Fluoroquinolones

Question 0

List the 8 Fluoroquinolones:

Answer 0

Ciprofloxacin, Ofloxacin, Gemifloxacin, Gatifloxacin, Norofloxacin, Lomefloxacin, Levofloxacin, Moxifloxacin

Question 1

What are the main causes of UTIs?

Answer 1

E. Coli (70%), S. Saprophyticus (10-15%)

Proteus, Klebsiella, Pseudomonas and Serratia (all from catheters)

Question 2

Fluoroquinolones are fluorinated analogs of what acid?

Answer 2

Naladixic acid

Question 3

How to fluoroquinolones work?

Answer 3

Fluoroquinolones are bactericidal agents that function to inhibit DNA replication. They do this by blocking the activity of DNA gyrase and Topoisomerase IV.

Question 4

What type of bacteria are all fluoroquinolones active against?

Answer 4

All fluoroquinolones are active against aerobic gram negative rods such as citrobacter, serratia and Neisseria

Question 5

Which fluoroquinolone(s) is/are good at attacking G+ bacteria including MRSA?

Answer 5

moxifloxacin and gemifoxacin

Question 6

which fluoroquinolone has antipseudomonal capabilities?

Answer 6

ciprofloxacin

Question 7

Ciprofloxacin can be used as prophylaxis against what?

Answer 7

Anthrax

Question 8

In general, fluoroquinolones are ineffective against what group of bacteria? Also, which fluoroquinolones can be used with these bacteria?

Answer 8

anaerobic bacteria

moxifloxacin, gemifloxacin and trovafloxacin (no longer in use –> hepatotoxicity)

Question 9

Describe the pharmacokinetic properties of fluoroquinolones:

Answer 9

fluoroquinolones should be taken orally and their absorption is hindered by calcium, iron and magnesium. they have excellent tissue penetration but poor CNS penetration. they are undergo renal excretion (inhibited by probenecid)

Question 10

Which fluoroquinolones can be used to treat prostatitis; what pharmacokinetic property allows them to do this?

Answer 10

norfloxacin and ofloxacin can treat prostatitis because of their excellent tissue penetration

Question 11

what ways can bacteria develop resistance to fluoroquinolones?

Answer 11

change the target (alter the DNA gyrase/topoisomerase IV proteins), decrease the permeability, and have enzymes that modify the antibiotic upon entrance

Question 12

what are some of the important effects of fluoroquinolones?

Answer 12

GI disturbances, tendon rupture, and collagen erosion

Question 13

what are the contraindications for fluoroquinolone use?

Answer 13

pregnancy and children under the age of 18

Question 14

treatment for infections caused by enterobacter, citrobacter and serratia:

Answer 14

these are aerobic G- rods and therefore are treated by fluoroquinolones (quinolones)

Question 15

what type of bacteria is shigella and how do we treat it?

Answer 15

shigella is an aerobic G- rod that is treated with quinolones

Question 16

What type of bacteria are Legionella species, how do we treat them?

Answer 16

Legionella species are aerobic G- rods that are treated with a combination of quinolones and rifampin

Question 17

What is metronidazole (MOA)?

Answer 17

metronidazole is an inactive prodrug that must be activated once it is in bacteria. it is metabolized non-enzymatically by ferredoxin which is only found in anaerobic bacteria

Question 18

how do metronidazole metabolites function?

Answer 18

they become incorporated into the DNA and form unstable molecules causing death of the bacteria. they are bactericidal

Question 19

Metronidazole spectrum:

Answer 19

G-/G+ anaerobes (bacilli). they are used to treat intra-abdominal infections, vaginitis, RTI, Pseudomembranous colitis, endocarditis and acute gingivitis (plus other dental infections). they are used in a multi drug therapy for H. pylori (bismuth, metronidazole, tetracycline or amoxicillin)

Question 20

Pharacokinetics of metronidazole

Answer 20

can be administered orally, IV or topically. it is metabolized by the liver but excreted in the urine

Question 21

Metronidazole (MOA) adverse effects:

Answer 21

GI complaints, CNS and PNS concerns (seizures and peripheral neuropathy), candida superinfections and hypersensitivity reactions)

Question 22

what are the three exclusive UTI drugs?

Answer 22

Nitrofurantoin, methenamine, naladixic acid

Question 23

properties of exclusive UTI drugs

Answer 23

renal excretion; only reach therapeutic levels in the urine; bacteriocidal

Question 24

How does nitrofurantoin work?

Answer 24

Prodrug is reduced by bacterial cells. the metabolites are highly reactive and interact with ribosomal proteins, DNA, metabolism and other macromolecules to kill the cell

Question 25

Nitrofurantoin spectrum:

Answer 25

G-/G+ –> E. coli, S. pyogenes, Citrobacter, Klebsiella, Enterobacter, Salmonella, Shigella, Serratia and indole positive proteus

Question 26

which types of bacteria often show resistance to nitrofurantoin?

Answer 26

proteus and pseudomonas

Question 27

what is the clinical use of nitrofurantoin

Answer 27

nitrofurantoin is used to treat uncomplicated lower UTIs or when E. coli is resistant to TMP-SMZ and fluoroquinolones

Question 28

if creatine clearance is below what level, we do not use Nitrofurantoin?

Answer 28

<50 mL/min

Question 29

at what pH does nitrofurantoin work and what happens to your urine while taking nitrofurantoin?

Answer 29

pH<5.5 (the more acidic the better). it turns your urine brown

Question 30

toxicity associated with nitrofurantoin?

Answer 30

GI, allergies (hepatocellular damage and hemolytic anemia), interstitial pulmonary fibrosis, and polyneuropathies

Question 31

Contraindications for nitrofurantoin?

Answer 31

38-42 weeks pregnant, less than 1 month old, impaired renal function or allergic reaction

Question 32

what is methenamine?

Answer 32

methenamine is a prodrug that is taken orally and decomposes to form formaldehyde and ammonia in the acidic urinary tract.

Question 33

methenamine spectrum:

Answer 33

G- bacteria especially E. coli

Question 34

methenamine resistance

Answer 34

bacteria are incapable of developing resistance to formaldehyde

Question 35

Proteus bacteria and methenamine treatment

Answer 35

methenamine treatment against proteus bacteria tends to be less effective bc the proteus are able to increase the pH of the urine, making it less acidic. to get around this, methenamine is often administered with a weak acid when treating proteus infections

Question 36

methenamine toxicity:

Answer 36

minimal b/c decomposition occurs in the urine. you can have some GI distress and an occasional allergic reaction

Question 37

contraindications for methenamine:

Answer 37

hepatic or renal insufficiency (crystalluria –> low urinary output)

Question 38

use of Naladixic acid

Answer 38

non fluorinated quinolone. it inhibits DNA synthesis and is most active on G- bacteria. it does not have antipseudomonal activity. it is not good for systemic use and Fe/Ca/Mg decreases its oral bioavailability which is normally very high.

Question 39

Naladixic Acid toxicity

Answer 39

antagonized by nitrofurantoin.

GI/allergic reactions including photosensitivity, photophobia, convulsions and many more

Question 40

Ciprofloxacin uses:

Answer 40

systemic infections, UTIs, anthrax prophylaxis, pseudomonas aeruginosa

Question 41

Norfloxacin uses:

Answer 41

UTIs, prostatitis

Question 42

Ofloxacin uses:

Answer 42

prostatitis, some systemic infections, TB and STDs

Question 43

Lomefloxacin uses:

Answer 43

UTIs, and bronchitis

Question 44

Levofloxacin uses:

Answer 44

community acquired pneumonia (CAP)

Question 45

Moxifloxacin uses:

Answer 45

penicillin resistant S. pneumonia and anaerobes

Question 46

Gatifloxacin uses:

Answer 46

ocular application only

Question 47

Gemifloxacin uses:

Answer 47

penicillin resistant s. pneumonia, CAP and anaerobes