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deck_5740358 Flashcards

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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
levofloxacin is a ___ generation quinolone/fluoroquinolone
3rd
26
which quinolone/fluoroquinolone retains gram - activity while also gaining improved activity for atypicals and some gram +
levofloxacin
27
what are the three clinical uses that levofloxacin is used for as an alternative?
* alternative for s. pneumoniae or h. influenzae respiratory infections, when resistant to beta lactams * alternative for gonorrhea * alternative for anthrax - prophylaxis or therapy
28
what is the clinical use that levofloxacin is used for as an add on?
complicated UTIs and/or prostratitis
29
what is the only CNS penetrant fluoroquinolone, and what generation is it?
oxfloxacin, 3rd generation
30
moxifloxacin is a ___ generation fluoroquinolone, and is considered the best ___ fluoroquinolone
* 4th generation | * respiratory
31
describe the activity of moxifloxacin
* enhanced gram + s. pneumoniae activity * excellent anaerobic activity (bacteriodes fragilis) * poor p. aeruginosa activity
32
how are fluoroquinolones typically administered?
PO (up to 95% absorbed orally) or IV
33
what interferes with the oral absorption of fluoroquinolones?
* Al+ and Mg+ antacids | * dietary supplements with divalents (Zn++ or Fe++)
34
fluoroquinolones distribute through all ___ and ___
tissues and body fluids
35
___ levels in the lung actually exceed those detected in serum
fluoroquinolonethis is because they distribute through all tissues and body fluids
36
which is the only fluoroquinolone that reaches CSF in clinically-active levels?
oxfloxacin - 3rd generation
37
which enzyme removes RNA primers, allowing DNA ligase to attach okazaki fragments together by forming covalent bonds between nucleotides?
DNA polymerase I
38
fluoroquinolones are excreted by ___
kidneys
39
why is there a once-daily dosing for the "respiratory quinolones"?
due to long 1/2 lives and accumulation in the lungs
40
what are the two respiratory quinolones?
* moxifloxacin (best) | * levofloxacin
41
what are the 5 adverse effects of fluoroquinolones?
* GI upset  * CNS (headache, dizziness) * photosensitivity * prolongation of QT interval (especially moxifloxacin) * connective tissue problems
42
___ is the most often cause of c. difficile superinfection
ciprofloxacin
43
___ should be used with caution in patients with epilepsy, since it may provoke seizures at toxic doses
ciprofloxacin
44
___ interferes with the metabolism of theophylline inhalers (asthma) and can produce toxic doses that may provoke seizures
ciprofloxacin
45
what is the containdication for fluoroquinolones?
concomitant administration of a nonsteroidal anti-inflammatory drug (NSAID) with any fluoroquinolone may increase the risks of CNS stimulation and convulsions
46
what are the connective tissue problems associated with fluoroquinolones?
* 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
what are the 2 known drug interactions of fluoroquinolones?
* antacids decrease absorption | * inhibits drug metabolism of theophylline 
48
which 3 non-quinolone drugs disrupt nucleic acid synthesis?
* metronidazole * rifampin * nitrofurantoin
49
what is the mechanism of metronidazole
inhibits DNA replication
50
what are the clinical uses for metronidazole?
* drug of choice for diarrhea due to superinfection with c. difficile (pseudomembranous colitis) * drug of choice for tetanus
51
what is the contraindication for metronidazole?
do not take with alcohol - disulfuram (antabuse) like interaction (instant hangover)
52
what is the mechanism of rifampin?
inhibits DNA-dependent bacterial RNA polymerase
53
describe the spectrum of rifampin
gram +, gram -, and mycobacteria
54
what are the clinical uses of rifampin?
treatment of mycobacteria * tuberculosis, leprosy, and legionella * h. influenzae B and meningococcal disease
55
rifampin is absorbed well orally, distributed widely, extensive liver metabolism, and is excreted in what 5 places?
* saliva * tears * sweat * urine * feces (orange/red color)
56
the following adverse effects describe what antibiotic?turns urine, sweat, and tears a red-orange colordose-dependent hepatoxicity riskCYP450 inducer (increases metabolism of drugs so may need to increase doses of the other drug)
rifampin
57
what is the mechanism for nitrofurantoin?
forms highly reactive intermediates that attach bacterial ribosomal proteins, DNA, and other macromolecules essential for survival
58
bacterial cells reduce ___ more rapidly into its intermediates than the host.
nitrofurantointhis describes its selectivity, and it is not known which of the actions is primarily responsible for the bactericidal activity of nitrofurantoin
59
what are the clinical uses of nitrofurantoin?
* treatment of uncomplicated UTIs | * prophylaxis against UTIs in people prone to recurrent UTIs
60
what are the contraindications of nitrofurantoin?
* decreased renal function | * last 4 weeks of pregnancy or in neonates up to 1 month
61
nitrofurantoin is a good ___ agent that quickly reaches therapeutic levels in the bladder
bacteriocidal
62
___ is taken orally and ___% absorbed from intestines into urine, and ___% is excreted within 45 minutes unchaged
* nitrofurantoin * 90% * 40%
63
tissue penetration of nitrofurantoin outside the urinary tract is ___
negligiblethat is why it is so effective for treating UTIs

Drugs - Smith (9 decks)

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