MOA's of all drugs

Question 1

Triphosphorylation:

1. Catalyzed by viral thymidine kinase
2. Human kinases from infected cells catalyze it

Answer 1

Acyclovir

Question 2

Inhibits viral DNA by:

1. Competitive inhibition for viral DNA polymerase resulting in irreversible binding to DNA template
2. Chain termination

Answer 2

Acyclovir

Question 3

Triphosphorylation:

1. Catalyzed by the viral phosphotransferase UL97
2. Human kinases catalyze steps 2 & 3

Competitively inhibits viral DNA polymerase causing termination of elongation

Answer 3

Ganiciclovir

Question 4

Biphosphorylation does not require viral enzymes:

1. Potent inhibitor of viral DNA polymerase
2. Alternative substrate for viral DNA polymerase

Competitively inhibiting DNA synthesis

Answer 4

Cidofovir

Question 5

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

Answer 5

Foscarnet

Question 6

Triphosphorylation is done via human kinases

Binds to DNA polymerase catalytic site and competitively inhibits DNA polymerase activity of the enzyme causing chain termination

Answer 6

Zidovudine and Tenofovir

Question 7

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.

Answer 7

Nevirapine

Question 8

Inhibits protease enzyme in HIV-1 and HIV-2 which prevents the cleavage of Gag-pol resulting in immature viral particles-prevents budding

Answer 8

Ritonavir and Saquinavir

Question 9

Binds to gp41 subunit of viral envelope preventing conformational change blocking entry of the virus into the cell

Answer 9

Enfuviritide

Question 10

Binds to and blocks CCR5 on CD4 cells blocking viral entry into CD4 cells

Cxcr4 other coreceptor for hiv entry

Answer 10

Maraviroc

Question 11

Inhibits HIV-1 integrase enzyme preventing viral DNA from integrating with cellular DNA

Answer 11

Raltegravir

Question 12

Phosphorylated via cellular kinases

Competitively inhibits HBV DNA polymerase resulting in chain termination

Answer 12

Adefovir

Question 13

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

Answer 13

Interferon Alfa

Question 14

Triphosphorylation via host cell enzymes

MOA not clear 3 effects reported:

1. Interferes with the synthesis of guanosine triphosphate
2. Inhibits capping of viral mRNA
3. Inhibits viral RNA-dependent RNA polymerase

Answer 14

Ribavirin

Question 15

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.

Answer 15

Simeprevir

Question 16

inhibits the HCV NS5B RNA-dependent RNA polymerase enzyme, which is essential for viral replication

Answer 16

Sofosbuvir

Question 17

inhibit viral neuramidase enzyme (viral release)

Answer 17

Zamivir

Oseltamivir

Question 18

Binds to antithrombin causing a conformational change which increases it’s anticoagulant properties—inhibits clotting factor proteases especially thrombin (2a), 9a, and 10a

Answer 18

Heparin

Question 19

High affinity for antithrombin

Inhibits all three clotting factor proteases (2a, 9a, 10a)

Answer 19

HMWH

Question 20

Inhibits clotting factor 10a—less of an effect on thrombin (2a)

Answer 20

LMWH

Question 21

Directly bind to the active site of thrombin (2a)

*Does not bind to antithrombin

Answer 21

Dabigatran, Lepirudin, Bivalirudin, Desirudan, Aragatroban

Question 22

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

Answer 22

Warfarin

Question 23

Binds to plasminogen forming an enzymatic complex which catalyzes the conversion of inactive plasminogen to active plasmin

Answer 23

Streptokinase

Question 24

Directly converts plasminogen to plasmin

Answer 24

Urokinase

Question 25

Activates plasminogen that is bound to fibrin and is highly selective for the formed thrombus and avoids systemic activation of plasminogen

Answer 25

t-PA

Question 26

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

Answer 26

Aspirin

Question 27

Inhibit ADP pathways by binding irreversibly to and blocking the P2Y12 ADP receptor resulting in reduced platelet aggregation

Answer 27

Thienopyrimidine (Clopidogrel, Prasugrel, Ticlopidine)

Question 28

Block the platelet glycoprotein 2b/3a receptor complex which is a membrane receptor for fibrinogen and vibronectin resulting in reduced platelet aggregation

Answer 28

Abciximab (Blockers of Platelet GP 2b/3a Receptor Complex)

Question 29

Inhibits the binding of fibrinogen to the GP 2b/3a receptor complex—they do NOT block the vibronectin binding site

Answer 29

Eptifibatide
Tirofiban
(Blockers of Platelet GP 2b/3a Receptor Complex)

Question 30

Inhibits platelet uptake of adenosine

Blocks ADP-induced platelet aggregation

Answer 30

Dipyridamole

Question 31

blocks protease-activated receptor-1 (PAR-1), the major thrombin receptor on platelets, and inhibits thrombin-induced platelet aggregation.

Answer 31

Vorapaxar

Question 32

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

Answer 32

Ticagrelor

Question 33

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

Answer 33

Rivaroxaban

Question 34

binds to antithrombin with high affinity and inhibits factor Xa indirectly through antithrombin without neutralizing thrombin

Answer 34

Fondaparinux