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Ok Pharmacology... Let's Do This... Be Gentle > Inhibitors of DNA Function > Flashcards

Inhibitors of DNA Function Flashcards

1
Q

what are the 3 inhibitors of DNA function

A
  1. fluoroquinolones
  2. nitrofurantoin
  3. metronidazole
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2
Q

which fluoroquinolone has good pseudomonal coverage

A

cipro

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3
Q

which fluoroquinolone has good urinary and respiratory coverage

A

levo

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4
Q

what fluoroquinolone has good gram (+) coverage

A

moxi

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5
Q

what part of bacteria do fluoroquinolones target

A

bacterial DNA gyrase and topoisomerase IV

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6
Q

what is the fxn of bacterial DNA gyrase

A

required for normal DNA replication → transcription and some aspects of DNA repair and recombination

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7
Q

DNA inhibitors inhibit DNA __

A

precursors

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8
Q

what is fluoroquinolones MOA

A

bactericidal → rapid w.in 2 hr

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9
Q

how does strep pneumo develop resistance against fluoroquinolones

A

point mutations in DNA gyrase/topoisomerase

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10
Q

strep pneumo resistance to fluoroquinolones is a __ process

A

step wise

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11
Q

strep pneumo prevents drug-target against fluoroquinolones via ___

and ___ gene

A

drug efflux

MDR

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12
Q

what is the holy trinity of URI infxn

A

strep pneumo

m. cat
h. flu

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13
Q

what are the respiratory quinolones

A

levo

moxi

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14
Q

which quinolone covers bacillus anthracis

A

cipro

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15
Q

quinolones should only be used in

A

very serious infxns

→ ex don’t use levo for m.cat for sinusitis or bronchitis

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16
Q

cipro and levo should be used for pseudo and e.coli only in

A

complicated UTIs

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17
Q

which quinolone has good coverage against atypical organisms (chlamydia, mycoplasma pneumoniae, rickettsia)

A

moxi

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18
Q

fluoroquinolones are well absorbed __

and also available __

A

orally

IV

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19
Q

fluoroquinolones have good penetration into most tissues, including high __

A

urinary levels

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20
Q

fluoroquinolones are primarily excreted by the __,

except for __

A

kidneys

moxi

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21
Q

renal dosing is needed for levo and cipro, but not for __

A

moxi

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22
Q

fluoroquinolones are generally well tolerated, the most two common adverse rxns are mild

A
  1. GI tract
  2. CNS (HA, dizzy, insomnia)
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23
Q

what are the 2 box warnings for quinolones

A
  1. 3-4 fold risk of tendon rupture → rare
  2. potential for athropathies → limits use in pregnancy and children <12 yo
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24
Q

what cardiac adverse effect do quinolones have

A

prolonged QT interval

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25
Q

what are the 3 drug-drug interactions w. quinolones

A
  1. antacids
  2. theophylline and caffeine
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26
Q

which quinolone are drug-drug interactions most associated with

A

cipro

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27
Q

theophylline rxn w. cipro is of less importance now bc

A

theophylline is hardly ever used

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28
Q

nitrofurantoin is most commonly used for

A

urinary tract antiseptic

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29
Q

nitrofurantoin is not used for __ infxns

bc __ can not be obtained w. safe doses

A

systemic

effective Cp

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30
Q

nitrofurantoins are ___

by __

to intermediates that

___

A

reduced

bacterial enzymes

damage bacterial DNA

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31
Q

nitrofurantoins are generally (cidal or static)

A

bactericidal

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32
Q

why is nitrofurantoin selectively toxic

A

bc mammalian enzymes don’t reduce nitrofurantoin as rapidly

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33
Q

nitrofurantoin is used for what class of bacteria

A

gram negative rods

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34
Q

nitrofurantoin is used for what type of infxn

A

uncomplicated UTIs

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35
Q

nitrofurantoin works well against __

but __

and __ are resistant

A

e.coli

pseudomonas and proteus

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36
Q

nitrofurantoin has rapid and complete __ absorption

A

oral

37
Q

nitrofurantoin is excreted into the ___

and requires __ dosing

A

urine

renal

38
Q

use of nitrofurantoin is contraindicated in

A

renal insufficiency

39
Q

mabrobid is

A

bid nitrofurantoin

40
Q

macrodantin is

A

qid nitrofurantoin

41
Q

most common adverse rxns of nitrofurantoin occur in the

A

GI tract

42
Q

___ forms of nitrofurantoin are better tolerated

A

macrocrystalline

43
Q

what are 3 serious adverse rxns of nitrofurantoin

A
  1. hemolytic anemia
  2. neuropathies → chronic use
  3. category B for pregnancy → but should NOT be given in 3rd trimester dt hemolytic anemia
44
Q

metronidazole is a __ transformed to reactive radicale in organisms

with __

A

prodrug

negative redox potential

45
Q

metronidazole is effective against what 2 bacteria

A
  1. anaerobic
  2. protozoa
46
Q

metronidazole kills via

A

DNA strand breaks

inhibition of replication

47
Q

metronidazole is (static or cidal)

A

cidal

48
Q

resistance to metronidazole is via __

which ___

A

expression of nitroimidazole reductase

stops formation of nitroso-group

49
Q

metronidazole has esecially good activity against which anaerobes

A
  1. bacteroides
  2. c.diff
50
Q

the bioavailability of metronidazole is __

and absorption is not __

A

80%

affected by food

51
Q

metronidazole has good distribution, including __

and __

A

CSF

bone

52
Q

metronidazole is primarily metabolized via __ metabolism,

and __ dosing is required

A

hepatic

liver

53
Q

what is a concern for nursing moms with metronidazole

A

it is excreted in breast milk

54
Q

drug interactions w. metronidazole are possible w.

A

CYP450 inhibitors

55
Q

the most common adverse rxns with metronidazole are (4)

A

nausea

HA

dry mouth

metallic taste

56
Q

metronidazole is contraindicated in pregnancy during the __

A

1st trimester

57
Q

metronidazole can have a drug-drug interaction w.

A

etoh

58
Q

what are the 2 inhibitors of intermediary metabolism

A
  1. sulfonamides
  2. trimethroprim/sulfamethoxazole
59
Q

resistance to sulfonamides is widespread and persistent in vivo in

A

meningococci

gonococci

b-hemolytic strep

enteric gram-negative rods

60
Q

what are the 2 mechanisms of acquired resistance to sulfonamides

A
  1. increased production of PABA
  2. altered DHPS
61
Q

resistance to sulfonamides occurs in a __ fashion,

not during __

A

stepwise

therapy

62
Q

bacteria obtain DNA precursors from __,

which is why ___ is important

A

pus

surgical drainage

63
Q

organisms with no __ requirement are not susceptible to sulfonamides

A

folic acid

64
Q

sulfonamides are synergistic w. ___

A

trimethoprim

65
Q

sulfonamides are (cidal vs static)

A

cidal

66
Q

is trimethoprim a sulfonamide

A

no!

67
Q

trimethoprim is __ more potent

than __

A

5-20%

sulfonamides

68
Q

resistance to sulfonamides is via

A

altered DHFR

69
Q

what is DHFR

A

dihydrofolate reductase

70
Q

pyrimethamine inhibits __ DHFR

which is __

A

protozoal

malaria

71
Q

methotrexate inhibits ___ DHFR

which is ___

A

mammalian

neoplasms

72
Q

the target of sulfonamides is

A

the enzyme that makes folic acid

73
Q

trimethoprim targets

A

another step of folic acid formation

74
Q

does TMP/SMX cover MRSA

A

yes

75
Q

sulfonamides plus trimethoprim work well for what types of gram negative infxns

A

uncomplicated UTI → e. coli

burn infxns → pseudomonas

76
Q

sulfonamides are ___ that are well absorbed

from the ___

A

weak acids

GI tract

77
Q

sulfacetamide is

A

topical sulfonamide + trimethoprim

78
Q

sulfacetamide is used for

A

conjunctivitis

79
Q

sulfonanides should be taken

A

on an empty stomach

80
Q

sulfonamides have good distribution in body water, including (4)

A
  1. pleural
  2. ocular
  3. synovial fluids
  4. CSF
81
Q

sulfonamides can cause displacement of ___

in ___,

predisposing them to ___

A

bilirubin

neonates

kernicterus

82
Q

what can be a source of drug-drug interactions with sulfonamides

A

displacement of protein-bound drugs

83
Q

sulfonamides are not used in what pt population

A

neonates

pregnant women

84
Q

the major metabolic pathway for sulfonaides is __,

which may be toxic dt ___

A

n-acetylation

low solubility in urine

85
Q

do sulfonanides require renal dosing

A

yes

86
Q

sulfonamides should be taken with

A

lots of fluids

87
Q

sulfonamides are the worst drug for what type of rxn

A

hypersensitivity rxns

88
Q

what is a severe adverse rxn with sulfonamides

A

stevens-johnson

Ok Pharmacology... Let's Do This... Be Gentle (6 decks)

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