Coagulant and anticoagulant

what is coagulants, their mechanism of clotting and classification of coagulants. anticoagulants and their classification

1. B pharmthird year, semester fifth
Coagulants and
Anticoagulants
Presented by
Miss. AshviniGovande
Assistant Professor
KandharCollege of Pharmacy, Kandhar

2. Coagulants
•Coagulants are drugs which promote clotting. These drugs are
used in hemorrhagic states.
•Coagulation is the process of transforming a liquid into solid,
especially of the blood and it means blood clotting.
•Coagulants are classified as:•Coagulants are classified as:
1)Local acting: Adrenaline, Gelatinspongue, sodium alginate,
oxidised cellulose
2)Replacement of clotting factor: Whole blood transfusion,
vitamin K, calcium
3)Antiheparinacting drugs: Protamine, toluidineblue,
hexadimethrinebromide

3. Mechanism/processing of clotting
Thromboplastin
calcium

4. Local acting drugs
1)Adrenaline:Itproducesvasoconstrictionwhenappliedlocally.It
increasedcoagubilityofbloodduringemotions,stressand
endogenousadrenalineliberation.
2)Sodiumalignate:Itisobtainedfromseaweedsalgaenamely
laminariacloustoniisusedaslocalhomostatic.
3)Oxidizedcellulose:Itispreparedbynitrogendioxideoxidationof3)Oxidizedcellulose:Itispreparedbynitrogendioxideoxidationof
surgicalgauzeorcotton.Itshaemostaticactiondependsuponthe
formationofartificialclot.Itisusedforthecontrolofhaemorrhagein
surgicalprocedure.Itisapplieddryintheformofcottonpads,gauze
strips.
4)Gelatinsponge:Itispreparedbyheatinggelatincontainingsmall
quantityofformalin,whiskingtoaporousfoam,freezdrying,packed
andsterilizedbydryheat.Absorbablegelatinspongeisusedas
hemostatic.Whenappliedtobleedingsurfaceaclotisrapidlyformed.

5. Replacement of clotting factor
•Wholebloodtransfusion:
Transfusionofwholehumanblood,horseserumwhich
containsthrombinandprothrombin,theyreplacetheclotting
factorwhicharedeficient.factorwhicharedeficient.
Freshwholebloodorbloodplasmaprovidesallfactors
requiredforcoagulationandisbesttreatment/therapyfor
deficiencyofanyclottingfactor.

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•VITAMINK:
•VitaminkItisafatsolublevitaminrequiredforthesynthesis
ofclottingfactors.
•Itisfoundinplants.
•Itisrequiredforformationofprothrombinbyliver.Itisthe•Itisrequiredforformationofprothrombinbyliver.Itisthe
normalconstituentofblood,wheninjuryoccursithelps
clottingofblood.
•VitaminKiscalledasKoagulationvitamin.In1939similar
vitaminwaspreparedfromalfaalfagrassandwascalledas
vitamink1,fromsardine(seafish)vitaminKpreparedwas
labeledask2,syntheticcompoundspreparedandislabeledas
vitamink3.

7. Phytonadione (Vitamin K1)
•Vitamink1,phytonadioneisfatsolublevitamin.Itisobtained
fromalfaalfagrass.Itisneededforbloodclotting.
•MOA:Itshowstheclottingeffectbyclotting,theclotting
factorII,VII,IX,X.

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•Indications:Preventionofhemorrhagicdiseaseofnewborn,
vitaminKmalabsorption,hypoprothrombinemia.
•Dosage:hemorrhagicdiseaseofnewborn-NewnatesSC/1M
0.5to1mgafterbirthrepeatafter6-8hrsifrequired.
•Hypoprothrombinemia:Adult-Orallyorintramuscular2-
25mg.Child-bymouthor1Minjection5-10mg.Infants-Orally25mg.Child-bymouthor1Minjection5-10mg.Infants-Orally
1Minjection2mg.
•Contraindications:Hypersensitivity,severeliverdisease,
pregnancy(lastfewweeks).
•Sideeffects:Headache,withlargedosebraindamageoccurs,
nausea,skinrash,urticaria,hemolyticanaemia,
hyperbilirubinemia.

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•Pharmacokinetics:Itismetabolizedinliver,excretedin
urine.
•Druginteraction:Decreasedactionoforalanticoagulants
drugs.
•Brandname:VitaminK-TabletCardisperC,Gystat,Kaplin,•Brandname:VitaminK-TabletCardisperC,Gystat,Kaplin,
Stypindontablets.
•Precautionsforpatients:
Totakedietarysourceofvit.klikespinach,tomatoes,coffee,
liver,lettuce.
Patientshouldnottakeanymedicinethanprescribed.

10. Fibrinogen
•Thefractionofhumanplasmafibrinogenisusedtocontrol
bleedinginhaemophilia,antihaemophilicglobulin(AHG)
deficiency.
•MOA:
Liver tissue factor platelet factorLiver tissue factor platelet factor
Vitamin K-independent factors
Vitamin K-dependent factors
factor Xa
Thrombin
Fibrinogen soluble plasma protein fibrinogen insoluble clot
Circulation

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•Dosage:Adult0.5gmiv.
•Available:TabletcadisperCcontainingmenadionesodium
bisulphite20mg,methylhesperidin40mg,Rutin60mg,
vitaminC-100mgadrenochromemonosemicarbazine1mg,
dibasiccalciumphosphate100mg
.
dibasiccalciumphosphate100mg
.

12. Ethamsylate
•Itisusedtoreducecapillarybleedingwhenplateletsare
adequate.
•Usedintreatmentandpreventionofcapillarybleedingincase
ofmenorrhagia,malena,hematuria,epistaxis,andaftertooth
extraction,haemoptysis,haematemesis,postabortion,post
partumhaemorrhage.
•Dosage:Adult250-500mg3timesaday.•Dosage:Adult250-500mg3timesaday.
•Sideeffects:Headache,nausea,skinrash,hypotension
transientwithinravenousinjection.
•Contraindications:Hypersensitivity,pregnancy,lactation,
acuteporphyria.
•Brandnames:Ethamsylate-tablet,injectioncosklot,alstat,
dicynene,ethaclot,ethamstat,ethasyl,zylate250mg,500mg
tablet,injection250mg/ml.

13. Calcium dobesilate
•Itactoncapillarywallsbyregulatingtheimpaired
physiologicalcondition,itincreasespermeabilityand
decreasesresistance.Itopposesthebreakdownofcollage.
•Indication:Postthrombicsyndrome,treatmentofprimaryand
secondaryvericoseveins.secondaryvericoseveins.
•Dosage:Adultorally500mgto1gmoncedailywithmeals.
Forfewweekstoseveralmonthaccordingtothedisease,
treatment/therapy.
•Contraindications:Hypersensitivity,pregnancy,lactation.
•Sideeffects:Vomiting,nausea,diarrhoea,skinrash,fever.
•Brandname:Calciumdobesilate-capsuledobest,dobium,
vasoflo,doxium500mg,caldob,dobesil500mgcapsule.

14. Adrenochrome mono semicarbazone
•Itreducescapillaryfragility,controlsoozingfromraw
surfaces,microvesselbleeding.
•Indications:Hematuria,epistaxis,retinalhaemorrhage,
secondarybleedingfromwounds.
•Dosage:Adult1-5mgorally,iminjection.•Dosage:Adult1-5mgorally,iminjection.
•Contraindications:Hypersensitivity,usewithprecautionsin
pregnancy,lactation,elderperson.

15. Protamine sulphate
•Itisheparinantagonist,alowmolecularweightprotein.Itis
usedasantidoteforheparininuncontrolledbleeding.
•MOA:itbindsheparinsodiumbymakingitineffectiveandis
usedinheparinoverdose.Itishighlycationicpeptidethat
bindstoeitherheparinorlowmolecularweightheparintobindstoeitherheparinorlowmolecularweightheparinto
formastableionpair,whichdoesnothaveanticoagulant
activity.Theioniccomplexisthenremovedandbrokendown
bythereticuloendothelialsystem.
•Indication:Antidoteforheparin,heparinoverdose.
•Dosage:Adultandchild1mlofprotaminesulphateneutralize
theeffectofheparin.

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•Contraindications:Hypersensitivity,usewithcarein
pregnancy,lactation,children.
•Sideeffects:Vomiting,nausea,lossofappetite,urticaria,
anaphylaxis,pulmonaryedema,dyspneahypotension,
bradycardia,circulatorycollapse.bradycardia,circulatorycollapse.
•Pharmacokinetics:Onsetaction(IV)5min,durationofaction
2hrs,excretedinurine.
•Brandname:Protamin:Injectionprota,protaminesulphate,
newtain50mg/mlinjectionpervial.

17. Anticoagulants
•Anticoagulants Drugs which helps prevent the clotting of
blood.
•Anticoagulants are classified as-
1)Drugs used in vivo:
a)Heparin, Low molecular weight heparin-a)Heparin, Low molecular weight heparin-
heparinoids-Heparin sulphate
Danaparoid-Ancrod, lepirudin.
b)Coumarinderivatives-Dicoumarol, Warfarinsodium,
Ethylbiscoumacetate.
2)Drugs used in vitro:
sodium citrate, sodium oxalate, ethylene diaminetetra acetic
acid (EDTA), sodium edetate.

18. Heparin
•HeparinMcLean,amedicalstudent,discoveredthatliver
containsapowerfulanticoagulant.HowellandHoltnamedit
‘HEPARIN’-obtainedfromliver.
•MixtureofmucopolysaccharideswithMW10,000to20,000.
•ItcontainsD-glucosamine-L-iduronicacidandD-•ItcontainsD-glucosamine-L-iduronicacidandD-
glucosamineD-glucuronicacid.
•Itcarriesstrongelectronegativechargeandisthestrongest
organicacidpresentinthebody.
•Foundinthesecretarygranulesofmastcells.Richestsources
arelung,liverandintestinalmucosa.
•Commerciallyproducedfromoxlungandpigintestinal
mucosa.

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•MOA:
•Intrinsic pathway extrensic pathway
Factor Xa Heparin
Prothrombin Thrombin
Fibrinogen Fibrin
Clotting

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•Metabolism:Heparinafteroraladministrationisnoteffective.
Itiswellabsorbedbyscandiminjections.Itismetabolizedin
liverbyanenzymecalledasheparinase.Itisexcretedinurine.
•Adverseeffect(toxicity)ofheparin:
1)Duetooverdose,dangerofbleddingismostserious
complicationsofheparin.Hematuriaoccurs.complicationsofheparin.Hematuriaoccurs.
2)Alopeciaonprolongeduseofheparin
3)Allergicandanaphylacticreactions.
4)Onlongtermuseofheparinosteoporosismaydevelopwith
higherdoses.
5)Thereisoccurrenceofthrombocytopeniaduetowhich
numberofplateletisreduced.

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•Indications:Heparinisusedasanticoagulantintransfusion
anddialysisprocedure,thromboembolicconditions,deepvein
thrombosis,openheartsurgery,disseminatedintravascular
clottingsyndrome,myocardialinfarction.
•Dosage:Deepveinthrombosisandmyocardialinfarction
•Adult:IV5000-10000unitsevery4-6hrsordeepscinjection•Adult:IV5000-10000unitsevery4-6hrsordeepscinjection
25000U12-24hourly.
•Children:50-100units/kgbodyweightevery4-6hrs.
•Openheartsurgery:AdultIVinfusion150-300Uperkg
bodyweight.
•Sideeffects:Bleedingduetooverdose,transientand
reversiblealopecia,osteoporosis,hypersensitivity,vomiting,
nausea,fever,chills,hepatitis,abdominalcramps,hematuria,
thrombocytopenia,skinrash,urticaria.

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•Contraindications:Hypersensitivity,bleedingdisorder,
hemophilia,pepticulcerdisease,severehypertension,piles,
thrombocytopenia,threatenedabortion,tuberculosis,chronic
alcoholics,aspirinandotherantiplateletdrugs.Incaseof
pregnancyitisclearlyindicatediftakenneardeliverytherepregnancyitisclearlyindicatediftakenneardeliverythere
maybeexcessivebleeding,elderly.
•Pharmacokinetics:IVpeakconc.5min,durationofaction2-
6hrs,SConset20min,duration8-12hrs,doesnotcross
placenta,breastmilknotaltered,excretedinurine.
•Druginteraction:Heparindecreaseactionofcorticosteroids,
increaseactionofheparin,actionofheparinisincreasedwith
oralanticoagulants,aspirin,steroids,dextran.

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•Brandname:Heparin:injection,heploc,unihep,caprin,
beparin,declot,heparin,inhep,thromboparin1000,5000IU
perml.
•Treatmentofoverdose:
•Discontinueuseofheparin,administerprotaminesulphate.•Discontinueuseofheparin,administerprotaminesulphate.

24. Heparinoids
•Itissubstitutesofheparin.
•Thesearesulfatedpolysaccharideshavingstrongnegative
charges.
•Heparinsulphate:
•Itisheparinlikenaturalsubstancefoundincellsurfaceand•Itisheparinlikenaturalsubstancefoundincellsurfaceand
intracellularsurfacematrixinmanytissues.
•Heparinsulphateislesspotentanticoagulantthanheparin.

25. Danaparoid
•Itispreparationcontainingmainlyheparinsulphateobtained
frompig,gutmucosa.Itisusedincasewithheparininduced
thrombocytopenia.Itislowmolecularweightheparinitactsas
anticoagulant.
•MOA:•MOA:
•Danaparoidpreventsfibrinformationinthecoagulation
pathwaybyinhibitingthrombingenerationthroughthe
inhibitionofcoagulationfactorXaandthrombin(factorIIa).
Unlikeheparin,however,danaparoidpreferentiallypotentiates
theinhibitionofcoagulationfactorXa,witharatioofanti-
factorXaactivitytoanti-factorIIaactivitygreaterthan22:1.

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•Indications:Preventionofveinthrombosisinhemodialysis
hipfracturesurgery,totalhipreplacement.
•Dosage:Venousthrombosisprevention
•Adult:SCinjection750antiXaunitstwicedailyfor1week.
•Hemodialysis:IV2400-4800antiXaunitspredialysis.•Hemodialysis:IV2400-4800antiXaunitspredialysis.
•Hipfracturesurgery:Adult-SCantiXaunitstwicedailyfor
10-12dayspostoperatively.
•Sideeffects:Hypersensitivity,skinrash,thrombocytopenia.

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•Contraindications:Hypersensitivity,hemophilia,leukemia,
severehypertension,cardiacdisease,purpura.
•Pharmacokinetics:whenadministeredSCiswellabsorbed.
Peakplasmaconc.Isattained4hrs,plasmahalflife2-3hrs,
excretedbykidneys.excretedbykidneys.
•Druginteraction:increasedriskofbleedingwithoral
coagulants,aspirin.
•Treatmentofoverdose:protaminesulphate1%IV.

28. Ancrod
•Itisanenzymeobtainedfrommalayanpitvipertoxin.
•Itdegradefibrinogentounstablefibrinwhichistakenupby
reticuloendothelialcells,fibrinogengetsdepletedandheparin
likeeffectapparentlyresults.
•Itisadministeredslowlybyinfusion2Uperkgin6hrsfor•Itisadministeredslowlybyinfusion2Uperkgin6hrsfor
deepveinthrombosisinpatientswhodevelop
thrombocytopenia.
•Brandname:Orgaran750unitIV,SC.

29. Lepirudin
•Itisapreparationofhirudin,whichisapolypeptide
anticoagulantsecretedbysalivaryglandofleech-whichact
directlybyinhibitingthrombinformation.
•Itisadvisedtoorrecommendedtopatientwithheparin
inducedthromocytopenia.inducedthromocytopenia.
•MOA:Lepirudinisadirectandirreversibleinhibitorof
thrombin,whichisakeyserineproteaseinthehemostatic
system.Thrombinisgeneratedviaactivationofits,pro-
thrombin,bytheprothrombinasecomplex.
•Indication:heparininducedthrombocytopenia
•Brandnames:Refludanpowder50mg1mlIV.

30. Coumarin derivatives
•Dicoumarol(Bishydroxycoumarin):
•Itisavailableascolorlesscrystallinesolidinsolubleinwater.
Itisusedaloneorwithheparin
•Indication:postoperativethrombophelebitis,pulmonary
embolism,coronaryocclusion.embolism,coronaryocclusion.
•Pharmacokinetics:orallyitabsorbsslowly.Metabolism
dependsondose
•Contraindications:liverdisease,renalfunctionimpairmentand
whoarebleedingfromanycase.

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•Side effects: the colour of urine patient may be changes due to
hematuria, when administered orally it causes gastro intestinal
disturbance.
•Dose:first day administer dose 5 mg/kg of body weight 200-
300 mg orally is administered check prothrombin time if found 300 mg orally is administered check prothrombin time if found
normal omit the dose or reduce dose. In adult maintenance
dose is 50mg-75mg daily. Toxic dose of drug is 40mg/kg body
weight causes death in animal through damaging liver.

32. Warfarin sodium
•Itiswhitecrystallinepowdersolubleinwater.
•MOA:
CompetitiveantagonistofVit.Klowerstheplasmalevelofvit.
Kdependentclottingfactors–InhibitsvitaminKepoxide
reductase(VKOR)neededtogenerateactiveVit.K.reductase(VKOR)neededtogenerateactiveVit.K.
Synthesisofclottingfactorsdiminisheswithinfewhours,at
differenttimesbydiff.factors.
Butanticoagulantactionstartsin1-3daysonly.
•Indication:postcardiacvalvereplacement,pulmonary
embolismvenousthrombosis,myocardialinfarction.
•Sideeffects:Vomiting,nausea,anorexia,stomatitis,hepatitis,
skinrash,urticaria,fever.

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•Contraindications:Hypersensitivity,pregnancy,lactation,
hepaticdiseases,renalimpairmet,cerebrovascularhemophilia,
leukemia,severehypertension,cardiacdisease,purpura.
•Pharmacokinetics:orallyonsetaction12-24hrs,peakplasma
conc.1-2days,durationofaction3-5days,metabolisedinliver,
crossesplacenta,excretedinurine.crossesplacenta,excretedinurine.
•Druginteraction:increasedactionofwarfarinwithdruglike
chloramphenicol,disulfiram,metronidazol,sulfonamide,
chloralhydrate,phenylbutazone,isoniazide.Actionof
warfarinisdecreasedbydruglikerifampin,barbiturates,
griseofulvin,oralcontraceptives,estrogen.
•Brandname:Warfarin:Tabletwarf,uniwarfin,sofarin,
1,2,5mgtablets.

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•Precautionsforpatient:
•Tousesofttoothbrushtoavoidgumbleeding.
•Avoiduseofrazors.
•Toavoidsmoking
•Toavoidplayingwithfootball,hockey,workwithheavy•Toavoidplayingwithfootball,hockey,workwithheavy
machinary,dangerousworkthatcausesinjury.
•Totakevitaminmineralrichdiet
•Informdentistorotherphysiciandoctorregarding
anticoagulantdrugtherapy.
•Treatmentoverdose:administervitamink.

35. Ethyl biscoumaactate(Tromexan)
•Itissyntheticanticoagulantdrugofthecoumarinseries.
•ItwassynthesizedbyLinkandhisassociatesin1942.
•Itiscolorless,crytallinepowder.
•Itisinsolubleinwater.
•Itislesspotentthanbishydroxycoumarin.•Itislesspotentthanbishydroxycoumarin.
•Itisrapidlyabsorbedandrapidlyexcreted.Ithasshort
durationofaction.
•Itcanbeadministeredtopatientofthromboembolicdisease
forlongperiod.
•Doseis600-900mgdailyindivideddoseorally.
•Whendoseisnotproperlyregulatedseverebleedingcan
occur.

36. In vitro anticoagulants
•Thesecompoundsarechelatingagentslikecitrate,oxalates,
filuorides,ethylenetetraaceticacid(EDTA).
•Thesecompoundsactbyremovingcalciumions.
•MOA:Isanessentialfactorofbloodcoagulation,when
anticoagulantslikeoxalatesaltsareaddedtobloodcalciumanticoagulantslikeoxalatesaltsareaddedtobloodcalcium
oxalateisformed.Thiscalciumoxalateformedprecipitatedin
aninsolubleform,thusbloodlackingcalciumionsisfailedto
clot.

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•Doubleoxalate:Mixturecontain6partsofammonium
oxalateandfourpartsofpotassiumoxalate.
•Use2mg/mlofbloodi.eitcontain1.2mgofammonium
oxalate0.8mgofpotassiumoxalatepermlofblood.
•Usedforhemoglobinestimation,bloodgrouping,RBCcount,•Usedforhemoglobinestimation,bloodgrouping,RBCcount,
totalleukocytecount,ESR.Doubleoxalatemixturecannotbe
usedforbloodurea,serumpotassiumestimation.
•Trisodiumcitrate:3.8%aqueoussolutionoftrisodiumcitrate
isusedforstudyESR.
•Sodiumfluoride:itisusedforbloodsugarestimation10-
20mg/mlofbloodisused.

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•EDTA:
•ThedipotassiumordisodiumsaltofEDTAareusedinthe
conc.of1mg/mlofbloodusedforbloodstudy.
•Anticoagulantsandpreservativessolutionsusedas
preservativeforblood.preservativeforblood.
•Sterilepyrogenfreesolutionsofsodiumcitrateorsodiumacid
citrateanddextroseinwaterforinjectionaresuitablesolution
forbloodpreservation.

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•Acid(Acidcitrate,dextrosesolution):
•Thesolutionispreparedasperformula-Sodiumcitrate22gm,
citricacidmonohydrate8gm,dextrosemonohydrateforIV
use24.5gm,waterforinjection1000ml.Volumefor
collectionof100mlofwholehumanbloodisrequired15ml.collectionof100mlofwholehumanbloodisrequired15ml.
•Thesolutionisusedtopreventcoagulationofbloodwhichis
collectedforbloodtransfusion.
•Theotherformulaiscitratephosphatedextrosesolution,which
isrequired14mlforcollectionof100mlofblood.
•Sodiumedetate:itisusedasanticoagulant2mgin1mlof
bloodandsodiumoxalate10mg/mlblood,usedinbloodtaken
forlaboratoryinvestigation.