Antiretroviral Agents Flashcards
Classes of Antiretroviral drugs
NRTIs NNRTIs Fusion inhibitors PIs Co-receptor antagonists Integrase Inhibitors
NRTIs general characteristic, MOA
Target is reverse transcriptase
Mimic nucleotides, inhibit binding to catalytic site
Require cellular kinases to convert to triphosphate form
NRTI general adverse
Lactic acidosis, fatty liver disease, and lipodystrophy
Abacavir MOA
Guanosine analogue NRTI, given orally
Abacavir Adverse
Allergic reaction w/ HLA B5707=> rash, fever, nauea, vomiting, etc.
Increased risk for CV events
May lower effectiveness of methadone
Abacavir Resistance and indications
Multiple mutations needed for resistance
Tx for naive and experienced HIV infections
Lamivudine MOA
Cytosine analogue NRTI, given orally but low serum half life
Lamivudine adverse
Very safe, but higher than recommended doses yield GI and CNS effects
Lamivudine Resistance and indications
Single base change=>high resistance
Tx for naive and experienced HIV pts,
Safe for pregnant mothers and neonates
Emtricitabine MOA
Fluorinated analogue of lamivudine=> oral, longer half life
Emtricitabine adverse
Headache, nausea, diarrhea, hyperpigmentation of palms and soles
Emtricitabine resistance and indications
single mutation in reverse transcriptase
Tx for naive and experienced HIV
Emtricitabine Contraindications
Young children, pregnant women, pts w/ renal or hepatic failure
Tenofovir MOA
Adenosine analogue NRTI, oral, usually given as prodrug
Tenofovir Adverse
Normal GI issues
Renal and bone toxicity
Can cross placenta=>decreased bone density and fetal growth
Tenofovir resistance and Indications
Single codon change=>resistance
Naive and experienced HIV pts, can reduce transmission
Tx of chronic hep B w/ interferon
Zidovudine (AZT) MOA
Deoxythymidine analogue NRTI, oral, well absorbed
Zidovudine Adverse
Myelosuppresion, nail hyper-pigmentation, normal GI effects
Zidovudine Resistance and Indications
Multiple mutations needed for resistance
Naive and experienced HIV, reduction in vertical transmission
NNRTIs MOA
Target is reverse transcriptase, bind to site distinct from active site
do not require phosphorylation for activation
Not active against HIV 2
NNRTI adverse effects
Rash, Steven Johnson syndrome, hepatotoxicity
Drug-drug ineractions common b/c of effects on cytochrome P450 enzymes
Efavirenz pharmkinetics
Once daily oral, on empty stomach
Efavirenz adverse
CNS, rash, headache/nausea
Induces CYP3A4
Efavirenz resistance and indications
Single base change can confer resitance. Cross resitance w/ Nevirapine common
Naive and experienced HIV
Efavirenz contraindications
Pregnancy
Nevirapine pharmkinetcs
NNRTI, oral, lipophilic
Nevirapine adverse
rash, hepatitis, nausea, headache
Nevirapine resistance and indications
Single base change=>resistance
Prevents vertical transmission
Protease Inhibitors
Target=HIV protease, blocks maturation of virion particles after budding
Multiple mutations needed for resistance
Protease Inhibitor adverse
**Drug interactions due to alteration of cytochrome P450 enzymes
Hyperlipidemia, lypodystrophy, hepatotoxicity, GI problems, increased bleeding
Atazanavir Pharmkinetics
Once daily oral, requires acid for absorption, do not use with PPIs
Atazanavir adverse
peripheral neuropathy, indirect hyperbilirubinemia
Inhibitor of CYP3A4 and CYP2C9
Atazanavir resistance and adverse
Multiple codon changes needed for resistance
naive and experienced HIV, approved for use in children over 6 y.o.
Ritonavir pharmkinetics
PI, oral, 75% bioavailable
Ritonavir adverse
Potent inhibitor of CYP3A4
Nausea/diarrhea, paresthesia, hepatitis
Ritonavir resistance/indications
multiple mutations needed for resistance
Often used in low doses as a booster to increase the half life of co-administered ARV drug due to CYP3A4 effect
Duranavir pharmkinetics
PI, oral, coadministed with pharmacokinetic enhancer
Darunavir adverse
increased liver enzymes,increased serum amylase, other general adverse
Darunavir resistance and indications
Very little resistance
Used for naive and experienced HIV pts
Maraviroc-Class and pharmkinetics
Co-receptor antagonist, oral administration, substrate of CY34A
Maraviroc Adverse
URT infections, postural hypotension, sleep disturbance, allergic rxn
Maraviroc resistance and indications
Occurs through tropism of the virus, or mutations in gp120
Screen for tropism before use
Enfuvirtide MOA
Fusion inhibitor-inhibits fusion of virion w/ the plasma membrane
**Only parenteral antiretroviral agent
Enfuvirtide adverse
Painful, erythematous nodule @injection site
insomnia, headache, nausea, etc.
Enfuvirtide resistance/indications
Multiple mutations needed for resistance
Treatment for experienced pts w/evidence of HIV replication even with ARV treatment
Integrase Inhibitors MOA
prevents integration of viral DNA into chromosome DNA
Raltegravir pharmkinetics
integrase inhibitor, oral admin
Raltegravir adverse
creatine kinase elevation
myopathy, rhabdomyolysis
Raltegravir resistance/indications
Single mutaiton in gene confers resistance
Naive and experienced HIV pts
Elvitegravir pharmkinetics
Integrase inhibitor, oral administered, co-administered w/ cobicistat or ritonavir
Elvitegravir adverse
normal systemic: nausea, diarrhea, headache, fatigue
Elvitegravir resistance/indications
Single mutation confers resistance
Experienced and naive HIV pts
Dolutegravir
Integrase inhibitor, oral admin
Dolutegravir adverse
insomnia/headache, hypersensitivity, fat redistribution syndrome
Dolutegravir resistance/indications
retains activity against some viruses that are resistant to other integrase inhibitors
HIV infection pts at least 12 y.o. and weighing at least 40 kg
General features of ARV therapy
Combination of at least three ARV drugs, from at least two different classes
Preferred combo ARV therapies for initial therapy
1 PI (ritonavir) + 2 NRTIs
1 Integrase inhibitor + 2 NRTIs
