Micro - Antimicrobials (Antiviral therapy)

Question 1

What are 2 types of HIV antiviral therapy that work on fusion? What part of fusion is inhibited by each?

Answer 1

FUSION (1) Attachment: Maraviroc (2) Penetration: Enfuvirtide

Question 2

What HIV antiviral therapy is an example of an Integrase Inhibitor?

Answer 2

Raltegravir

Question 3

Give 7 examples of protease inhibitors used as HIV antiviral therapy.

Answer 3

(1) Lopinavir (2) Atazanavir (3) Darunavir (4) Fosamprenavir (5) Saquinavir (6) Ritonavir (7) Indinavir

Question 4

What are the 2 types of Reverse transcriptase inhibitors used as HIV Antiviral therapy?

Answer 4

NRTIs, NNRTIs

Question 5

What are 7 examples of NRTIs used as Reverse transcriptase inhibitors in HIV antiviral therapy?

Answer 5

NRTIs: (1) Tenofovir (TDF) (2) Emtricitabine (FTC) (3) Abacavir (ABC) (4) Lamivudine (3TC) (5) Zidovudine (ZDV, formerly AZT) (6) Didanosine (ddl) (7) Stavudine (d4T)

Question 6

What are 3 examples of NNRTIs used as Reverse transcriptase inhibitors in HIV antiviral therapy?

Answer 6

NNRTIs: (1) Nevirapine (2) Efavirenz (3) Delavirdine

Question 7

What are the 4 major categories of drugs used as HIV antiviral therapy?

Answer 7

(1) Fusion (2) Integrase inhibitors (3) Protease inhibitors (4) Reverse transcriptase inhibitors

Question 8

What are the 4 major categories of drugs (based on function of inhibition) used as other (non-HIV) antiviral therapy?

Answer 8

(1) Protein synthesis (2) Uncoating (3) Nucleic Acid synthesis (4) Release of progeny virus

Question 9

What is an example of an antiviral therapy that functions via protein synthesis?

Answer 9

Protein synthesis: Interferon-alpha

Question 10

What are 2 examples of antiviral therapy that functions via inhibition of uncoating?

Answer 10

Uncoating: (1) Amantadine (2) Rimantadine

Question 11

What are the 3 major categories of antiviral therapy that function via inhibition of nucleic acid synthesis? Give at least one example of a drug in each category.

Answer 11

Nucleic Acid Synthesis: (1) Guanine nucleotide synthesis - Ribavirin (2) Viral DNA polymerase inhibitors - Foscarnet, Cidofovir (3) Guanosine analogs - Acyclovir, etc., Ganciclovir

Question 12

What is an example of an antiviral therapy that works via inhibition of guanine nucleotide synthesis? What are 2 viruses treated by this drug?

Answer 12

Ribavirin (RSV, HCV)

Question 13

What are 2 examples of antiviral therapy that work as viral DNA polymerase inhibitors? What are 2 viruses treated by either of these drugs? Which of these 2 viruses is only treated if acyclovir-resistant?

Answer 13

(1) Foscarnet (2) Cidofovir; CMV, HSV; HSV is acyclovir-resistant

Question 14

What are 2 examples of antiviral therapy that work as guanosine analogs? What is at least one virus treated by each of these drugs?

Answer 14

(1) Acyclovir, etc (HSV, VZV) (2) Ganciclovir (CMV)

Question 15

What is the major category of antiviral therapy that works via inhibition of progeny virus?

Answer 15

Neuraminidase inhibitors

Question 16

What are 2 examples of Neuraminidase inhibitors? What are 2 examples of viruses that may be treated by either of these drugs?

Answer 16

(1) Zanamivir (2) Oseltamivir; Influenza A, B

Question 17

For which virus is antiviral therapy that inhibits uncoating (i.e., amantadine/rimantadine) no longer useful, and why?

Answer 17

No longer useful for influenza due to high resistance

Question 18

Draw a visual depicting the following 4 methods of HIV antiviral therapy in a CD4 T cell: (1) Inhibition of Fsion (2) Integrase inhibitors (3) Reverse transcriptase inhibitors (4) Protease inhibitors.

Answer 18

See p. 191 in First Aid 2014 for visual on left

Question 19

Draw a visual depicting the following 4 methods of other (non-HIV) antiviral therapy in mammalian cell: (1) Protein synthesis (2) Inhibition of uncoating (3) Inhibition of nucleic acid synthesis (4) Inhibition of release of progeny virus

Answer 19

See p. 191 in First Aid 2014 for visual on right

Question 20

What is the mechanism of Zanamivir and its effect? What other drug shares this mechanism/effect

Answer 20

Inhibit influenza neuraminidase –> decrease the release of progeny virus; Oseltamivir

Question 21

What is the clinical use for Zanamivir and Oseltamivir?

Answer 21

Treatment and prevention of both influenza A and B

Question 22

What is the mechanism and effect of Ribavirin?

Answer 22

Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase

Question 23

What are 2 clinical uses of Ribavirin?

Answer 23

(1) RSV (2) Chronic hepatitis C

Question 24

What are 2 toxicities associated with Ribavirin?

Answer 24

(1) Hemolytic anemia (2) Severe teratogen

Question 25

What kind of drug is Acyclovir? How do cellular enzymes change its form? What is its mechanism? What other 2 drugs are the same as Acyclovir in these ways?

Answer 25

Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells --> few adverse effects. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination; Famciclovir, Valacyclovir

Question 26

To what extent do acyclovir/famiclovir/valacyclovir have adverse effects, and why?

Answer 26

Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells --> few adverse effects.

Question 27

What are the 2 main viruses for which acyclovir/famiclovir/valacyclovir are used? Against what virus do they have weak activity? In what contexts do they have no activity?

Answer 27

HSV and VZV. Weak activity against EBV. No activity against CMV. No effect on latent forms of HSV and VZV.

Question 28

For what HSV-related conditions are acyclovir/famiclovir/valacyclovir clinically used?

Answer 28

Used for HSV-induced mucocutaneous and genital lesions as well as encephalitis.

Question 29

How are acyclovir/famiclovir/valacyclovir clinically used in immunocompromised patients?

Answer 29

Prophylaxis in immunocompromised patients

Question 30

What is Valacyclovir? How does it compare to acyclovir in terms of bioavailability?

Answer 30

Valacyclovir, a prodrug of acyclovir, has better oral bioavailability

Question 31

Of acyclovir/famiclovir/valacyclovir, which is used in the case of herpes zoster?

Answer 31

For herpes zoster, use a related agent, famiclovir

Question 32

What are 2 toxicities associated with acyclovir/famiclovir/valacyclovir?

Answer 32

(1) Obstructive crystalline nephropathy and (2) Acute renal failure if not adequately hydrated

Question 33

What is the mechanism of resistance against acyclovir/famiclovir/valacyclovir?

Answer 33

Mutated viral thymidine kinase

Question 34

What is the mechanism of ganciclovir?

Answer 34

5'-monophosphate formed by a CMV viral kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase.

Question 35

What is the clinical use for ganciclovir?

Answer 35

CMV, especially in immunocompromised patients.

Question 36

What is Valganciclovir, and how does it compare to ganciclovir in terms of bioavailability?

Answer 36

Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability

Question 37

What are 4 toxicities associated with ganciclovir?

Answer 37

(1) Leukopenia (2) Neutropenia (3) Thrombocytopenia (4) Renal toxicity

Question 38

How does ganciclovir compare to acyclovir in terms of toxicity?

Answer 38

More toxic to host enzymes than acyclovir.

Question 39

What is the mechanism of resistance against ganciclovir?

Answer 39

Mutated CMV DNA polymerase or lack of viral kinase

Question 40

What is the mechanism of foscarnet?

Answer 40

Viral DNA polymerase inhibitor that binds the pyrophosphate-binding site of the enzyme; Think: "FOScarnet = pyroFOSphate analog"

Question 41

How is foscarnet different from acyclovir/famiclovir/valacyclovir and ganciclovir?

Answer 41

Does not require activation by viral kinase

Question 42

What is the clinical use of foscarnet?

Answer 42

CMV retinitis in immunocompromised patients when ganciclovir fails; Acyclovir-resistant HSV

Question 43

What is the toxicity associated with foscarnet?

Answer 43

Nephrotoxicity

Question 44

What is the mechanism of resistance against foscarnet?

Answer 44

Mutated DNA polymerase

Question 45

What is the mechanism of Cidofovir?

Answer 45

Preferentially inhibits viral DNA polymerase.

Question 46

How Cidofovir different from acyclovir/famiclovir/valacyclovir and ganciclovir? Which other antiviral drug also shares this quality?

Answer 46

Does not require phosphorylation by viral kinase; Foscarnet

Question 47

What is the clinical use of Cidofovir? What other antiviral drug has the same clinical use?

Answer 47

CMV retinitis in immunocompromised patients; Acyclovir-resistant HSV; Foscarnet

Question 48

What kind of half-life does cidofovir have?

Answer 48

Long half-life

Question 49

What toxicity does Cidofovir have? What can be done to reduce this toxicity?

Answer 49

Nephrotoxicity (coadminister with probenecid and IV saline to decrease toxicity)