anticoagulants

Question 1

what are Parental anticoagulants?

Answer 1

heparin and other LMW heparins

Question 2

what are Oral anticoagulants?

Answer 2

warfarin and newer inhibitors

Question 3

what is heparin?

Answer 3

Sulfated polysaccharide, glycosaminoglycan (GAG).

anticoagulant

Question 4

where is heparin found?

Answer 4

Found in mast cells of the liver, intestine and lung (role not known).
•Heparin sulfate present in luminal endothelium

Question 5

what is pharmaceutical heparin usually derived from?

Answer 5

porcine intestine

Question 6

what is the average weight of heparin?

Answer 6

12kDA

Question 7

how does heparin exert its anticoagulant activity?

Answer 7

Heparin exerts its anticoagulant activity by binding to an enzyme known as antithrombin III

Question 8

is heparin polar?

Answer 8

very polar with lots of ionizable groups

Question 9

why must heparin be administered IV?

Answer 9

lipinskis rule

Question 10

is heparin stable?

Answer 10

yes, high degree of stability for acids and bases

unstable to oxidants

Question 11

does heparin have a 3d structure?

Answer 11

no-does not fold

Question 12

what is antithrombin 3?

Answer 12

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

Question 13

what effect does LMW heparins have?

Answer 13

retained its activity against Xa whilst its activity against IIa was reduced

Question 14

what are the benefits with LMWHs?

Answer 14

longer half life

better safety

Question 15

why is warfarin not desired as first line anymore?

Answer 15

many drug-drug / drug-food interactions- usually vit K

Question 16

what are warfarin and acenocoumarol based on?

Answer 16

heterocyclic system known as coumarin (2H-benzopyran-2-one)

Question 17

what is Tautomerism?

Answer 17

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

Question 18

when is the enol in the stable form?

Answer 18

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

Question 19

how many diastereomers are in the hemiketal form ?

Answer 19

4

Question 20

what is the prodrug of dabigatran?

Answer 20

Dabigatran etexilate

Question 21

dabigatran is a zwitterionic true/false?

Answer 21

true

Question 22

what is the MOA of Dabigatran?

Answer 22

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

Question 23

what are the problems associated with dabigatran MOA?

Answer 23

llipophillic molecules have affinity for plasma- therfore lower activity

Question 24

whats the MOA of newer drugs?

Answer 24

direct factor Xa inhibitors

Question 25

what is the MOA of clopidigrol?

Answer 25

operates by forming a disulphide bridge with its target following oxidation and opening of a thiophene ring system.