Drugs_that_Affect_the_Blood.pptx

Drugs that Affect the Blood Chapter 14 by Susan Hartfield PA-C, PharmD Overview Review of hemostasis and the clotting cascade Review of Anticoagulants Antiplatelet agents Thrombolytic drugs Phosphodiesterase inhibitors We will NOT be covering drugs that treat anemia or sickle cell Classification  A...

Drugs that Affect the Blood Chapter 14 by Susan Hartfield PA-C, PharmD Overview Review of hemostasis and the clotting cascade Review of Anticoagulants Antiplatelet agents Thrombolytic drugs Phosphodiesterase inhibitors We will NOT be covering drugs that treat anemia or sickle cell Classification  Anticoagulant Inhibits one or more proteins in the coagulation cascade Used to prevent or treat venous clots  Due to hypercoagulability and venous stasis  Platelets and endothelial dysfunction are less important contributors  Antiplatelet agents Affects aggregation or activation The Coagulation Cascade  End result: Thrombin converts fibrinogen to fibrin  Following vascular injury-exposure of collagen activates factor XII The intrinsic pathway  Exposure of tissue factor activates factor VII The extrinsic pathway  Eventually leads to formation of fibrin and stable platelet plug  Plasmin will break down fibrin leading to fibrin degradation products The Coagulation Cascade Wordpress.com Indirect Thrombin Inhibitors  Prototype is unfractionated heparin (UFH)  Glycosaminoglycans obtained from bovine or porcine tissue  Binds to and activates antithrombin III Heparin (UFH) General information  Prepared from porcine/bovine intestinal mucosa  Large molecule  Too large to be absorbed from GI tract or across placental barrier Can be used in pregnancy  Broken down by GI enzymes and acidic pH before it reaches the circulation, thus cannot be given po. Heparin (UFH)  Mechanism of action Heparin combines readily with plasma proteins, notably Anti-thrombin (ATIII) Accelerates the action of ATIII Inactivates thrombin (IIa), activated coagulation factors IXa, Xa, XIa, XIIa, and plasmin Prevents the conversion of fibrinogen to fibrin Heparin Heparin (UFH)  Administration IV infusion SC injection NOT IM (intramuscular) due to risk of hematoma formation  Onset of action I.V. has an immediate effect SC gradual effect with an onset of 20 to 60 minutes and maximum effect seen in 2-3 hours Heparin (UFH)  Duration of Effect  SC dose frequency is every 8-12 hours This route used for prophylaxis of DVT and PE Example: 5000 units SC q8 or 12 hours  IV infusion has a quick onset and quick off An important advantage to IV UFH  Metabolism and Excretion Liver metabolism Small amounts excreted in urine unchanged  No dose adjustment for renal impairment Heparin (UFH) Major Uses Prophylaxis of DVT and PE Treatment of DVT and PE Artificial pumps and filters (i.e. renal dialysis and bypass pumps)  Acute coronary syndromes     PCI STEMI Unstable angina/NSTEMI  Catheter patency/flush Heparin (UFH)  Adverse Effects Major hemorrhage: retroperitoneal, intracranial Minor hemorrhage: hematoma, hematuria Injection site reaction: pain, hematoma, ecchymosis, erythema Careful timing around neuraxial anesthesia (epidural and spinal puncture) Thrombocytopenia  Precautions History of recent GI bleeding Severe uncontrolled HTN Neuraxial anesthesia (spinal or epidural) Heparin (UFH) Contraindications Active major bleeding Thrombocytopenia (platelets 1% (e.g. post-op surgical patients or medical patients with cancer) Slideshare.net Heparin Induced Thrombocytopenia (HIT)  HIT-type I. 10% mild thrombocytopenia (rarely D/C LMWH when INR is therapeutic x 2 consecutive days.  Prevention of DVT > Dalteparin 2500-5000 units SC once daily > Enoxaparin 30mg SC every 12 hours or 40mg SC once daily Fondaparinux (Arixtra®)  Synthetic anticoagulant  Anti-Xa activity: increases the neutralizing action of ATIII on activated Factor X by 300-fold  SC injection solution (prefilled syringe)  Clinical uses: Tx and prophylaxis of DVT, knee, hip, abdominal surgery Tx of PE Tx and Prophylaxis of DVT in patients with HIT (off label)  Renal dose adjustment needed  Does NOT cross placenta Fondaparinux (Arixtra®) Direct Thrombin Inhibitors  Lepirudin-discontinued in 2012 d/t anaphylactic reactions  Bivalirudin IV infusion; Quick onset (half life 25 mins); a little longer with reduced renal function Also inhibits platelet aggregation FDA approved for use in PCI  Argatroban Also approved for PCI Continuous IV infusion No adjustment for renal function however will need to adjust for liver disease Novel Oral Anticoagulants (NOAC’s)  Dabigatran (Pradaxa®)-direct thrombin inhibitor Afib, DVT/PE treatment, VTE prevention post hip Comparable overall bleeding to warfarin Reversal agent is Praxbind (idarucizumab)-Binds to dabigatran Rivaroxaban (Xarelto®) Apixaban (Eliquis®) Edoxaban (Savaysa®) Indications: Treat and prevent DVT, PE, prevent stroke in Afib  Not affected by vitamin K in the diet  Routine anticoagulation tests are not needed     Apixaban (Eliquis ) ®  Direct factor Xa inhibitor  Indication/dosing Stroke prevention in nonvalvular Afib: 5 mg po BID→2.5mg BID for patients with 2 of the following (age >80, weight 1.5 mg/dl) VTE prevention post hip or knee replacement: 2.5 mg po bid x 35 days for hip or 12 days for knee DVT/PE treatment: 10mg po bid x 7 days, then 5 mg bid DVT/PE prevention: 2.5 mg bid after at least 6 months of therapy  Less bleeding as compared to warfarin or at least comparable  NOT recommended with prosthetic heart valves, severe liver impairment Apixaban (Eliquis®)  Drug Interactions Reduce dose 50% with strong inhibitors of BOTH CYP p450 3A4 and P-gp  Itraconazole, ketoconazole, ritonavir Avoid with strong inducers cyp p450 3A4 and p-gp  Phenobarbital, carbamazepine, phenytoin, rifampin Caution with antiplatelet agents Rivaroxaban (Xarelto®)  Direct factor Xa inhibitor  Approved indications/Dose VTE prevention post hip or knee: 10mg once daily x 35 days (hip); x12 days (knee)  Avoid CrCl