Module 2.3.1 (Pharmacology of the drug treatments for DVT:PE) Flashcards
For Pharmacological Management of DVT and PE;
A) What drugs are used for VTE prophylaxis?
B) What drugs are used for acute management?
A)
- LMWH
- UFH
B)
- Thrombolytics
- Antiplatelets
- Anticoagulants
What drugs are used to prevent or treat the formation of “red thrombi?”
Anticoagulant drugs
Coagulation involves two pathways – intrinsic and extrinsic. Describe the following FOUR steps after this.
- The pathways converge with activation of factor X
- Factor Xa, then converts prothrombin to thrombin (Factor IIa)
- Thrombin cleaves fibrinogen to form fibrin –> formation of fibrin clot
- Coagulation is controlled by enzyme inhibitors (e.g. Antithrombin III) and fibrinolysis
What is the MOA of heparin? How does the MOA of LMW heparin differ from this?
- Heparin potentiates the action of ATIII (antithrombin) which is a natural inhibitor of clotting factors Xa and thrombin (IIa)
- Anticoagulant activity is due to its high affinity for ATIII
- Prevents conversion of fibrinogen to fibrin
- Stops clot propagation –> immediate effect
> LMW heparin such as enoxaparin and dalteparin inactivates MAINLY factor Xa, less effect on thrombin (IIa)
What are the examples of direct thrombin inhibitors? What is their MOA?
- Bivalirudin (Angiomax®)
- Dabigatran (Pradaxa®)
Directly inhibit thrombin (clotting factor IIa)
What are examples of Factor Xa Inhibitors? What is the MOA?
- Fondaparinux (Arixtra®)
- Rivaroxaban (Xarelto®)
- Apixaban(Eliquis®)
selectively inhibit clotting Factor Xa
What is the MOA of warfarin?
Warfarin inhibits epoxide reductase and prevents the formation of active Vit. K
- Factors II, VII, IX & X require post-translational carboxylation of glutamic acid groups
- Vitamin K is a cofactor for carboxylation
Compare Heparin and Wafarin (both anticoagulants) by the following properties:
A) Active in vitro
B) Routes of administration
C) Onset of action
D) Mechanism of action
E) Safe to take during pregnancy
F) Antidote
A)
- H: yes
- W: No
B)
- H: Parenteral
- W: Oral
C)
- H: Immediate
- W: Delayed
D)
- H: Inactivate clotting factors
- W: Inhibit the synthesis of clotting factors
E)
- H: yes
- W: No
F)
- H: Protamine sulfate
- W: Phytonadione (vitamin K1)
What are the main drugs used to prevent or treat the formation of platelet-rich “white thrombi”?
white thrombi = arterial thrombosis
Antiplatelet drugs
What are the FIVE steps for the activation of platelet aggregation?
- Adherence of platelets to damaged endothelium
- Activation of platelets
- Synthesis and release of mediators of platelet aggregation
- Mediators increase the expression of GP IIb/IIIa receptors
- Promote platelet aggregation
For Antiplatelets;
A) What is the MOA of aspirin?
B) What is the MOA of thienopyridines?
C) What is the MOA of Gyp IIb/IIIa inhibitors
A)
- Aspirin inhibits synthesis of mediators (TXA2)
B)
- Thienopyridines inhibit the effects of mediators of platelet aggregation –> clopidogrel, ticlopidine, prasugrel
C)
- GP IIb/IIIa inhibitors block platelet aggregation by preventing the binding of fibrinogen to platelets –> abciximab, eptifibatide, tirofiban
What are examples of the following antiplatelets;
A) Acetyl salicylic acid
B) Thienopyrididnes
C) Phosphodiesterase inhibitor
D) Glycoprotein IIb/IIIa inhibitors
A)
- Aspirin
B)
- Clopidogrel, Ticlopidine, Prasugrel
C)
- Dipyramidole
D)
- Abciximab
- Eptifibatide
- Tirofiban
What do thrombolytics (fibrinolytics) do?
Degrade an existing thrombus in patients having a myocardial infarction, thrombotic stroke, or pulmonary embolism
For thrombolytics:
A) What are examples of first-generation drugs?
B) What are examples of second-generation drugs (1st line therapy)?
C) What is the mechanism of action of second-generation thrombolytics?
D) What is the MOA of first-generation thrombolytics?
A)
- streptokinase, a protein obtained from beta-haemolytic streptococci
B)
- Alteplase (Actilyse®)
- Reteplase (Rapilysin®)
- Tenecteplase (Metalyse®)
- Rarely used- Urokinase—enzyme isolated from human urine
C)
- These are plasminogen activators produced by recombinant DNA technology
> plasminogen degrades fibrin clots
- More fibrin-specific than streptokinase, because they activate plasminogen associated with thrombi in preference to circulating plasminogen
> More commonly used and much more expensive than streptokinase
D)
- Streptokinase must first combine with plasminogen to form an activator complex which converts inactive plasminogen to plasmin –> dissolves fibrin clots
Provide a summary of preventing and treating thrombosis
