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39 Cards in this Set
- Front
- Back
common precursor to cholesterol and ergosterol
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Squalene Epoxide
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Chitin
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structural carbohydrate formed by the enzyme, chitin synthase, and broken down by chitinase
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1, 3-beta-D-glucan synthesis inhibition
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inhibits cell wall biosynthesis makes cell walls weaker
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14-alpha-Lanosterol demethylase (CYP51A1)
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converts lanosterol to a precursor of ergosterol (not cholesterol)
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Agents that treat superficial dematophytoses (fungal infections) OTC
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1) Fatty acids = longish chain of fatty acids that decrease pH in fungal cells
2) Salicylic acid = decrease pH in fungal cell 3) Tolnaftate & allyl amines = distortion of hyphae 4) Ciclopirox = involves chelation & ion transport |
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MOA of Griseofulvin
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binds dimers of alpha and beta tubulin to inhibit microtubule formation
Treats Deep dematophytoses (infections of skin and nails) |
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MOA of Azole antifungals
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inhibition of CYP51 (15-alpha-lanosterol demethylase in fungi
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MOA of flucytosine
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PRODRUG
converted to 5-FU by fungi only ---inhibits fungal nucleotide synthesis not toxic to humans |
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MOA of polyene macrolides (amphotericin B, Nystatin, etc)
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association with ergosterol of fungal cell membrane to form pores, through which Potassium ions and other cell contents are lost = cells burst
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Side effects of polyene macrolides (amphotericin B & Nystatin)
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Nephrotoxicity = old formulations released drug to rapidly, distribution to kidneys too fast
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MOA of 1,3-beta-D-glucan synthesis inhibitors
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inhibit 1, 3 beta-D-glucan synthesis ==weak cell walls in fungi
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Viral Life Cycle
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1) Adsorption
2) Penetration 3) Uncoating 4) Early transcription 5) Early translation 6) DNA synthesis and late transcription 7) Late translation 8) condensation 9) assembly 10) Release |
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HIV Cycle
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1) Virus attach and fusion
2) Reverse transcription 3) Integration 4) Transcription 5) Translation 6) Assemble, budding, maturation |
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Targets of Antiviral Drug action
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1) inhibit viral attachment, penetration, and/or uncoating
2) Inhibit viral enzymes (nucleic acid biosynthesis) 3) Inhibit transcription of viral genome and translation of viral proteins 4) inhibit viral proteins 5) Interfere with post transcriptional modification of viral proteins 6) Interfere with viral componenet assembly 7) interfere with viral release |
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MOA of Ionizable adamantane amine derivatives
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*Inhibit uncoating*
M2 protein in Flu Type A produce a proton transport channel drug can plug proton transport channel, blocking transport of ions. Disturbs the pH balance AND prevents conformational change - no uncoating |
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Ionizable Adamantane Amine Derivatives
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1) Amantadine (Symmetrel)
2) Rimantadine (Flumadine) |
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Mechanism of Resistance to Ionizable Adamantane Amine Derivatives
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mutations in the transmembrane region of the M2 protein alter drug binding
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MOA of docosanol (Abreva)
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inhibit viral fusion
unusual phospholipids are incorporated into the cell membrane, diminishing the extent of viral fusion |
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MOA of sialic acid analogs (Zanamavir, Oseltamavir)
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Neuraminidase catalyzes hydrolytic removal of sialic acid residue on host cell surface = link is broken, virion detach, infect another host cell
INHIBIT NEURAMINIDASE = decrease release of viral particles |
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Resistance to sialic acid analogs (Zanamavir, Oseltamavir)
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site mutations of neuraminidase and hemagglutinin
Decrease binding affinity |
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MOA of viral DNA strand elongation inhibitors (DNA Polymerase inhibitors)
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mimic dGTP and are incorporated by DNA polymerase into growing primer strand of DNA = terminate DNA chain elongation
competitive inhibitor of viral DNA polymerases, template unable to progress toward 5' end |
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Bioactivation of DNA Polymerase inhibitors
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Pre-Prodrug (Viral Thymidine Kinase) Monophosphate (Host GMK) Tryphosphate
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Resistance to DNA Polymerase Inhibitors
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Mutations result in altered viral thymidine kinase or viral DNA polymerases
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MOA of Trifluorothymidine (DNA polymerase inhibitors)
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compete with dTTP for incorporation into a growing primer strand of DNA
Strand Elongation continues BUT modified base is unstable, falls off, and misreading of the DNA strand |
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Resistance to Trifluorothymidine
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reduced viral thymidine kinase activity
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MOA of Foscarnet (DNA Polymerase Inhibition)
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competes with pyrophosphate for the pryophosphate binding site on DNA polymerase
prevents hydrolysis from dNTPs during chain elongation **Also inhibits reverse transcriptase |
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Resistance to Foscarnet
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mediated by alteration of viral DNA polymerase
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MOA of Ribavirin
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*Requires bioactivation*
RMP - inhibits inosine monophosphate dehydrogenase = decreased purine synthesis RTP - inhibits viral RNA polymerases |
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Resistance to Ribavirin
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mutation in viral RNA polymerases (drug can't bind)
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Targets for activity against HIV
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1) Attachment, fusion, uncoating
2) Reverse transcriptase 3) Integration, transcription, translation 4) HIV Protease |
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MOA of Nucleoside-type Reverse Transcriptase Inhibitors (NRTIs)
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terminators of DNA strand elongation (No 3' - OH)
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Resistance of NRTIs
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point mutation in reverse transcriptase
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MOA of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
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inactivates RT by a non-competitive mechanism via an allosteric binding site on the enzyme
do not interfere with normal binding of the substrate, SLOW DOWN the incorporation of dNTPs into the growing DNA strand |
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Resistance of NNRTIs
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point mutations in reverse transcriptase = decreased binding at allosteric sites
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MOA of Protease Inhibitors (PI)
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inhibit the normal hydrolysis of hte bond between Tyr & Pro by a competitive mechanism
Gag-pol protein remains unprocessed - functional polypeptides not able to carry out their functions = viral progeny cannot infect new host cells |
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Viral Fusion Inhibitors
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Drug Inhibits THIS:
1) Viral gp120 binds to host CD4 receptor = conformation change 2) binding site for CCR5 revealed = virus binds and another conformation change occurs 3) N-terminal hydrophobic region of gp41 exposed to CD4 receptor 4) heptad repeats of gp41 interact with one another = form hairpin structure = fuses viral/host cells |
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MOA of Enfuvirtide
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*synthetic 36-residue peptide*
prevents interaction of HR1 & HR2 and the formation of the hairpin structure Overall: NO HAIRPIN STRUCTURE = no viral fusion |
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MOA of Maraviroc
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*CCR5 Receptor Antagonist*
blocks CCR5 and renders virus unable to fuse with and enter the host cell |
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MOA of Integrase Inhibition
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inhibits the splicing of host genome and inserts viral double strand genome
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