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164 Cards in this Set
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5 indications for initiating ART therapy
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hx of AIDS definining illness
CD4 < 350 pregnancy HIV-associated nephropathy HBV co-infection when tx of HBV is indicated |
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goals of ART
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suppress HIV replication to undetectable levels by 12-24 wks
reduce HIV-related morbidity/mortality prevent vertical transmission |
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how are results of ART evaluated
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plasma HIV RNA levels
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characteristics of preferred HAART regimen
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at least 3 drugs used
the regimens have combinations of drugs that have diff mechanisms of action class-sparing |
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regimen #1 for ART in naive pts
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efavirenz
+ tenofovir/emtricitabine |
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regimen #2 for ART in naive pts
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atazanavir (or darunavir)
+ ritonavir + tenofovir/emtricitabine |
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ritonavir is used at a lower dose that is not antiretroviral, but it does ___
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inhibit the P450 system
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regimen #3 for ART in naive pts
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raltegravir
+ tenofovir/emtricitabine |
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preferred antiretroviral regimen for pregnant women
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lopinavir/ritonavir
+ zidovudine/lamivudine |
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what is the strongest predictor of subsequent HIV progression and survival
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CD4+ count
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acute HIV infection: how to diagnose
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detectable plasma HIV RNA with a negative or indeterminate HIV antibody test
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zidovudine: class
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NRTI
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zidovudine: indications
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prevention of maternal-fetal HIV transmission
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zidovudine: ADRs
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myelosuppression, neutropenia, severe anemia
rare cases of lactic acidosis w/hepatic steatosis |
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zidovudine: DIs
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no DI with P450
major hematologic toxicity with cytotoxic agents and ganicyclovir |
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didanosin: ADRs
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pancreatitis
lactic acidosis and severe hepatomegaly w/steatosis peripheral neuropathy |
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lamivudine: ADRs
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peripheral neuropathy
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Combivir: combination of what 2 drugs
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lamivudine
+ zidovudine |
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abacavir: boxed warning
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hypersensitivity rxns
d/c promptly if symptoms appear |
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emtricitabine: P450 activity
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NO effects
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tenofovir: class
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nucleotide RTI
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Truvada: combination of what 2 drugs
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tenofovir
+ emtricitabine |
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NNRTI: stands for what? mech of action?
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non-nucleoside inhibitors of reverse transcriptase
noncompetitive inhibitors of HIV-1 reverse transcriptase do not compete with NRTIs do not require initial cellular activation |
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nevirapine: class? P450 activity?
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NNRTI
induces P450 3A4 enzyme |
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nevirapine: ADRs
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severe, life-threatening rxns, including SJS and toxic epidermal necrolysis have occurred
potentially fatal hepatotoxity |
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first anti-HIV drug that is given once daily
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efavirenz
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efavirenz: ADR? P450 activity?
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CNS/psych symptoms
3A4 mixed inducer/inhibitor |
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protease inhibitors: mech of action
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not active against already infected cells, but reduce viral ability to infect other cells
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class ADRs of protease inhibitors
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hypercholesterolemia and hyperTGemia
insulin resistance, hyperglycemia |
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saquinavir: class? P450 activity?
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protease inhibitor
inhibits 3A4 metabolism of numerous drugs |
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ritonavir: class? P450 activity?
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protease inhibitor
strong inhibitor of P450 |
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indinavir: ADRs
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acute nephrolithiasis with flank pain with or without hematuria
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what is the first protease inhibitor that is dosed once daily
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atazanavir
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enfuvirtide: class? mech of action?
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fusion inhibitor
binds to the region of HIV that is involved with the fusion to host membrane |
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what is the only approved agent that prevents HIV entry into host cell
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enfuvirtide
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how is enfuvirtide administered
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SC twice daily
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maraviroc: class? mech of action?
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chemokine receptor 5 antagonist
binds to CCR5 coreceptor to prevent HIV from infecting T cells |
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raltegravir: class? mech of action?
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integrase inhibitor
inhibits the enzyme needed by HIV for viral reproduction |
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significance of integrase? what drug blocks its action?
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enables the HIV-1 to integrate its DNA into the cellular DNA of host cells
raltegravir |
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class ADRs fo NRTIs
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lactic acidosis
hepatomegaly w/steatosis |
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class ADRs of protease inhibitors
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hyperglycemia
new onset DM insulin resistance hyperlipidemia |
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class ADRs of NNRTIs
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rash
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what is the duration of all regimens for post-exposure prophylaxis of HIV
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4 weeks
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basic regimen of post-exposure prophylaxis of HIV
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zidovudine and lamivudine
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for exposures posing an increased risk for HIV transmission, the preferred expanded regimen is ____
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basic regimen (zidovudine + lamivudine)
+ lopinavir/ritonavir |
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amphotericin B: mech of action
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binds to the ergosterol component of fungal membranes and alters permeability to allow leakage of ions
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how is amphotericin B administered
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not absorbed po, must be given IV
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DOC for major systemic fungal infections, especially in immunocompromised pts
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amphotericin B
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what is the advantage of lipid encapsulated amphotericin B
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have increased circulation time and reach higher concentrations, while being essentially impermeable to normal tissues
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what formulation of ampho B is given to pts who cant tolerate the conventional IV formulation
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lipid-encapsulated drug
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douching is ___
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BAD
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amphotericin B: ADRs
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infusion rxns (fever, chills, HA, nausea)
usually occur 1-3 hrs after starting infusion nephrotoxicity (80%) |
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flucytosine: mech of action
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synthetic pyrimidine antimetabolite used in combination with ampho B for tx of systemic mycoses and meningitis
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what drug is commonly used in combination with flucytosine
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amphotericin B
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does flucytosine penetrate the CSF?
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yes
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azole antifungal agents: mech of action
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inhibit P450 isoenzyme that converts lanosterol to ergosterol
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concurrent use of azoles and ____ is contraindicated
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amphotericin B
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what azole inhibits gonadal steroid synthesis, thus suppressing testosterone production
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ketoconazole
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what 4 things impair ketoconazole absorption
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food
antacids H2 antagonists PPIs |
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what enhances ketoconazole absorption
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acidic cola drinks
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does ketoconazole penetrate CSF?
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no
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ketoconazole: ADRs
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endocrine: gynecomastia, impotence
blackbox: hepatotoxicity |
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ketoconazole: DIs? P450 activity?
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antacids
inhibits P450 |
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DOC for cryptococcal meningitis and coccidiodomycosis
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fluconazole
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fluconazole: brand name? P450 activity?
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Diflucan
inhibits P450 |
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DOC for onychomycosis
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itraconazole
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itraconazole: boxed warning? P450 activity?
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risk of CHF
potent inhibitor of P450 |
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itraconazole: take with ____ and ____
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food and high acidic beverage
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1st line agent for tx of acute invasive aspergillosis
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voriconazole
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indications for voriconazole
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acute invasive aspergillosis
non-neutropenic pts with candidemia or deep tissue candidal infx |
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posaconazole: indications
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prophylaxis of invasive aspergillosis and candidiasis in pts who are severely immunocompromised
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posaconazole: ADRs
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hepatic failure, sometimes severe
QT prolongation |
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caspofungin: indications
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empirical tx of presumed fungal infx in febrile, neutropenic pts
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what OTC is used for tinea pedis, cruris, and corporis
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clotrimazole (Lotrimin)
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griseofulvin: mech of action
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interacts with fungal cell microtubules to disrupt the mitotic spindle and inhibit mitosis
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griseofulvin: active only vs. ____
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dermatophytes
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griseofulvin absorption is enhanced with ____
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high fat meal
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griseofulvin: concentrates in what 3 types of tissue
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skin, hair, nails
(keratinized tissue) |
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terbinafine: brand name? mech of action?
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Lamisil
fungicidal agent that inhibits squalene epoxidase (essential for sterol synthesis) |
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terbinafine: indications
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tx of onychomycosis of the toenail or fingernail due to dermatophytes
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ciclopirox: indications? administered how?
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dermatophytic infections (tinea)
lotion |
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when is medical care warranted for vulvovaginal candidiasis
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if symptoms persist or recur within 2 months after using an OTC product
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nystatin: mech of action
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polyene antibiotic similar to ampho B
broad spectrum too toxic for systemic administration |
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nystatin: clinical uses
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topical for superficial candidal fungal infx of skin, mucus membranes, and intestinal tract
also oral suspension for tx of thrush |
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clotrimazole: fungicidal vs ____
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candida species
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clotrimazole: indications
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vaginal formulation for local tx of VVC
buccal tablet for local tx of oropharyngeal candidiasis |
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miconazole: what formulations are available
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intravaginal
dermatologic - for cutaneous candidiasis and tinea versicolor |
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DOC for trichomoniasis
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metronidazole
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metronidazole: preferred regimen
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single dose, 2 g po
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mebendazole: preferred regimen
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100 mg chewable tablet
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DOC for helminthic infections (pinworm, roundworm, hookworm, whipworm)
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mebendazole
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chemoprophylaxis of TB infx without active disease
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isoniazid and pyroxidine
qd for 9 months if INH resistant, rifampin po qd for 4 months |
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tx of active TB in HIV+ pts
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initial phase (8 wks): qd regimen of INH, RIF, PZA, EMB
continuation phase (18 wks): INH and RIF qd |
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RIF is not recommended for pts receiving ____ due to its inducing effects
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protease inhibitors
(rifabutin is preferred) |
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primary chemoprophylaxis for myco avium complex with HIV infection
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clarithromycin (or azithro)
avoid combination with rifabutin |
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tx of active MAC infection
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clarithromycin (preferred)
ethambutol addition of rifabutin may be considered |
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chronic maintenance therapy of MAC
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clarithromycin + ethambutol with/without RFB
must be used for rest of life |
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rifabutin: ADRs
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orange-brown discoloration of urine, feces, saliva, etc
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primary prophylaxis of candidiasis
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NOT recommended
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preferred agent for initial episode of oropharyngeal candidiasis
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fluconazole
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DOC for esophageal candidiasis
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fluconazole
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secondary prophylaxis of candidiasis
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fluconazole (both oropharyngeal and esophageal)
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primary prophylaxis of cryptococcosis
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NOT indicated
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DOC for cryptococcal meningitis
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amphotericin B deoxycholate
+ flucytosine |
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prevention of recurrence of cryptococcal meningitis
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fluconazole
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primary prophylaxis of coccidioidomycosis
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fluconazole
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tx for mild coccidioidomycosis
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fluconazole
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tx for severe non-meningeal coccidioidomycosis infections
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amphotericin B
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DOC for active aspergillosis infection
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voriconazole
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DOC for CMV retinitis
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gancicyclovir intraocular implant and valganciclovir po bid for 14-21 days, then qd
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ganciclovir ocular implant cannot prevent _____
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CMV infection in the contralateral eye or systemic CMV infection
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advantage of cidofovir over ganciclovir and foscarnet
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long half life allowing once weekly dosing
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cidofovir: ADRs
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nephrotoxicity and proteinuria
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secondary prophylaxis of CMV retinitis
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valganciclovir
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DOC for orolabial lesions and initial/recurrent genital HSV
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valacyclovir
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tx for moderate-severe mucocutaneous HSV
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initial: acyclovir
after lesions regress: valacyclovir |
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tx for acyclovir-resistant HSV
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IV foscarnet
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tx for post-exposure VZV
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varicella-zoster immune globulin as soon as possible but within 96 hrs after close contact
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tx for uncomplicated varicella
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acyclovir po 5x daily
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tx for severe/complicated varicella
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IV acyclovir
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tx for extensive cutaneous lesions or visceral involvement of herpes zoster
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IV acyclovir
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DOC for aciclovir-resistant VZV
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IV foscarnet
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primary prophylaxis of pneumocystis jirovecii pneumonia
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TMP-SMX
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p. jirovecii pneumonia: alternative regimen when TMP-SMZ cant be tolerated
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dapsone
aerosolized pentamidine |
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DOC for p. jirovecii pneumonia
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TMP-SMZ
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alternative agents for moderate-severe PCP
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pentamidine isethionate IV
primaquine + clindamycin |
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alternative agents for mild-moderate PCP
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dapsone + trimethoprim
primaquine + clindamycin atovaquane |
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primary prophylaxis of toxoplasmic encephalitis
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TMP-SMX
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DOC for toxoplasmic encephalitis
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pyrimethamine + sulfadiazine + leucovorin
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sulfadiazine: ADRs
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crystalluria
nephrolithiasis |
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lifelong maintenance therapy for chronic suppression of toxoplasmic encephalitis
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pyrimethamine + sulfadiazine + leucovorin
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atovaquone: class
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antipneumocystic
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pyrimethamine: mech of action
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folic acid antagonist
inhibits dihydrofolate reductase |
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what do you give if signs of folate deficiency develop in pts taking pyrimethamine
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leucovorin
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zanamavir: class? indications?
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neuraminidase inhibitor
tx of uncomplicated acute illness due to influenza virus in pts >7 years |
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zanamavir: contraindications
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not recommended for tx or prophylaxis in pts with underlying airway dz (asthma, COPD)
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oseltamavir: indications
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tx of uncomplicated acute illness due to influenza virus in pts >1 yr
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oseltamavir: mech of action
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oral prodrug which is converted by hepatic esterases to the active agent in vivo
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ribavarin: mech of action
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synthetic guanosine nucleoside analog
interfere with critical rxns needed for viral replication |
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tx of severe lower resp tract infx due to RSV
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ribavarin
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how is ribavarin administered
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aerosol
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whats the warning for ribavarin
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drug precipitation within endotracheal tubes and ventilators
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ribavarin: ADRs
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teratogenic
contraindicated in pregnant women and male partners of pregnant women |
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palivizumab: indications
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prevention of serious lower resp tract dz caused by RSV in high risk pediatric pts
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what virus is resistant to acyclovir
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CMV
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what viruses are sensitive to acyclovir
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HSV-1
HSV-2 VZV EBV |
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acyclovir: indications
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tx of initial and recurrent mucosal and cutaneous HSV1, HSV2, and VZV infx in immunocompromised pts
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acyclovir: kinetics
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poor oral availability
slowly and incompletely absorbed |
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acyclovir: ADRs
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nephrotoxicity if given as IV bolus
give only by slow infusion over atleast 1 hr with adequate hydration |
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ganciclovir: mech of action
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synthetic analog of acyclovir
prodrug which is converted intracellulary to an active triphosphate form |
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advantage of ganciclovir over acyclovir? whats the caveat though?
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active vs CMV
but is NOT a cure for CMV retinitis |
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ganciclovir: ADRs
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myelosuppression
netropenia anemia thrombocytopenia |
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ganciclovir: DIs
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nephrotoxic drugs
probenecid zidovudine |
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famciclovir: mech of action? clinical uses?
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prodrug of the antiviral agent penciclovir
tx of acute herpes zoster |
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valacyclovir: advantage over acyclovir
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po bioavailability increased 3-5
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foscarnet sodium: active vs what 3 things
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CMV
HSV-1 HSV-2 |
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foscarnet sodium: ADRs
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renal dysfunction
seizures anemia |
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foscarnet sodium: clinical uses
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2nd line agent to ganciclovir for CMV
active vs. ganciclovir-resistant CMV and ACY-resistant HSV and VZV |
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cidofovir: mech of action
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nucleoside analog that suppresses CMV replication by selective inhibition of viral DNA synthesis
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cidofovir: ADRs
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nephrotoxicity
neutropenia |
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valganciclovir is a _____ of ganciclovir
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ester prodrug
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indicated for tx of HSV infx of the conjunctiva and cornea (3 drugs)
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idoxuridine
vidarabine trifluridine |
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trifluridine: indications
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primary keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1 and 2
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indicated for tx of recurrent herpes labialis (cold sores)
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penciclovir
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