115391PathwayLepirudin Mechanism of Action Action Pathway Lepirudin is a synthetic peptide thrombin inhibitor that binds reversibly to the catalytic site and anion-binding exosite inhibiting the cleavage of fibrinogen into fibrin. Lepirudin is used to treat heparin-induced thrombocytopenia as well as to prevent thrombosis. It is used in patients that are undergoing percutaneous coronary intervention or who have a risk in acute coronary syndromes caused by unstable angina or non-ST segment elevation. Thrombin is an important proteinase as it cleaves fibrinogen into fibrin monomers which help form the thrombus that forms the clot at the site of vascular injury. Because Lepirudin inhibits thrombin, clotting cannot form which is ideal for heart surgeries and some heart conditions. Lepirudin should be monitored as it inhibits clotting so other injuries won't clot and it also can cause blood stagnation. Monitoring changes in hematocrit and blood pressure is extremely important when taking this drug. It is normally administered intravenously so that it is delivered to the site of action right away and can be controlled more easily. Production of lepirudin by Bayer Pharmaceuticals has been stopped in 2012. Drug ActionPW124549CenterPathwayVisualizationContext12482520002200#FFFFFFPathwayVisualization115254115391Lepirudin Mechanism of Action Pathway Lepirudin is a synthetic peptide thrombin inhibitor that binds reversibly to the catalytic site and anion-binding exosite inhibiting the cleavage of fibrinogen into fibrin. Lepirudin is used to treat heparin-induced thrombocytopenia as well as to prevent thrombosis. It is used in patients that are undergoing percutaneous coronary intervention or who have a risk in acute coronary syndromes caused by unstable angina or non-ST segment elevation. Thrombin is an important proteinase as it cleaves fibrinogen into fibrin monomers which help form the thrombus that forms the clot at the site of vascular injury. Because Lepirudin inhibits thrombin, clotting cannot form which is ideal for heart surgeries and some heart conditions. Lepirudin should be monitored as it inhibits clotting so other injuries won't clot and it also can cause blood stagnation. Monitoring changes in hematocrit and blood pressure is extremely important when taking this drug. It is normally administered intravenously so that it is delivered to the site of action right away and can be controlled more easily. Production of lepirudin by Bayer Pharmaceuticals has been stopped in 2012. Drug133608618520712Jennings LK, Saucedo JF: Antiplatelet and anticoagulant agents: key differences in mechanisms of action, clinical application, and therapeutic benefit in patients with non-ST-segment-elevation acute coronary syndromes. Curr Opin Cardiol. 2008 Jul;23(4):302-8. doi: 10.1097/HCO.0b013e3283021ad9.115391Pathway33608712173205Walker CP, Royston D: Thrombin generation and its inhibition: a review of the scientific basis and mechanism of action of anticoagulant therapies. Br J Anaesth. 2002 Jun;88(6):848-63. doi: 10.1093/bja/88.6.848.115391Pathway33608830513232Laine M, Lemesle G, Dabry T, Panagides V, Peyrol M, Paganelli F, Bonello L: Bivalirudin during percutaneous coronary intervention in acute coronary syndromes. Expert Opin Pharmacother. 2019 Feb;20(3):295-304. doi: 10.1080/14656566.2018.1551361. Epub 2018 Dec 4.115391Pathway33608918449412115391Pathway2Platelet CL:00002331CellCL:00000004Cardiomyocyte CL:00007463NeuronCL:00005408Beta cellCL:00006396MyocyteCL:00001875HepatocyteCL:00001821Homo sapiens9606EukaryoteHuman12Mus musculus10090EukaryoteMouse3Escherichia coli562Prokaryote6Caenorhabditis elegans6239EukaryoteRoundworm18Saccharomyces cerevisiae4932EukaryoteYeast4Arabidopsis thaliana3702EukaryoteThale cress5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat10Drosophila melanogaster7227EukaryoteFruit fly5CytoplasmGO:000573710Cell MembraneGO:00058861CytosolGO:000582911Extracellular SpaceGO:000561519sarcoplasmic reticulumGO:00165292MitochondrionGO:00057397Endoplasmic Reticulum MembraneGO:000578924Mitochondrial Intermembrane SpaceGO:000575825Golgi ApparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574313Endoplasmic ReticulumGO:00057836LysosomeGO:000576416Lysosomal LumenGO:004320236MembraneGO:00160202Endothelium BTO:00003935cardiocyteBTO:00015391LiverBTO:000075972918PancreasBTO:00009888Blood VesselBTO:000110274116KidneyBTO:00006717189MuscleBTO:00008871411816212PW_BS0000168511PW_BS00000814101PW_BS0000142111PW_BS00000215111PW_BS000015215114PW_BS0000213551914PW_BS0000353211PW_BS00000346114PW_BS000046471914PW_BS00004749711PW_BS000049422411PW_BS000042432511PW_BS0000435811411PW_BS000058171211PW_BS000017181311PW_BS0000189611PW_BS000009711113PW_BS00007172513PW_BS00007229111PW_BS0000296618518PW_BS000066101711PW_BS0000102811611PW_BS0000281115121PW_BS000111101531PW_BS000101205561PW_BS0000242111018PW_BS0000241601181PW_BS0001601901118PW_BS0000242137181PW_BS0000241985181PW_BS00002421013181PW_BS0000241644PW_BS0001642851041PW_BS000024151141PW_BS0001513081011PW_BS00002411PW_BS0000013317121PW_BS0000281151012PW_BS0001151321121PW_BS00013235625121PW_BS00002834524121PW_BS00002813013121PW_BS0001301141112PW_BS0001147413PW_BS000074228361PW_BS0000245181PW_BS000051122551PW_BS000122405105PW_BS000115124151PW_BS0001244182451PW_BS0001154192551PW_BS000115383751PW_BS0001001251351PW_BS000125409115PW_BS0001151355171PW_BS0001353761017PW_BS0000531181171PW_BS00011845424171PW_BS00011545525171PW_BS0001153987171PW_BS00011313613171PW_BS0001361371117PW_BS0001372975101PW_BS0000244781010PW_BS00011548924101PW_BS0001152991101PW_BS00002449025101PW_BS0001154957101PW_BS000115209106PW_BS0000245062461PW_BS000115388161PW_BS0001125072561PW_BS000115390761PW_BS0001127906111PW_BS0005248346111PW_BS000549509516PW_BS00005041811PW_BS000041801111PW_BS000080261115PW_BS000026353CalciumHMDB0000464Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.14127-61-8C0007627129108CA%2b2266DB01373[Ca++]CaInChI=1S/Ca/q+2BHPQYMZQTOCNFJ-UHFFFAOYSA-Ncalcium(2+) ion40.07839.9625911550calcium(2+) ion22FDB003513Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ionPW_C000353Ca2+276163038553146012941159932199735104631163461164471478491491421552432116582138172796182937931597131607239422941866647821048222853401115780101717920572322117258160728119011774213118371981184221012198164122152851528815115350308693361773893317760011578154132782663567852634578724130789081148041374805892288182651120220122120465405121049124121300418121377419121850383121923125122370409122895135123099376123613118123870454123936455124403398124476136124924137125571297125711478125981489126009299126050490126533495127203209127434506127460388127502507128105390140676790140677834140695501730Coagulation factor XP00742Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clottingHMDBP02011F1013q34L0039513.4.21.624711513653541136539511395828013977221795Coagulation factor VP12259Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombinHMDBP02118F51q23DQ377944113654051139583805692ThrombinP00734BC05133213.4.21.595914246415456418456828267480136541515693Fibrinogen alpha chainP02671J0012712476151361684113654251139584805694Fibrinogen beta chainP02675J0012912477151361694113654351139585801699Fibrinogen gamma chainP02679Fibrinogen has a double function:yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregationHMDBP01954FGG4q28CH4710561247815136170411365445113958680636Coagulation factor XIII A chainP00488Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin.
HMDBP00672F13A16p25.3-p24.3M2199612.3.2.1324871513654551139591805695Coagulation factor XIII B chainP05160M64554124881513654651139592801570Coagulation factor VIIIP00451Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor XaHMDBP01727F8M8863312463151365364113653751139579801571Coagulation factor IXP00740Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIaHMDBP01730F9S6675213.4.21.221141162472151365344113653851139578801732Coagulation factor VIIaP08709Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calciumHMDBP02013F713q34DQ14291113.4.21.214972630702913948051139581805701Tissue factorP13726AF487337113948151139580805749LepirudinDB00001133351514092680133Coagulation factor X1PW_P00013315117302923531632Prothrombinase Complex1PW_P000632678179567917302933531247515138Prothrombin1PW_P0001381565692140Thrombin1PW_P0001401585692633531634Fibrinogen1PW_P000634681569368256946831699635Fibrin (loose)1PW_P000635684569368556946861699637Fibrin (mesh)1PW_P000637689569369056946911699144Coagulation factor XIII A chain1PW_P000144162636643531638Coagulation factor XIIIa1PW_P00063869263669356952953531145Coagulation factor XIII B chain1PW_P0001451635695627Tenase complex1PW_P000627672157067315712913531245615643Tissue factor:Coagulation factor VIIa1PW_P000643700173270157012963531250415818Lepirudin1PW_P00081894257491213217PW_R213217Right8198451331ProteinComplexfalse8198466321ProteinComplexfalse1389falsePW_R001389Right52711381ProteinComplexfalse52721401ProteinComplexfalse11086323.4.21.61391falsePW_R001391Right52756341ProteinComplexfalse52766351ProteinComplexfalse11101403.4.21.53185ActivationPW_I0031856369635ProteinComplex16370637ProteinComplex13186ActivationPW_I0031866371144ProteinComplex16372638ProteinComplex13187ActivationPW_I0031876373145ProteinComplex16374638ProteinComplex13203ActivationPW_I0032036405627ProteinComplex16406133ProteinComplex13174ActivationPW_I0031746347643ProteinComplex16348632ProteinComplex13204ActivationPW_I0032046407632ProteinComplex16408138ProteinComplex13205ActivationPW_I0032056409140ProteinComplex16410634ProteinComplex13497InhibitionPW_I0034976993818ProteinComplex16994140ProteinComplex13097867353809false181100510regular100253097868353809false961102020regular100253097869353809false1481100510regular100253097870353809false1236120010regular100253097871353809false158260710regular100253097872353809false190777720regular100253097873353809false42682520regular100253097874353809false107584419regular1002511958551730802false15610208subunitregular15070119585617958097false93110408subunitregular15070119585717308097false81110208subunitregular1507011958581730802false145610208subunitregular1507011958595692802false56112178proteinregular15070119586056928097false121112158subunitregular1507011958615693802false84813568subunitregular1507011958625694802false77314018subunitregular1507011958631699802false85314368subunitregular1507011958645693802false155313768proteinregular1507011958655694802false155813968proteinregular1507011958661699802false155814218proteinregular1507011958675693802true198817068subunitregular1507011958685694802true198816968subunitregular150701195869169980136false11353718proteinregular1751551195870636802false15576178subunitregular150701195871636802true229720028subunitregular150701195872569580113false18777128proteinregular1608011958735695802false15578178subunitregular15070119587415708097false4868108subunitregular15070119587515718097false4117708subunitregular15070119587617328097false105578410subunitregular15070119587757018097false11358248subunitregular150701195879574980246false151111728subunitregular17515594029213311525480119089711958554045130978674225557Cofactor9402936321152548011908981195856119089911958574045230978684225559Cofactor94029413311525480119090011958584045330978694225561Cofactor940295138115254801190901119585994029614011525480119090211958604045430978704225565Cofactor94029763411525480119090311958611190904119586211909051195863940298635115254801190906119586411909071195865119090811958669402996371152548011909091195867119091011958681190911119586994030014411525480119091211958704045530978714225571Cofactor9403016381152548011909131195871119091411958724045630978724225573Cofactor94030214511525480119091511958739403036271152548011909161195874119091711958754045730978734225577Cofactor9403046431152548011909181195876119091911958774045830978744225580Cofactor940306818115254119092111958794225557M481 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2252.380887721186 966.5751343230784false4225569M1713 1451 C1895 1454 1831 1454 1957 1454 C1958 1298 1959 1051 1957 792 149false184225570M1310 451 C1545 456 1961 452 1958 604 C1958 704 1957 640 1957 712 149false18trueM 2294.9468550441647 1432.261556296296 L 2280 1431 L 2286.380887721186 1444.5751343230784false4225571M887 1392 L887 1442 L937 1392 z10true184225572M1632 687 C1632 717 2197 1507 2197 1537 149true184225573M817 1627 L817 1677 L867 1627 z10true184225574M1877 752 C1800 749 1808 655 1707 652 149false18trueM 2660.9468550441647 1432.261556296296 L 2646 1431 L 2652.380887721186 1444.5751343230784false4225575M1632 887 C1632 917 2522 1560.75 2522 1590.75 149true184225576M1877 752 C1803 751 1807 852 1707 852 149false18trueM 2660.9468550441647 1240.261556296296 L 2646 1239 L 2652.380887721186 1252.5751343230784false4225577M811 1380 L811 1430 L861 1380 z10true184225578M486 840 C486 870 936 1502.5 936 1532.5 149true184225579M561 1046 C561 1016 561 910 561 880 149false18trueM 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Complex8131093201.51.51601587217715Vascular Injury1081443201.01.01601587217815Extracellular Space1712358201.91.91601587217915The fibrin mesh/clot forms at the site of vascular injury, blocking the leaking blood. Without the activation of fibrinogen into fibrin, the fibrin mesh cannot be formed. This impedes blood clotting so the thrombus cannot form. 1297428201.61.61601587218015Extrinsic Pathway294514202.22.21601587218115Intrinsic Pathway938599202.22.21601587218215Lepirudin is administered intravenous so it is delivered to the site of action.17021173201.31.31601587218315Lepirudin binds to the catalytic site of thrombin as well as the anion-binding exosite. This prevents the enzymatic activity of thrombin to cleave fibrinogen into fibrin monomers. 11701034201.31.3160152795531007218107348211115494420041201