MOA's of all drugs Flashcards
Triphosphorylation:
- Catalyzed by viral thymidine kinase
- Human kinases from infected cells catalyze it
Acyclovir
Inhibits viral DNA by:
- Competitive inhibition for viral DNA polymerase resulting in irreversible binding to DNA template
- Chain termination
Acyclovir
Triphosphorylation:
- Catalyzed by the viral phosphotransferase UL97
- Human kinases catalyze steps 2 & 3
Competitively inhibits viral DNA polymerase causing termination of elongation
Ganiciclovir
Biphosphorylation does not require viral enzymes:
- Potent inhibitor of viral DNA polymerase
- Alternative substrate for viral DNA polymerase
Competitively inhibiting DNA synthesis
Cidofovir
Directly inhibits viral DNA polymerase, RNA polymerase, and HIV reverse transcriptase.
Block the pyrophosphate binding sit and inhibits cleavage of it from deoxynucleotdie triphosphates.
HSV,CMV, VZV, HIV-1
Foscarnet
Triphosphorylation is done via human kinases
Binds to DNA polymerase catalytic site and competitively inhibits DNA polymerase activity of the enzyme causing chain termination
Zidovudine and Tenofovir
Binds directly to HIV-1 reverse transcriptase resulting in inhibition of RNA and DNA polymerase
(allosteric inhibition).
Binds near the catalytic site blocking DNA polymerase activity.
Nevirapine
Inhibits protease enzyme in HIV-1 and HIV-2 which prevents the cleavage of Gag-pol resulting in immature viral particles-prevents budding
Ritonavir and Saquinavir
Binds to gp41 subunit of viral envelope preventing conformational change blocking entry of the virus into the cell
Enfuviritide
Binds to and blocks CCR5 on CD4 cells blocking viral entry into CD4 cells
Cxcr4 other coreceptor for hiv entry
Maraviroc
Inhibits HIV-1 integrase enzyme preventing viral DNA from integrating with cellular DNA
Raltegravir
Phosphorylated via cellular kinases
Competitively inhibits HBV DNA polymerase resulting in chain termination
Adefovir
Bind to JAK-STAT receptors leading to nuclear translocation of cellular protein complex that binds to genes containing IFN-specific response element leading to synthesis of over 24 antiviral proteins inhibiting viral protein synthesis
Bind to specific membrane receptors and initiate enzyme induction, suppression of cell proliferation, and inhibition of viral replication
Interferon Alfa
Triphosphorylation via host cell enzymes
MOA not clear 3 effects reported:
- Interferes with the synthesis of guanosine triphosphate
- Inhibits capping of viral mRNA
- Inhibits viral RNA-dependent RNA polymerase
Ribavirin
It inhibits the NS3/4A protease enzyme in HCV genotype 1 –> it inhibits the cleavage of HCV encoded polyproteins that are necessary for viral replication
It is an inhibitor of CYP3A4 and the drug transporters P-glycoprotein (P-gp) and OATP1B1/3.
Simeprevir
inhibits the HCV NS5B RNA-dependent RNA polymerase enzyme, which is essential for viral replication
Sofosbuvir
inhibit viral neuramidase enzyme (viral release)
Zamivir
Oseltamivir
Binds to antithrombin causing a conformational change which increases it’s anticoagulant properties—inhibits clotting factor proteases especially thrombin (2a), 9a, and 10a
Heparin
High affinity for antithrombin
Inhibits all three clotting factor proteases (2a, 9a, 10a)
HMWH
Inhibits clotting factor 10a—less of an effect on thrombin (2a)
LMWH
Directly bind to the active site of thrombin (2a)
*Does not bind to antithrombin
Dabigatran, Lepirudin, Bivalirudin, Desirudan, Aragatroban
Acts in the liver by blocking the gamma-carboxylation reaction in the synthesis of vitamin-K dependent clotting factors prothrombin (2) and factors 7, 9, 10 resulting in biologically inactive forms by inhibiting the vitamin K epoxide reductase enzyme which will catalyze the reductive metabolism of the of the inactive vitamin K epoxide back to its active hydroquinone form
Warfarin
Binds to plasminogen forming an enzymatic complex which catalyzes the conversion of inactive plasminogen to active plasmin
Streptokinase
Directly converts plasminogen to plasmin
Urokinase
Activates plasminogen that is bound to fibrin and is highly selective for the formed thrombus and avoids systemic activation of plasminogen
t-PA
Inhibits the synthesis of TXA2 by irreversible acetylation of both the COX-1 and COX-2 enzymes to prolong bleeding times
Inhibits platelet aggregation by inhibiting COX-1
Aspirin
Inhibit ADP pathways by binding irreversibly to and blocking the P2Y12 ADP receptor resulting in reduced platelet aggregation
Thienopyrimidine (Clopidogrel, Prasugrel, Ticlopidine)
Block the platelet glycoprotein 2b/3a receptor complex which is a membrane receptor for fibrinogen and vibronectin resulting in reduced platelet aggregation
Abciximab (Blockers of Platelet GP 2b/3a Receptor Complex)
Inhibits the binding of fibrinogen to the GP 2b/3a receptor complex—they do NOT block the vibronectin binding site
Eptifibatide
Tirofiban
(Blockers of Platelet GP 2b/3a Receptor Complex)
Inhibits platelet uptake of adenosine
Blocks ADP-induced platelet aggregation
Dipyridamole
blocks protease-activated receptor-1 (PAR-1), the major thrombin receptor on platelets, and inhibits thrombin-induced platelet aggregation.
Vorapaxar
inhibits platelet activation and aggregation by binding to and reversibly blocking the P2Y12 ADP receptor on platelet membranes
reversible blocker for the P2Y12 ADP receptor
Ticagrelor
highly selective, competitive and reversible inhibitor of factor Xa.
Inhibition of factor Xa activity leads to inhibition of thrombin production via both intrinsic and extrinsic pathways in the clotting cascade
Rivaroxaban
binds to antithrombin with high affinity and inhibits factor Xa indirectly through antithrombin without neutralizing thrombin
Fondaparinux
