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Flashcards in Antimicrobials IV Deck (16)
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1

name the 9 steps of the viral lifecycle that can be inhibited

  1. recognition
  2. attachment
  3. penetration
  4. uncoating
  5. transcription
  6. protein synthesis
  7. replication
  8. assembly
  9. lysis and release

2

describe the M2 protein inhibitors

Adamantanes e.g. Amantadine

  • viral RNA in virion is protein-bound, including to M1 protein
  • must be released from M1 in order to enter nucleus
  • M2 protein in viral membrane forms channel
  • channel enables entry of protons from endosome into virion
  • entry of protons lowers pH --> release of viral RNA from M1
  • Adamantanes block mechanism of action of M2 
    • no protons enter virion --> no acidification --> no release of viral RNA --> no viral replication
    • resistance via changes to M2 an increasing issue

3

name the types of reverse-transcriptase inhibitors (RTIs)

  1. nucleoside analog RTIs (NRTIs)
  2. nucleotide analog RTIs (NtRTIs)
  3. non-nucleoside RTIs (NNRTIs)
  • NRTIs and NtRTIs are functionally similar
    • lack 3-hydroxyl group (N3 instead)
    • once incorporated into DNA --> chain termination
    • many must be intracellularly activated
      • phosphorylation to triphosphate form
  • NNRTIs
    • non-competitive inhibitors of RT: bind directly to enzyme

4

describe acyclic guanosine inhibitors and what it treats

5

what can be used to monitor treatment efficacy?

viral load (burden/titer) can be used to monitor treatment efficacy

  • quantify amounts of virus present in plasma, CSF and other fluids
    • usually NA-amplification based
  • look at # of copies of nucleic acid per mL
  • most frequently used to monitor antiretroviral therapy
    • aim to reduce viral load to below level of detection : 20-80 copies RNA/mL

6

describe the various factors that contribute to antiviral drug resistance

  • resistance has increased alongside expanded clinical use of antiviral agents
  • primarily a problem in specific patients with:
    • long-term or progressive infections
      • particularly if exposed to long-term or repeated therapy
    • impaired immune systems
  • contributing factors:
    • sub-therapeutic drug concentrations
    • plasticity of viral genomes --> high mutation rate
    • mutation might change target but leave function unaffected

7

describe the plaque reduction assay

plaque reduction assay is the gold standard for phenotypic analysis of clinical isolates

8

describe the function of integrase strand transfer inhibitors (ISTIs) and reverse transcriptase inhibitors (RTIs)

9

describe the factors contributing to unsuccessful chemotherapeutic treatment of parasitic infections

  • similarities between eukaryotic parasites and human host
  • limited money and resources to commit to treatment/control in resource-limited countries (high % of infxns occur)
  • inidividuals can be infected by multiple parasites
  • high level re-exposure --> risk of re-infection
  • immunocompromise: inadequate nutrient intake and other infections
  • poverty and poor sanitation (liitle/no sewage disposal, clean water access limited)

10

summarize the target and effect of metronidazole and pentamidine (antiprotozoal drugs)

11

name the 3 groups of anti-protozoal drugs

in general, single drug usually targets single stage of Plasmodium life cycle

  • quinines
    • chloroquine
    • quinine
    • mefloquine
  • protein synthesis inhibitors
    • doxycycline
  • artemisinins

12

describe the function of quinine

  • interferes with parasite's hematin detoxification 
  • blood schizotocides

13

describe the function of doxycycline

  • member of cycline antibiotic family
    • synthetic tetracycline
  • protein synthesis inhibitor
    • mitochondrial ribosomes (70s)
    • interferes with apicoplast
      • organelle containing survival-relevant biosynthetic pathways
  • targets both blood and liver stages of the malaria parasite

14

describe the function of sesquiterpenes

Artemisinin

  • mechanism: release free-radicals into parasite vacuoles, damaging membranes
  • effect: inhibition of major metabolic processes including glycolysis
  • usually combined, e.g. with aminoquinolone = Artemisinin Combination Therapy (ACT)
    • to delay development of resistance

15

describe the challenges with treatment of helminthic infections

  • high incidence of infection in all age groups
  • limited range of current drugs
  • potential for development of resistance
  • repeated, regular treatments necessary
  • polyparasitism
  • drugs can be specific to one stage
    • e.g. many of antifilarial drugs treat microfilariae; limited activity against adult worms

16

summarize the antihelminthic drugs