DNA Synthesis Inhibitors

Question 1

Name the class of antibiotics that inhibit DNA synthesis and the 3 drugs in the class

Answer 1

Fluoroquinolones - Ciprofloxacin, Levofloxacin, Moxifloxacin

Question 2

Fluoroquinolones inhibit which enzymes in Gram negative and positive bacteria?

How does it affect bacteria? MOA

Answer 2

Inhibit DNA gyrase (Gram neg) - Prevent negative supercoils from converting to positive supercoils

Inhibit Topoisomerase IV (Gram pos) - Prevents separation of chromosomal DNA into daughter cells in DNA replication

Question 3

Do fluoroquinolones inhibit DNA synthesis in mammals?

Answer 3

It can. Topoisomerase II in mammals resemble DNA gyrase. High concentrations of fluoroquinolones can thus act on topoisomerase II

Question 4

Fluoroquinolones are administered by _____

Answer 4

Oral route and also parenteral or ophthalmic preparations

Question 5

Patient counselling advice for fluoroquinolones taken by mouth

Answer 5

Food drug interactions between calcium/aluminum/magnesium/iron/zinc containing antacids and dietary supplements.

Take 2h before meals on an empty stomach or 6h after meals

Question 6

Fluoroquinolone chemical derivative

Answer 6

Nalidixic Acid

Question 7

Fluoroquinolone distribution - High levels in ?

Answer 7

Bones, urine (except moxifloxacin), prostatic tissue, lungs

Question 8

Fluoroquinolones Clearance: Ciprofloxacin by ____ and Levofloxacin / Moxifloxacin by ______

Answer 8

Renal, Hepatic

Question 9

Ciprofloxacin Spectrum activity

Answer 9

1. Gram negative strains including Pseudomonas
2. Enteric Coliform
3. Strains resistant to penicillin, cephalosporin, aminoglycosides

Question 10

6 Clinical indications of Ciprofloxacin

Answer 10

1. Traveler’s Diarrhea (E coli)
2. Food poisoning (Enterobacterale spp and Campylobacter jejuni)
3. Typhoid Fever (Salmonella)
4. Serious UTI
5. Anthrax (Bacillus anthracis)
6. Prostatitis

Question 11

Ciprofloxacin should not be used in what kind of infections?

Answer 11

MRSA, anaerobes, enterococci and streptococci

Question 12

Name the respiratory quinolones and explain why they are named as such?

Answer 12

Levofloxacin and Moxifloxacin have greater coverage to include Gram positive (Streptococcus pneumoniae especially) and Atypicals

They are respiratory quinolones because they also cover Mycobacterium tuberculosis

Question 13

The 10 Adverse Reactions of Fluoroquinolones

Answer 13

1. GI-related Nausea, vomiting and diarrhea (Most common)
2. Dysglycemia (Caution in DM patients)
3. Aortic aneurysms
4. Headache and dizziness (Caution in CNS disorders like epilepsy)
5. QTc prolongation (Caution in arrhythmic patients)
6. Tendinitis / Tendon Ruptures
7. Arthropathy (Caution against use in young children < 18 y.o.)
8. Phototoxicity
9. CDAD (Particularly ciprofloxacin)
10. Peripheral Neuropathy

Question 14

Contraindications of fluoroquinolones and why contraindicated?

Answer 14

Pregnancy (Advice against use) - Risk of arthropathy (although rare)

Breastfeeding (Not recommended) - Risk of arthropathy (although rare)

Myasthenia Gravis - Worsen muscle weakness caused by this autoimmune neuromuscular disease

Question 15

Ciprofloxacin drug interaction

Answer 15

Theophylline metabolism inhibited

Question 16

Quinolone drug interactions

Answer 16

Warfarin and Cyclosporine serum levels raised