Step 1 Antivirals Flashcards
Immunoglobulin MOA, Clinical uses, Administration
MOA - IgG (prepared from pooled human serum or plasma) binds to virus, blocking its attachment to the receptor/host cell Clinical uses: Given pre-exposure to prevent infection/disease or post-exposure to abort infection/modify disease course (eg., post-exposure prophylaxis for Hepatitis A) Viruse-specific hyperimmunoglobulin available for some diseases (HBIG, VZVIG, RIG) Administration - Parenteral
Amantadine, Rimantadine MOA, Clinical uses, Side Effects, Administration, Resistance
MOA - Inhibit entry and uncoating of Influenza A virus by preventing acidification of the endosome (interfere w/M2 protein of influenza A) Clinical Uses - Prophylaxis and treatment of influenza A virus infection (specific for influenza A) Side Effects: Amantadine - Elevated concentrations (usually seen with reduced renal function (elderly) - renally excreted) -< ataxia, dizziness, slurred speech (CNS effects) Rimantadine - low risk of CNS effects (met by liver, doesn’t cross BBB), some GI sx Administration - well absorbed oral Resistance - single aa change in M2 (emerges very quickly)
Fomiversen MOA, Clinical Uses, Administration
MOA - Antisense oligonucleotide (21nucleotides long, complementary to mRNA from the major immediate-early transcriptional unit of CMV) inhibiting synthesis of essential proteins for CMV infection Clinical Use - CMV retinitis in AIDS pts who cannot take other meds (intolerance/contraindication) Administration - Intravitreal injection
Interferons MOA, Clinical Use, Side Effects, Administration
MOA: (Bind cell receptor and induce multiple effects) Induce synthesis of antiviral proteins (including RNase and protein kinase) that protect the cell against subsequent challenges by both RNA and DNA viruses Clinical Use: IFN-a - chronic hepatitis B and C (pegylated ifn + ribavirin), Kaposi’s sarcoma, leukemias, malignant melanoma IFN-b - MS IFN-g - NADPH oxidase deficiency (Chronic Granulomatous Disease) Side Effects: Influenza-like sx (esp. in first wk) BM suppression (neutropenia) Depression Fatigue, myalgia, wt loss and increases susceptibility to bacterial infection Administration - parenteral (once/wk dose due to long half life w/PEG)
Ribavirin MOA, Clinical Use, Side Effects
MOA - Synthetic nucleoside analog that inhibits viral RNA synthesis by altering the nucleotide pools and normal mRNA formation (competitively inhibits IMP dehydrogenase) (needs to be phosphorylated in cell to become active) Clinical Use: Given orally in combo w/a-IFN for chronic Hep C Aerosol tx for RSV pneumonia and bronchiolitis in infants Unlabeled uses include tx of other viral infections (influenza A and B, West Nile Virus, Lassa fever, Hantavirus Hemorrhagic fever w/renal syndrome) Side Effects: BM suppression (anemia) Teratogenic (pregnancy should be avoided for at least 6mo after termination of tx)
Acyclovir MOA, Clinical Use, Side Effects, Administration, Resistance
MOA - Guanosine analog, rapidly phosphorylated by virus-specific thymidine kinase (only slowly by phosphorylated by host thymidine kinase) to monophosphate (further phosphorylated by host cell to triphosphate). Preferentially inhibits viral DNA polymerase by chain termination. Clinical Use: HSV (oral) - used for HSV induced mucocutaneous and genital lesions as well as for encephalitis, prophylaxis in immunocompromised VZV - Can treat chickenpox or shingles, decrease posherpetic neuralgia No effect on latent forms of HSV/VZV Side Effects: (well tolerated) Local irritation/burning (topical) Rare Nephrotoxicity due to crystallization in renal tubules Administration - Given PO, IV, topical (topical not very effective) Resistance (usually in immunocompromised) - No viral thymidine kinase (most common), mutation that affect acyclovir affinity/phosphorylation by thymidine kinase
Famciclovir MOA, Clinical Use, Side Effects
MOA - Rapidly converted to active compound, penciclovir, by enzymes in the intestinal wall and liver, then same MOA as acyclovir (monophosphorylated by virus, triphosphate formed by cell, preferential DNA pol inhibitor) Clinical Use - Preferred over Acyclovir for VZV (decreases new lesions, shedding, duration of pain and postherpetic neuralgia), can also be used for HSV (but no more effective and more expensive than acyclovir) Side effects - well tolerated (mild headache, nausea, diarrhea)
Valacyclovir MOA, Clinical Use, Side Effects
MOA - Rapidly converted to active compound, acyclovir, by enzymes in the intestinal wall and liver, then same MOA as acyclovir (monophosphorylated by virus, triphosphate formed by cell, preferential DNA pol inhibitor) Clinical Use - Preferred over Acyclovir for VZV (decreases new lesions, shedding, duration of pain and postherpetic neuralgia), can also be used for HSV (but no more effective and more expensive than acyclovir) Side effects - well tolerated (mild headache, nausea, diarrhea)
Ganciclovir MOA, Clinical Use, Side Effects, Administration, Resistance
MOA - Phosphorylated to monophosphate by protein kinase in herpes virus, then triphosphate by host cell enzymes. Preferentially inhibits viral DNA polymerase. Clinical Use: Active vs. all Herpes viruses (but no better activity than acyclovir for HSV/VZV) - used for CMV CMV retinitis in AIDS pts Prevention of CMV disease in immunocompromised (transplant recipients) Side Effects: Neutropenia, Thrombocytopenia, Leukopenia Renal toxicity Teratogen, carcinogen, mutagen (only use if life or sight threatening infection) Administration - PO or IV Resistance - mutated CMV DNA polymerase or lack of viral kinase
Foscarnet MOA, Clinical Use, Side Effects, Administration, Resistance
MOA - Pyrophosphate analogue that acts as a noncompetitive inhibitor or viral DNA polymerase (no activation required by viral kinase) Clinical Use: Ganciclovir-resistant CMV Acyclovir-resistant HSV or VZV Side Effects - Nephrotoxicity (usually reversible but may cause renal failure), electrolyte imbalances Administration - infused in large volumes of fluid Resistance - Mutated DNA polymerase
Zanamivir, Oseltamivir MOA, Clinical Use, Administration
MOA - Inhibit influenza neuraminidase, decreasing release of progeny virus (NA is essential for release of newly assembled virions) Clinical Use - Influenza A and B Administration: Zanamivir - aerosol (low PO bioavailability) Oseltamivir - PO
Maraviroc MOA, Clinical Use
MOA - CCR5 antagonist that interferes w/necessary interaction w/co-receptor molecules Clinical Use - HIV (pts must have virus that uses CCR5 as coreceptor)
Enfuvirtide Class, MOA, Clinicla Use, Side Effects, Adminstration, Resistance
Class - Fusion inhibitor MOA - Peptide that binds viral gp41 subunit and inhibits conformational change required for fusion w/CD4 cells, blocking entry and replication. Clinical Use - HIV (used in pts w/persistent viral replication despite antiretroviral therapy) Side Effects - hypersensitivity reaction, reactions at injection site, increase risk of bacterial pneumonia Adminsitration - SubQ injection Resistance - Develops due to mutations in envelope protein
Zidovudine (AZT) Class, MOA, Clinical Use, Side Effects, Resistance
Class - NRTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA chain (lack 3’ OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use - HAART, used for general prophylaxis and during pregnancy to reduce risk of fetal transmission Side Effects: BM suppression - reversed w/G-CSF and EPO Megaloblastic anemia Lactic acidosis (mt toxicity) GI intolerance, Headache Resistance - enhancement of chain terminator removal
Didanosine (DDI) Class, MOA, Clinical Use, Side Effects, Resistance
Class - NRTI MOA - Competitively inhibits nucleotide binding to RT and terminates DNA chain (lack 3’ OH). Must be phosphorylated by thymidine kinase to be active. Clinical Use - HAART Side Effects: BM suppression - reversed w/G-CSF and EPO Peripheral neuropathy Pancreatitis Lactic acidosis (mt toxicity) Resistance - enhancement of chain terminator removal or steric hindrance
