Drugs used in anticoagulation Flashcards
What are the 3 classes of drugs used in anticoagulation?
1) Anticoagulants (including vitamin K antagonists)
2) Antiplatelets
3) Fibrinolytic drugs (thrombolytics)
Where in the circulation are anticoagulants most effective? give examples of situations.
Anticoagulant drugs are best suited to preventing and treating venous thrombosis and embolism, because the slower moving circulation allows the formation of thrombi composed of a fibrin web enmeshed with platelets and red blood cells. Thrombin is what converts Fibrinogen to Fibrin, and seeing as aticoagulants affect thrombin production they are particularly suited.
Examples: DVT, prevention of post-operative thrombosis, atrial fibrillation, patients with artificial heart valves.
Where in the circulation are antiplatelets most effective? Give examples of situations.
Anti platelets are best suited to treating and preventing arterial thrombosis seeing as thrombi in the faster moving circulation are mostly composed of platelets.
Examples: reducing the risk of MI in patients with unstable angina, increasing the survival of patients who have had an MI, reduce the risk of stroke in patients who experience TIA.
What is the process by which arterial thrombi occur?
It is the lipid rich plaques which rupture in atheromatous arteries, exposing subendothelial collagen which in turn activates platelet aggregation.
This releases thromboxane-A2 (TXA2), adenosine diphosphate (ADP) and 5-hydroxytryptamine (5HT), which promote 1) further platelet aggregation, 2) vasoconstriction and 3) activation of the clotting cascade.
How do fibrinolytics work?
They rapidly lyse thrombi by activating plasminogen to form plasmin.
What does plasmin do?
Plasmin is a proteolytic enzyme that degrades fibrin and so dissolves thrombi.
In what instances are fibrinolytic drugs used?
They are used, often in combination with antiplatelets, in the treatment of MI.
When and which fibrinolytics should be used in the case of an MI?
Beneficial effects are greatest if the drug is administered within 30 mins and become progressively less effective over 24hrs. Any are good, and it has been shown that speed rather than choice is the most effective factor.
Name 3 fibrinolytic drugs.
Streptokinase
Alteplase
Reteplase
How are fibrinlytic drugs administered?
I.V.
What is their effectiveness?
They probably cause repercussion in about 50% of arteries if administered within 3hrs.
What are the side-effects of fibrinolytics/ thrombolytics? Are thrombolytics the best form of treatment for MI?
SEs include nausea, vomiting, bleeding (mostly from injection site) and in the case of streptokinase allergic reactions.
PCI has been shown to be more effective than lytic therapy for an MI if performed within 90 mins after first medical contact.
How does streptokinase work?
It binds to circulating plasminogen to form an activator complex that converts further plasminogen to plasmin.
Because there is a large excess of plasmin inhibitors in the blood which neutralise circulating plasmin, bleeding s not normally a problem.
Due to the fact that there is a low level of plasmin inhibitors in clots, streptokinase has some selectivity for clots.
What is alteplase and how does it work? When is it used?
Alteplase is a recombinant tissue-type plasminogen activator (rt-PA). It acts by activating plasminogen to plasmin.
It does not cause allergic reaction like streptokinase so is used when streptokinase has failed or is contraindicated due to risk of anaphylaxis.
Name 4 types of anticoagulant, and how they work.
Warfarin - Inhibits vitamin K reductase and so blocks vitamin K dependent gamma-carboxylation of the glutamate residues on clotting factors 2, 7, 9, 10
Heparin (unfractionated) - Highly acidic naturally occurring glycosaminoglycan. Its anticoagulant effect requires the presence of Antithrombin III. This is a protease inhibitor in the blood that forms a 1:1 complex with thrombin. Heparin increases the rate of the formation of the antithrombin III-thrombin complex by x1000, which essentially causes the almost instantaneous deactivation of thrombin. The heparin-antithrombin III complex also inhibits factor 10a and some other factors.
Heparin (Low-molecular weight): Dalteparin & Enoxaparin- The LMW heparin-antithrombin complex only inhibits factor 10a. They have a longer half-life than unfractionated, require only one daily dose by sub cut, and prophylactic doses do not require monitoring.
Fondaparinux - A synthetic polysaccharide that bind to antithrombin with high specificity and inhibits factor 10a. May be superior to LMW heparin
