Anticoagulant Drugs and Antiplatelets Flashcards
what is haemostasis?
arrest of blood loss from damaged blood vessels
how does haemostasis occur?
- vascular constriction
- formation of platelet plug
- formation of blood clot as a result of coagulation
- growth of fibrous tissue into clot to close hole permanently
what are some causes of acquired clotting defects?
- liver disease
- vitamin k deficiency
- ingestion of oral anti-coagulants
how are acquired clotting defects treated?
- natural vitamin k (phytomenadione)
- menadiol sodium phosphate (synthetic)
what are clinical uses of vitamin k?
- treatment and/or prevention of bleeding from excessive oral anticoagulant use
- in babies to prevent haemorrhagic disease of newborn
- vitamin k deficiency in adults
what are features of warfarin?
- main oral anticoagulant in uk
- prevents reduction of vitamin k
- many hours to act (time taken for degradation of factors already formed)
- main side effect haemorrhage
when does vitamin k acts as a co-factor?
in the post-translational processing of factors II, VII, IX and X
what factors increase the effect of oral anticoagulants?
- decreasing availability of vitamin k
- broad spectrum antibiotics
- liver disease
- some drugs
what properties of drugs increase effect of oral anticoagulants?
- impair platelet function
- displace warfarin from binding sites in plasma albumin
- agents which inhibit microsomal enzymes in liver
what factors decrease the effect of oral anticoagulants?
- drugs which increase drug metabolism
- oral contraceptive
what are some injectable anticoagulants?
- heparin (e.g dalteparin)
- heparin sulphate (not used therapeutically)
what are features of heparin?
- e.g. dalteparin
- family of sulphated gylcosaminoglycans
- naturally occurring
- found in mast cells, plasma, endothelial cells
- starts acting almost immediately
what are features of heparan sulphate
- not used therapeutically
- a related glycosaminoglycan
- occurs extracellularly in many tissues
- important endogenous anticoagulant
what is the role of heparin?
acts mainly on fibrin formation:
- acts on antithrombin III (naturally occuring inhibitorof thrombin) and other serine proteases in coagulation cascade (XIIa, XIa, IXa and Xa)
- antithrombin forms 1:1 complex by with thrombin by binding to active site
- heparin accelerates rate of this inhibition
what are direct inhibitors of factor Xa?
rivaroxaban or apixaban
what are features of direct factor Xa inhibitors?
- both orally active
- do not require PT/INR monitoring
- takes a few hours to act
- effects last 8-12 hours
- no antidote
what do antiplatelet drugs do?
decrease platelet aggregation and inhibit thrombus formation - not anticoagulants
what are some examples of antiplatelets?
- aspirin
- clopidogrel
what is the action of aspirin?
inhibit cyclooxegenase
what is the action of clopidogrel?
- inhibits P2Y12 purinergic receptors
- inhibits ADP-induced platelet aggregation
what is fibrinolysis?
- clot dissolving system
- set in motion when intrinsic coagulation system is activated
- involves generation of plasminogen activators
what is plasminogen?
inactive pro-enzyme
- deposited in fibrin strands within thrombus
what is plasmin?
- trypsin-like enzyme acting on ARG-LYS bonds
- formed and acts locally on fibrin meshwork of the clot
what does plasmin do?
- digests not only fibrin but other blood proteins such as factors II, V and VII
- plasmin which escapes into circulation is inactivated by various plasmin inhibitors
name a fibrinolytic agent?
streptokinase
what are features of streptokinase?
- non-enzymatic protein
- acts indirectly
- forms a stable complex with plasminogen
what is an example of a TPA (tissue plasminogen activator)?
alteplase
what are features of alteplase?
- synthesised in vivo by endothelial cells
- can be made by recombinant technology
- enzymatic activity enhanced more in presence of fibrin-bound plasminogen than plasma plasminogen (clot selective)
which anticoagulant is used for venous thromboembolism?
heparin: short-term action
oral anticoagulants: prolonged therapy
what are therapeutic anticoagulants used for?
- DVT
- PE
- thromboembolism from atrial fibrillation
- prosthetic heart valves
- clotting during kidney dialysis
what are therapeutic uses for fibrinolytic agents plus aspirin (antiplatelet)?
- used in therapy of acute myocardial infarction
- former needs to be given within 4-6 hours of onset
what are therapeutic uses for aspirin?
can reduce risk of occlusive cardiovascular disease in patients already diagnosed as being at risk
