Antiretrovirals Flashcards
What allows HIV to mutate so rapidly?
Really error prone reverse transcriptase
What is the enzyme that integrates HIV genetic material into host DNA?
integrase
What is the enzyme that is packaged with the HIV virus, and cleaves viral proteins to mature proteins?
Protease
What is the viral antigen of HIV that is measured in the serum to follow the early course of the disease?
p24
What is the antibody that is followed with HIV infections?
Anti-HIV ab (gp120)
What is the MOA of Nucleotide reverse transcriptase inhibitors?
Mimic nucleotides to inhibit nucleotide binding to the catalytic site, and cause chain termination
What are the adverse effects of Nucleoside reverse transcriptase inhibitors?
Lactic acidosis
Fatty liver disease
Lipodystrophy
Why can NRTIs be used in Hep B infections?
Has reverse transciptase
What type of drug is Abacavir? Route of administration? Adverse effects?
NRTI
PO
Increase chances of MI
What drug does Abacavir interfere with?
Methadone
How is resistance to abacavir brought about?
Multiple mutations in HIV reverse transcriptase
What type of drug is Lamivudine? Route of administration? Adverse effects?
NRTI
PO
CNS effects, but safer than most
How is resistance to Lamivudine brought about?
Single base change
Which HIV drugs are safe for use in pregnancy?
Lamivudine
Nevirapine
***
What type of drug is Emtricitabine? Route of administration? Adverse effects?
Fluorinated analog of lamivudine (NRTI)
PO
HA, n/v/d
How is resistance to Emtricitabine brought about?
single mutation in reverse transcriptase
What type of drug is Tenofovir? Route of administration? Adverse effects?
NRTI
PO
Renal and bone toxicity
How is resistance to Tenofovir brought about?
single mutation in reverse transcriptase
What type of drug is Zidovudine (AZT)? Route of administration? Adverse effects?
NRTI
PO
Myelosuppression
How is resistance to Zidovudine brought about?
Multiple mutations in HIV needed
What is the MOA of Non-nucleoside reverse transcriptase inhibitors? What is the major difference between these and NRTIs?
bind to a site on the enzyme distinct from the active site
Do NOT need to be phosphorylated to become activated
How is resistance to NNRTIs brought about?
Single amino acid change
What is the major adverse reaction that is common to the class of NNRTIs?
Drug-Drug interactions d/t p450 effects
Stven-Johnson syndrome
What type of drug is Efavirenz? Route of administration? Adverse effects?
NNRTI
PO
CNS effects
Resistance to Efavirenz will often mean resistance to what other NNRTI?
Nevirapine
What type of drug is Nevirapine? Route of administration? Adverse effects?
NNRTI
PO
Hepatitis
What is the MOA of the proteases used for treating HIV?
mimic peptides for the protease
Generally, how is resistance to protease inhibitors brought about?
Multiple mutations
What are the common adverse effects of protease inhibitors?
Drug-drug interactions high d/t p450
What is the major difference between mature and immature HIV viruses?
Well formed blob on EM with mature, whilst immature have poorly defined blob
What type of drug is Atazanavir? Route of administration? Adverse effects?
Protease inhibitor
PO
Peripheral neuropathy, cardiac effects
What class of drugs cannot be administered concurrently with Atazanavir? Why?
PPIs, since acid required for absorption
What type of drug is Ritonavir? Route of administration? Adverse effects?
Peptidomimetic protease inhibitor
PO
POTENT inhibitor of p450
What is the therapeutic indication for Ritonavir?
Booster to increase the half-life of coadministered ARV drugs d/t inhibiting p450 effects
What type of drug is Darunavir? Adverse effects?
Protease inhibitor
Increased serum amylase
What is different about the resistance with Darunavir?
90% of HIV-1 isolates that are resistant to multiple protease inhibitors are still susceptible to this
What is the MOA of CCR5 receptor antagonists?
Inhibits the coreceptor CCR5
What are the two coreceptors for HIV? Which causes a lower susceptibility to HIV infection?
CCR5
CXCR4–cause lower susceptibility***
What is the role of gp120 on HIV?
Envelope protein/anchor on cells
What is the role of gp41 protein on HIV?
Fusion protein
What type of drug is Maraviroc? Adverse effects?
Co-receptor antagonist
URT infections/increased cardiac events
What is the therapeutic indications for Maraviroc?
For HIV experience pts, who have a predominantly CCR% tropic virus
How is resistance brought about with Maraviroc?
Change in tropism or mutations in gp120
What is the MOA of fusion inhibitors?
Inhibits gp41 from fusing cell membranes of HIV
What is the only type of antiretroviral that is administered IV?
Fusion inhibitors
What type of drug is Enfuvirtide? Adverse effects?
Peptide fusion inhibitor
Injection pain, bacterial pneumonia
How is resistance to Enfuvirtide brought about?
Multiple mutations in gp41
What is the therapeutic index of enfuvirtide?
Treatment experienced patients with evidence of ARV resistance
What is the MOA of integrase inhibitors?
Inhibit HIV integrase, and prevents DNA strand transfer
What type of drug is Raltegravir? Adverse effects?
Integrase inhibitor
Myopathy/rhabdo
How is resistance to Raltegravir ad Elvitegravir brought about?
Single mutation in integrase gene
What type of drug is Elvitegravir? Adverse effects?
Integrase inhibitor
Usual side efects
What type of drug is Dolutegravir? Adverse effects?
Integrase inhibitor
Elevation of serum aminotransferases, fat redistribution syndrome
What is the therapeutic indications for Dolutegravir?
Need to weigh 40 kg and be over 12 yo
What is significant about the resistance profile of Dolutegravir?
Retains activity against some viruses resistant to both raltegravir and elvitegravir
What is the clinical definition of AIDS?
Less than 250 cells/mm3 of CD4 cells
True or false: all pts who have HIV are recommended to take antiretroviral agents
True
What is the standard of care for HIV?
Use at least 3 antiretroviral drugs, usually form at least two different classes.
1 PI + 2 NRTIs
1 II + 2 NRTIs
