Antiviral Therapy Flashcards
Zanamivir, oseltamivir mech
inhibit influenza neuraminidase : decrease the release of progeny virus
Zanamivir, oseltamivir clinical use
Treatment and prevention of both influenza A and B
Ribavirin Mech
Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate DH
clinical use of Ribavirin
RSV, Chronic Hep C
Ribavirin toxicity/SE
Hemolytic anemia. Severe teratogen.
Acyclovir, famciclovir, valacyclovir mech
Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells: few adverse effects. Guanosine analog. Triphosphate analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase chain termination
Acyclovir, famciclovir, valacyclovir clinical use
HSV and VZV; HSV-induced mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in immunocompromised patients. No effect on latent forms of HSV and VZV.
Acyclovir, famciclovir, valacyclovir have weak activity against what virus?
EBV
Acyclovir, famciclovir, valacyclovir has NO activity against what virus?
CMV
What is a prodrug of acyclovir? what is its advantage?
Valacyclovir; better bioavailability!
What is the treatment for herpes zoster?
Famciclovir! (I took this, wasn’t a hug fam of zoster haha)
Acyclovir, famciclovir, valacyclovir Toxicity
Obstructive crystalline nephropathy and acute renal failure if not adequately hydreated
What is the mech of resistance to acyclovir, famciclovir, valacyclovir?
Mutate viral thymidine kinase
Ganciclovir mech
5’-monophosphate formed by a CMV viral kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase.
Ganciclovir Clinical use
CMV, especially in immunocompromised patients. Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability
Ganciclovir Toxicity
Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir
What is the mech of resistance to Ganciclovir?
Mutated CMV DNA polymerase or lack of viral kinase
Foscarnet mech
Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does not require activation by viral kinase.
What is the mneumonic for foscarnet?
Foscarnet = pyrofosphate analog
Foscarnet (2) clinical uses?
1) CMV retinitis in immunocompromised patietns when ganciclovir FAILS; 2) acyclovir-resistant HSV
Foscarnet toxicity?
Nephrotoxicty
What is the mech of resistance to Foscarnet?
Mutated DNA polymerase
Cidofovir mech
Preferentially inhibits viral DNA pol. Does not require phosphorylation by viral kinase.
What is the clinical use of Cidofovir?
CMV retinitis in immunocompromised patients; acyclovir-resistant HSV.
Does Cidofovir have a long or short half life?
long
When is HAART initiated?
when patients present with AIDS defining illness, low CD4 counts (
What is the HAART regimen?
2 nucleoside reverse transcriptase inhibitors (NRTIs) + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) OR 1 protease inhibitor or 1 integrase inhibitor
What are the Protease inhibitors? stating the suffix is good fucking enough
Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Ritonavir, Saquinavir
Mech of protease inhibitors
Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.
Which protease effects metabolism of other drugs? how?
Ritonavir can boost other drug concentrations by inhibiting CYP-450.
Navir tease a protease
haha
Protease inhibitor Toxicity
Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy. Nephropathy.
What protease can cause hematuria?
Indinavir
What are the Nucleoside Reverse transcription inhibitors?
Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zidovudine (ZDV, formerly AZT)
What is the mech of NRTIs?
Competively inhibit nucleotide binding to reverse transcriptae and terminate the DNA chain (lack a 3’OH group). The nucleosides need to be phosphorylated to be active
Which NRTI is actually a nucleotide?
Tenofovir
Which NRTI is used for general prophylaxis and during pregnancy to decrease the risk of fetal transmission?
ZDV
Toxicity of NRTI’s
Bone marrow suppression (can be reversed with granulocyte colony-stimulating factor and erythropoietin, peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), anemia (ZDV), pancreatitis (didanosine).
NNRTIs
Efavirenz, Nevirapine, Delavirdine
Efavirenz, Nevirapine, Delavirdine mech
Bind to reverse transcriptae at site different from NRTIs. Do no require phosphorylation to be active or compete with nucleotides.
Efavirenz Nevirapine, Delavirdine SE/Toxicity profile
Rash and hepatotoxicty are common to all NNRTIs. Vivid dreams and CNS symptoms are common with efavirenz. Delavirdine and efavirenz are contraindicated in pregnancy
What is the integrase inhibitor?
Raltegravir
Raltegravir mech
Inhibits HIv genome integration into host cell chromosome by reversibly inhibiting HIV integrae
Raltegravir SE/toxicity
Hypercholestrolemia
What are the fusion inhibitors?
Enfuvirtide, Marviroc
Enfuvirtide mech
binds gp41, inhibiting viral entry
Maraviroc mech
Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120
Skin reaction at injection site is a SE of which drug?
Enfuvirtide
What are interferons?
Glycoproteins normally synthesize by virus-infected cells
What is the mech of interferons?
antivrial and antitumoral properties
IFN-alpha clinical usage?
Chronic Hep B & Hep C, Kaposi Sarcoma, Hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
IFN-beta
multiple sclerosis
IFN-gamma
Chronic granulomatous disease
Interferon toxicity
Neutropenia, myopathy
Antibiotics to avoid in pregnancy + adverse effect?
The following are examples…..
Sulfonamides
Kernicterus
Aminoglycosides
Ototoxicty
Fluoroquinolones
Cartilage damage
Clarithromycin
Embryotoxic
Tetracyclines
Discolored teeth, inhibition of bone growth
ribavirin
Teratogenic
Griseofulvin
Teratogenic
Chloramphenicol
Gray Baby
