CH26 Coagulation Modifier Drugs Lecture Notes PDF

Preview

Summary

These are notes are chapter notes and outlines based from pharmacology spring 2021 zoom class powerpoint lecture...

Description

NUR120

CH25 Coagulation Drugs

PHARMACOLOGY OVERVIEW • Drugs that affect coagulation are commonly associated with adverse drug reactions. • Coagulation modifiers work by preventing/promoting clot formation, lysing a preformed clot, and/or reversing the action of anticoagulants. Coagulation modifiers include anticoagulants, antiplatelets, thrombolytics, antifibrinolytics, and reversal drugs. Anticoagulants

•

inhibit the action or formation of clotting factors

•

prevent clots from forming.

•

prevent platelet plugs from forming

•

inhibit platelet aggregation

Hemorheologic

•

alter platelet function without preventing the platelets from working.

Thrombolytic Antifibrinolytic

• •

lyse (break down) clots, or thrombi, that have already formed (hemostatic drugs), have the opposite effect of these other classes of drugs;

•

they actually promote blood coagulation and are helpful in the management of conditions in which excessive bleeding would be harmful.

Antiplatelet

Anticoagulants • aka antithrombotic drugs ( no direct action on blood clot) o prevent the formation of a clot or thrombus by decreasing coagulability • Used prophylactically to prevent o Clot formation o An embolus Heparin Factors IIa thrombin and Xa • Inhibits activated factor II (thrombin), activated factor Xa • usually refers to unfractionated heparin o relatively large molecule derived from various animal sources. o Low molecular weight heparins (LMWHs) are synthetic and have a smaller molecular structure o enoxaparin (Lovenox) and dalteparin (Fragmin). • DVT prophylaxis 5000 units SQ 2-3 x daily (no need for aPTT for prophylaxis) • For therapeutic use, continuous IV infusion (10 – 40,000 units/mL) o Monitor aPTT every 6 hours until therapeutic effects are seen! o no need when using heparin flush (10-100 units/mL) • The LMWHs much more specific for activated factor X (Xa) than for activated factor II (IIa, or thrombin). o More predictable anticoagulant response o aPTT not needed with LMWH Warfarin (Coumadin) • works by inhibiting vitamin K synthesis by bacteria in the gastrointestinal tract. • inhibits production of clotting factors II, VII, IX, and X, which are known as vitamin K–dependent clotting factors. • Prevents clot formation

Page 1 of 8

NUR120

CH25 Coagulation Drugs

Other factor Xa drugs • Fondaparinux (Arixtra) inhibits thrombosis by its specific action against factor Xa alone. • Rivaroxaban (Xarelto) is a new oral-acting factor Xa inhibitor approved in 2011. • Apixaban (Eliquis) Direct Thrombin inhibitors • inhibit the thrombin molecules directly, o natural drug  human antithrombin III (Thrombate), isolated from the plasma of human donors. o synthetic drugs are :  lepirudin (Refludan),  argatroban (Argatroban)  bivalirudin (Angiomax)  dabigatran (Pradaxa). Anticoagulants • prevent clot formation is of benefit in certain settings in which there is likelihood of clot formation, including o MI o unstable angina o atrial fibrillation o use of indwelling devices such as mechanical heart valves o conditions in which blood flow may be slowed and blood may pool such as:  major orthopedic surgery  prolonged periods of immobilization, for example, hospitalization or even long plane rides. • Clots may cause stroke, heart attack, DVT, PE, • Patients at risk for clots are given medications for DVT prophylaxis while in the hospital and after major surgery. • LMWHs (enoxaparin) used as anticoagulant bridge therapy in situations o patient must stop warfarin for surgery or other invasive medical procedures. o Enoxaparin acts as a bridge to provide anticoagulation while the patient must be without warfarin therapy. o o

Warfarin is indicated for prevention of any of these events, LMWHs, direct thrombin inhibitors, and factor Xa inhibitors are used for both prevention and treatment.

Contraindications • known drug allergy • any acute bleeding process, or high risk for such an occurrence. • Warfarin is strongly contraindicated in pregnancy • other anticoagulants are rated in lower pregnancy categories (B or C). • LMWHs are contraindicated in patients with an indwelling epidural catheter o they can be given 2 hours after the epidural is removed. o epidural hematoma!!

Page 2 of 8

NUR120

CH25 Coagulation Drugs

Adverse effects • Bleeding is the main complication of anticoagulation therapy o risk increases with increasing dosages. o may be localized or systemic. o Aspirin! Drugs impairing platelet function • heparin-induced thrombocytopenia (HIT), heparin-associated thrombocytopenia. (paradoxical thrombosis) o Type I  Gradual platelet reduction  Continue heparin o Type II  Acute platelet decrease (more than 50% from baseline)  D/C heparin  Clinical manifestations o Fatal! o Tx: thrombin inhibitors (lepirudin, argatroban) o Warfarin use can cause necrosis and purple toes syndrome Heparin toxicity • toxic effects of heparin, LMWH, and warfarin are hemorrhagic in nature o the management is different for each drug. o Symptoms  hematuria, melena, petechiae, ecchymoses, and gum or mucous membrane bleeding.  heparin toxicity, STOP DRUG IMMEDIATELY.  Stopping heparin alone may be enough to reverse the toxic effects  short half-life (1 to 2 hours).  In severe cases, (IV) injection of protamine sulfate is indicated. (5 minutes!) Warfarin toxicity or overdose  the first step D/C WARFARIN  may take 36 to 42 hours before the liver can resynthesize enough clotting factors to reverse the warfarin effects  Giving vitamin K1 (phytonadione) can hasten the return to normal coagulation.  Anaphylaxis risk – give diluted over 30 minutes  High dose (10mg IV) will reverse anticoagulation in 6 hrs  Use lowest amt possible based on situation.  Warfarin resistance up to 7 days post VitK administration  Use heparin or LMWH  Transfuse plasma if bleeding is severe  Administer clotting concentrates (Kcentra, Profiline) Andexxa for rivaroxaban and apixaban reversal. (life threatening or uncontrolled bleeding

Page 3 of 8

NUR120

CH25 Coagulation Drugs

Argatroban • Synthetic direct thrombin inhibitor • Indicated for active HIT, percutaneous procedures for patient at risk for HIT • IV • Lower dosage in liver dysfunction Dabigatran (Pradaxa) • first oral direct thrombin inhibitor o approved for prevention of strokes and thrombosis in patients with nonvalvular atrial fibrillation. • prodrug activated in the liver. o specifically and reversibly binds to both free and clot-bound thrombin. • excreted extensively in the kidneys o dose is dependent on renal function. • !!! bleeding!!! - DO NOT GIVE OTHER ANTICOAGULANTS!! o increased GI bleeding as compared with warfarin. • No coagulation monitoring is required. • St. John’s wort (which cause a decreased effect)  Idarucizumab (Praxbind) o specific dabigatran antidote that reverses the anticoagulant effects of dabigatran o emergency surgery or in life-threatening or uncontrolled bleeding. Enoxaparin (Lovenox) • prototypical LMWH o small fragments of unfractionated heparin o greater affinity for factor Xa than for factor IIa o higher degree of bioavailability and a longer elimination half-life than • aPTT not required • injectable only (prefilled) Fondaparinux (Arixtra) SQ only!!!! • selective inhibitor of factor Xa, • indicated for prophylaxis or treatment of DVT or PE. • contraindicated with known allergy • contraindicated n patients with a creatinine clearance less than 30 mL/min or a body weight of less than 50 kg. • Bleeding is the most common and serious adverse reaction. o Thrombocytopenia has also been reported\ o therapy should be stopped if platelet count falls below 100,000 platelets per microliter. • It should not be given for at least 6 to 8 hours after surgery • caution in conjunction with warfarin. • There is no antidote for fondaparinux, o effect cannot be measured by standard anticoagulant tests.

Page 4 of 8

NUR120 •

CH25 Coagulation Drugs

!!! black box warning regarding potential spinal hematomas if the patient has an epidural catheter.

Rivaroxaban (Xarelto) • first oral factor Xa inhibitor. • approved for: o prevention of strokes in patients with nonvalvular atrial fibrillation o postoperative thromboprophylaxis with knee and hip replacement surgery o and treatment of DVT and PE. • adverse effects include peripheral edema, dizziness, headache, bruising, diarrhea, hematuria, and bleeding. • St. John’s Wort!!! Grapefruit Juice!!! Warfarin sodium (Coumadin) • pharmaceutical derivative of the natural plant anticoagulant known as coumarin. • available in oral form • requires careful monitoring of the (PT/INR) o which is a standardized measure of the degree to which a patient’s blood coagulability has been reduced by the drug. o A normal INR is 1, therapeutic INR (with warfarin) ranges from 2 to 3.5 • coumadin and amiodarone !! (reduce warfarin in half!) • diet! VIT K reduces ability to prevent clots, be consistent in diet! • Herbal products!!!! o increased risk for bleeding gingko, garlic st. john wort. Antiplatelet Drugs •

Antiplatelet drugs work to prevent platelet adhesion at the site of blood vessel injury, before the clotting cascade.

Aspirin is officially recommended by the American Stroke Society for stroke prevention in daily doses of 50 to 325 mg/daily (common dose 81mg/day)  Reye’s Syndrome! Contraindicated for children (hepatic and CNS damage!)  Cross reactivity between asprin and NSAIDS  o

Clopidogrel Plavix o Most widely used ADP o Oral use only o Similar drugs Plasugrel, ticagrelor o Increased risk of bleeding in patient 75 and up w Stroke HX or weigh less than 60 kg. Eptifibatide (Integrilin tirofiban (Aggrastat abciximab (ReoPro).

• •

Administered in ICU or cardiac cath settings IV use only

Page 5 of 8

NUR120

CH25 Coagulation Drugs

Thrombolytics • •

Break down or lyse preformed clots

Thrombolytic Drugs • Thrombolytics are coagulation modifiers that lyse thrombi in the coronary arteries.  If the blood flow is reestablished early, the heart muscle and left ventricular function can be saved. • The indications for thrombolytic therapy include:  acute MI  arterial thrombosis  DVT  occlusion of shunts or catheters  pulmonary embolism  acute ischemic stroke. •

•

The most common undesirable effect of thrombolytic therapy is:  internal, intracranial, and superficial bleeding.  hypersensitivity  anaphylactoid reactions  nausea, vomiting  hypotension  These drugs can also induce cardiac dysrhythmias. Treatment for toxicity is symptomatic and supportive because thrombolytic drugs have a relatively short half-life and no specific antidotes.

Alteplase (Activase) • t-Pa made through recombinant DNA techniques. • fibrin specific and therefore does not produce a systemic lytic state. • present in the human body in a natural state o does not induce an antigen-antibody reaction. o readministered immediately in the event of reinfarction. • t-Pa has a very short half-life of 5 minutes. o open the clogged artery rapidly, but its action is short-lived. o given with heparin to prevent reocclusion of the affected blood vessel. • Alteplase is available only in parenteral form. • smaller dosage form (Cathflo Activase) used to flush clogged IV or arterial lines. • Tenecteplase (TNKase) is a form of alteplase that is given by IV push after MI

Page 6 of 8

NUR120

CH25 Coagulation Drugs

Antifibrinolytic Drugs • prevent the lysis of fibrin;  promote clot formation.  Used for:  prevention of excessive bleeding from hyperfibrinolysis  surgical complications  hemophilia  von Willebrand’s syndrome • Three synthetic antifibrinolytics are available: 1. aminocaproic acid 2. tranexamic acid 3. desmopressin. Adverse effects • uncommon, mild • rare thrombotic events: acute cerebrovascular thrombosis and acute MI. Aminocaproic acid (Amicar) • synthetic antifibrinolytic drug • prevent and control the excessive bleeding that can result from surgery or overactivity of the fibrinolytic system. • PO, IV Desmopressin (DDAVP) • is a synthetic polypeptide. • very similar to vasopressin, which is antidiuretic hormone, the natural human posterior pituitary hormone • contraindicated in: o drug sensitivity o diabetes insipidus o hemophilia • Nasal spray used for nocturnal enuresis Tranexamic acid • antifibrinolytic drug • forms a reversible complex that displaces plasminogen from fibrin o results in the inhibition of fibrinolysis. • It is administered intravenously prior to surgery. • contraindicated in: o hypersensitivity o patients with a history of active thromboembolic disease o concurrent use of combination hormonal contraceptives. • Hypotension is frequently noted with rapid IV injection. NURSING PROCESS • Coagulation modifiers have a variety of uses, including the following: (1) prevention or elimination of clotting in a peripherally inserted catheter, (2) maintenance of patency (without clotting) of central venous catheters, (3) clot

Page 7 of 8

NUR120

• •

•

• • • •

• • •

• •

CH25 Coagulation Drugs

prevention in coronary artery bypass grafting, (4) prevention of clotting after major vessel injury, (5) treatment of thrombophlebitis to prevent venous and/or arterial thromboembolism, and (6) prevention of clotting with use of prosthetics (e.g., heart valve replacements) and in atrial fibrillation. Perform a thorough patient assessment to identify the presence of risk factors. It is also important to assess the skin, oral mucous membranes, gums, urine, and stool for any evidence of bleeding. Assess patients for any blood in the urine or stool, easy bruising, excessive bleeding from toothbrushing or shaving, or unexplained nosebleeds while receiving these medications, and report any such findings. It is crucial to patient safety to remember that heparin is not interchangeable unit for unit with drugs in another class of anticoagulants, the LMWHs. Heparin sodium contains benzyl alcohol; therefore, assess for allergy to this additional component. With antiplatelet drugs, obtain a thorough nursing history and medication history, and perform a physical assessment before beginning drug therapy. Aspirin is not to be used in children and teenagers, in patients with any bleeding disorder, in pregnant or lactating women, or in patients with vitamin K deficiency or peptic ulcer disease. Before use of thrombolytics, assess for a history of hypotension and cardiac dysrhythmias. Antifibrinolytics require the same skillful assessment of baseline parameters and laboratory testing; however, there are additional concerns for patients with dysrhythmias, hypotension, bradycardia, convulsive disorders, nausea, vomiting, and abdominal pain or diarrhea. Routinely monitor vital signs, heart sounds, peripheral pulses, and neurologic status in all patients during and immediately after anticoagulant therapy. The antidote to hemorrhage or uncontrolled bleeding resulting from heparin or LMWH therapy is protamine sulfate. Therapeutic levels of anticoagulants and other clotting-altering drugs or coagulation modifier drugs are also monitored by laboratory studies such as activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR.) Some of the therapeutic effects include decreased chest pain and a decrease in dizziness as well as in other neurologic symptoms. Adverse effects of anticoagulants include bleeding and hematoma formation (heparin); thrombocytopenia (heparin and LWMHs); bleeding, dizziness, shortness of breath, and fever (direct thrombin inhibitors); bleeding, hematoma, dizziness, and gastrointestinal distress (selective factor Xa inhibitors); and bleeding, lethargy, and muscle pain (warfarin). Early signs of drug overdose for any of the clotting-altering drugs (i.e., anticoagulants) include bleeding of the gums during toothbrushing, unexplained nosebleeds or bruising, and heavier-than-usual menstrual bleeding.

Page 8 of 8...