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Host and Defense > EXAM 2 Antibiotics III > Flashcards

EXAM 2 Antibiotics III Flashcards

1
Q

both ___ and ___ are enzymes necessary for bacterial DNA replication to occur properly

A
  • topoisomerase II (aka DNA gyrase)
  • topoisomerase IV
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2
Q

without topoisomerase II and IV, DNA replication will ___

A

fail

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3
Q

___ and ___ are key bacterial enzymes that convey antimicrobial drug selectivity

A

topoiseromase II and IV

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4
Q

DNA replication is carried out by which 6 enzymes?

A
  • topoisomerase II (DNA gyrase)
  • topoisomerase IV
  • helicase
  • DNA polymerase III
  • RNA primase
  • DNA polymerase I
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5
Q

which enzyme is responsible for affecting the degree of supercoiling of the bacterial chromosome?

A

topoisomerase II (DNA gyrase)

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6
Q

what enzyme unwinds DNA and breaks hydrogen-bonds between base pairs?

A

helicase

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7
Q

what enzyme attaches nucleotides in a 5’ - 3’ direction?

A

DNA polymerase III

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8
Q

what enzyme leaves RNA primers on the lag strand?

A

RNA primase

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9
Q

what enzyme facilitates bacterial cell division by unlinking DNA following DNA replication?

A

topoisomerase IV

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10
Q

are quinolones/fluoroquinolones bactericidal or bacteriostatic? broad or narrow spectrum?

A

bactericidal and broad spectrum

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11
Q

what is the mechanism of quinolones/fluoroquinolones?

A

can block DNA gyrase (topo II) and topo IV

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12
Q

___ is the primary target on gram - microbes

A

DNA gyrase

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13
Q

___ is the target on gram + microbes

A

topo IV

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14
Q

DNA gyrase prevents tangles and supercoils in DNA so it can be cut, relaxed, and realigned during replication, so inhibition of DNA gyrase leads to what?

A

fragmentation of the DNA

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15
Q

what is the clinical use of first generation quinolones/fluoroquinolones?

A

inhibit DNA gyrase only (gram - coverage only)

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16
Q

what is the clinical use of second, third, and fourth generation quinolones/fluoroquinolones?

A

broad gram - coverage and/or add topo IV inhibition to give them gram + coverage

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17
Q

ciprofloxacin is a ___ generation quinolone/fluoroquinolone

A

2nd

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18
Q

describe the coverage of ciprofloxacin

A
  • extended gram - coverage
  • intracellular atypicals
  • bacillus anthracis (causes anthrax)
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19
Q

what is the drug of choice for prophylaxis or treatment of anthrax?

A

ciprofloxacin

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20
Q

___ can be used for chronic bone infections (osteomyelitis) due to enterobacteriaceae

A

ciprofloxacin

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21
Q

ciprofloxacin is the best quinolone for treating ___

A

pseudomonas

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22
Q

ciprofloxacin can be used to treat what 8 bacteria/infections?

A
  • anthrax
  • osteomyelitis due to enterobacteriaceae
  • p. aeruginosa
  • gonorrhea (but not the drug of choice)
  • uncomplicated UTIs
  • resistant tuberculosis
  • typhoid fever
  • systemic gram - infections, such as traveller’s diarrhea (e. coli)
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23
Q

ciprofloxacin is the best quinolone for treating p. aeruginosa (and other pseudomonas spp.). why is this important?

A

high risk of pulmonary infection in patients with cystic fibrosis

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24
Q

ciprofloxacin is useful against systemic gram - infections, is a good alternative to ___, and acts synergistically if given with ___

A
  • toxic drugs
  • beta-lactams
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25
Q

levofloxacin is a ___ generation quinolone/fluoroquinolone

A

3rd

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26
Q

which quinolone/fluoroquinolone retains gram - activity while also gaining improved activity for atypicals and some gram +

A

levofloxacin

27
Q

what are the three clinical uses that levofloxacin is used for as an alternative?

A
  • alternative for s. pneumoniae or h. influenzae respiratory infections, when resistant to beta lactams
  • alternative for gonorrhea
  • alternative for anthrax - prophylaxis or therapy
28
Q

what is the clinical use that levofloxacin is used for as an add on?

A

complicated UTIs and/or prostratitis

29
Q

what is the only CNS penetrant fluoroquinolone, and what generation is it?

A

oxfloxacin, 3rd generation

30
Q

moxifloxacin is a ___ generation fluoroquinolone, and is considered the best ___ fluoroquinolone

A
  • 4th generation
  • respiratory
31
Q

describe the activity of moxifloxacin

A
  • enhanced gram + s. pneumoniae activity
  • excellent anaerobic activity (bacteriodes fragilis)
  • poor p. aeruginosa activity
32
Q

how are fluoroquinolones typically administered?

A

PO (up to 95% absorbed orally) or IV

33
Q

what interferes with the oral absorption of fluoroquinolones?

A
  • Al+ and Mg+ antacids
  • dietary supplements with divalents (Zn++ or Fe++)
34
Q

fluoroquinolones distribute through all ___ and ___

A

tissues and body fluids

35
Q

___ levels in the lung actually exceed those detected in serum

A

fluoroquinolone

this is because they distribute through all tissues and body fluids

36
Q

which is the only fluoroquinolone that reaches CSF in clinically-active levels?

A

oxfloxacin - 3rd generation

37
Q

which enzyme removes RNA primers, allowing DNA ligase to attach okazaki fragments together by forming covalent bonds between nucleotides?

A

DNA polymerase I

38
Q

fluoroquinolones are excreted by ___

A

kidneys

39
Q

why is there a once-daily dosing for the “respiratory quinolones”?

A

due to long 1/2 lives and accumulation in the lungs

40
Q

what are the two respiratory quinolones?

A
  • moxifloxacin (best)
  • levofloxacin
41
Q

what are the 5 adverse effects of fluoroquinolones?

A
  • GI upset
  • CNS (headache, dizziness)
  • photosensitivity
  • prolongation of QT interval (especially moxifloxacin)
  • connective tissue problems
42
Q

___ is the most often cause of c. difficile superinfection

A

ciprofloxacin

43
Q

___ should be used with caution in patients with epilepsy, since it may provoke seizures at toxic doses

A

ciprofloxacin

44
Q

___ interferes with the metabolism of theophylline inhalers (asthma) and can produce toxic doses that may provoke seizures

A

ciprofloxacin

45
Q

what is the containdication for fluoroquinolones?

A

concomitant administration of a nonsteroidal anti-inflammatory drug (NSAID) with any fluoroquinolone may increase the risks of CNS stimulation and convulsions

46
Q

what are the connective tissue problems associated with fluoroquinolones?

A
  • contraindicated in pregnancy, nursing mothers, and children
  • contraindicated in patients with myesthenia gravis (FDA “black box” warnings on all packaging)
  • tendinitis - increased risk of ruptured tendons even several months after discontinuing therapy (FDA “black box” warnings now required)
47
Q

what are the 2 known drug interactions of fluoroquinolones?

A
  • antacids decrease absorption
  • inhibits drug metabolism of theophylline
48
Q

which 3 non-quinolone drugs disrupt nucleic acid synthesis?

A
  • metronidazole
  • rifampin
  • nitrofurantoin
49
Q

what is the mechanism of metronidazole

A

inhibits DNA replication

50
Q

what are the clinical uses for metronidazole?

A
  • drug of choice for diarrhea due to superinfection with c. difficile (pseudomembranous colitis)
  • drug of choice for tetanus
51
Q

what is the contraindication for metronidazole?

A

do not take with alcohol - disulfuram (antabuse) like interaction (instant hangover)

52
Q

what is the mechanism of rifampin?

A

inhibits DNA-dependent bacterial RNA polymerase

53
Q

describe the spectrum of rifampin

A

gram +, gram -, and mycobacteria

54
Q

what are the clinical uses of rifampin?

A
  • treatment of mycobacteria
    • tuberculosis, leprosy, and legionella
  • h. influenzae B and meningococcal disease
55
Q

rifampin is absorbed well orally, distributed widely, extensive liver metabolism, and is excreted in what 5 places?

A
  • saliva
  • tears
  • sweat
  • urine
  • feces (orange/red color)
56
Q

the following adverse effects describe what antibiotic?

turns urine, sweat, and tears a red-orange color

dose-dependent hepatoxicity risk

CYP450 inducer (increases metabolism of drugs so may need to increase doses of the other drug)

A

rifampin

57
Q

what is the mechanism for nitrofurantoin?

A

forms highly reactive intermediates that attach bacterial ribosomal proteins, DNA, and other macromolecules essential for survival

58
Q

bacterial cells reduce ___ more rapidly into its intermediates than the host.

A

nitrofurantoin

this describes its selectivity, and it is not known which of the actions is primarily responsible for the bactericidal activity of nitrofurantoin

59
Q

what are the clinical uses of nitrofurantoin?

A
  • treatment of uncomplicated UTIs
  • prophylaxis against UTIs in people prone to recurrent UTIs
60
Q

what are the contraindications of nitrofurantoin?

A
  • decreased renal function
  • last 4 weeks of pregnancy or in neonates up to 1 month
61
Q

nitrofurantoin is a good ___ agent that quickly reaches therapeutic levels in the bladder

A

bacteriocidal

62
Q

___ is taken orally and ___% absorbed from intestines into urine, and ___% is excreted within 45 minutes unchaged

A
  • nitrofurantoin
  • 90%
  • 40%
63
Q

tissue penetration of nitrofurantoin outside the urinary tract is ___

A

negligible

that is why it is so effective for treating UTIs

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