2, 7, 9, 10 |
| direct thrombin inhibitors (DTIs) | inhibits Xa or II, depending on their class |
| LMWH heparin | binding to antithrombin makes it more effective and inhibits thrombin |
| OTC aspirin inhibits | TXa which leads to less platelet activation |
| P2Y12 inhibitors | receptors that bind to ADP |
| oral antiplatelets | aspirin (ASA) P2Y12 inhibitors: clopidogrel, prasugrel, ticagrelor PDE-3 inhibitors: cilostazol, dipyridamole, dipyridamole/ASA |
| parenteral antiplatelets | IV P2Y12 inhibitor: cangrelor Glycoprotein IIb/IIIa inhibitors: Eptifibatide, tirofiban |
| indications for antiplatelets | ASCVD - secondary and primary prevention ACS - like STEMI or NSTEMI percutaneous coronary intervention (PCI) acute ischemic stroke |
| secondary prevention | preventing recurrent event |
| primary prevention | preventing first even |
| aspirin mechanism | Inhibits COX-1 enzyme leading to less XA2-mediated platelet activation which leads to less coagulation |
| do you need a prescription for ASA | no, baby aspirin = 81 mg |
| ASA is used to treat | Coronary artery disease (CAD) Peripheral arterial disease (PAD) Acute coronary syndrome (ACS) Percutaneous coronary intervention (PCI) Acute ischemic stroke |
| adverse events/monitoring for ASA | bleeding rash GI events - upset stomach and nausea |
| P2Y12 inhibitors | Clopidogrel, Prasugrel, Ticagrelor, Cangrelor |
| Prasugrel, Ticagrelor are more potent that | Clopidogrel |
| P2Y12 inhibitors used for | dual anti-platelet therapies, used with ASA |
| mechanism of P2Y12 inhibitors | inhibits ADP from binding to P2Y12 receptor leading to antiplatelet effect |
| indications for P2Y12 inhibitors | cardiovascular, neurovascular and peripheral vascular |
| P2Y12 inhibitors adverse events/monitoring | bleeding dyspnea, bradycardia (ticagrelor) - rare! |
| oral anticoagulants | warfarin Direct thrombin inhibitors: Dabigatran Selective factor Xa inhibitors: Rivaroxaban, Apixaban, Edoxaban |
| Direct thrombin inhibitors and Selective factor Xa inhibitors are | direct oral anticoagulants (DOACs) - dont require a cofactor |
| parenteral anticoagulants | heparins: Unfractionated heparin (UFH), low-molecular-weight heparins (LMWH) - Enoxaparin, Dalteparin Selective factor Xa inhibitors: fondaparinux |
| parenteral anticoagulants seen if pt cant take heparin due to HIT or allergy | direct thrombin inhibitors - Argatroban, Bivalirudin |
| indications for anticoagulation | venous thromboembolism - DVT, PE ACS severe LV systolic dysfunction intra cardiac thrombus heart valve replacement atrial arrythmias - afib, atrial flutter malignancy |
| warfarin class | vitamin K antagonists (VKA) |
| warfarin mechanism | Inhibits VKORC1 (protein target in the liver), which is responsible for activation of vitamin K-dependent clotting factors (II, VII, IX, X) and protein C and S |
| initial dose of warfarin can inhibit | clotting factors (II, VII, IX, X) |
| Adverse events/monitoring for warfarin | Bleeding (PT/INR) Skin necrosis Purple toe syndrome |
| bleeding (PT/INR) | PT- prothrombin time INR- international normalized ratio |
| warfarin and bleeding (PT/INR) | warfarin has narrow therapeutic window so monitor INR - should be 1 sec till blood sample forms clot |
| warfarin drug-drug interactions | Abx NSAIDs - inc risk of bleeding Vit k - less effective steroids alcohol Vit e statins |
| vit k is an | antidote to warfarin |
| indications of warfarin | Tx of DVT, PE prevention of systemic embolism mechanical prosthetic valves (aortic and mitral) |
| warfarin adverse effects | Unusual bleeding (stool, coughing)/bruising (in they fall or hit head) |
| warfarin pt counseling | Signs/symptoms of clotting INR monitoring and dosage changes Diet: consistent intake of dietary vitamin K (IN MODERATION) Common drug interactions Tablet identification |
| warfarin onset | Slow onset of effect, therefore, requiring parenteral anticoagulant for “bridging” |
| warfarin monitoring INR | daily until therapeutic for > 2 days, then 2m to 3 times weekly, then less often |
| warfarin is the most common medication associated with | bleeding complications |
| warfarin is often help for | procedures or line placements (i.e., until INR < 2 but can vary) |
| when is warfarin generally administered | in the evening per institutional recommendations (standard administration time) |
| warafin reversal | Discontinue/hold warfarin Vitamin K1 - if there is bleeding Fresh frozen plasma (FFP) Prothrombin complex concentrates - 3-factor or 4-factor Recombinant factor VIIa |
| Fresh frozen plasma (FFP) is used | for large volume, if there is a more concerning blood loss |
| Prothrombin complex concentrates - 3-factor or 4-factor | more concentrated so good for fluid overload, gives 2, 7, 9, 10 back! |
| DOACs are preferred to | warfarin because they are less likely to have bleeding and are safer |
| DOACs examples | direct thrombin inhibitors - dabigatran Selective factor Xa inhibitors - Rivaroxaban, Apixaban, Edoxaban |
| DOACs should not be used for certain pt populations | mechanical heart valve, severe mitral stenosis, advanced kidney disease (may warrant dose adjustment), hypercoagulable states |
| DOACs do not require | hematologic monitoring, unlike warfarin - do not have hematologic lab marker like warfarin does (INR) |
| DOAC cost | remains a major barrier for many pts |
| unfractioned heparin (UFH) structure | comes from pig, is a complex structure of sugar and AA |
| heparin - prophylaxis | low dose SQ injection |
| heparin as a treatment | IV bolus and continuous IV infusion Starting dose is indication-based Titrated to aPTT or anti-factor Xa concentrations using institutional nomograms |
| heparin has a | short half life, reversible with protamine |
| use of heparin requires | monitoring for bleeding and thrombocytopenia (low platelets) |
| HIT immune mediated | type I: no type II: yes |
| HIT Nadir platelet count | type I: 100,000 type II: 50,000 - platelets are clumping so platelet # decreases |
| HIT timing of onset | type I: early (day 1) type II: delayed (day 5); rapid if recent exposure (~ 100 days) |
| HIT incidence | type I: 10-20% type II: 1-3% |
| HIT Thromboembolic sequelae | type I: no type II: 30-50% |
| HIT treatment | type I: observe pt type II: D/C heparin by all routes, select non-heparin anticoagulant |
| if pt needs to be D/C of heparin by all routes, make sure to | DOCUMENT NO HEPARIN |
| Low-Molecular-Weight Heparins (LMWH) | primarily inhibits factor X |
| Low-Molecular-Weight Heparins (LMWH) is a | heparin derived anticoagulant - so if HIT/allergy then can't give it |
| Low-Molecular-Weight Heparins (LMWH) route and time | Injectable (SQ), given once or twice daily (fixed dose) |
| Low-Molecular-Weight Heparins (LMWH) is not | monitored or fully reversible |
| Low-Molecular-Weight Heparins (LMWH) needs to be used cautiously with | procedures because has a longer half life |
| Low-Molecular-Weight Heparins (LMWH) is used for | VTE prophylaxis or treatment (weight-based) |
| Low-Molecular-Weight Heparins (LMWH) is cleared by | the kidneys; adjust dose or avoid if renal failure |
| Low-Molecular-Weight Heparins (LMWH) needs to be monitored for | bleeding |
| Fondaparinux is a | Synthetic analog of the pentasaccharide binding sequence of heparin |
| Fondaparinux only binds to Xa so it is a | Selective factor Xa inhibition |
| Fondaparinux is not | related to heparin |
| Fondaparinux route and time | Injectable (SQ), given once daily (fixed dose) |
| Fondaparinux is not | monitored |
| Fondaparinux half-life | Long half-life and not reversible |
| Fondaparinux needs to be used cautiously with | procedures because long half-life |
| Fondaparinux is used for | VTE prophylaxis or treatment |
| Fondaparinux is cleared by | the kidneys, adjust dose or avoid if renal failure |
| Fondaparinux needs to be | monitored for bleeding |
| Direct Thrombin Inhibitors (DTIs) are | Non-heparin anticoagulants |
| DTIs is used to treat pts | with documented or suspected HIT |
| DTIs: Argatroban | metabolized by liver; falsely increase INR (not reflective of drug) |
| DTIs: Bivalirudin | metabolized by enzymes in blood and partial clearance through kidneys |
| fibrinolytics | recombinant tPA, alteplase rPA, reteplase TNK-tPA, tenecteplase |
| tPA | tissue plasminogen activator |
| Fibrinolytics: Mechanism of Action | plasminogen: precursor to plasmin which digests and breaks down fibrin |
| breakdown of fibrin | allows slow clearing of clot |
| fibrinolytic indications | STEMI Acute ischemic stroke: Symptom onset < 3 hrs (or < 4.5 hrs) Pulmonary embolism Peripheral arterial occlusion Clotted catheter |
Created by:
leh195