EXAM #4: ANTIRETROVIRALS Flashcards
What does NRTI stand for?
Nucelotide Reverse Transcriptase Inhibitor
List the NRTIs.
Zidovudine Lamivudine Abacavir Tenofovir disoproxil Emtricitabine
What is the MOA of the NRTIs?
Analogs of nucleotides that inhibit nucleotide binding to REVERSE TRANSCRIPTASE and cause DNA chain termination
What is required for conversion of the NRTIs into their active form?
Cellular kinases
What infection aside from HIV can be treated with NRTIs?
HBV
What are the adverse effects common to the NRTIs?
1) Lactic acidosis
2) Fatty liver disease
3) Lipodystrophy
What is Abacavir?
Guanosine analog NRTI
What specific adverse effects are associated with Abacavir?
Allergic reaction
Think “A” for allergic reaction*
What is the allergic reaction in with Abacavir associated with?
HLA-B5707–must do genetic testing first!
What type of drug is Lamivudine?
Cytosine analog NRTI
What is unique about the toxicity associated with Lamivudine?
LEAST toxic of the antiretrovirals
What is the unique clinical utility associated with Lamivudine?
Safe in pregnancy
What type of drug is Emtricitabine?
Fluorinated analog of Lamivudine–NRTI
What specific adverse effect is associated with Emtricitabine?
Hyperpigmentation of the palms and soles
When is Emtricitabine contraindicated?
1) Young children
2) Pregnant women
3) Hepatic or renal failure
What type of drug is Tenofovir?
Nucleotide analog of adenosine–NRTI
How is Tenofovir administered?
Orally; however, not that is is normally given as “Tenofovir disoproxil” that has more oral bioavalibility
What adverse effects are associated with Tenofovir?
1) Bone marrow toxicity (Faconi anemia)
2) Decreased bone density and fetal growth
What type of drug is Zidovudine or AZT?
Deoxythymidine analog NRTI
What unique adverse effects are associated with Zidovudine?
Myelosuppression
What is the unique clinical indication for Zidovudine?
Post-exposure prophylaxis
What does NNRTI stand for?
Non-nucleoside Reverse Transcriptase Inhibitors
What is the MOA of the NNRTIs?
Binds to Reverse Transcriptase at a site OTHER THAN THE ACTIVE SITE and inhibits the enzyme
How do the NNRTIs compare to NRTIs?
NNRTIs do NOT require phosphorylation for activation
What strain of HIV are the NNRTIs NOT active against?
HIV-2
What adverse reactions are common to the NNRTIs?
1) Rash
2) Steven Johnson Syndrome
3) Hepatotoxicity
4) Major drug-drug interactions b/c of CYP450
List the NNRTIs.
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What specific adverse effects are associated with Efavirnez?
1) Teratogenic
2) Adverse CNS effects
3) CYP 450 inducer
When is Efavirnez contraindicated?
Pregnancy
What specific toxicity is associated with Nevirapine?
Hepatitis
What is unique about the clinical indications for Nevirapine?
Can be used to prevent VERTICAL transmission
What is the MOA of the protease inhibitors in HIV therapy?
Block the protease necessary for maturation of virion proteins
What adverse effects are associated with the Protease Inhibitors?
1) Hyperlipidemia
2) Iipodystrophy
3) Hepatotoxicity
4) GI intolerance
5) Increased bleeding risk
6) Drug-drug interactions via CYP p450
List the Protease Inhibitors.
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What type of drug is contraindicated with Atazanavir?
PPIs–requires acid for absorption
What major adverse effects are associated with Atazanavir?
1) Peripheral neuropathy
2) Hyperbilirubinemia
3) Adverse cardiac effects
What effect does Atazanavir have on the CYP p450 enzymes?
Inhibition
What is the effect of Ritonavir on liver metabolism?
Potent INHIBITOR or CYP p450 enzymes
How is Ritonavir used clinically?
“Booster” to increase the half-life of co-administered drugs
How is Darunavir administered?
Orally + pharmacokinetic enhancer e.g. Ritonavir
What are the specific adverse effects seen with Darunavir?
1) Increased liver enzymes
2) Increased serum amylase
What is Darunavir specifically good for treating?
Drug resistant HIV-1
What is the MOA of the CCR5 Receptor Antagonists?
Blocks interaction of HIV (gp120) with the CCR5 co-receptor
What drug is a CCR5 receptor antagonist?
Maraviroc
What is the major toxicity associated with Maraviroc?
Increased cardiac events in those with underlying heart disease
What is the mechanism of resistance to Maraviroc?
Change in HIV tropism i.e. switch from CCR5 to CXCR4 tropism
What are the indications for Maraviroc?
HIV “experienced” patients with a tropsim for CCR5
What is the mechanism of the Fusion Inhibitors?
Blockade of the gp41 fusion protein
What is the Fusion inhibitor?
Enfurvirtide
What is the only anti-viral that is given parenterally?
Enfurvirtide
*Given SubQ
What are the adverse effects associated with Enfurvirtide?
1) Injection site reaction
2) Allergy to drug
3) Increased risk for bacterial pneumonia
What is the clinical utility of Enfurvirtide?
HIV experienced patients with resistance
What is the MOA of the Integrase Inhibitors?
Inhibit viral integration into the host genome
List the Integrase Inhibitors.
Raltegravir
Elvitegravir
Dolutegravir
What major toxicities are associated with Raltegravir?
1) Mypoathy
2) Rhabdomyolysis
How is Elvitegravir administered?
Orally with a CYP p450 inhibitor e.g. ritonavir
What specific adverse effect is associated with Elvitegravir ?
Elevated lipase enzymes
What are the adverse effects associated with Dolutegravir?
1) Hypersensitivity reaction
2) Elevation of liver enzymes
What is unique about Dolutegravir in terms of resistance?
Retains activity against strains that are resistant to other integrase inhibitors
How much does a patient need to weigh to be given Dolutegravir?
At least 40 kg
When do you initiate ARV therapy?
ALL HIV infected individuals
At what point is there the strongest recommendation for ART initiation?
CD4+ T-cell count less than 350
What is the standard of care for ART?
Combination of at LEAST 3 antiretroviral drugs/classes
What is the preferred combination of ART for initial therapy?
1) Protease inhibitor (Ritonavir)
2) 2x NRTIs
OR
1) Integrase Inhibitor
2) 2x NRTIs
