Coagulants & anti coagulant Drugs

anticoagulants

1. Drugs Affecting Coagulation;
Bleeding & Thrombosis
By:-Dr. Manish Pal Singh,
Associate Professor
1
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA

2. Some Important Terminology’s:
✓Haemostasis-Limitingbloodlossconsequenttobleeding.
✓Thrombus-Aclotthat“adheres”toavesselwall.
✓Embolus-Intravascularclotthat“floats”inblood.
✓“Detached”thrombus–Embolus.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Fslideplayer.com

3. Blood coagulation
➢Bloodcoagulationinvolvecomplexinteractionsbetweentheinjuredvesselwall;
platelets&coagulationfactors.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Falevelbiology.co.uk
PROTHROMBINASE*

4. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
4
Source*-https%3A%2F%2Fwww.quora.com

5. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Two In-vitro Tests for Coagulation Efficacy of Blood System

6. Coagulants:
❑These are agents which promote coagulation and are indication in haemorrhagic
states.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Note*-Vitamin K2-(Produced by bacteria)-Menaquinones
Source*
-
https%3A%2F%2Fwww.youtube.com

7. VITAMIN K:
❑Inourbodysystemitisfatsolublevitamin,requiredforsynthesizedofclotting
factors.
❑‘Dam’(1929)-firstdescribethatbleedingdisorderinchickenbyfeeding
deficientdiet.
❑Asimilarvitaminwasisolated(1939)-from“AlfalfaGrass”&labelledVit.K1;
whilethatseafish(sardinemeal)waslabelledk2
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*
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https%3A%2F%2Fwww.123rf.com%2Fphoto_83348596_chemical
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formula
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of
-
vitamin
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k
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and
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some
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pills
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close
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up
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8. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Vit. K-
Naphthoquinone
Source-
green leaf,
spinach,
liver etc.
3-10 µg/day
Total req.
adult-50-
100µg/day

9. ➢Vit.Kactsasacofactoratalatestageinthesynthesisbyliverofcoagulation
proteins-(Prothrombin;VII;IX&X).
➢Fatsolubleformabsorbbyintestinevialymph&watersolubledirectlyabsorb
viaportalblood.
➢Deficiencyofitfoundsinliverdiseaseslike–jaundice;superinfectionby
antimicrobialuses.
➢Marketpreparationsare:-
➢Phytonadinone“KENADION”i.minjection(10mg/ml)
➢Menadione“GYNAE”
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Fwww.unitedpharmacies.md%2FKenadion-Phytomenadione.

10. ✓Indications of Vitamin K:-
✓Dietary deficiency
✓Prolong antimicrobial use
✓Malabsorption
✓Liver disorders –Viral hepatitis
✓Newborns (due to low level of Prothrombin)
✓Overdose of oral anti-coagulants (Hypo-prothrombinaemia).
✓Toxicity:-
✓Rapid i.v. injection produces-flushing, sense of constriction in the chest
✓Fall in BP
✓Menadionecan cause-haemolysis ( Patients with G-6-PD deficiency and neonates)
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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11. Anti-Coagulants
❑Drugsthatimpedebloodcoagulationandpreventtheoccurrenceorexpansion
ofathrombus.
❑Thesearedrugstoreducethecoagulabilityofblood.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*
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https%3A%2F%2Fwww.formularywatch.com%2Ffda
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approval%2Fblockbuster
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anticoagulant
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12. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Fwww.acrosspg.com%2Fnotes%2Fpharmacology%2Fclassification-of-anticoagulants%2F&psig

13. Heparin:
✓‘McLean’-1916-wasdiscoveredthatlivercontainpowerfulanticoagulant.
✓Heparinitsnameduetofoundin“Liver”.
✓Mainlyitispresentinalltissuescontaining“Mastcells”-(Lungsaretherichest
source).
✓Heparinusedbothin-vivo&in-vitro.
✓Anti-thrombinIII-Irreversiblyinactivatesthrombin&factorXa
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Fwww.indiamart.com%2Fproddetail%2Fheparin-sodium-injection

14. ➢Theheparin–ATIII-complexthenbindstoclottingfactorsoftheintrinsic&
commonpathways(Xa;IIa;IXa;Xia;XIIa&XIIIa)butnotextrinsicsystem.
➢LowconcentrationofheparinprolongaPTTwithoutsignificantlyprolongingPT;
highconcentrationprolongboth.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*
-
http%3A%2F%2Fread.nxtbook.com%2Fmedreviews%2Freviewscardiovascularmedicin

15. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*
-
https%3A%2F%2Fwww.nejm.org

16. ➢Injectionofheparinclearsturbidpost-prandillipaemic-byreleasinga
‘Lipoprotein-lipase’fromthevesselwall&tissue(LIPAEMIACLEARING).
➢Heparinisahighlyionizedmolecule;notabsorbedorally;i.v.injectionprefer.
➢Butrecenttrialsoralheparininunder‘Phase-III’-trial(SNAC-Heparin).
➢Dosesofheparini,.v.(5,000-10,000U;{Children50-100U/Kg).
➢ADR’s:-
➢Bleedingduetooverdose.
➢Haematuria
➢Thrombocytopenia
➢TransientAlopecia
➢Osteoporosis
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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17. Lowmolecularweightheparins(LMWH):-
✓Canbeadministereds.c.
✓Effectsareconsistent&dosinglessfrequent(Longt1/2&elimin.By1st
orderkinetics)
✓DonotprolongaPTT&CT(Responseispredictable&monitoringnot
required)
✓Doseisgiveninmg(notinunits)canbeeasilycalculatedonbodyweight
basis
✓Chanceofhaemorrhagechanceisless
✓Riskofosteoporosisisdecreased
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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18. HeparinAntagonist:-(ProtamineSulfate);
➢Itslowmolecularweightproteinobtainedfromthespermofcertainfish.
➢Doserequired1mgisneededforevery100Uofheparin.
➢Indicatedinthetreatmentofheparininducebleeding
➢Protamineismorecommonlyusedwhenheparinactionneedstobeterminatedrapidly;-Ex-
Aftercardiacorvascularsurgery.
➢Brand-“PROTA”-50mgin5mlinj.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*
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https%3A%2F%2Fwww.omnia
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health.com%2Fproduct%2Fprotamine
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sulphate
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injection
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50mg5ml&psig

19. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Heparinoids:-
▪HeparanSulfate-foundoncell
surface.
▪Danaparoid-Obtainedfrompiggut
mucosa(usedinheparininduced
thrombocytopenia).
▪Leprirudin-recombinantpreparation
ofhirudinactsbyinhibitingthrombin
directly
Source*
-
https%3A%2F%2Fsg.carousell.com%2Fp%2Fhirudoid
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heparinoid
-
cream
-

20. Oral Anti-Coagulants:
❑Warfarin-wasinitiallyusedasratpoison;itisnowcommonlyemployedoral
anticoagulantdrug.
❑Warfarinanditscongenersactsasanti-coagulantsonlyinvivo,notinvitro.
❑Theyactascompetitiveantagonistsofvit.K&reducetheplasmalevelsof
functionalclottingfactors.
❑CompetitivelyinhibitsvitaminKepoxidereductase&inhibitsthe
posttranslationalcarboxylationofglutamateresiduesonvitaminKdependent
coagulationfactorsII(prothrombin),VII,IX,andX.
❑ThecarboxylationisessentialfortheabilityoftheclottingfactorstobindCa++
&togetboundtophospholipidsurfaces-necessaryforcoagulation.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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21. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Fwww.cambridge.org

22. ❑RecemicWarfarinsod.-thecommercialpreparationofwarfarinisamixtureof
R(dextrorotatory)&S(levorotatory)enantiomers.
❑TheSformmorepotentthantheRform.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
22
Source*-http%3A%2F%2F119.9.73.171%2FUniwarfin-Warfarin-p-6349.

23. ADR’s:-
▪Bleeding(hematuria)
▪Treatment(specificantidote-Vit.K1).
▪Contraindicationsin-Pregnancy;inearlypregnancycausebirthdefects(Skeletal
abnormalities).
▪FoetalWarfarinSyndrome-Hypoplasiaofnose,eyesocket,handbones&growthretardations.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Drug Interactions:-
Source*
-
https%3A%2F%2Fwww.cmaj.ca%2Fcontent

24. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*
-
https%3A%2F%2Fwww.researchgate.net

25. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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•Haemodialysis•Cerebrovascular
disease
•Unstable angina•Myocardial infarction

26. Fibrinolytics (Thrombolytics)
❑Thesearedrugsusedtodissolve(lyse)clot(thrombi)toclearaoccludedblood
vessels(CAD).
❑Inbodysystemtheenzyme“Plasminogenactivator(t-PA),actasfibrinolytic
producedbyvascularendothelium.
▪Urokinase
▪Streptokinase
▪Anistreplase
▪Alteplase
▪Reteplase
▪Tenecteplase
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Clinically
Fibrinolytics

27. Mechanism of action:
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
27
Source*-http%3A%2F%2Fwww.pharmacy180.com%2Farticle%2Ffibrinolytics-(thrombolytics)

28. ➢Streptokinase-Itisobtainedfrom-‘Streptococci’groupC.Antigenic-cause
hypersensitivityreactions.
➢Urokinase-Itisanenzymeisolatedfromhumanurine;nowpreparedfrom
culturedhumankidneycells.Feverduringtreatment.
➢Alteplase-rt-PA(recombinanttissueplasminogenactivator)producedby
recombinantDNAtechnologyfromhumantissueculture.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Fwww.facebook.com%2FEMNote.org

29. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Uses of Fibrinolytics
Acute
myocardial
infarction
Deep vein
thrombosis
Pulmonary
embolism
Peripheral
arterial
occlusion
Stroke

30. Anti-Platelet Drugs
❑Thesearedrugswhichinterferewithplateletfunctionandareusefulintheprophylaxisof
thromboembolicdisorders.
❑Plateletsexpressseveralglycoproteinontheirsurface.
❑Theyareexposedwhenthereisdamagetovascularendothelium&interactwithplateletreceptor
protein.
AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Fwww.quora.com%2FWhat-is-the-function-of-the-blood-platelets

31. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*-https%3A%2F%2Fthoracickey.com%2Fantiplatelet-therapy

32. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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Source*
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https%3A%2F%2Fwww.researchgate.net%2Ffigure%2FFig
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1
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33. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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UsesofAntiplateletdrugs;-
▪MI-LowdoseAspirin
▪Unstableangina-Aspirin/Clopidogrel
▪Coronarybypassimplants
▪Prostheticheartvalves
▪Arteriovenousshunts
▪Venousthromboembolism
▪Peripheralvasculardisease
▪Cerebrovasculartransientischemicattacks