Ch 40 - Quinoloneas, Folic Acid Antagonists, And Urinary Tract Antiseptics

Question 1

What is the predecessor to all fluoroquinolones?

Answer 1

Nalidixic acid

Question 2

What gives us “collateral damage”?

Answer 2

• fluoroquinolones

- 3rd genereation cephalosporin

Question 3

How does the fluoroquinolones enter the bacteria?

Answer 3

through porin channels

Question 4

What is the pharmacological mechanism of action of fluoroquinolones?

Answer 4

• to G(-): they inhibit DNA gyrase (bacterial topoisomerase II)
• to G (+): topoisomerase IV

thus blocking bacterial DNA synthesis

Question 5

What does the inhibition of topoisomerase IV do?

Answer 5

it impacts chromosomal stabilization during cell division, thus interfering with the separation of newly replicated DNA.

Question 6

Are fluoroquinolones bactericidal or bacteriostatic?

Answer 6

bactericidal

Question 7

What is fluoroquinolones effective against?

Answer 7

• G(-) organisms (E.coli, P. aerguinosa, Haemophilus influenzae)
• atypical organisms (Chlamydiaceae, Legionellaceae)
• G(+) organisms (streptococci)
• some mycobacteria (Mycobacterium tuberculosis)

Question 8

Which fluoroquinolones are called the “respiratory fluoroquinolones”? and why?

Answer 8

• levofloxacin and moxifloxacin

- because they have excellent activity against S. pneumoniae

Question 9

How are fluoroquinolones classified?

Answer 9

into generations

Question 10

What is a part of the first generation of fluoroquinolones?

Answer 10

nonfluorinated quinolone -nalidixic acid-

Question 11

What is a part of the second generation of fluoroquinolones? And why?

Answer 11

• Ciprofloxacin and norfloxacin

- because of their activity against aerobic gram-negative and atypical bacteria

Question 12

What is a part of the third generation of fluoroquinolones? And why?

Answer 12

• levofloxacin

- because of its increased activity against gram-positive bacteria

Question 13

What is a part of the fourth generation of fluoroquinolones? And why?

Answer 13

• moxifloxacin

- because of its activity against anaerobic and gram-positive bacteria

Question 14

Norfloxacin (fluoroquinolones):

Answer 14

• poor oral bioavailability
• short half-life
• effective in treating nonsystemic infections, such as UTI, prostatitis, and infectious diarrhea

Question 15

Ciprofloxacin (fluoroquinolones):

Answer 15

• used to treat systemic infections caused by gram-negative bacilli
• of the fluoroquinolones it has the best activity against
• used to treat traveler´s diarrhea (caused by E.coli) and typhoid fever (caused by salmonella)
• used as a second-line agent in the treatment of tuberculosis

Question 16

Levofloxacin (fluoroquinolones):

Answer 16

• is the L-isomer of ofloxacin
• utilized in a wide range of infections, including prostatitis, skin infections, CAP, and nosocomial pneumonia
• 100%bioavailability
• dosed once daily

Question 17

Moxifloxacin (fluoroquinolones):

Answer 17

• gram-positive organisms and anaerobes

- not used for UTIs

Question 18

Resistance (fluoroquinolones):

Answer 18

• primarily due to chromosomal mutation in bacterial genes. Both topoisomerase IV and DNA gyrase may undergo mutations
• decreased accumulation

Question 19

Which of the fluoroquinolones can be taken orally?

Answer 19

• ciprofloxacin
• levofloxacin
• moxifloxacin
• norfloxacin
• ofloxacin

Question 20

Which of the fluoroquinolones can be taken IV?

Answer 20

• ciprofloxacin
• levofloxacin
• moxifloxacin

Question 21

How is the distribution of fluoroquinolones?

Answer 21

• distributes well into all tissues and bodily fluids
• levels are high in bone, urine (except moxifloxacin), kidney, and prostatic tissue (but not prostatic fluid)
• concentration in the lungs exceed those in serum

Question 22

Elimination of fluoroquinolones:

Answer 22

• excreted renally
• dose adjustment in patients with renal dysfunction
• moxifloxacin is excreted primarily by the liver, no doe adjustment is required for renal impariment

Question 23

Adverse reactions to fluoroquinolones:

Answer 23

• CNS effects: headache, dizziness, insomnia
• GI effects: diarrhea, nausea, abnormal liver function tests
• Photosensistivity
• Tendinitis or tendon rupture
  (p. 516)

Question 24

Can fluoroquinolones be used in children?

Answer 24

no, because they cause cartilage erosion, which also rules out their use during pregnancy and nursing