anticoagulants Flashcards
what are Parental anticoagulants?
heparin and other LMW heparins
what are Oral anticoagulants?
warfarin and newer inhibitors
what is heparin?
Sulfated polysaccharide, glycosaminoglycan (GAG).
anticoagulant
where is heparin found?
Found in mast cells of the liver, intestine and lung (role not known).
•Heparin sulfate present in luminal endothelium
what is pharmaceutical heparin usually derived from?
porcine intestine
what is the average weight of heparin?
12kDA
how does heparin exert its anticoagulant activity?
Heparin exerts its anticoagulant activity by binding to an enzyme known as antithrombin III
is heparin polar?
very polar with lots of ionizable groups
why must heparin be administered IV?
lipinskis rule
is heparin stable?
yes, high degree of stability for acids and bases
unstable to oxidants
does heparin have a 3d structure?
no-does not fold
what is antithrombin 3?
erpin (serine protease inhibitor)- slow acting inhibitor that becomes a rapid inhibitor in the presence of heparin
The binding of heparin to ATIII induces a conformational change in ATIII, which makes ATIII a potent inhibitor of thrombin, XIIa, XIa, IXa, and Xa
what effect does LMW heparins have?
retained its activity against Xa whilst its activity against IIa was reduced
what are the benefits with LMWHs?
longer half life
better safety
why is warfarin not desired as first line anymore?
many drug-drug / drug-food interactions- usually vit K
what are warfarin and acenocoumarol based on?
heterocyclic system known as coumarin (2H-benzopyran-2-one)
what is Tautomerism?
Any reaction that involves the intramolecular transfer of a proton is called tautomerisation
example we use- keto-enol=-enolization
can be acid or base catalysed
when is the enol in the stable form?
intramolecular H-bonding can help to stabilise the enol form
1,3-dicarbonyl compounds
conjugated with the C=C bond of the enol will help to stabilise it
how many diastereomers are in the hemiketal form ?
4
what is the prodrug of dabigatran?
Dabigatran etexilate
dabigatran is a zwitterionic true/false?
true
what is the MOA of Dabigatran?
Selectively binds to the enzyme thrombin (Factor IIa) - limited binding with other serine protease enzymes.
•Binding site of the enzyme consists of three regions
–P, D and S1.-hydrophobic
what are the problems associated with dabigatran MOA?
llipophillic molecules have affinity for plasma- therfore lower activity
whats the MOA of newer drugs?
direct factor Xa inhibitors
what is the MOA of clopidigrol?
operates by forming a disulphide bridge with its target following oxidation and opening of a thiophene ring system.
