Antivirals I Flashcards
What are the five different classes of anti-retroviral therapy?
- Nucleoside Reverse Transcriptase Inhibitors (NRTI’s)
- –Nucleotide RTI’s (tenofovir)
- Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI’s)
- Protease Inhibitors (PI’s)
- Entry Inhibitors: enfuvirtide; CCR5 antagonists
- Integrase Inhibitors
NRTIs include
Lamivudine = Emtricitabine
Tenofovir
Abacavir
Zivovudine (AZT)
Truvada is a combination of which two NRTIs
Tenofovir/Emcitrabine
Epzicom is a combination of which two NRTIs
Abacavir/Lamivudine
MOA of NRTIs
They act as DNA analogs that inhibit reverse transcriptase leading to viral chain termination
What are the side effects of Tenofovir?
Nephrotoxicity—Fanconi Syndrome
What are the side effects of Abacavir?
hypersensitivity reaction - send for HLA test first
What are the side effects of Lamivudine/emtricitabine?
very few side effects
What are the side effects of Zidovudine
anemia - not used anymore for long term use
What are the side effects of the NRTIs as a class?
lactic acidosis and GI upset
Which drugs are the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)?
Efavirenz, EFV
Nevirapine, NVP
Rilpivirine, RPV
Etravirine
MOA of NNRTIs?
bind directly to the reverse transcriptase enzyme and causing direct enzyme inhibition
What are the common side effects of Efavirenz?
CNS symptoms!!
**vivid dreams
-drowsiness
Teratogenic
What are the common side effects of Nevirapine?
Rash
Hepatits including hepatic necrosis!!
What are the common side effects of Etravirine?
Rash
Increased LFT’s
What are the common side effects of Rilpivirine?
Rash
QT prolongation
Which drugs belong to the class of Protease Inhibitors? "Navir tease a pro!"
Ritonavir, RTV Fosamprenavir, fAPV Lopinavir/ritonavir, KAL Atazanavir, ATZ Darunavir
MOA of PI
Bind within active pocket of protease, causing conformational change inhibiting binding of virus. Without protease cleavage, virus cannot cleave protein chains and cause infection!
Protease Inhibitors and Ritonavir Boosting
Mechanism P4503A4 inhibition in the liver and gut
Inhibition of P-glycoprotein transport
—So Ritonavir at low doses enhances blood levels of other PI’s when given together
—patients don’t have to take drugs as often
*Usually Lopinavir/Ritonavir known as Kaletra
What are the adverse effects of PIs as a class?
- N/V/D
2. Metabolic Toxicities Dyslipidemia Hyperglycemia Lipodystrophy *Pt. predisposed to diabetes
Which drug is considered an viral entry inhibitor?
Enfuvirtide/Maravaroc - it is given by Injection
a salvage drug when you have no other choice
CCR5 Antagonists targets a receptor in humans and it is the only drug called?
Maravaroc - it inhibits the co-receptor on the humans from allowing the virus to gain entry into the CD4 T-cell
Adverse effects of CCR5 Antagonists include
Hepatotoxicity – appears to be rare
Common: cough, fever, upper respiratory infections, rash, musculoskeletal symptoms, abdominal pain, and dizziness
HIV-Integrase Inhibitors MOA
Inhibit viral integrase necessary for insertion of viral DNA into human genomic DNA
Drugs in the Integrase Inhibitor class
Raltegravir
Elvitegravir
Dolutegravir
Adverse side effects of Integrase Inhibitors?
Myopathy and rhabdomyolysis, elevated CK
Generally few adverse effects
Common: nausea, headache, diarrhea, pyrexia
HAART Therapy uses 3 HIV agents from two different classes
the cocktail includes:
2 NRTIs + PI (± ritonavir boosting)
2 NRTIs + NNRTI
2 NRTIs + Integrase Inhibitor
Resistance to HAART
Very important
Can quickly limit treatment options
Once resistance has develop to an antiretroviral agent it is permanent
Cross-resistance can occur within antiretroviral classes
Directly associated with adherence and attainment of virologic goals
