Study Guide: Coagulation Meds Pharm

ANTICOAGULANT MEDS HEPARIN AND LMWH ARE INDIRECT THROMBIN INHIBITORS *** HEPARIN Anticoagulant- Indirect thrombin inhibitor MOA: binds to antithrombin III to inactivate several clotting factors and inhibit thrombin activity . IT CAN NOT DISSOLVE A CLOT It can only prevent formation of new clots or prevent existing clots from getting bigger. ** Different from LMWH Low doses: to PREVENT thromboembolic events arising from open heart and vascular sx, dialysis procedures, or pts w unstable angina or in acute stages of MI Higher doses: to TREAT conditions in which immediate coagulation is needed . ex: confirmed DVT, PE DOSING IS HIGHLY DUE TO APTT VALUES AND WEIGHT !!!! (+ clinical indication for the drug) Indications for admins: ppx for thromboembolic events d/t immobility or vascular sx/procedure. Admin: SQ (never aspirate or massage site can = increase bleeding/tissue damage) or IV AVOID IM INJECTIONS D/T R/O INCREASED BLEEDING. S/E: Unusual bleeding/bruising, bleeding gums, nose bleed, occult blood in still , hematuria, low bp, tachy HEPARIN INDUCED THROMBOCYTOPENIA- serious complication that occurs in 30% pts. HIT causes the opposite effect of heparin → an INCREASE in thromboembolic events. ( life threatening) → which equals increased r/o MI,STROKE, PE. Contraindications: don’t admin in pts w active internal bleeding/bleeding in general, bleeding disorders, severe HTN, recent trauma, IC hemorrhage, or bacterial endocarditis—THEY WILL BLEED OUT. U don’t give heparin to ppl w severe HTN bc of hemorrhagic stroke- INCREASED BP= stroke , the hemorrhagic stroke happens bc if they have a stroke while on heparin theyre blood is already thinned out d/t the medicine and they will just continue to bleed. High bp can rupture a blood vessel (Stroke) And make u bleed out. Must check platelet levels REGULARLY. And APTT values . normal APTT 25-35 seconds . APTT is the time it takes for ur body to form a clot Nml platelet levels: 150,000-450,000** Tx for overdose: PROTAMINE SULFATE. (onset-5mins) → also works w LMWH LMWH – LOVENOX & dalteparin (Fragmin) Similar MOA to Heparin except their inhibition is more specific to a certain factor : ACTIVE FACTOR X ! think lovenoX Advantages over heparin: duration of action 2-4 times longer Produce a more STABLE response which = fewer follow up labs < likely to cause thrombocytopenia -Not necessary to monitor ApTT values. Based of patients WEIGHT. -dosages don’t fluctuate like for heparin based on labs. More consistent? s/e : same as Heparin r/t increased bleeding. Watch for the same things. Make sure to rotate sites for injections to prevent bruising * Keep in mind for anticoagulants you want to make sure they avoid ROUGH sports/activities to prevent them from bleeding out. Their blood is thinning so they will bleed more bc it takes longer for them to clot. BLACK BOX WARNING: Epidural/Spinal hematomas can happen when using LMWH. Monitor for neuro impairment bc can result in permanent paralysis. Warfarin (Coumadin) – ORAL anticoagulant; VITAMIN K ANTAGONIST MOA: warfarin acts by inhibiting the action of vit k . Inhibiting Vit K→ suppressed hepatic synthesis of coagulation factors II, VII, IX, & X→ LESS COAGULATION-→ increased bleeding time. (ONSET CAN TAKE DAYS TO HAPPEN. 2-7 DAYS) Indications: PPX for thromboembolic events r/t AFIB. To prevent pt from making clot. Prevention of CVA, MI, DVT, PE in pts undergoing hip sx or w LT indwelling central venous caths or prosthetic heart valves. Therapeutic range of warfarin: 1-10 mcg/mL to Keep INR at → 2-3 (PT/INR are labs used to dose warfarin) → NML PLATELETS 150,000-450,000 / NML INR 2-3 * s/e: unusual bruising – DC warfarin but note s/s can continue for up to 10 days. BLACK BOX WARNING: Can cause major/fatal bleeding, so monitor INR frequently * IF life threathning bleeding occurs → ANTIDOTE: VIT K + Kcentra: contains 4 vit k dependent factors that allow increase of coagulation. INSTRUCT patients to: use soft toothbrush, electric razon, prolong pressure over small nicks, careful cutting of food, avoid contact sports, amusement parks, jolting activities, bumping, etc. Patient teaching: Avoid foods that are high in vit K : GREEN LEAFY VEGETABLES. B/c they will be absorbed in blood and act as antidote → decrease effectiveness of warfarin and INCREASE clot formation. (foods high in vit K : spinach, Brussel sprouts, broccoli, collard greens asparagus, kale, kiwi, cabbage, lettuce, avocado, parsley, etc. Contraindications: recent trauma, active internal bleeding, bleeding disorders, IC hemorrhage, severe HTN, bacterial endocarditis, Severe liver or kidney disease. (warfarin is metabolized in the liver.) Interactions: don’t take OTC meds . check w MD 1st. LASTLY: WARFARIN IS PREGNANCY CATEGORY X !!!! DO NOT TAKE WHEN PREGNANT. !! DIRECT THROMBIN INHIBITORS: argatroban (Acova) , Pradaxa, Desirudin, Bivalirudin, MOA: binds to thrombin to prevent clot formation. Its used for HIT . ( Remember HIT will cause opp effect of heparin → increased clot formation. ) Pradaxa- ONLY PO DIRECT THROMBIN INHIBITOR – reduces r/o CVA, embolism, DVT, PE . its antidote is → PRAXBIND ( idarucizumab) Desirudin – used for dvt ppx during hip sx. Acova and bivalirudin- in pts w percutaneous coronary intervention for ppx of thrombocytopenia induced by heparin ( HIT) s/e of Pradaxa include heartburn, belching, acid or sour stomach- may need to admin OMEPRAZOLE to counteract that s/e FACTOR XA inhibitors- api[XA]ban (Eliquis) PO anticoagulants that inhibit factor XA in clotting cascade Used for ppx of dvt, pe, cva, systemic embolism , Advantage over warfarin: don’t require INR monitoring + few drug interactions. Anticoagulant effect clean in 1-2 days after dc BLACK BOX WARNING: don’t dc quickly bc can → serious ischemic event ex: MI/STROKE . ALSO don’t use in pts undergoing neuraxial anesthesia or spinal cord puncture d/t r/o epidural or spinal hematoma which can = LONG TERM PARALYSIS ** ANTIDOTE FOR FACTOR XA INHIBITORS → andeXAnet alfa ( andeXXA) ANTIPLATELET DRUGS Produce anticoagulant effect by interfering w platelet aggregation. They prevent clumping of platelets. Remember NML platelet levels : 150,000-450,000 Used to prevent clot formation in arteries * ASA- aspirin Binds to enzyme cyclooxygenase (COX-1)→ inhibits formation of thromboxane A2 (inducer of platelet aggregation) * Remember COX-1 is the PROTECTIVE ENZYME of the body. One of the ways it protects is clot formation by platelet aggregation in times of need to prevent pts from bleeding out. THIS is the action that is inhibited. COX-1 other actions: GI protect by decreased acid production, increased mucus production, increased platelet, renal protect, vasodilation, bronchodilation. CLOPIDROGEL (PLAVIX) – Plavix think “P”revents “P”latelet aggregation- ad”P” receptor blocker. Antiplatelet drug; ADP receptor blocker. MOA: inhibits platelet aggregation by blocking adp receptor sites on thrombocytes – binding is irreversible and platelet will be affected for the remainder of its lifespan (When there is injury to vessel, platelets become sticky and bind to site, they then recruit other platelets by release of substances such as → ADP) Tx: reduce rate of MI, CVA in pts w unstable angina, acute ST-elevation, those receiving coronary bypass procedures. (in pts w atherosclerosis) Also to prevent thrombi in pts w coronary artery stents and to prevent post-op dvts (off-label) DC 5 days prior to sx to prevent bleeding out. s/e dizziness, flu-like s/s, bruising, HA, rash, pruritis, bleeding (GI/Cerebral) BLACK BOX WARNING- effectiveness of med depends on CYP 450 enzymes, poor metabolizers= less therapeutic effects and more r/o adverse cardiovascular events. (> 50% Asians have this poor metabolizing action) Contraindications: patients w active bleeding Interactions: use w anticoagulants, NSAIDS, asa → increase r/o bleeding Overdose: platelet transfusions may be necessary to prevent hemorrhage. AGGRASTAT – Glycoprotein IIb/IIIa Inhibitors – prevent platelet “AGG”REGATION MOA: inhibits platelet aggregation by blocking IIB/IIIA proteins from adhering to each other. Glycoprotein IIB/IIIA is a receptor that is needed for platelets to aggregate. They wait for signals of injury to recruit Tx: patients w recent MI, CVA, PCI Cons: expensive and only admin IV CILOSTAZOL (PLETAL) & PENTOXIFYLLINE (TRENTAL ) * - intermittent claudication IC- pain or cramping in ble, that worsens w walking and exercise. Primary s/s of peripheral vascular disease. Pentoxifylline- acts on RBCS to reduce viscosity and increase their flexibility , allowing them to enter vessels that are partially occluded and reduce hypoxia which = reduced pain in muscle. Cilostazol- inhibits platelet aggregation and promotes vasodilation which brings additional blood to ischemic muscles. BOTH GIVEN PO BOTH NEED ADDITIONAL EXERCISE AND THERAPEUTIC LIFESTYLE CHANGES FOR MAX BENEFITS THROMBOLYTICS Thrombolytics promote the process of FIBRINOLYSIS – clot destruction. CLOT BUSTERS * work by converting plasminogen → PLASMIN PLASMIN digests FIBRIN and breaks it DOWN into small fragments. Given when clot has actually formed already , its not to PREVENT formation its to DESTROY formation Goal → quickly restore blood flow THROMBOLYTICS WORK BEST WHEN ADMINISTERED WITHIN 4HRS OF BLOOD CLOT FORMATION Alteplase- (Activase) & Reteplase, streptokinase, tenecteplase → ALL THE “ASE”’s MOA: dissolves blood clots obstructing the coronary arteries , restoring blood supply to the myocardium Must be given within 12 hrs of onset of s/s of MI, and within 3 hrs of thrombotic stroke for max effect. (POWERPOINT SAYS: SHOULD BE GIVEN WITHIN 30 MINS OF ARRIVAL TO ER) NO OTHER INJECTIONS WHILE ON ALTEPLASE TO PREVENT R/O BLEEDING- AVOID IT !! + avoid invasive procedures- if no other option maintain pressure for 30 mins after procedure. s/e bleeding, epistaxis, hematomas, spontaneous ecchymoses , a/e: GI or cerebral bleeding. (noted by hypotension*) → monitor VS, LOC, s/s bleeding !! WEIGHT is used to dose alteplase. contraindications: active bleeding , hx of recent hemorrhagive CVA or sx, head injury within last 3 months , uncontrolled HTN, IC neoplasm or arteriovenous malformation HEMOSTATICS Aka antifibrinolytics have OPPOSITE action of anticoagulants → SHORTEN bleeding time/ SLOW blood flow→ used to prevent excessive bleeding/bleeding out S/P SX procedures. Aminocaproic acid (Amicar) Think: aMINOcaproic acid → they MINO-MIZE the bleeding time → increase clotting. MOA: inactivates plasminogen so that it cannot turn to plasmin so that it can not attack fibrin and does not dissolve or prevent clots. Admin: tx acute hemorrhage – give IV to reduce bleeding in 1-2 hrs Can also do tabs Patients w hemophila a (bleeding disorder) – can take it after dental procedures to prevent excess bleeding. Therapeutic level 100-400mcg s/e : hypotension/bradycardia during rapid IV infusion a/e: monitor for thromboembolic disease d/t increased clotting interactions: contraception and estrogen increase coagulation effects