Pharmacology of Haemostasis and Anticoagulation Flashcards
what are the four types of drugs for haemostasis and anticoagulation?
anticoagulants
postracyclin/ nitric oxide
anti-platelet drugs
fibrinoylsis
what to anticoagulants do?
prevent unwanted thrombosis
oral anticoagulants
warfarin: vit. K antagonist (can be reverse by vit K injections)
block vit. K reductase (acts as cofactor for vit K) in liver
function of vitamin K
production of prothrombin and factors VII, IX and X
post- ribosomal carboxylation of glutamic acid residues of the factors
when is warfarin used
after surgery patients with replaced heart valves- foreign surface can form clots AF PE- prevent further clots DVT
how is warfarin monitored?
INR
2.5 narrow TW as risk of haemorrhage bleed in brain
drug interactions of warfarin
can be potentiated by drugs
reduced by enzyme inducers
increased actions of warfarin can lead to bleeding:
gastric cerebral haemoptysis(coughing up blood) blood in faeces, urine easy bruising
injectable anticoagulants
action
unfractioned heparin (liver derived) LMWH
activate antithrombin III- serine protease inhibitor (no thrombin made)
- inactivate factor X
immediate action
prevent thrombosis and prevent clotting on collection
when are injectable anticoagulants given
when warfarin takes effect, not long term as can cause thrombocytopenia
pregnancy- first 3 months then swap to heparin
monitored via APTT
Direct oral anticoagulants DOACs
Dabigatran: oral thrombin inhibitor
Rivaroxaban: oral inhibitor of factor X
prevents thromboembolism- less bleeding than warfarin, fewer drug interactions, doesnt need monitoring,
not as easily reversed
Prostacyclin/ nitric oxide are
endothelial derived vasodilators
PGI2 prostacyclin mechanism
Arachidonic acid in membrane -> free AA (PLA2)-> endoperoxides (COX)-> PGI2, prostaglandin, thromboxane
Prostaglandins increase/ associated with
pain, asthma, uterine function
PGI2 function
prevents platelet aggregation, acts on platelets to incresase cAMP
Thromboxane function
promotes platelet aggregation by decreasing cAMP
Nitric Oxide mechanism
L-arginine + O2-> NO+ citrulline
Nitrix oxide function
prevents platelet adhesion and aggregation by increasing platelet cGMP
Anti-platelet drugs
low dose aspirin
prevents secondary MI (patients had previous MI)
used to prevent CVD
reduces stroke incidence
inhibits cyclo-oxygenase irreversibly by acetylating N terminal serine on COX
how do anti-platelet drugs favour PGI2 production over TXA2
PGI2 produced in endothelium and TXA2 in platelets
platelets have no nuclei- cant produce anymore COX until new platelets are synthesised (7 days)- no TXA2
endothelial cells have nuclei- can produce more COX mRNA (2 hours) so PGI2 produced to inhibit platelets
Dipyridamole is
anti-platelet drug
phosphodiesterase inhibitor: prevents breakdown of cAMP and cGMP
ATP-> cAMP-> inhibits aggregation
cAMP-> AMP (phosphodiesterase)
when is dipyridamole used
in conjunction with aspirin
prevent thrombosis
also inhibits adenosine uptake
Glycoprotein IIb/ IIa
ADP from aggregating platelets leads to expression of GP IIb/ IIa
binds fibrinogen- crosslinking of platelets
Clopidogrel
irreversibly inhibits ADP-induced activation of GP. new for patients who cannot take aspiring
in ischaemic stroke it is given with aspirin
