Lower Extremity Dissection

Coagulation Modifier DrugsPharmacology Summer 2013Prof. Andrea BrooksLone Star College CyFairAbedukola Adelekan, Derek Shelton, Staci Solorzano & Michael DunbarChapter 26

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Introduction A&P ReviewHemostasis is a general term for any process that stops bleeding.When hemostasis occurs as a result of clotting blood, called coagulation.Blood clot is termed a thrombus when stationary, when moving through blood vessels, it is called a embolus.

CoagulationSubstances that promote coagulation:Plateletsvon Willebrand factorActivated clotting factorsTissue thromboplastinSubstances that inhibit coagulation:ProstacyclinAntithrombin IIIProteins C and SCoagulation system is called a cascade, each activated clotting factor serves as a catalyst that amplifies the next reaction.

Coagulation Modifier DrugsDrugs that affect coagulation by preventing/promoting clot formation, lysing a preformed clot, and/or reversing the action of anticoagulants.Anticoagulants Inhibit the action or formation of clotting factors.Antiplatelet Drugs Inhibit platelet aggregation, prevent platelet plugs.Thrombolytic Drugs Lyse existing clotsHemostatic or Antifibrinolytic Drugs Promote blood coagulation.

AnticoagulantsDrugs that reduce the ability of the blood to clot.Necessary if the blood clots too much as mobile clots (embolus) can block blood vessels and lead to stroke or myocardial infarction.

Have no direct effect on blood clots already formed.

Anticoagulants - IndicationsThere are a variety of conditions that require usage of anticoagulants; they are most commonly prescribed to prevent clot formations in patients with a medical condition that places them at risk for:Deep Vein Thrombosis (DVT)Myocardial InfarctionPulmonary EmbolismAtrial FibrillationHigh-risk of stroke

Anticoagulants Mechanism of ActionVary, depending on the drug and work on different aspects of clotting physiology.Does not lyse existing clots.

Heparin Binds to antithrombin III and turns off activating factors that develop clots.Warfarin Inhibits vitamin K synthesis, inhibiting clotting factors.Arixtra Inhibits thrombosis by a specific action against clotting factor Xa.Xarelto Factor Xa inhibitor.

Anticoagulants Dosages, Half-Life & InteractionsHeparin Adults - 5000 units by IV bolus, 20,000-40,000 units/day by IV infusion.1-2 hour half-lifeHerb use may increase risk of bleeding.Smoking may interfere with anticoagulation effect.

Anticoagulants Dosages, Half-Life & InteractionsWarfarin 2 to 5 mg PO or IV daily.20-60 hour half-lifeAvoid acetaminophen, ginko, ginseng as they may increase bleeding.Cranberry juice may increase risk of severe bleeding.Alcohol may enhance anticoagulation effects, avoid large quantities.

Anticoagulants Dosages, Half-Life & InteractionsArixtra (Fondaparinux) Adults 2.5 mg Sub-Q for DVT, 5 to 10mg Sub-Q for acute DVT with Warfarin.17-21 hour half-lifeNSAIDs may increase risk of hemorrhage; must stop these drugs before receiving first dosage.

Anticoagulants Dosages, Half-Life & InteractionsXarelto (Rivaroxaban) 10 mg PO once daily.5-9 hour half-lifeSt. Johns wort may significantly decrease levels.

Anticoagulants Adverse EffectsBleeding is primary complication of anticoagulation therapy.Bleeding can be localize or systemic.Severe liver disease can occur.Additional Side Effects include:NauseaVomitingCrampingDisorientationMuscle Weakness/Reduced Motor Skills

Anticoagulants Toxicity/OverdoseToxic effects are hemorrhagic in nature.Diagnosed symptoms may include:Hematuria (Blood in urine)Melena (Blood in stool)Petechiae (Skin spotting caused by bleeding)Ecchymoses (Discoloration of skin)Gum/Mucous membrane bleeding.

Discontinue drug immediatelyRemain with patient & monitor vitals.Notify prescribing physician.

Antiplatelet DrugsAntiplatelet drugs work to prevent platelet adhesion at the site of blood vessel injury, which occurs before the clotting cascade.Many antiplatelet drugs prevent platelet adhesion by affecting enzymatic pathways found within platelets and on blood vessel walls.Common antiplatelet drugs broken down by pharmacologic class include:Salicylate antiplatelet drugsADP InhibitorsGlycoprotein IIb and IIIa inhibitors

Salicylate Antiplatelet (Aspirin)Mechanism of Action:Aspirin inhibits platelet enzymes by suppressing cyclooxygenase.The effects of aspirin last the lifespan of each platelet.Aspirin promotes vasodilation and prevents platelet aggregation.

Salicylate Antiplatelet (Aspirin)Therapeutic Effects & Uses:Aspirin is widely used for its analgesic, antiinflammatory, and antipyretic (antifever) properties, but it also has antiplatelet effects. Aspirin has many therapeutic effects, but many of them vary depending on the dosage. Aspirin is officially recommended for stroke prevention by the American Stroke Society in daily doses of 50 to 325 mg. Adverse Effects:Central Nervous System- Drowsiness, dizziness, confusion, flushingGastrointestinal- Nausea, vomiting, gastrointestinal bleeding, diarrheaHematologic-Thrombocytopenia, agranulocytosis, leukopenia, neutropenia, hemolytic anemia, bleeding

Salicylate Antiplatelet (Aspirin)Contraindications: Include, but not limited to: Hypersensitivity to the actual drug itself, sensitivity to other NSAIDs, patients with aspirin triad (aspirin sensitivity, nasal polyps, asthma); acute bronchospasm, chronic rhinitis, GI ulcer, vitamin k deficiency, recent stroke, hemophilia, bleeding, traumatic injury, and third trimester pregnancyCautious Use:The potential adverse effects of the various antiplatelet drugs can be serious, and they all pose a risk for inducing a serious bleeding episode. The use of aspirin with other coagulation modifier drugs and other non-steroidal anti-inflammatory drugs (NSAIDs) produces additive antiplatelet activity and increased bleeding potential. The combined use of steroids or nonaspirin NSAIDs with aspirin can increase the ulcerogenic effects of aspirin.Usual Dosage Range:Adult- PO: 40-325 mg once daily (max: 4 g/day)Child: PO: 10-15 mg/kg in 4-6 h (max: 3.6 g/day)Note- Can be administered rectally and dosage can be adjusted as prescribed

ADP InhibitorsThese drugs inhibit platelet aggregation by preventing the binding of adenosine diphosphate (ADP) to its platelet receptor. Like aspirin, these drugs irreversibly inhibit platelet aggregation. ADP inhibitors include such drugs as Clopidogrel, Prasugrel (Effient), Cilostazol and Ticagrelor (BRILINTA).Mechanism of Action:ADP inhibitors inhibit platelet aggregation by altering the platelet membrane so that it can no longer receive the signal to aggregate and form a clot.

ADP InhibitorsTherapeutic Effects & Uses:Clopidogrel prolongs bleeding time, thereby reducing atherosclerotic events in high risk patients. Clopidogrel is given to reduce the risk for thrombotic stroke and is used for prophylaxis against transient ischemic attacks as well as for post-MI prevention of thrombosis.

Adverse Effects:Cardiovascular- Chest pain, edemaCentral Nervous System- Flulike symptoms, headache, dizziness, fatigueGastrointestinal- Abdominal pain, diarrhea, nauseaMiscellaneous- Rash, itching, epistaxis

ADP InhibitorsContraindications:Hypersensitivity to the actual drug itself, Intracranial hemorrhage, peptic ulcer, or any other pathologic bleeding

Cautious Use:Discontinue use 7 days before surgery and during lactation, hepatic impairment, renal impairment. Safety and efficacy not established in children.

Usual Dosage Range:Adult- PO: 75 mg once daily; 300 mg may be given as a one-time loading dose after coronary stent implantation

Glycoprotein IIb/IIIa InhibitorsDrugs in this class include: tirofiban (Aggrastat), eptifibatide (Integrilin), and abciximab (ReoPro).

Mechanism of Action:Glycoprotein (GP) IIb/IIIa inhibitors work by blocking the receptor protein by the same name that occurs in the platelet wall membranes. This protein serves to facilitate platelet aggregation in preparation for fibrin clot formation.

Glycoprotein IIb/IIIa InhibitorsTherapeutic Effects & Uses:Acute coronary syndromes (unstable angina, myocardial infarction, angioplasty) and acute percutaneous coronary interventions.Their purpose is to prevent the formation of thrombi, which is preferred over the method of lysing a formed thrombus.

Adverse Effects:Cardiovascular- Bradycardia, hypotension, edemaCentral Nervous System- DizzinessHematologic- Bleeding, thrombocytopenia

Glycoprotein IIb/IIIa InhibitorsContraindications:Hypersensitivity to the actual drug itself, bleeding, thrombocytopenia, recent stroke, surgery or trauma within 3 days, severe hypertension, lactationCautious Use:Severe renal insufficiency, safety and efficacy in children younger than 18 is unknown

Usual Dosage Range:Adult- IV: Single bolus followed by continuous infusion; specific doses are based on patient weight from 37 to more than 121 kg

Thrombolytic DrugsThrombolytic Drugs lyse thrombi in blood vessels that supply the heart with blood, the coronary arteries. This reestablishes blood flow to the heart to prevent necrosis of the heart muscle, if flow is established early enough.

Thrombolytic Drugs Mechanism of ActionNatural fibrinolytic system does not act fast enough to lyse a thrombi in the coronary arteries. Thrombolytics activate the fibrinolytic system to act quickly. They convert plasminogen to plasmin (which break down fibrin that builds the clot)Thrombolytic drugs mimic the bodys natural own ability of clot destruction. The tissues plasminogen is not sufficient enough to dissolve a coronary thrombus.

Thrombolytic Drugs Indications:Used to activate conversion of plasminogen to plasmin (enzyme that breaks down a thrombus). Indicated for the presence of a thrombus that significantly interferes with blood flow on either venous or arterial side of circulation. Acute Myocardial Infarction, arterial thrombosis, Deep Venous Thrombosis, occlusion of shunt or catheter, pulmonary embolism, acute ischemic stroke.

Contraindications:Known drug allergies, concurrent use of other drugs to alter clotting

Thrombolytic DrugsAdverse effects:Internal intracranial and superficial bleeding, hypersensitivity, anaphalactic reactions, nausea, vomiting, hypotension, and could induce cardiac dysrhythmia

Toxicity and Management of OverdoseUsually an extension of adverse effects. Treatment is symptomatic and supportive. Short half life

Thrombolytic DrugsInteractions:High bleeding tendency resulting from concurrent use with anticoagulants, antiplatelets, and other drugs that effect platelet function.

Current Thrombolytic Drugs:Activase (alteplase), Eminase (anistreplase), Retavase (reteplase), and TNKase (tenecteplase)

Thrombolytic Drugs are infused via IV only and onset of action is approximately 30 minutes. Dosages range from 100mg over 90min duration as a 15mg bolus, then 35mg over 60min.

Antifibrinolytic DrugsAdvate Alphanine SD Amicar Benefix Crosseal Fibrin Sealant (Human) Cyklokapron DDAVP Evithrom Helixate FS Hemofil-M HyateKogenate FS Novoseven NovoSeven RT Recothrom Thrombin-JMI Trasylol

Dosage Forms:TabletSyrupSolution

Antifibrinolytic Drugs - IndicationsAntifibrinolytic agents are used to treat serious bleeding, especially when the bleeding occurs after surgery (particularly in patients with hemophilia) or certain other kinds of surgery. These medicines are also sometimes given before an operation to prevent serious bleeding in patients with medical problems that increase the chance of serious bleeding. Antifibrinolytic agents may also be used for other conditions as determined by your doctor. This medicine is available only with your doctor's prescription

Antifibrinolytic Drugs Mechanism of ActionAntifibrinolytics, such as aminocaproic acid (-aminocaproic acid) and tranexamic acid are used as inhibitors of fibrinolysis.These lysine-like drugs interfere with the formation of the fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators (primarily t-PA and u-PA) which takes place mainly in lysine rich areas on the surface of fibrin. These drugs block the binding sites of the enzymes or plasminogen respectively and thus stop plasmin formation.

Antifibrinolytic Drugs DosageThe amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Antifibrinolytic Drugs Oral DosageAdults - For the first hour, the dose is 5 grams. Then the dose is 1 or 1.25 grams per hour for eight hours.

Children - Dose is based on body weight or size and must be determined by your doctor. For the first hour, the dose is usually 100 milligrams (mg) per kilogram (kg) (45.4 mg per pound) of body weight. Then the dose is 33.3 mg per kg (15.1 mg per pound) of body weight per hour.

Antifibrinolytic Drugs Injection DosageAdults - At first, the dose is 4 to 5 grams injected into a vein, over a period of one hour. Then the dose is 1 gram per hour, injected into a vein over a period of eight hours.

Children - Dose is based on body weight or size and must be determined by your doctor. At first, the dose is usually 100 mg per kg (45.4 mg per pound) of body weight, injected into a vein over a period of one hour. Then the dose is 33.3 mg per kg (15.1 mg per pound) of body weight per hour, injected into a vein.

Antifibrinolytic Drugs Side EffectsDizzinessHeadacheMuscle pain or weakness (Severe and continuing) ringing or buzzing in earsSkin rash Slow or irregular heartbeatwith the injection only Stomach cramps or pain Stuffy noseSudden decrease in amount of urineSwelling of face, feet, or lower legsUnusual tiredness or weaknessWeight gain (rapid)

ConclusionCoagulation modifiers have a variety of uses:Prevention or elimination of clotting in peripherally inserted catheterMaintenance of patency (without clotting) of central venous cathetersClot prevention in coronary artery bypass graftingPrevention of clotting after major vessel injury Treatment of thrombophlebitis to prevent thromboembolismPrevention of clotting with use of prosthetics (heart valves)

Conclusion Nursing ImplicationsAccess:Perform thorough patient assessment to identify risksPatient historyMedication historyAllergiesContraindicationsBaseline vital signs, laboratory valuesPotential drug interactions MANY!History of abnormal bleeding conditionsFollow guidelines for preparation and administrationSix Rights.Routinely monitor vital signs, heart sounds, peripheral pulses, neurological status.

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