Pharmacology - Antiviral Therapy I and II Flashcards
Class: Acyclovir; Penciclovir
Purine analog (guanosine)
Class: Valacyclovir; Famciclovir
Purine analog (guanosine)
MOA: Valacyclovir; Famciclovir
Prodrug converted to Acyclovir & Penciclovir,respectively –> After phosphorylation, causes viral DNA chain termination
MOA: Acyclovir; Penciclovir
After phosphorylation, causes viral DNA chain termination
Class: Ganciclovir
Purine analog (guanine)
MOA: Ganciclovir
After phosphorylation, causes viral DNA chain termination
Class: Foscarnet
Pyrophosphate congener
MOA: Foscarnet
Directly inhibits HSV DNA polymerase or HIV reverse transcriptase
Use: Foscarnet
Broad spectrum (HSV/VZV/CMV, and RNA viruses including HIV)
use for resistant strains only due to toxicity concerns
Use: Ganciclovir
Treatment & prophylaxis of CMV infection (but also HSV, VZV)
**Valganciclovir for PO bc of much higher bioavailabiltiy
Use: Valacyclovir; Famciclovir;
Acyclovir; Penciclovir
HSV, VZV (requires higher dose than HSV)
Side effects: Valacyclovir; Famciclovir;
Acyclovir; Penciclovir
CNS changes and renal dysfunction possible when used at higher doses
Side effects: Ganciclovir
Neutropenia, thrombocytopenia
Side effects: Foscarnet
Dose-dependent renal and CNS toxicities, electrolyte & metabolic abnormalities;
Myelosuppression
What specific scenario is Foscarnet recommended for?
Used for invasive HSV/VZV infections from acyclovir resistant strains; alternative to ganciclovir for CMV
Side effects: Tenofovir
Nephrotoxicity;
Lactic acidosis;
GI issues
Side effects: Abacavir
Hypersensitivity reaction;
Lactic acidosis;
GI issues
Side effects: Zidovudine
Anemia;
Granulocytopenia
Lactic acidosis;
GI issues
Class: Zidovudine
NRTI
Class: Lamivudine (Epivir); Emtricitabine (Emtriva)
NRTI
Class: Tenofovir
NRTI
Class: Abacavir
NRTI
Class:
Efavirenz (Sustiva);
Nevirapine (Viramune); Rilpivirine (Edurant);
Etravirine (Intelence)
NNRTI
MOA: NRTIs Zidovudine; Lamivudine; Emtricitabine; Tenofovir; Abacavir
Inhibits reverse transcriptase
Use: Abacavir, Zidovudine
HIV
Use: Lamivudine, Emtricitabine, Tenofovir
HIV and HBV
Side effects: Lamivudine (Epivir); Emtricitabine (Emtriva)
Headache; N & V; rash; neutropenia; pancreatitis
Side effects: Efavirenz
• CNS symptoms!!
-vivid dreams
-drowsiness
• Teratogenic
Side effects: Nevirapine
Rash;
Hepatitis including hepatic necrosis
Side effects: Etravirine
Rash;
Increased LFTs
Side effects: Rilpivirine
Rash;
QT prolongation
Class: Efavirene;
Nevirapine;
Rilpivirine;
Etravirine
NNRTIs
MOA: NNRTIs Efavirene; Nevirapine; Rilpivirine; Etravirine
Inhibit reverse transcriptase through direct enzyme inhibition instead of a nucleoside base
Use: NNRTIs Efavirene; Nevirapine; Rilpivirine; Etravirine
HIV
Side effects: Protease Inhibitors
GI intolerances - N/V, diarrhea;
Dyslipidemia;
Hyperglycemia;
Lipodystrophy
Class:Ritonavir (Norvir);
Protease inhibitor
Class: Fosamprenavir
Protease inhibitor
Class: Atazanavir
Protease inhibitor
Class: Darunavir
Protease inhibitor
Class: Lopinavir
Protease inhibitor
MOA: Protease inhibitors
Prevent cleavage of protein chain into functional subunits
Use: Protease inhibitors Ritonavir Fosamprenavir Atazanavir Darunavir Lopinavir
HIV
T/F: Resistance can develop slowly with use of protease inhibitors.
True
These drugs belong to what class and are used to treat HIV: Ritonavir Fosamprenavir Atazanavir Darunavir Lopinavir
Protease inhibitors
Side effects: Enfuvirtide
Local injection sight reaction (pain, erythema, induration, nodules, and cysts)
Increased rate of bacterial pneumonia
Hypersensitivity reaction
Class: Enfuvirtide
Entry inhibitor (also its MOA)
Class: Maraviroc
CCR5 antagonist (entry inhibitor)
Must test to see if virus is using CCR5 before administration
Use: Enfuvirtide, Maraviroc
HIV
How is Enfuvirtide administered?
Injectable
Side effects: Maraviroc
Hepatotoxicity - rare;
Cough, fever, upper RTIs, Rash, musculoskeletal symptoms, abdominal pain, dizziness
HIV often uses what co-receptors for entry into T-cells?
Chemokine (C-C motif) receptor 5 (CCR5) AND CXCR4
Maraviroc inhibits CCR5, no inhibitor exists yet for CXCR4.
Class: Raltegravir
HIV Integrase inhibitor
Class: Elvitegravir
HIV Integrase inhibitor
Class: Dolutegravir
HIV Integrase inhibitor
What is the function of HIV integrase?
Inserts viral DNA into human genome
MOA: HIV Integrase inhibitors
Raltegravir;
Elvitegravir;
Dolutegravir
Binds to HIV integrase to prevent viral DNA strand transfer
Use:
Raltegravir;
Elvitegravir;
Dolutegravir
HIV
Side effects: HIV Integrase inhibitors
Headache;
Low side effect profile
What are the common combinations for HAART?
- Integrase inhibitor + 2 NRTIs
- PI (+/- Ritonavir boosting) + 2NRTIs
- NNRTI and 2 NRTIs
Class: Sofosbuvir
NS5B Polymerase Inhibitor
Class: Paritapevir
NS5B Polymerase Inhibitor
MOA: NS5B Polymerase Inhibitors (Sofosbuvir, Paritapevir)
Compete with viral nucleotide to cause viral chain termination of HCV RNA
Use: Sofosbuvir, Paritaprevir
HCV
Side effects: Sofosbuvir, Paritaprevir
Few side effects; fatigue, headache, anemia possible
Class: Ledipasvir
NS5A inhibitor
Class: Daclatasvir
NS5A inhibitor
Class: Ombitasvir
NS5A inhibitor
What is the function of NS5A in HCV?
NS5A is a viral phosphoprotein required for viral replication.
Use: Ledipasvir; daclatasvir; ombitasvir
HCV
MOA: Simeprevir; Bocepravir; Telapravir
Prevent viral maturation through the inhibition of protein synthesis
NS3/4A protease inhibitors
Use: Simeprevir; Bocepravir; Telapravir
HCV
Side effects: Simeprevir; Bocepravir; Telapravir (NS3/4A protease inhibitors)
Anemia, rash, itching, GI side effects
Class: Simeprevir
NS3/4A protease inhibitors
Class: Bocepravir
NS3/4A protease inhibitors
Class: Telapravir
NS3/4A protease inhibitors
Are HCV treatments typically given in combination?
YES
For example:
Sofosbuvir + Ledipasvir;
Simeprevir + Sofosbuvir;
Ombitasvir + Paritaprevir + Ritonavir
Drug therapy for treatment of influenze should be started when?
Early in the course of the disease, otherwise the clinical benefits are limited
Class: Oseltamivir
Neuraminidase inhibitor
Class: Zanamivir
Neuraminidase inhibitor
Class: Peramivir
Neuraminidase inhibitor
MOA: Neuraminidase inhibitors - Oseltamivir, Zanamivir, Peramivir
Inhibits an enzyme critical in penetration of respiratory tract mucus and in the release of virus from infected cells
Effective against influenza A and B
What is the route of administration of Zanamivir?
Inhaled therapy
Side effects: Neuraminidase inhibitors - Oseltamivir, Zanamivir, Peramivir
Neuropsychiatric toxicity has been reported, GI side effects, brochospasm with zanamivir