-
Abacavir
- NRTI
- Guanosine analog
- good oral bioavalibility 83%
- Elimination T1/2 1.5 h
- Intracellular T1/2 12-26 h
- CSF con 1/3 of plasma
- Requires 2 mutations of HIV to be resistant to this drug.
- Side effects: hypersensitivity, fever, malaise, n/v, diarrhea, skin rashes, pancreatitis(rare)
-
Didanosine
- NRTI
- deoxyadenosine analog
- oral bio 30-40% on empty stomach
- Buffer (packaged with pills) interferes with: indinavir (PI), antivirals, and fluoroquinolones
- Levels increase with: tenofovir ganciclovir
- Levels decrease with: antivirals tipranavir, atazanavir
- Side effects: dose dependent pancretitis(augmentited by alcoholism), peripheral neuropathy, diarrhea, hepatitis, CNS toxicity, optic neuritis
-
Emtricitabine
- NRTI
- Fluorinated analog of Lamivudine
- Oral bioavailability 93%
- T1/2 >39 h
- CSF conc is low
- improvement on lamivudine cuz of longer T1/2
- side effects: HA, diarrhea, Nausea, hyperpigmentation (3%)(more frequent in African americans
-
Lamivudine
- NRTI
- Cytosine analog
- active against AZT resistant strains
- low dose effective against HBV
- Oral bio: >80%
- T1/2: 10.5-15.5 hr
- CSF conc: 20% better than emtricitabine
- side effects: HA, insomnia, fatigue, GI discomfort
-
Tenofovir
- NRTI
- adenosine analog
- Atripla: tenofovir, emtricitabine, efavirenz
- Oral bio: 25% in fasting, 39% with high fat meal
- T1/2: 60 h
- CSF conc 55% of plasma
- Used in place of stavudine in cases of dyslipidemia
- renal secretion
- Side effects: HA, n/v, diarreha, asthma, renal toxicity (rare)
- Bone toxicity in animals only
-
Zalcitabine (ddC)
- NRTI
- cytosine analog
- Oral bio: 80%
- T1/2: 10 h
- CSF conc 20% of plasma
- renal secretion
- Side effects: Dose-dep peripheral neuropathy in 10-20%, drug withdrawl nullify, oral and esophageal ulcerations, self limiting HA, nausea, rash, Pancreatitis(rare)
-
Zidovudine (AZT)
- NRTI
- deoxythymidine analog
- Okay in pregnacy and after birth
- t1/2: 3-7h
- CSF conc 60-65% of plasma
- renal secretion
- Side effects: dyslipidemia and insulin resistance, myelosuppresion, anemia, neutropenia, thrombocytopenia, depigmentation(rare), self limiting HA, GI intolerance, insomnia
-
Nevirapine (general info)
- NNRTI
- lipophilic noncompetitive inhibitor
- Oral bio: 90% NOT FOOD DEPENDENT
- 60% plasma bound
- CSF conc 45% of plasma
- Metabolized by P450 excreted by urine
- Therapeutic use: monotherapy and used in combo with other antiretrovirals
-
Nevirapine (drug interactions)
- Inducers of CYP, including CYP3A4: ketoconazole, oral contraceptives, methadone
- Conc of Nivirapine increase with: cimetidine or macrolide agents
- Drugs metabolized by CYP3A4 or CYP2B6: rifampin, rifabutin (problem with treating TB and HIV people)
-
Nevirapine (Side effects)
- Common: skin rash (17%), sometimes toxic epidermal necrolysis, hepatic toxicity
- Rare: abnormal liver function tests, chlils, fever, sore throat, pain in arm legs or feet, sleepiness, sores in mouth
- Uncommon: aching joints and muscles, sore lips, dark urine, little appetite, N/V, yellow skin or eyes
-
Delavirdine
- NNRTI
- 400mg tid
- INHIBITOR OF CYP450
- Oral bio: 85%
- 98% protein bound
- Side effects: HA, N/D, fatigue, skin rash (18%), steven-johnson syndrome (rare)
-
Efavirnez
- NNRTI
- 600mg qd
- T1/2: 40-55h
- INHIBITOR OF CYP450
- Oral bio: 85%
- 99% protein bound
- Side effects: HA, insomnia, confusion
- Increased LFT
- Congenital anamolies
-
Indinavir (general info)
- PI: inhibit HIV1(more potent for this one) and HIV2 proteases
- Oral bio: 65% MUST TAKE ON EMPTY STOMACH
- 60% protein bound
- CSF conc 75% (highest among PI)
- Metabolized in liver (CYP3A4), excreted in feces
- Resistance due to multiple codon substitutions
-
Indinavir (side effects)
- Common: blood in urine (crystalluria and nephrolithiasis, sharp back pain below ribs
- Uncommon: hyperbilirubinemia, GI upset, ab pain, HA, fatigue, insomnia
- Rare: confusion, dehydration, dry skin, fatigue, n/v, weightloss
-
Saquinavir
- PI
- high protein bound
- poor CNS penetration
- excreted in feces
-
Ritonavir
- PI
- bind to active site on HIV protease
- metabolized extensively eliminated mainly in feces
- 98-99% protein bound
- Side effects: Dose dependent GI upset
- (only prescribed now to boost other drugs, inhibits CYP3A4)
-
Lopinavir/Ritonavir
- PI
- More potent against HIV-1 than ritonavir (boosts lopinavir by P450)
- only in co-form with ritonavir
- Fast Absorption INcreased by HIGH FAT MEAL
- highly protein bound
- low CNS penetration
- Side effects: GI upset
-
Nelfinavir
- PI
- Slow Absorption INcreased by HIGH FAT MEAL
- highly protein bound
- M8 is active metabolite
- Side effects: diarrhea, flatulence
-
Amprenavir
- PI
- active site inhibitor of HIV protease
- Fast absorption DEcreased by high fat meal
- highly protein bound
- Side effect: GI intolerance
-
Fosamprenavir
- PI
- Phosphonooxy prodrug of amprenavire
- increased water solubility
- improved oral bioavailability over amprenavir
-
Darunavir
- New PI
- well tolerated reduced side effects
- combo with ritonavir cuz CYP3a4
- ONCE A DAY DOSING (800mg)
- Take with FOOD
-
Atazanavir
- New PI
- ONCE A DAY DOSING (300mg)
- combo with ritonavir
- less likely to cause lipodystrophy
- DONT use with PPI
- DONT use with INDANAVIR cuz both inhibit UGt1a1
-
Enfuvirtide
- Fusion/entry inhibitor
- Binds to gp41 subunit of viral envelope to prevent the conformational changes required for fusion of viral and cellular membranes
- no cross resistance with other classes of antiretrovirals
- subcutaneous injection
- Side effects: location reaction, hypersensitivity
- high cost; reserved for people who fail other regimesn
-
Maraviroc
- CCR5 inhibitor
- combo with other antiretroviral
- 150-300 mg oral
- Side effects: hepatotoxicity, cardiovascular events, immune reconstitution syndrome, potential risk of infection, potential risk of malignancy
-
Raltegravir
- Integrase inhibitor (binds to integrase to inhibit strand transfer)
- no interaction with P450
- metabolized by glucoronidation
- combo therapy only cuz resistance requires only a single point mutation
- Drug interactions: through UGT1a1, rifampin, efavirenz, tipranavir, ritonavir, atanzanavir
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