DNA Synthesis Inhibitors - 2.4

Question 1

MOA of fluoroquinolones

Answer 1

Inhibit topoisomerase II & IV; blocking relaxation of positive supercoiled DNA.

Topo IV for Gram +, Topo II for Gram -

Question 2

How are fluoroquinolones excreted?

Answer 2

Renally, except for Moxifloxacin, which is done by the biliary system

Question 3

Which fluoroquinolone treats Pseudomonas best?

Answer 3

Ciprofloxacin; use Gemifloxacin for Cipro resistant bacteria

Question 4

Which fluoroquinolone treats anaerobic bacteria?

Answer 4

Moxifloxacin

Question 5

MOR of fluoroquinolone

Answer 5

High level by point mutation in quinolone binding region of topoisomerase, decreasing permeability.

Low level by plasmid-coded acetyltransferase which modify quinolone (same as aminoglycoside)

Question 6

Uses of fluoroquinolone

Answer 6

1. UTI (except Moxifloxacin)
2. STD (chlamydia)
3. Anthrax and prophylaxis (Ciprofloxacin)
4. Pseudomonas (Ciprofloxacin)
5. Atypical pneumonia including Legionella
6. Resistant pneumococci (Levofloxacin)
7. Bacterial diarrhea (Salm, Shig, E.Coli, Camplyo)
8. Skin, soft tissues, bone

Question 7

What is avoided with administration of fluoroquinolone?

Answer 7

Iron, and limiting calcium absorption (same as Tetracyclines)

Question 8

Adverse effects of fluoroquinolone

Answer 8

1. Arhropathy in children
2. Tendinitis and tendon rupture in children
3. Prolonged QT interval (gatifloxacin, levofloxacin, gemifloxacin, moxifloxacin)
4. Photosensitivity
5. Hypoglycemia
6. Inhibit p450; may induce seizures

Question 9

Contraindications of fluoroquinolones?

Answer 9

1. Avoid use with class Ia, III anti-arrhythmic drugs.
2. Erythromycin
3. TCA
4. Cisapride
5. Children and pregnancy

Question 10

MOA of Metrondiazole

Answer 10

Unclear; reduced and form unstable molecules with DNA. Reduction rxns only take place in anaerobic bacteria.

Question 11

Uses of Metrondiazole

Answer 11

1. Clostridium difficle (first choice)
2. Gardnerella
3. H. pylori
4. Bacteroides
5. The protozoa; Giardia, Trichomonas, Entomaeba

Question 12

Side effects of Metrondiazole

Answer 12

Disulfuram like reaction; metallic taste in mouth. Avoid MTT groups, and can prolong bleeding time with Warfarin

Question 13

MOA of Nitrofurantoin

Answer 13

Unclear, but disrupts DNA, RNA, and protein processes

Question 14

Use of Nitrofurantoin

Answer 14

Uncomplicated UTIs

Question 15

ADR of Nitrofurantoin

Answer 15

N&V, pulmonary fibrosis, various hypersensitivity rxns, G6PD deficiency, hemolytic anemia, neutropenia

Question 16

MOA of polymyxin B

Answer 16

Destabilize gram negative bacteria outer cell wall through ionic interactions