Antivirals II Flashcards
Simeprevir, Bocepravir, Telapravir are drugs used to treat HCV infection. They belong to which class?
NS3/4A protease inhibitors
What is the mechanism of NS3/4A protease inhibitors?
Prevent Hepatitis viral maturation through inhibition of protein synthesis
Sustained viral Response is treated
for 12 weeks and see if they stayed unresponsive and are cured
Interferon for HCV-pegylated works by
Inducing interferon-stimulated genes (ISGs) that help establish an antiviral state within cells
What were the toxicities acquired by Interferon Treatment?
Numerous toxicity concerns!!
Flu-like symptoms, Cytopenias, depression, fatigue
*Unstable psychiatric problems; baseline severe cytopenias
Ribavirin major side effects?
Hemolytic anemia
Teratogenic
Sofosbuvir belongs to a category of
Nucleoside/nucleotide NS5B POLYMERASE inhibitors
MOA of Sofosbuvir?
Inhibitor of HCV NS5B RNA-dependent RNA polymerase. Once phosphorylated, competes with natural viral nucleotide (uridine) to cause chain termination of HCV RNA
*safe but it is still new
Ledipasvir is sold in combo w. Sofosbuvir. Since Ledipasvir is a NS5A Inhibitor, what is its MOA?
Inhibits HCV NS5A, a viral phosphoprotein required for viral replication.
*safe
Which drugs are the NS3/4A Protease Inhibitors?
Simeprevir, Boceprevir, Telaprevir
What is the MOA of NS3/4A Protease Inhibitors
Prevent viral maturation through the inhibition of protein synthesis
*anemia, rash, itching, GI side effects, drug interactions
MOA of Viral Guanosine Antivirals
Drug is using the viral Thymidine kinase to phosphorylate itself, acyclovir and penciclovir are only
phosphorylated in infected cells.
Acyclovir (IV/PO/topical) covers
*prodrug is Valacyclovir (much more easily absorbed)
Herpes simplex 1+2
Varicella-zoster
Penciclovir (IV,PO, topical)
*prodrug is Famciclovir (PO)
Herpes simplex 1+2
Varicella-zoster
Ganciclovir (IV/PO)
*prodrug is Valganciclovir (PO)
Cytomegalovirus
Herpes simplex 1+2
Varicella-zoster
Foscarnet spectrum of activity
Cytomegalovirus,
Herpes simplex 1+2
Varicella-zoster
Toxicity of Acyclovir
Central nervous system - Malaise, headache, confusion
Nausea, vomiting, diarrhea
Renal dysfunction: only seen with higher doses of IV therapy due to drug crystallization in the kidney
Toxicity of Valgancyclovir/Gancyclovir is
Myelosuppression (neutropenia 25-40% of patients)
Monitor CBC – may need to d/c drug
CNS toxicity (HA, seizures, confusion)
Hepatotoxicity, GI intolerance in limited patients
Foscarnet MOA
MOA: directly inhibits herpesvirus DNA polymerase or HIV reverse transcriptase
Does not undergo significant intracellular metabolism so you don’t have to worry about resistance
Generally active against acyclovir / penciclovir /ganciclovir resistant viruses
Toxicity of Foscarnet
Nephrotoxicity (occurs in 1/3 of patients)
Dose limiting side effects
Electrolyte/Metabolic abnormalities: (10-45% of patients)
Hypo / hypercalcemia
Hypo / hyperphosphatemia
Hypomagnesemia
Hypokalemia
Infuse at maximum rate of 1 mg/kg/minute to minimize these effects
CNS side effects (1/4 of patients)
Tremor, irritability, seizures (up to 10%), hallucinosis
Myelosuppression
***so you don’t give this drug unless you have to for resistant bugs
Take home, which drug is best for Herpes Virus?
Gancyclovir is better for?
Acyclovir
—CMV
Influenza Drugs -
Oseltamivir (Tamiflu) - prevents penetration and release of virus
Zanamivir (Relenza)
**active against both A/B
**must start w/in 2 days of symptoms
Side Effects of Influenza Drugs
Oseltamavir:
GI side effects including nausea/vomiting/diarrhea
Neuropsychiatric events reported in older patients
Agitation, anxiety, altered mental status
Zanamavir-
Bronchospasm
