Micro - Antimicrobials (Antiviral therapy) Flashcards Preview

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Flashcards in Micro - Antimicrobials (Antiviral therapy) Deck (49):
1

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

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

2

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

Raltegravir

3

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

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

4

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

NRTIs, NNRTIs

5

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

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

6

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

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

7

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

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

8

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

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

9

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

Protein synthesis: Interferon-alpha

10

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

Uncoating: (1) Amantadine (2) Rimantadine

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.

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

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?

Ribavirin (RSV, HCV)

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?

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

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?

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

15

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

Neuraminidase inhibitors

16

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

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

17

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

No longer useful for influenza due to high resistance

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.

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

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

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

20

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

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

21

What is the clinical use for Zanamivir and Oseltamivir?

Treatment and prevention of both influenza A and B

22

What is the mechanism and effect of Ribavirin?

Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase

23

What are 2 clinical uses of Ribavirin?

(1) RSV (2) Chronic hepatitis C

24

What are 2 toxicities associated with Ribavirin?

(1) Hemolytic anemia (2) Severe teratogen

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?

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

26

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

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

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?

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

28

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

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

29

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

Prophylaxis in immunocompromised patients

30

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

Valacyclovir, a prodrug of acyclovir, has better oral bioavailability

31

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

For herpes zoster, use a related agent, famiclovir

32

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

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

33

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

Mutated viral thymidine kinase

34

What is the mechanism of ganciclovir?

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

35

What is the clinical use for ganciclovir?

CMV, especially in immunocompromised patients.

36

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

Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability

37

What are 4 toxicities associated with ganciclovir?

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

38

How does ganciclovir compare to acyclovir in terms of toxicity?

More toxic to host enzymes than acyclovir.

39

What is the mechanism of resistance against ganciclovir?

Mutated CMV DNA polymerase or lack of viral kinase

40

What is the mechanism of foscarnet?

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

41

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

Does not require activation by viral kinase

42

What is the clinical use of foscarnet?

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

43

What is the toxicity associated with foscarnet?

Nephrotoxicity

44

What is the mechanism of resistance against foscarnet?

Mutated DNA polymerase

45

What is the mechanism of Cidofovir?

Preferentially inhibits viral DNA polymerase.

46

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

Does not require phosphorylation by viral kinase; Foscarnet

47

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

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

48

What kind of half-life does cidofovir have?

Long half-life

49

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

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

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