Anticoagulants Flashcards
source of heparin
mast cells
basophils
what are low molecular weight heparins (LMWH)?
fractionated heparins with MW < 8000 Da
how does heparin inhibit factor Xa?
binds only to ATIII
how does heparin inhibit thrombin?
binds to both ATIII and factor IIa
LMWH binding to thrombin
most are too short to bind to exosite 2 of thrombin
Its ability to inhibit thrombin increases when the MW increases
what is warfarin a synthetic derivative of?
coumarin
warfarin MoA
Blocks vitamin K epoxide reducatase enzyme, which uses vitamin K to produce clotting factors
which stereoisomer of warfarin is more potent?
S-warfarin (x5 more potent)
metabolism of warfarin
[via CYP P450 enzymes]
S-Warfarin = CYP2C9
R-Warfarin = CYP2C19
pros of warfarin
cost effective
has an antidote (vitamin K)
cons of warfarin
Complex pharmacokinetics & liver metabolism
Polymorphism in VKORC1
→ Asian Americans = more sensitive (group A haplotypes)
→ African Americans = more resistant (group B haplotypes)
Polymorphism in CYP2C9
→ Caucasian patients = reduced warfarin metabolism
what increases plasma levels of warfarin?
excess alcohol
Drugs that displace warfarin from albumin (e.g. aspirin, NSAIDs + Clofibrate)
Diseases (e.g. liver diseases + hyperthyroidism)
what decreases plasma levels of warfarin?
Drugs that reduce GI absorption
Chronic alcoholism (increases activity of P450 enzymes)
Hypothyroidism
Diet - excessive consumption of green plants (vitamin K source)
general therapeutic applications of anticoagulants
Treatment of unstable angina + prevention of STEMI (with aspirin + antiplatelets)
Prophylaxis of stroke, DVT and PE
general adverse reactions of anticoagulants
Bleeding
Subcutaneous haemorrhage
Immune thrombocytopenia
Hyperkalaemia
