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Antivirals

Terms in this set (33)

used to be prophylaxis against influenza A, block M2 proton channel so virus can't get in?
amantadine and rimantadine - not recommended anymore because of resistance
Mechanism of Action of Neuraminidase inhibitors
blocks cleavage of syacilic acid residues so hemagluttinin can't release new virus particles
Oseltamivir, Zanamivir
Neuraminidase inhibitors active against influenza A and B,
zanamivir is inhalation and can cause bronchospasms, oseltamivir has cause suicide in teens
Mechanism of action of nucleoside analogs
nucleoside analog = base + deoxyribose, must be phosphorylated inside the viral cell (viral thymidine kinase), then human kinases add 2nd and 3rd phosphate then acyclovir acts as alternative substrate for DNA polymerase but lacks 3' OH so chain termination
characteristics of acyclovir
low oral bioavailability, active against HSV1 and HSV2 (low VZV); may cause reversible nephropathy, GI issues, and headache
Resistance to acyclovir
mutation in polymerase or change in activity of viral thymidine kinase
What nucleoside analog is commonly given in transplantation prophylaxis and for CMV infections
Ganciclovir, may cause granulocytopenia, thrombocytopenia
Foscarnet MOA
binds phosphate binding site of polymerases used to treat highly resistant CMV or HSV or VZV
Describe some important cellular proteins necessary for HIV infection
GP120 protein recognizes CD4+ and is then recognized by coreceptor
Need CCR5 of CXCR4
Structure of nucleoside reverse transcriptase inhibitors
RNA base + ribose sugar, still needs to be phosphorylated to become nucleotide and still lacks 3' OH
Zidovudine, Emtricitabine, Didanosine
nRTI's - zidovudine may cause hematotoxicity, didanosine may cause peripheral neuropathy and pancreatitis
Two combinations of anti-vitals you can't do?
Didanosine (DDI) + Zalcitabine (DDC) because of additive toxicity
Zidovudine (AZT) + Stavudine (D4T) because of competition for activation
What is the mechanism of toxicity with nRTI's?
inhibition of mitochondrial function because of inhibition of DNA pol gamma -> lactic acidosis, anemia, granulocytopenia, peripheral neuropathy
Nevirapine, Efavirenz, and their MOA?
non-nucleoside RTI's - don't need to be phosphorylated, non-competitive inhibitors (bind to different site than nRTI's), can work synergistically with nRTI's or PI
Side effects of nnRTI's
nevirapine - rash, efavirenz - CNS or psychiatric problems, teratogenic
Atazanavir, Darunavir, Fosamprenavir, Lopinavir, Saquinavir
HIV protease inhibitors
Ritonavir
Protease boosting - give sub therapeutic dose to inhibit P450 metabolism of protease inhibitors
MOA of protease inhibitors?
aspartate protease (pol gene) cleaves polypeptides to form mature viral proteins - it has dipeptide structure that our proteases don't - PI's bind to the dipeptide
Adverse effects of PI's
GI distress,
most PI's are metabolized by CYP3A4, some inhibit and some induce it
Raltegavir
integrase inhibitor - blocks insertion of HIV DNA into host DNA - may have data skin reactions
Enfurvirtide
fusion inhibitor for HIV - binds gp41, used when resistant to other HIV therapies
Mariviroc
binds CCR5, does not bind CXCR4
Describe some of the long term effects of anti-HIV therapy
Lipodystrophy syndrome (lose fat from face and other normal places and goes to abdomen and buffalo hump), elevated cholesterol and triglycerides, hyperglycemia (insulin resistant)
Goal of HepB treatment vs HepC treatement
HepB treatment goal is suppressive, the goal of HepC treatment is to eradicate the virus
Mechanism of Action of IFN-alpha
increases JAKS activity which phosphorylate signal transducers and activators of transcription (STATS) to make antiviral proteins. Also increases NK cells.
Why pegylated IFN
adding polyethylene glycol reduced proteolytic hydrolysis in kidney and so can be administered 1x/wk (instead of daily)
Side effects of IFNalpha
life threatening neuropsychiatric, autoimmune, or ischemic disorders
cardiac arrest, suicide
Ribavarin MOA?
Guanosine analog that inhibits guanosine triphosphate formation to prevent capping of viral mRNA to block RNA dependent RNA polymerase
Uses of Ribavarin
influenza, RSV, Hantavirus, HepC (with pegylated IFN)
Side Effects of Ribavarin
Hemolytic anemia, cardiac issues, serious teratogen
What protein is necessary to cleave HepC polyproteins to active forms
NS3/4 serine protease
Simeprevir
2nd generation NS3 protease inhibitor for HCV - may cause photosensitivity rash
Sofosbuvir
nucleotide analog inhibitor of HCV NS5B polymorphism, prodrug that is metabolized and then phosphorylated to terminate the elongating RNA strand
*active against HCV genotypes 1,2,3,4
*PegIFN + ribavarin + sofusbuvir = 12 wks (instead of 48)
crazy expensive
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