Micro - Antimicrobials (Antiviral therapy) Flashcards
Pg. 191-193 in First Aid 2014 Sections include: -Antiviral therapy -Zanamivir, oseltamivir -Ribavirin -Acyclovir, famciclovir, valacyclovir -Ganciclovir -Foscarnet -Cidofovir
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
What HIV antiviral therapy is an example of an Integrase Inhibitor?
Raltegravir
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
What are the 2 types of Reverse transcriptase inhibitors used as HIV Antiviral therapy?
NRTIs, NNRTIs
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)
What are 3 examples of NNRTIs used as Reverse transcriptase inhibitors in HIV antiviral therapy?
NNRTIs: (1) Nevirapine (2) Efavirenz (3) Delavirdine
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
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
What is an example of an antiviral therapy that functions via protein synthesis?
Protein synthesis: Interferon-alpha
What are 2 examples of antiviral therapy that functions via inhibition of uncoating?
Uncoating: (1) Amantadine (2) Rimantadine
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
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)
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
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)
What is the major category of antiviral therapy that works via inhibition of progeny virus?
Neuraminidase inhibitors
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
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
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
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
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
What is the clinical use for Zanamivir and Oseltamivir?
Treatment and prevention of both influenza A and B
What is the mechanism and effect of Ribavirin?
Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
What are 2 clinical uses of Ribavirin?
(1) RSV (2) Chronic hepatitis C
What are 2 toxicities associated with Ribavirin?
(1) Hemolytic anemia (2) Severe teratogen
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
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.
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.
For what HSV-related conditions are acyclovir/famiclovir/valacyclovir clinically used?
Used for HSV-induced mucocutaneous and genital lesions as well as encephalitis.
How are acyclovir/famiclovir/valacyclovir clinically used in immunocompromised patients?
Prophylaxis in immunocompromised patients
What is Valacyclovir? How does it compare to acyclovir in terms of bioavailability?
Valacyclovir, a prodrug of acyclovir, has better oral bioavailability
Of acyclovir/famiclovir/valacyclovir, which is used in the case of herpes zoster?
For herpes zoster, use a related agent, famiclovir
What are 2 toxicities associated with acyclovir/famiclovir/valacyclovir?
(1) Obstructive crystalline nephropathy and (2) Acute renal failure if not adequately hydrated
What is the mechanism of resistance against acyclovir/famiclovir/valacyclovir?
Mutated viral thymidine kinase
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.
What is the clinical use for ganciclovir?
CMV, especially in immunocompromised patients.
What is Valganciclovir, and how does it compare to ganciclovir in terms of bioavailability?
Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability
What are 4 toxicities associated with ganciclovir?
(1) Leukopenia (2) Neutropenia (3) Thrombocytopenia (4) Renal toxicity
How does ganciclovir compare to acyclovir in terms of toxicity?
More toxic to host enzymes than acyclovir.
What is the mechanism of resistance against ganciclovir?
Mutated CMV DNA polymerase or lack of viral kinase
What is the mechanism of foscarnet?
Viral DNA polymerase inhibitor that binds the pyrophosphate-binding site of the enzyme; Think: “FOScarnet = pyroFOSphate analog”
How is foscarnet different from acyclovir/famiclovir/valacyclovir and ganciclovir?
Does not require activation by viral kinase
What is the clinical use of foscarnet?
CMV retinitis in immunocompromised patients when ganciclovir fails; Acyclovir-resistant HSV
What is the toxicity associated with foscarnet?
Nephrotoxicity
What is the mechanism of resistance against foscarnet?
Mutated DNA polymerase
What is the mechanism of Cidofovir?
Preferentially inhibits viral DNA polymerase.
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
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
What kind of half-life does cidofovir have?
Long half-life
What toxicity does Cidofovir have? What can be done to reduce this toxicity?
Nephrotoxicity (coadminister with probenecid and IV saline to decrease toxicity)
