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56 Cards in this Set
- Front
- Back
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Heparin
MOA? |
ACCELERATES ANTITHROMBIN III activity (natural anticoagulant) => binds thrombin & inactivates tissue factors
Binds & interferes with platelet aggregation (high doses) Others: Increase lipoprotein lipase activity & Inhibit smooth cell proliferation |
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Heparin
Use? |
Treatment: venous thrombosis, pulmonary embolism, early in unstable angina & acute MI
Prophylaxis, in surgery: prevent postoperative deep vein thrombosis & pulmonary embolism Prophylaxis: clotting in blood transfusions, dialysis, blood samples, etc DOC IN PREGNANCY: does not cross placenta, so it is the anticoagulant used if pregnant |
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Heparin
Kinetics? |
Poor oral absorption => only IV or subQ forms (Immediate onset in IV; Short delay in subQ)
Metabolized by liver (depolymerization, desulfation); Metabolites excreted by kidney T1/2 depends on dose (non-linear) |
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Heparin
Monitoring? |
APTT (activated partial thromboplastin time): coagulation monitoring, via measure of clotting time
Dose adjusted based on APTT measures Monitor skin lesions (bleeding), thrombotic complications & UFH/platelets (HIT toxicity) |
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Heparin
Toxicity? |
Bleeding: most common side effect, due to GPIIb/IIIa antagonism (platelet receptors); dose dependent bleeding
Thrombocytopenia: heparin associated (HAT – benign; 2days) vs. heparin induced (HIT – serious; 1week) HIT: autoimmune rxn to unfractionated heparin (UFH) => ↓platelets, but get unwanted thrombotic events Others: Liver toxicity (elevated LFTs), Osteoporosis (heparin binds osteoblasts, activating osteoclasts |
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Heparin
CI? |
Severe thrombocytopenia: major risk for bleeding
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Heparin
Drug Interactions? |
↓effect: digoxin, tetracycline, nicotine, antihistamine
↑effect: anticoagulants, NSAIDs, ASA, dipyridamole, Plavix, direct thrombin inhibitors ANTAGONISM, DURING OVERDOSE: PROTAMINE SULFATE tightly binds heparin & neutralizes it |
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Low Molecular Weight Heparins
Name them. |
Dalteparin, Enoxaparin, Tinzaparin
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Low Molecular Weight Heparins
DESCRIPTION/MOA |
DESC: Derived from standard heparin, depolymerized to approximately 1/3 size, 4000-5000 daltons
MOA: Smaller fragment than heparin, can only bind and inactivate factor Xa |
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Low Molecular Weight Heparins
USE |
(Similar to heparin); Special populations – end stage renal failure, obesity, pregnancy
Tx/Prophylaxis of DVT, PE; unstable angina & MI; orthopedic surgery; hemodialysis |
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Low Molecular Weight Heparins
KINETICS |
SubQ injection
Not interchangeable between other anticoagulant agents => ie must continue with drug to continue effects T1/2: reduced binding to macrophages & endothelial cells => increase in half life for once a day dosing |
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Low Molecular Weight Heparins
MONITORING |
Does not need monitoring: reduced nonspecific plasma protein binding => predictable response (don’t need APTT)
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Low Molecular Weight Heparins
TOXICITY |
Bleeding: major bleeding, rare; minor bleeding at injection site
***Advantages: ↓incidence HIT (↓binding to platelets) & ↓incidence osteoporosis (↓binding to osteoblasts)*** |
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Heparinoids
Name it. DESCRIPTON/MOA |
Danaproid sodium
DESC: Mixture of 3 sulfated glycosaminoglycnas: Heparan, Dermatan, Chondroitin (no heparin) MOA: Accelerates antithrombin & heparin cofactor II => inhibits factor Xa, IIa Does not bind platelets |
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Heparinoids
USE |
Prophylaxis: venous thromboembolism in hip replacement surgery
Alternative to heparin in patients with HIT (minimal cross reactivity to heparin induced antibodies) |
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Heparinoids
KINETICS |
SubQ injection; Kidney elimination
T1/2 of anti-factor Xa activity: 22 hours (4-5 day for steady state) Does not cross placenta (pregnancy use) |
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Heparinoids
MONITORING |
Does not require therapeutic monitoring
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Heparinoids
TOXICITY |
Bleeding: major bleeding, rare; minor bleeding at injection site
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Direct Thrombin Inhibitors
MOA |
***Interacts directly with thrombin molecule (does not require antithrombin or heparin cofactor II)
Inhibits both circulating & clot-bound thrombin (potential advantage over heparins/LMWHs)*** |
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Direct Thrombin Inhibitors
USE |
***Alternative to heparin in patients with HIT (minimal cross reactivity to heparin induced antibodies)***
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Direct Thrombin Inhibitors
TOXICITY |
Bleeding: major bleeding incidence is high (15%)
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Direct Thrombin Inhibitors
Hirudin |
Prototype, isolated from salivary secretions of medicinal leeches; All given IV
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Direct Thrombin Inhibitors
Lepirudin |
Analog of Hirudin; Irreversibly binds thrombin; IV; Excreted through kidneys
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Direct Thrombin Inhibitors
Argatroban |
Synthetic molecule; Reversibly binds thrombin; IV; Liver metabolism
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Direct Thrombin Inhibitors
Bivalirudin |
Synthetic molecule; Reversibly binds thrombin; IV; Excreted through kidneys
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Direct Xa Inhibitor
Name it. MOA |
Fondaparinux
MOA: Synthetic molecule; Reversible binds and accelerates Antithrombin III => inhibition of factor Xa |
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Direct Xa Inhibitor
USE |
***Alternative to heparin in patients with HIT (minimal cross reactivity to heparin induced antibodies)***
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Direct Xa Inhibitor
KINETICS |
SubQ, with long half life (once a day dosing); Eliminated unchanged by kidney
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Warfarin (Coumadin)
DESCRIPTION |
Racemic mixture of R, S isomers => S is stronger (5x more potent)
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Warfarin (Coumadin)
MOA |
Interferes with hepatic synthesis of vitamin K dependent clotting factors
Interferes with synthesis of anticoagulants, protein C & S Note: may see both bleeding or clotting as potential complications, since it blocks clotting factors & anticoagulants |
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Warfarin (Coumadin)
USE |
Prophylaxis/Treatment of venous thrombosis & pulmonary embolism
Cardiac diseases Atrial fibrillations with risk of embolism; Prosthetic heart valve & Rheumatic valve disease ***(Start within 24 hours of Heparin; overlap of therapy, Heparin given while waiting for Warfarin)*** |
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Warfarin (Coumadin)
KINETICS |
***Oral, good absorption***
T1/2 of drug, 1-2 days; Liver metabolized and Urine/Feces excreted; highly protein bound Time to see full effect: months, since clotting factors have a very long T1/2 & it takes awhile to deplete them |
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Warfarin (Coumadin)
FOOD INTERACTION |
***Food high in vitamin K (leafy greens): must be consistent in diet; don’t binge on greens***
Herbals increase the anticoagulant effects: Ginkgo, Ginger, Garlic, Vitamin E, St. John’s wart |
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Warfarin (Coumadin)
DRUG INTERACTION |
"Look at lecture..."
lol I hate this class. |
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Warfarin (Coumadin)
TOXICITY |
Bleeding & ***Coumadin induced skin necrosis
Antidote: fresh frozen plasma (replaces clotting factors)*** |
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Warfarin (Coumadin)
CI |
Pregnancy (crosses placenta)
Uncontrolled bleeding & GI ulcers |
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Warfarin (Coumadin)
Monitoring |
PT: pro-time (bleeding time), expressed in INR (PTpatient/PTnormal)
International normalized ratio (INR): looks at thinning of blood compared to normal (1) => INR of 5.2 = 5x thinner Most therapeutic indications require INR to be ~2-3 As INR gets higher, more adverse effects are seen => at very high INR may need to give vitamin K & take off drug |
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Aspirin
MOA |
***Irreversibly inhibit cyclooxygenase (COX)*** => prevents synthesis of Thromboxane A2
Thus, inhibits platelet aggregation & vasoconstriction |
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Aspirin
KINETICS |
Permanent action on platelet (irreversible), lasting for life of platelet (7-10 days)
Increased dose does not increase efficacy; it just increases toxicity (bleeding) |
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Dipyridamole
MOA |
Exact mechanism unknown; multiple things involved
Inhibit phosphodiesterase, which degrades cAMP => ↑cAMP in platelets, resulting in reduction of aggregation Stimulates prostacyclin => anti-platelet effects |
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Dipyridamole
USE |
Prevent embolization from prosthetic heart valves (given with Warfarin)
Reduce thrombosis in thrombotic disease (given with Aspirin) |
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Ticlopidine
MOA |
***Irreversibly inhibits platelet ADP receptor*** => impairs activation of glycoprotein IIb/IIIa => prevents aggregation
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Ticlopidine
KINETICS |
Once a day dosing; Liver metabolism
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Ticlopidine
TOXICITY |
Bleeding, GI problems
***Severe neutropenia: must monitor CBC closely; therefore, drug not commonly used*** |
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Clopidogrel
MOA |
***Irreversibly inhibits platelet ADP receptor*** => impairs activation of glycoprotein IIb/IIIa => prevents aggregation
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Clopidogrel
KINETICS |
Twice a day dosing; Liver metabolism
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Clopidogrel
TOXICITY |
***Well tolerated (Clean version of Ticlopidine)***
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Glycoprotein IIb/IIIa receptor antagonists
Name them. |
Eptifibatide, Tirofiban, Abciximab
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Glycoprotein IIb/IIIa receptor antagonists
MOA |
Direct binding of receptor => no platelet cross linking
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Glycoprotein IIb/IIIa receptor antagonists
USE |
Acute coronary syndrome at high risk for further MI; Ischemia
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Glycoprotein IIb/IIIa receptor antagonists
TOXICITY |
Bleeding & Thrombocytopenia (much less than Heparin)
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Anti-Platelets
Name them. |
Aspirin, Dipyridamole, Ticlopidine, Clopidrogrel, Glycoprotein IIb/IIIa receptor antagonists
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Thrombolytics
Name them. |
Streptokinase, Urokinase, Alteplase, Anistreplase, Reteplase
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Thrombolytics
MOA |
***Converts plasminogen to plasmin (all are tPA, except Streptokinase) => digestion of fibrin***
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Thrombolytics
USE |
***Dissolve the formed clot (This and direct thrombin inhibitors do this)***
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Thrombolytics
CI |
Bleeding risks: surgery within past 10 days; serious GI bleed within past 3 months; active bleeding disorder
Cardiac: aortic dissection, acute pericarditis Previous stroke or other active intracranial problem |
