Antiviral and Antifungal Review Flashcards
- 5’ monophosphate formed by a CMV viral kinase
- guanosine analog
- triphosphate formed by cellular kinases
- preferentially inhibits DNA polymerase
ganciclovir
- guanosine analogs, monophosphorylated by HSV/VZV thymidine kinase and not in uninfected cells –> few adverse effects
- preferentially inhibit DNA polymerase by chain termination
acyclovir, valacyclovir, famciclovir
- preferentially inhibits viral DNA polymerase, does not require phosphorylation by viral kinase
- treats CMV retinitis in immunocompromised patients, acyclovir resistant HSV, long half life
- nephrotoxicity
cidofovir
- viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor
- binds to pyrophosphate binding site of enzyme
- treats CMV retinitis when ganciclovir fails, acyclovir resistant HSV
- nephrotoxic, electrolyte abnormalities, seizures
foscarnet
-for primary keratoconjunctivitis and recurrent epithelial keratitis caused by herpes simplex I and II
trifluridine
for herpes simplex of face or lips, OTC
docosanol
- thymidine analog, substrate/inhibitor for HIV reverse transcriptase
- inhibits stable infection of new cells
- well absorbed, CNS, rapidly metabolized
- use in 3 or 4 drug cocktail for HIV, resistant due to mutations in reverse transcriptase
- adverse: bone marrow depression, CNS, toxicity in drugs competing for glucoronidation
zidovudine
zidovudine zalcitabine lamivudine abacavir tenofovir (nucleotide) emtricitabine
nucleoside reverse transcriptase inhibitors
- first gen oral NNRTI
- non competitive, binds near but not in active site
- rapid resistance
- can be active against AZT resistant HIV
- life threatening skin rash
- CPY3A4 substrate
non-nucleoside reverse transcriptase inhibitors (NNRTI)
nevirapine efavirenz delavirdine etravirine rilpivirine
NNRTIs
- prevent viral particle production, prevent maturation of new viruses, pol gene cleaves polypeptide products of mRNA
- adverse: hyperglycemia, altered fat distribution, hyperlipidemia, insulin resistance
HIV protease inhibitors
- first HIV protease inhibitor
- well tolerated
- low oral bioavailability
- extensive 1st pass
- DDIs
- use in combo with RT inhibitors
saquinavir
coformulated with protease inhibitors to “boost” levels, inhibitor of CYP3A4
ritonavir
- CCR5 antagonist
- binds CCR5 on human CD4 cells
- inhibits gp120 conformational change required for HIV fusion with CD4 cell
maraviroc
interferes with entry of HIV-1 into host cells by inhibiting the fusion of virus and cell membranes, binds gp41
enfuvirtide
-inhibit catalytic activity of integrase
dolutegravir, elvitegravir, raltegravir
- antimetabolite, blocks GMP formation
- aerosol for RSV
- known teratogen, dose dependent myelosuppression
- treatment of hepatitis
ribavirin
- oral agent effective against all common influenza viruses
- pro drug
- NA inhibitor
oseltamivir
- oral inhalation
- influenza A and B
- effective in early infection
- bronchospasm in asthmatics
zanamivir
- treatment of acute, uncomplicated influenza in adults who’ve been symptomatic <2 days
- 600 mg single dose
peramivir
- block viral uncoating by blocking M2 proton channel
- given in first 48 hours of contact
- admin orally, protects only influenza A
amantadine, rimantadine
standard of care for treatment of HCV?
peginterferon alfa + ribavirin
- nucleotide analog, inhibits HCV RNA dependent RNA polymerase
- given in combo with peg interferon and ribavirin
sofosbuvir
______ have ergosterol in membrane instead of cholesterol
fungi
- IV drug that inhibits synthesis of glucan, a major fungal cell wall component
- use for invase aspergillosis in patients who fail ampho B therapy
caspofungin
amphotericin B binds ______ in fungal membranes, producing a pore causing leaking of contents
ergosterol
amphotericin B must be given _____ or ______, widely distributed except CNS, excretion 2 weeks
IV, intrathecal
-reservoir of amphotericin, has lower affinity for drug than fungal membrane but higher affinity for drug than patient’s membranes
liposomal
amphotericin B often combined with ________ to delay resistance and use lower doses due to synergism
flucytosine
infusion related reactions, fever, chills, muscle spasms, vomiting, headache, hypotension
- pretreat w/ antipyretics, antihistamines, aanalgesics, coticosteroids
- nephrotoxicity
amphotericin B
flucytosine activated by fungal ________ and converted to 5-flurouracil, blocks DNA and RNA synthesis
cytosine deaminase
- CNS, excreted in urine
- low toxicity to patient
- narrow spectrum, rapid resistance so only use with ampho B
flucytosine
- inhibit ergosterol synthesis
- oral antifungal for systemic
- inhibit CYPs, extensive DDI
- severe hepatotoxicity, gynecomastia, interactions w/ cyclosporines and antihistamines
ketoconazole
broader spectrum, less adverse than ketoconazole
itraconazole
-effective against aspergillosis, fluconazole susceptible and resistant candida, and cryptococcus neoformans
voriconazole
- water soluble azole
- good CSF delivery
- more selective for fungal P450s
fluconazole
newer and broad spectrum member of azole family, good for candida and aspergillus
-oral only
posaconazole
- inhibits synthesis of B(1,3)D-glucan, an essential component of fungal cell wall
- treats invase aspergillus
- candida: intra abdominal abscess, esophagitis, peritonitis, febrile neutropenic patients
- hypotension, tachycardia, fever, chills, rash, anemia, hypokalemia
caspofungin
-topical antifungal, too toxic for systemic use
nystatin
griseofulvin concentrates in _______ tissue, treats ringworm athlete’s foot, disrupts mitotic spindle in fungal cells, hepatitis and DDIs with warfarin and phenobarbital
keratinized
- topic or systemic
- concentrates in keratinized tissue
- inhibits squalene epoxidase
terbinafine
only ______ affects tissue schizonts
primaquine
- alters metabolism of hemoglobin by parasite, blocks nucleic acid synthesis
- highly effective blood schizonticide
- clears parasite from all 4 plasmodia (used w/ primaquine for vivax and ovale)
- prophylactic, preferred when resistance not a problem
chloroquine
- visual impairment with long term therapy
- widespread resistance
- p glycoprotein efflux mechanism (block with verapamil)
chloroquine
- destruction of asexual bloods forms of malarial pathogens falciparum and vivax
- oral only, metabolized in liver
- CNS psychotropic effects
- use for chloroquine resistant malaria
mefloquine
- anti folate drug combo effects on protozoa
- effective blood schizonticide for p falciparum, slow acting
- multi drug resistance common
fansidar (pyrimethamine-sulfadoxine)
- selectively inhibits parasite mitochondrial electron transport
- inhibits DHFR
- prevent or treat acute uncomplicated p falciparum malaria
- increased transaminase, headaches, dizziness
atovaquone plus proguanil
- treat chloroquine resistant p falciparum
- interferes with oxygen uptake and carb metabolism, intercalates into DNA
- cinchonisms: flushed, tinnitus, blurred vision, confusion
quinine, quinidine
- chinese herbal medicine
- activated by oxidative metabolism
- rapidly acting blood schizonticide, useful for MDR p falciparum
artemesinin
standard prophlactic drug for SE Asia with high rates of resistance to mefloquine
doxycycline
-derived from artemesinin, treats MDR p falciparum
artemether, lumefantrine
- tissue shizonticide
- metabolites are intracellular oxidants
- use in combo with chloroquine for prophylaxis/cure of p vivax, p ovale
- withheld until G6PD status is known
- hemolytic anemia, GI distress
primaquine
- tissue amebicide activated by electron donation
- used for urogenital trichomonas, giardia, aspiration pneumonia, anaerobics
- disulfiram effect
metronidazole and nitazoxanide
- concentrates in liver, spleen, kidney
- doesn’t enter CNS
- pneumocystic prophylaxis in sulfonamide intolerant pts
- resp stimulation then depression
pentamidine
diloxanide furoate, iodoquinol, paromomycin treat?
aymptomatic amebiasis intestinal infections
- depolarizing neuromuscular blocking agent on nicotinic receptor
- increases release of acetylcholine and inhibits cholinesterase in the worm
- use: ascariasis, pinworm, hookworm, whipworm
- n/v/d/anorexia
pyrantel pamoate
- increases chloride permeability, polarizing cells leading to paralysis
- use for strongyloidiasis, onchocerciasis
ivermectin
