Pathophysiology, drug targets and resistance in viruses, (myco)bacteria & fungi Flashcards

1
Q

Are targets dictated by pathogens or hosts?

A

pathogens

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2
Q

Advantage to have greater evolutionary distance between humans and pathogens

A

This would allow for them have more different targets which makes it easier to find specific drugs

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3
Q

Disadvantage to have closer evolutionary distance between human and pathogen?

A

tougher to find specific drugs

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4
Q

More essential pathogen targets (bigger genomes) means?

A

more drugs

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5
Q

Resistance mechanisms are dictated by?

A

pathogen or virus

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6
Q

Simple genomes of virus have how many genes?

A

5-50 genes

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7
Q

How do viruses acquire resistance?

A

through mutations in target genes occurring during lower fidelity gene replication

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8
Q

What is a resistant mechanism that bacteria and fungi have that viruses do not have?

A

Viruses do not have efflux pumps because they do not have a specific location for replication so there is no where for the efflux pump to be

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9
Q

Where do viruses replicate?

A

host cell

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10
Q

What does having complex genomes of thousands of genes mean for resistance mechanisms in bacteria and fungi?

A

lots of potential resistance mechanisms

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11
Q

What are three ways bacteria and fungi can acquire resistance through?

A
  1. modification of target genes and control elements and amplification of target genes
  2. activation of efflux pumps, lowered uptake, lowered activation of prodrugs
  3. activation of antibiotic metabolism/inactivation
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12
Q

Where does modification of target genes and control elements and amplification of target genes occur?

A
  1. pathogen chromosome or moveable elements like plasmids

2. Although mutations are genetic, most modified antibiotic-target interactions take place in the proteins these encode

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13
Q

What type of control occurs in activation of efflux pumps, lowered uptake, lowered activation of prodrugs?

A

genetic or non-genetic control

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14
Q

What type of control occurs in activation of antibiotic metabolism/inactivation?

A

genetic or non-genetic control

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15
Q

What is an advantage of viral targets?

A

humans can give selectivity

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16
Q

What is a disadvantage of viral targets?

A

small genomes mean few targets

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17
Q

What is true about viruses?

a. are always so small they can be seen with light microscope
b. are always obligate parasites of bacteria, archaea, or eukaryotes
c. never have genomes that code for enzymes important in their replication
d. all of the above are true
e. none of the above are true

A

b. are always obligate parasites of bacteria, archaea, or eukaryotes

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18
Q

What are two ways we treat viruses without antivirals?

A
  1. supportive therapy

2. vaccination

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19
Q

What is supportive therapy?

A

rest, fluids, OTC painkilers

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20
Q

When is supportive therapy appropriate?

A

only for mild, resolvable illness

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21
Q

What are 4 disadvantages of vaccinations?

A
  1. doesn’t always work
  2. constant mutations in viral genome can lead to different antigens
  3. for influenza, means you need a vaccine every year
  4. for HIV, no vaccine yet developed and approved
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22
Q

How do we treat viruses?

A

antiviral drugs

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23
Q

What are 2 main kinds of antiviral drugs?

A
  1. host directed immune therapies, e.g. interferons used in past for HepC
  2. Antiviral drugs
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24
Q

What are 3 downsides of antivirals?

A
  1. very few good targets available
  2. viruses have massive numbers of noisy replications, mutations in target genes can lead to resistance development
  3. targets usually species-specific, no real broad spectrum compounds, need species-level identification for treatment
25
Q

What are 2 advantages of

bacterial targets?

A
  1. can give good selectivity

2. bigger genomes means more targets

26
Q

What is a disadvantage of bacterial targets?

A

lots of resistance mechanisms

27
Q

What are 3 unique mycobacteria targets?

A
  1. thick waxy cell wall
  2. DNA synthesis
  3. ATP synthesis
28
Q

What drugs (4) have thick cell wall mycobacteria target?

A
  1. isoniazid
  2. ethambutol
  3. ethionamide
  4. delamanid
29
Q

What drug has DNA synthesis mycobacteria target?

A

para amino salicylate

30
Q

What drug has ATP synthase mycobacteria target?

A

bedaquiline

31
Q

What are 3 shared mycobacterial targets?

A
  1. peptidoglycan-difficult so broadly B lactam resistant
  2. DNA dependent RNA polymerase
  3. protein synthesis (ribosome)
32
Q

What drug has peptidoglycan mycobacterial target?

A

meropenem

33
Q

What drug has DNA dependent RNA polymerase mycobacterial target?

A

rifampin and other rifamycins

34
Q

What 5 drugs have protein synthesis mycobacterial targets?

A
  1. fluroquinolones
  2. aminoglycosides
  3. capreomycin
  4. linezolid
  5. macrolides
35
Q

What are 2 types of mycobacteria?

A
  1. TB

2. environmental non-tuberculous mycobacteria (NTMs)

36
Q

What is am exclusively pathogenic mycobacterai that can infect any human, and has no need for host susceptibility?

A

TB

37
Q

What are drug targets for TB? (7)

A
  1. thick waxy cell wall
  2. DNA synthesis
  3. ATP synthase
  4. peptidoglycan
  5. DNA dependent RNA polymerase
  6. protein synthesis, ribosome
  7. unknown
38
Q

Drugs that target thick waxy cell wall in TB? 5

A

isoniazid, ethambutol, ethionamide,

delamanid/pretomani

39
Q

Drugs that target DNA synthesis in TB? 1

A

para amino salicylate

40
Q

Drugs that target ATP synthase in TB? 1

A

bedaquiline

41
Q

Drugs that target peptidoglycan in TB? 1

A

meropenem

42
Q

Drugs that target DNA dependent RNA polymerase in TB? 1

A

rifampin, other rifamycins

43
Q

Drugs that target protein synthesis, ribosome in TB? 4

A

fluoroquinolones, aminoglycosides,

capreomycin, linezolid

44
Q

Drugs that have unknown targets in TB? 2

A

pyrazinamide, clofazimine

45
Q

In drug resistant TB which two big drugs do you lose?

A

isoniazid and rifampin

46
Q

Downside of drug resistant TB

A

Becomes increasingly difficult to develop an effective non-toxic regimen

47
Q

Environmental non-tuberculous mycobacteria

A

NTM

48
Q

NTM mainly infects (5)

A

susceptible patients, CF, COPD, Bronchiectasis, AIDS (rare now)

49
Q

What is the duration of NTM treatment?

A

long, can be years or incurable

50
Q

What drug is resistant of M. abscessus that makes this very difficult to treat

A

rifampin

51
Q

Disadvantages of fungal targets? (3)

A
  1. difficult to get selectivity
  2. similarity mean few unique targets
  3. Resistance mechanisms to most agents known
52
Q

Advantage of fungal targets?

A

Mostly pathogens of immuno-compromized

53
Q

Fungal drug targets? (3)

A
  1. unique outer cell wall
  2. unique sterols in plasma membranes
  3. DNA synthesis
54
Q

Drugs that target unique outer cell wall in fungus infections? 1

A

echinocandins

55
Q

Drugs that target unique sterols in plasma membranes in fungal infections? 2

A

polyenes (target sterol), azoles

target unique synthetic enzyme

56
Q

Drugs that target DNA synthesis in fungal infections? 1

A

5 fluorocytosine

57
Q

Which type of fungal resistance do most species have?

A

intrinsic resistance to some or many classes of

drugs

58
Q

Why do many species have intrinsic resistance?

A

most drugs being natural products, so many

fungi have ‘seen’ them before