Haem Drugs Flashcards
MOA of Aspirin
What is the goal?
When is it contraindicated?
Irreversibly acetylates COX-1 and inhibits COX-2 less strongly.
Inhibiting COX-1 prevents formation of thromboxane A2 which is needed for platelet activation, so platelet activation is hence inhibited for 7-10 days (platelet lifespan)
Produces prostaglandins- reduces adhesion
Preventing coagulation. NOT for asthmatics or renal disease
What is Dipyridamole?
How does it works and when is it used?
Relatively weak effect. Inhibits platelet phosphodiesterase and prevents cAMP breakdown, reducing intracellular Ca and inhibiting platelet activation.
Preventing clots. Usually given alongside aspirin as Asasantin SR
Name the ADP receptor antagonists
What is the MOA?
Ticlopidine, clopidogrel, prasugrel and ticagrelor
Thienopyridine
ADP receptor antagonists
Prodrugs (metabolised by hepatic cytochrome P450) that selectively inhibit ADP-induced platelet aggregation by irreversibly blocking P2Y12.
Name the GPIIb/IIIa receptor antagonists
What is the MOA?
When are they used?
Tirofiban, eptifibatide and abciximab
Block the glycoprotein IIb/IIIa receptor on platelet surface, preventing them from binding to ligands that let platelets aggregate
Usually used in combination with other anti-platelets to prevent coagulation.
How does Heparin work?
Activates antithrombin and increases its inhibitory rate 1000-fold, Neutralising thrombin and activated factor X (as well as IX, XI, XI, XII, also prevents I to Ia)
Must bind to both antithrombin and thrombin simultaneously .Binding to heparin causes a conformational change in antithrombin which also accelerates its interaction with factor Xa.
Preventing coagulation by halting the clotting cascade.
Name the Xa inhibitors and explain how they work
Inhibit factor Xa which is the active enzyme in the prothrombinase complex, inhibiting the coagulation cascade.
Low molecular weight heparin (Clexane), fondaparinux, rivaroxaban and apixaban
Warfarin MOA
Interferes with the synthesis of Vitamin K-dependent proteins (by blocking vitamin K epoxide reductase) (VKOR) including prothrombin and factors VI, IX and X. It also reduces levels of proteins C and S.
Preventing coagulation by halting the clotting cascade.
Also stabilises current clots due to inhibition of Protein C
TPA MOA
Used for?
Examples?
Convert plasminogen to plasmin, which degrades the fibrin matrix of thrombi and dissolves clots. tPAs are “clot-specific” because they preferentially activate fibrin-bound plasminogen.
Used for Fibrinolysis
Examples: Tenecteplase, alteplase and reteplase
Hydroxyurea MOA
Blocks conversion of the cytosine nucleotide to the deoxy derivative and further inhibits DNA synthesis through blocking incorporation of the thymidine nucleotide to DNA
Used for : Chemotherapy and sickle cell anaemia and CML
What is Prothrombinx and what factors does it include?
When is it used?
Sterile freeze dried powder containing purified human coagulation factors II, IX, X and low levels of V and VII
Used as a coagulation replacement when vitamin K deficient
What is Desmopressin
When is it used?
Releases VWF from platelet granules therefore increases circulating Factor VIII
Used for :
Factor VIII deficiencies- bleeding in Haemophilia A
MOA of Tranexamic acid
When is it used?
Class: Antifibrinolytic
MOA: Inhibits plasminogen activation and thus preventing fibrinolysis
USed for :
Bleeding or risk of bleeding- ie haemorrhage following dental procedure or Menorrhagia
Or bleeding after thrombolytic drug administration
What are some TKI? What is the MOA and When are they used?
Imatinib, Nilotinib, Dasatinib
Inhibitor of TK to reduce uncontrolled growth and proliferation
Used in CML
MOA of Methotrexate
Inhibits folic acid reductase so folic acid can’t be converted to tetrahydrofolic acid, blocking purine synthesis ∴ no DNA production
MOA of 5-Fluorouracil
What are the examples?
Acts as an antimetabolite and prevents synthesis of the thymidine nucleotide, blocking DNA production
Common names:
Gemcitabine and arabinosylcytosine act in similar ways.
