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63 Cards in this Set
- Front
- Back
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HAART |
highly active antiretroviral therapy |
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strongest indication for HAART use? |
low CD4+ count (<500) high viral load also: prophylaxis of childbirth |
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what are the 3-drug regimen options? why do you use 3 at one time? |
2 NRTIs and 1 NNRTI or protease inhibitor or integrase inhibitor prevent resistance |
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Your patient has been compliant/adherent to his or her HAART meds, but they become resistant. What do you do? |
after resistance testing, change to a regimen of 3 drugs to which the pt is NOT resistant, from at least 2 drug classes |
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review the steps/process of HIV infecting and leaving the cell |
mostly review |
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NRTI (nucleoside reverse transcriptase inhibitor) drugs |
abacavir (ABC) lamivudine (3TC) tenofovir (TDF) zidovudine (ZDV, formerly AZT) emtricitabine (FTC) didanosine (ddl) stavudine (d4T) |
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NNRTI drugs |
efavirenz nevirapine delavirdine |
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HIV-1 protease inhibitors |
atazanavir ritonavir darunavir fosamprenavir indinavir lopinavir saquinavir |
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fusion inhibitors |
enfurvitide maravaroc |
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DNA stand transfer/integrase inhibitor |
raltegravir |
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NRTI ADME |
A: PO once (QD) or twice (BID) daily M: minimal/no involvement of cyp pathways (abacavir, emtricitabine and zidovudine are glucuronide metabolites) -- CYP3A4 "neutral" E: in urine as drug+ metabolites |
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NNRTI ADME |
A: PO QD or BID M: delavirdine INHIBITS CYP3A4, 2D6, 2C9, 2C10; efavirenz and nevirapine INDUCE 3A4 and 2B6
E: urine/stool as metabolites |
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protease inhibitor A&E, (M on the next series of cards) |
A: PO QD or BID E: stool predominantly as metabolites |
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atazanavir (protease inhibitor) metabolism |
inhibits CYP3A4, UGT contraindicated with rifampin |
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darunavir (protease inhibitor) metabolism |
3A4 substrate used with ritonavir (HIV-1) protease to boost serum drug levels |
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fosamprenavir (protease inhibitor) metabolism |
3A4, 2D6, 2C9 P-gp, inhibitor of 3A4 |
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indinavir (protease inhibitor) metabolism |
3A4, P-gp, inhibitor of 3A4
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lopinavir (protease inhibitor) metabolism |
3A4 substrate used with ritonavir (HIV-1 protease) to boost serum drug levels |
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ritonavir (protease inhibitor) metabolism |
INHIBITS 3A4, 2D6, P-gp, UGT contraindicated with rifampin |
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saquniavir (protease inhibitor) metabolism |
INHIBITS 3A4, UGT contraindicated with rifampin |
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what drug are atazanavir, ritonavir and saquinavir contraindicated with? |
rifampin |
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enfurvitide (fusion inhibitor) ADME |
A: subQ q (every) 12hrs M: catabolized to amino acids E: -- |
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maraviroc (fusion inhibitor) ADME |
A: PO QD or BID M: 3A4, P-gp substrate E: stool/urine as drug+ metabolites |
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rategravir (integrase inhibitor) ADME |
A: PO QD or BID M: GLUCURONIDE METABOLITE E: stool/urine drug+ metabolites |
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cobicistat |
orally active CYP3A4 INHIBITOR used as pharmacokinetic ENHANCER to increase serum [] of CYP3A4 substrates (atazanavir, darunavir) NO ANTIVIRAL ACTIVITY |
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Truvada |
tenofovir (NRTI) + emtricitabine (NRTI) one pill daily with a NNRTI, PI, integrase inhibitor or maraviroc |
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Epzicom |
abacavir (NRTI) + lamivudine (NRTI) one pill daily with a NNRTI, PI, integrase inhibitor or maraviroc |
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Trizivir |
abacavir (NRTI) + lamivudine (NRTI) + zidovudine (NRTI) one pill daily with a NNRTI, PI, integrase inhibitor or maraviroc |
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Atripla |
tenofovir (NRTI) + emtricitabine (NRTI) + efavirenz (NNRTI) one pill daily that is a complete regimen, most commonly use single drug product |
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Stribild |
tenofovir (NRTI) + emtricitabine (NRTI) + elivitegravir + cobicistat one pill daily that is a complete regimen; recall cobicistat is a booster only |
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Complera |
tenofovir (NRTI) + emtricitabine (NRTI) + rilpivirine one pill daily that is a complete regimen; ONLY for viral loads <100,000 |
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Abacavir's contraindications? |
hypersensitivity and hepatic disease (in red) |
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NRTIs in obesity and prolonged exposure, esp in women, carry BBWs for what? |
hepatic disease and lactic acidosis |
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in what two NRTIs is pancreatitis a BBW? |
didanosine, stavudine |
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what are zidovudine's BBWs? |
anemia, myopathy, neutropenia |
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which NRTI has most likely neuropathy toxicity? least? |
stavudine most, didanosine least |
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what toxicities are common to all NNRTIs? |
rash and hepatotoxicity |
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which NNRTI commonly causes vivid dreams and CNS sx? |
efavirenz, resolves after 2-4 weeks of therapy |
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what NNRTIs are contraindicated in pregnancy? |
delavirdine, efavirenz |
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Nevirapine's safety issues/BBWs? |
females, hepatic disease, hepatitits, nevirapine hypersensitivity, serious rash |
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lipodystrophy |
facial fat loss, buffalo hump, fat loss of arms and legs, abdominal obesity observed in NRTIs, NNRTIs, maraviroc and (most commonly) PIs |
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PI toxicities |
GI intolerance (pain, N/V/D) lipodystrophy hyperglycemia/DM (PIs acutely inhibitor GLUT4) dyslipidemia (concern regarding MI and pancreatitis) nephrolithiasis (kidney stones, most commonly with indinavir) severe rash including Stevens-Johnson syndrome |
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peripheral neuropathy as consequence of HIV infection |
distal sensory polyneuropathy, inflammatory demyelinating polyneuropathy, multifocal mononeuropathy or progressive polyradiculopathy HIV-infected macrophages in DRG and neuronal injury related to HIV envelope protein gp 120 mainly attributed to myelinated fiber involvement toxic peripheral neuropathy is one long-term side effect of HAART via dysfunction of mitochrondrial oxidative metabolism, unmyelinated fiber damage |
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recommended NRTIs in pregnancy? |
lamivudine, zidovudine |
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alternate NRTIs in pregnancy? |
abacavir, didanosine, emtricitabine, stavudine |
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recommended NNRTI in pregnancy? |
nevirapine - no alternatives! |
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recommended PIs in pregnancy |
lopinavir/ritonavir |
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alternate PIs in pregnancy |
atazanavir/ritonavir, indinavir/ritonavir, nelfinavir, ritonavir, saquinavir |
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what's the prophylactic tx for Pneumocystis jirovci? |
trimethoprim-sulfamethoxazole (QT prolonger) |
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what's the prophylactic tx for M. tuberculosis? |
isoniazid + pyridoxine |
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what's the prophylactic tx for toxoplasmosis? |
trimethoprim-sulfamethoxazole (QT prolonger) |
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what's the prophylactic tx for CMV? |
valganciclovir, ganciclovir |
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what's the prophylactic tx for cryptococcosis, candidiasis, endemic fungal infections? |
fluconazole (CYP3A4, 2D6 inhibitor) |
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CMV infections in HIV pts |
occur primarily in setting of advanced immunosuppression and are typically reactivation of latent infection dissemination of infection results in end-organ disease, incl retinitis, colitis, esophagitis, CNS disease, pneumonitis clinical reactivation of CMV infection after organ transplantation still prevalent despite decreased incidence due to anti-retrovirals |
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when is valganciclovir (PO) used against CMV? |
CMV retinitis treatment CMV prophylaxis (transplant pts) |
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when is ganciclovir (IV) used against CMV? |
CMV retinitis tx |
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when is foscarnet (IV) used against CMV? |
CMV retinitis tx |
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when is cidofovir (IV) used against CMV? |
CMV retinitis tx |
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valganciclovir |
ester prodrug of ganciclovir - activated in GI and liver glomerular filtration and active RTS leukopenia, neutropenia, thrombocytopenia, renal toxicity resistance via mutated viral kinase |
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foscarnet |
viral DNA pol inhibitor - binds pyrophosphate binding site, viral activation not needed, resistance through mutated viral DNA pol very insoluble drug: saline hydrate and give by infusion --> genital ulcerations due to high levels of ionized drug in urine nephrotoxicity - electrolyte imbalances (hyper/hypocalcemia, phosphatemia, hypokalemia, hypomagnesemia can lead to seizures) |
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vidarabine |
for EBV nucleoside analog - requires phosphorylation for activity, ara-ATP is substrate and inhibitor for viral DNA pol, viral DNA pol mutation gives resistance very poor oral bioavailability - applied to eye as ointment low risk of systemic side effects due to drug insolubility and low ocular penetration |
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what can you give for Kaposi's sarcoma-associated herpesvirus? |
antiviral drugs, e.g. ganciclovir, valganciclovir, and cidofovir |
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cidofovir |
IV
intracellular conversion to active diphosphate form - competes with dCTP for viral DNA incorporation, selective for viral DNA pol vs host renal clearance with active RTS dose-dependent nephrotoxicity (proximal tubular cells) --> monitor serum creatinine and urinary protein adverse effects: neutropenia, ocular hypotonia, GI toxicity, rash/alopecia |
