Question

help 1-7

1. What are the two major pathways for maintaining blood hemostasis? 2. List the biological targets for pharmacological intervention that are involved in the steps of forming a platelet plug? 3. List FDA approved anti-platelet drugs 4. Describe the different MOAs for each sub-class of anti-platelet therapies and name a representative drug for each? 5. Compare and contrast clopidogrel, cangrelor, and prasugrel? 6. What is the MOA for abciximab, tirofiban, and eptifibatide? _; now list structural differences between the three drugs: 7. What is the mechanism of action for vorapaxar?

Answer 1

1 Intrinsic and extrinsic pathway of blood hemostasis.

2. platelet cyclic nucleotide phosphodiesterase, glycoprotein IIb/IIIa (GpIIb-IIIa) receptors on platelets, P2Y12 receptor, thromboxane A2 and PGI2 are the biological targets for pharmacological interventions.

3. Clopidogrel and prasugrel are fda approved.

4. antiplatelet drugs on basis of mechanism of action:

• inhibitors like aspirin
• Adenosine diphosphate (ADP) receptor inhibitors eg clopidogrel and prasugrel
• Phosphodiesterase inhibitor like Cilostazol
• Protease-activated receptor-1 (PAR-1) antagonists Eg. Vorapaxar
• Glycoprotein IIB/IIIA inhibitors for intravenous use only Eg. Abciximab , Eptifibatide, Tirofiban
• Adenosine reuptake inhibitors For eg. Dipyridamole
• Thromboxane inhibitors
  • Thromboxane synthase inhibitors
  • Thromboxane receptor antagonists Eg. Terutroban

5. clopidogrel and prasugrul are both adenosine diphosphate receptor inhibitors and for oral use but cangrelor also belong to same class but available in active form and does not require metabolic conversion and found for intravenous use

6. These all are glycoprotein IIb/IIIa inhibitor and prevent platelet aggregation. Abciximab is a human-murine chimeric monoclonal antibody (mAb) fragment, Eptifibatide is N6-(aminoiminomethyl)-N2-(3-mercapto-1-oxopropyl-l-lysylglycyl-l-α-aspartyl-l-tryptophyl-l-prolyl-l-cysteinamide, cyclic disulfide wheras Tirofiban is N-(butylsulfonyl)-O-(4-[4-piperidinyl]butyl)-L-tyrosine monohydrochloride monohydrate

7. vorapaxer is protease activated receptor antagonist . These receptors are found on platelets that need to be activated for platelet aggregation but this drug inhibits platelet aggregation.