Antibiotics: DNA Replication/Repair Inhibitors

Question 1

What are the 2 classes of DNA repair/replication inhibitors?

Answer 1

Quinolones

Rifampicin

Question 2

List 2 examples of quinolones.

Answer 2

Ciprofloxacin

Levofloxacin

Question 3

How quinolones administered?

Answer 3

Oral

Question 4

Describe the mechanism of action of quinolones. (2)

Answer 4

1. Quinolones inhibit topoisomerase II (a bacterial DNA gyrase which normally produces a negative supercoil in DNA)
2. Without the DNA supercoil, there is no transcription
   a. Therefore no replication

Question 5

Which species of bacteria are often resistant to quinolones?

Answer 5

Staph. aureus

P. aeruginosa

Question 6

List 4 adverse effects of quinolones.

Answer 6

GI toxicity
QT prolongation
Tendonitis
C. difficile infection

Question 7

In which conditions would you use ciprofloxacin, compared to levofloxacin?

What is the difference in activity between ciprofloxacin and levofloxacin?

Answer 7

CIPROFLOXACIN:

• UTIs
• Intra-abdominal infections
• Activity: weak for gram positives; strong for gram negatives

LEVOFLOXACIN:

• Respiratory tract infections
• Activity: strong for gram positives; weak for gram negatives

Question 8

How is rifampicin administered?

Answer 8

Oral

Question 9

Describe the mechanism of action of rifampicin. (2)

Answer 9

1. Inhibits RNA polymerase in prokaryotic but NOT eukaryotic cells
   a. Therefore only affects bacteria, and not human cells
   b. Therefore prevents transcription
2. Enters phagocytic cells and kills intracellular organisms too

Question 10

List 1 important drug interaction for rifampicin.

This particular aspect will cause problems with many other drugs - give 3 examples.

Answer 10

CYP450 inducer

Therefore affects all drugs that are metabolised by the liver, e.g.

• Warfarin
• Oestrogen (OCP)
• Anti-diabetics

Question 11

List 3 adverse effects of rifampicin.

Answer 11

Skin problems
Fever
GI toxicity

Question 12

Which 3 conditions is rifampicin used for?

Answer 12

Tuberculosis
Leprosy
Serious gram positive infections (in addition to other antibiotics)

Question 13

What are the 4 first line drugs used in combination therapy for TB?

How long is a standard course of treatment for TB?

Answer 13

Isoniazid
Rifampicin
Pyrazinamide
Ethambutol

Standard therapy course: 6 months

Question 14

Briefly describe the mechanisms of action of the 4 drugs used to treat TB.

Answer 14

Isoniazid - bactericidal to fast growing mycobacteria

Rifampicin - bactericidal to slow growing intracellular mycobacteria (especially in necrotic granulomas)

Pyrazinamide - bactericidal to slow growing mycobacteria

Ethambutol - bacteriostatic to slow growing mycobacteria

Question 15

List adverse effects of TB treatment, including those for:

a) Isoniazid (3)
b) Rifampicin (3)
c) Pyrazinamide (2)
d) Ethambutol (1)

Answer 15

ISONIAZID:
Hepatotoxicity
Peripheral neuropathy
B3 deficiency

RIFAMPICIN:
Liver toxicity
Bone marrow toxicity
Renal toxicity

PYRAZINAMIDE:
Hepatitis
Arthralgia

ETHAMBUTOL:
Optic neuritis

Question 16

Which drugs are second line therapy for TB?

Answer 16

Quinolones, e.g.

• Ciprofloxacin
• Levofloxacin

Aminoglycosides, e.g.
-Gentamicin