Antiretroviral Agents Flashcards by AJ Sheehan

Classes of Antiretroviral drugs

NRTIs
NNRTIs
Fusion inhibitors
PIs
Co-receptor antagonists
Integrase Inhibitors

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NRTIs general characteristic, MOA

Target is reverse transcriptase
Mimic nucleotides, inhibit binding to catalytic site
Require cellular kinases to convert to triphosphate form

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NRTI general adverse

Lactic acidosis, fatty liver disease, and lipodystrophy

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Abacavir MOA

Guanosine analogue NRTI, given orally

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Abacavir Adverse

Allergic reaction w/ HLA B5707=> rash, fever, nauea, vomiting, etc.
Increased risk for CV events
May lower effectiveness of methadone

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Abacavir Resistance and indications

Multiple mutations needed for resistance

Tx for naive and experienced HIV infections

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Lamivudine MOA

Cytosine analogue NRTI, given orally but low serum half life

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Lamivudine adverse

Very safe, but higher than recommended doses yield GI and CNS effects

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Lamivudine Resistance and indications

Single base change=>high resistance
Tx for naive and experienced HIV pts,
Safe for pregnant mothers and neonates

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Emtricitabine MOA

Fluorinated analogue of lamivudine=> oral, longer half life

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Emtricitabine adverse

Headache, nausea, diarrhea, hyperpigmentation of palms and soles

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Emtricitabine resistance and indications

single mutation in reverse transcriptase

Tx for naive and experienced HIV

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Emtricitabine Contraindications

Young children, pregnant women, pts w/ renal or hepatic failure

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Tenofovir MOA

Adenosine analogue NRTI, oral, usually given as prodrug

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Tenofovir Adverse

Normal GI issues
Renal and bone toxicity
Can cross placenta=>decreased bone density and fetal growth

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Tenofovir resistance and Indications

Single codon change=>resistance
Naive and experienced HIV pts, can reduce transmission
Tx of chronic hep B w/ interferon

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Zidovudine (AZT) MOA

Deoxythymidine analogue NRTI, oral, well absorbed

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Zidovudine Adverse

Myelosuppresion, nail hyper-pigmentation, normal GI effects

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Zidovudine Resistance and Indications

Multiple mutations needed for resistance

Naive and experienced HIV, reduction in vertical transmission

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NNRTIs MOA

Target is reverse transcriptase, bind to site distinct from active site
do not require phosphorylation for activation
Not active against HIV 2

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NNRTI adverse effects

Rash, Steven Johnson syndrome, hepatotoxicity

Drug-drug ineractions common b/c of effects on cytochrome P450 enzymes

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Efavirenz pharmkinetics

Once daily oral, on empty stomach

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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