Non-HIV Drugs Flashcards by Danielle Himelfarb

What drugs are in the category of neuraminidase inhibitors?

Zanamavir

Oseltamivir

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What is the mechanism of action of neuraminidase inhibitors?

Inhibits neuramidase – enzyme that cleaves bond between terminal sialic acid residues on host cell surface and progeny virus hemagglutinin (HA) protein

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What is the clinical use of neuraminidase inhibitors?

Treatment and prophylaxis of influenza virus

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What are side effects/toxicities of Zanamivir?

Nausea, allergy, diarrhea, respiratory distress

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What are side effects/toxicities of Oseltamivir?

Seizure events, respiratory distress

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What mechanisms of resistance are there for neuraminidase inhibitors?

Mutations in HA and/or NA

Cross resistance of Oseltamivir with Zanamavir

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Who can use Zanamavir?

Not recommended for <7 yo or those with underlying respiratory disease

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Who can use Oseltamivir?

Approved for treatment in >1 yo and prophylaxis in >13 yo

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Who should use neuramidase inhibitors as prophylaxis?

High-risk children, people in contact with high-risk children

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What is the method for administration for Zanamavir v. Oseltamivir?

Zanamavir - Inhalation

Oseltamivir - Oral

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What is the primary method for preventing influenza?

Influenza vaccine

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Who should not use the live attenuated influenza vaccine (Flumist)?

50 yo

People with medical condition that places them at high risk of influenza

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What is the mechanism of action of Ribavirin?

Inhibits IMP dehydrogenase, preventing GMP synthesis (and therefore reducing ATP formation)

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What are the clinical uses of Ribavirin?

Paramyxoviruses (RSV, parainfluenza)
Arenaviruses (Lassa fever)
Hepatitis C

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What are side effects/toxicities of Ribavirin?

Hemolytic anemia with high dose or prolonged therapy (has longer half life in RBCs)
Myocardial infarction
Teratogenic

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What are methods of administration of Ribavirin?

Inhalation (most common)
Oral (less effective)
IV (for Arenaviruses)

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What is standard of care for HCV?

Ribavirin combined with Pegylated interferons

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What comprises the new IFN-free regimen for HCV care?

Combination therapy of:

Ribavirin
Protease inhibitor
Polymerase inhibitor
Cyclophilin inhibitors

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What are the goals of HBV therapy?

Prevent complications like cirrhosis, hepatic failure, and hepatocellular carcinoma

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What therapies are approved for HBV?

IFNalpha, Peg-IFNalpha, 5 nucleoside analogs

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What is the first line therapy for HBV?

Entecavir and Tenofovir

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What therapy was successful in MERS-CoV and SARS studies in monkeys?

Ribavirin with IFNalpha2b

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What are the acyclic and carbocyclic guanosine analogs?

Study These Flashcards

Acyclovir
Valaciclovir
Famciclovir
Ganciclovir
Valganciclovir

What is the mechanism of action of Acyclovir?

Study These Flashcards

Guanosine analog
Monophosphorylated by viral thymidine kinase (TK)
Triphosphate formed by cellular enzymes to become acyclo-GTP
Inhibits viral DNA polymerase by chain termination

What is the clinical spectrum of acyclovir?

Genital HSV infections Chronic and recurrent mucocutaneous HSV or VZV infections Neonatal herpes HSV encephalitis

What are side effects/toxicities of acyclovir?

Very low overall Encephalopathy associated with renal insufficiency Obstructive nephropathy with high IV doses

What are methods of administration of acyclovir?

Oral (for genital lesions and recurrent HSV) Topical (genital lesions) IV (HSV encephalitis) IV and oral (for neonatal HSV)

What are mechanisms of resistance of acyclovir?

Mutations in viral TK and/or DNA polymerase

What is the oral prodrug of acyclovir?

Valaciclovir

What is mechanism of action of Famciclovir?

Same as acyclovir: Guanosine analog Monophosphorylated by viral thymidine kinase (TK) Triphosphate formed by cellular enzymes to become acyclo-GTP Inhibits viral DNA polymerase by chain termination Not as effective at pol inhibition, but similar antiviral activity due to better phosphorylation by cellular enzymes

What is the spectrum of clinical activity of Famciclovir?

Genital HSV | VZV

What are the methods of administration of Famciclovir?

Oral

What are mechanisms of resistance of Famciclovir?

Cross-resistance with acyclovir

What compound is Famciclovir the prodrug of?

Penciclovir

What is the mechanism of action of Ganciclovir?

Guanosine analog Monophosphorylated by CMV viral kinase pUL97 Triphosphate formed by cellular enzymes to become ganciclovir-GTP Inhibits viral DNA polymerase by chain termination

What is the spectrum of clinical activity of Ganciclovir?

Life or sight-threatening CMV in immunosuppressed patients | Pneumonitis in BMT recipients

What are side effects/toxicities of Ganciclovir?

Bone marrow suppression Neutropenia Thrombocytopenia CNS effects (headache, behavioral changes, psychosis)

What is method of administration of Ganciclovir?

What are mechanisms of resistance of Ganciclovir?

Mutations in CMV kinase pUL97 and/or DNA polymerase

What is the oral prodrug of Ganciclovir?

Valganciclovir

What is mechanism of action of Foscarnet?

Inhibits viral DNA pol and RT by interacting with pyrophosphate binding sites on these enzymes (distinct from Acyclovir sites)

What is the spectrum of clinical activity of Foscarnet?

Acyclovir-resistant HSV and CMV retinitis in AIDS patients

What are the side effects/toxicities of Foscarnet?

``` Risk of renal insufficiency Anemia Granulocytopenia Tremor, seizures, irritability Hypocalcemia ```

What is the method of administration of Foscarnet?

What are mechanisms of resistance of Foscarnet?

Mutations in DNA polymerase

What is the mechanism of action of Cidofovir?

Cytosine analog Phosphorylated to active form by cellular enzymes (not viral) Inhibits viral DNA polymerase by chain termination

What is spectrum of clinical activity of Cidofovir?

CMV retinitis in AIDS patients

What are side effects/toxicities of Cidofovir?

Irreversible renal toxicity (must be given with probenecid to protect kidneys)

What is method of administration of cidofovir?

What are mechanisms of resistance of cidofovir?

Resistant strain may develop with treatment

What disorders can immunoglobulins be used as prophylaxis for?

Hepatitis A RSV infection in high risk children/babies Rabies

What disorders can immunoglobulins be used as treatment for?

HBV (post exposure of liver transplant) CMV, Varicella, Measles Rabies Ebola

What are methods of administration of immunoglobulins?

Subcutaneous IM IV

What is the mechanism of action of antisense oligonucleotide Vitravene?

21 member oligonucleotide complementary to region of CMV IE (immediate early gene) that encodes several proteins required for virus replication

What is the spectrum of clinical activity of antisense oligonucleotide Vitravene?

CMV retinitis in AIDS patients who are intolerant or have contraindication for other treatments

What is method of administration of antisense oligonucleotide Vitravene?

Intravitreal injection

Non-HIV Drugs Flashcards

(56 cards)