Coagulation+Modifying+&+Anemia+Agents

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**Coagulation Modifying & Anemia Agent ** **Chase Buehler & Samantha Porter**



__ Anticoagulants __

 * "Drugs that prevent the formation of a clot by inhibiting certain clotting factors."--essentially anticoagulants stops blood from clotting.
 * They prevent new clots from forming and also existing clots from enlarging, but do not have the ability to dissolve a blood clot.
 * Clots have the potential to dislodge and travel through the bloodstream causing complications elsewhere.
 * Ex: If it obstructs a brain vessel-causes a stroke
 * If it goes to the lungs- it is a pulmonary embolism
 * If it goes to a vein in the leg- it is a deep vein thrombosis
 * Anticoagulants are beneficial in certain settings where there is a high likelihood of a clot to form
 * MI, unstable angina, atrial fibrilation, use of indwelling devices, and conditions where blood flow may be slowed and blood may pool

Mechanism of action:
** *In some way shape or form, all these drugs interupt the clotting cascade in which all aids in the cessation of clot forming* ** ** *Prophylaxis use ONLY, does NOT break down clots* **

Heparin- LMWH (Lovenox, Fragmin, and Innohep) Warfarin- (Coumadin) Fondaparinux (Arixtra)
 * Binds to a substance called antithrombin III, which turns off three main activating factors (activated factor II, X, and IX)
 * Antithrombin III is the major natural inhibitor of thrombin in the blood.
 * Indicated for prevention and treatment
 * Main effect of Heparin--> Turns off the coagulation pathway and prevents clots from forming.
 * Differ from Heparin- more specific for activating factor X as oppososed to factor II
 * Indicated for prevention and treatment
 * Works by inhibiting vitamin K synthesis by bacteria in the GI tract
 * As a result, this inhibits the production of clotting factors II, VII, IX, and X
 * Indicated for prevention
 * Final effect--> Prevention of clot formation
 * Inhibits thrombosis by specific action against factor Xa
 * Currently 4 antithrombin drugs that inhibit thrombin molecules directly

Contraindications:

 * Warfarin is strongly contraindicated in pregnant woman
 * LMWH's are contraindicated in patients with an indwelling catheter.
 * Known drug allergy

Adverse Effects:

 * ** Bleeding is the main complication **
 * Heparin effect- Heparin-induced thrombocytopenia (HIT)
 * Two Types:
 * Type I-more gradual reduction in platelets
 * Heparin therapy can normally be continued
 * Type II- acute fall in the number of platelets
 * Heparin therapy must be discontinued
 * Common adverse effects:
 * Heparins-->bleeding, hematoma, nausea, aneamia, fever, edema
 * Fonfaparinux-->bleeding, hematoma, dizziness, confusion, rash, GI distress, UTI, anemia, urinary retention

Toxicity and overdose:

 * Symptoms of toxicity or overdose:
 * hematoma, melena (blood in stool), petechiae, ecchymoses, and gum or mucous membrane bleeding.
 * Heparn or warfarin toxicity- drug should be discontinued ** immediately! **
 * Since heparin has a short half-life, stopping the drug alone may reverse the toxic effects
 * In case of emergency (severe cases)- IV injection of protamine sulface is indicated. This drug reverses its anticoagulation properties.
 * Since warfarin inactivates the vitamin K dependent clotting factors (which are synthesized in the liver), it can take up to 36-42 hours before the liver has the ability to resynthesize enough clotting factors to reverse the warfarin effects.

__ Antiplatelet: __

 * Major mechanism interferes with platelet function
 * Normal platelet function adheres to the collagen formation upon a damaged blood vessel
 * There are 9 commonly current drugs that are antiplatelets: Pletal, Plavix, Remodulin, ReoPro, Integrilin, Asprin, Aggrastat, Agrylin, Persantine

Mechanism of Action
***Alters platelet membrane so platelets cannot clot***


 * Asprin
 * Lasts the lifespan of a platelet (7 days)
 * Prevents the formation of TXA2 (Thromboxane) and prostaglandins by the permanent inhibition of the enzyme cyclooxygenase in the platelets
 * Thromboxane causes blood vessels to constrict and aggregate platelets
 * Persantine
 * Inhibits ADP, platelet factor 4, and thromboxane, all substances that causes platelets to clot
 * Plavix
 * Blocks signals from fibrogen molecules by inhibiting the glycoprotein receptors on the platelet's membrane
 * Pentoxifylline
 * Inhibits serotonin, platelet factor 4, and ADP, also stimulates the release of prostacyclin (helps with dilation and inhibits platelet activation) from the blood vessels
 * Cilstazol
 * Primarily used to inhibit platelet aggregation and vasodilation in the lower extremities
 * GP IIb/IIIa inhibitors (Aggrastat, Integrilin, ReoPro)
 * Blocks the receptor protein on the platelets membrane (GP IIb/IIIa) and by doing so, prevents aggregation of platelets
 * Only available for IV use
 * Extremely fast onset for emergencies

Indications

 * Asprin
 * Recommended by the American Stroke Society in doses of 81 to 325mg
 * Plavix
 * Reduce risk of thrombotic strokes, prophylaxis for MIs and post MI prevention of thrombosis.
 * Persantine
 * Adjunct with warfarin to prevent post-op thromboembolic complications
 * GP IIb/IIIa inhibitors
 * Treat acute angina and MI or given during angioplasty
 * Thromboprevention
 * Pentoxifylline
 * Peripheral vascular disease
 * Pletal
 * Pain and cramping in calf muscles
 * Improves exercise tolerance in the elderly

Contraindications

 * Allergies - KDAs
 * Conditions - Thrombocytopenia, active bleeding, leukemia, traumatic injury, GI ulcer, Vitamin K deficiency, or recent stroke

Adverse Effects

 * All drugs pose a risk for serious bleeding episodes
 * CNS - Stimulation, drowsiness, dizziness, confusion, flushing
 * GI - NVD, GI bleeding, heartburn
 * Hematologic - Thrombocytopenia, agranulocytosis, leukopenia, neutropenia, hemolytic anemia, bleeding
 * Plavix
 * CV - Angina, hypertension, edema
 * CNS - Flulike symptoms, headache, dizziness, fatigue
 * GI - Abdominal pain, dyspepsia, diarrhea, nausea
 * Misc. - Epitaxis and integumentary disorders, including rash and pruritis

Interactions

 * Dangerous drug reactions are possible
 * ** Common allergic cross-reactivity between Asprin and other NSAIDs **
 * Avoid the combined use of Asprin and Heparin with GP IIb/IIIa inhibitors

__ Antifibrinolytic: __

 * Major mechanism of action-** prevent the lysis of fibrin, **actually promoting clot formation
 * Fibrin is the substance that helps make a platelet plug insoluble and anchors the clot ot the damaged blood vessel
 * 3 synthetic drugs currently available-aminocaproic acid, tranexamic acid, and desmopressin
 * Drugs available for topic use to stop excessive bleeding
 * Useful drugs in the prevention and treatment of excessive bleeding resulting from systemic hyperfibrinolysis or surgical complications

Mechanism of Action/Drug effects:

 * *Promotes clot formation* **
 * Aminocaproic acid and tranexamic acid- inhibit the breakdown of fibrin, which prevents the destruction of the formed platelet clot
 * Desmopressin- causes increased platelet aggregation and clot formation

Adverse Effects:

 * Typically mild effects
 * Rare occasion of acute cerebrovascular thrombosis and acute MI
 * Do not mix with estrogen or oral contraceptives as additive effects may occur, resulting in increased coagulation

__ Thombolytic Drugs __

 * Lyse thrombi in blood vessels that supply heart with blood (coronary arteries)
 * Reestablishes blood flow to the heart
 * Founded from bacteria in a patients blood which released a substance that broke down fribrin clots
 * Substance was isolated from the beta-hemolytic streptococcus and was named streptokinase
 * Streptokinase and natural occuring urokinase were the first enzymes used for thrombolytic drugs
 * Current drugs - Eminase, Activase, Retavase, TNKase

Mechanism of Action

 * *Breaks down __EXISTING__ clots* **
 * Thombolytics activate the conversion of ** plasminogen to plasmin **which breaks down the thrombus.
 * ** Plasmin ** is a proteolytic enzyme which breaks down protein such as fibrin, fibrogen and platelet factors (substances that form clots)
 * Streptokinase and urokinase have been removed from the U.S. market due to their adverse effects, newer substances carry lesser bleeding chance
 * Tissue plasma activator or t-PA (activase) are naturally occuring, but not at a therapeutic level, current drugs use recombinant DNA techniques to produce extra t-PA for therapeutic effects
 * t-PA converts plasminogen to plasmin*

Indications

 * All thrombolytic drugs activate the conversion of ** plasminogen to plasmin **
 * Used for acute MI, arterial thrombosis, DVT, occlusion of shunts or catheters, pulmonary embolism, and acute ischemic stroke

Contraindications

 * KDAs
 * ** Any other drugs that alter clotting **

Adverse Effects

 * Internal, intracranial, and superficial bleeding, hypersensitivity, anaphylactoid reactions, nausea, vomiting, hypotension, and cardiac dyssrhythmia

Toxicity and Management of Overdose

 * ** Supportive treatment ** since half-life of thrombolytic drugs are short

Interactions

 * Increased bleeding when in concurrent use with anticoagulants, antiplatelets, or any other drug affecting platelet function



Jeopardy!!!


 * Anticoagulants || Antiplatelet || Antifibrinolytics || Thrombolytics ||
 * 100 || 100 || 100 || 100 ||
 * 200 || 200 || 200 || 200 ||
 * 300 || 300 || <span style="color: #85280a; font-family: 'Trebuchet MS',Helvetica,sans-serif; font-size: 140%;">300 || <span style="color: #85280a; font-family: 'Trebuchet MS',Helvetica,sans-serif; font-size: 140%;">300 ||
 * <span style="color: #85280a; font-family: 'Trebuchet MS',Helvetica,sans-serif; font-size: 140%;">400 || <span style="color: #85280a; font-family: 'Trebuchet MS',Helvetica,sans-serif; font-size: 140%;">400 || <span style="color: #85280a; font-family: 'Trebuchet MS',Helvetica,sans-serif; font-size: 140%;">400 || <span style="color: #85280a; font-family: 'Trebuchet MS',Helvetica,sans-serif; font-size: 140%;">400 ||