Nucleic Acid Synthesis Inhibitors (Bacterial Topoisomerase)

Question 1

State drugs of all generations of Fluro/Quinolones

Answer 1

1st Gen → Nalidixic Acid
2nd Gen → Ciprofloxacin / Ofloxacin
3rd Gen → Levofloxacin
4th Gen → Moxifloxacin / Delafloxacin

Question 2

Properties of Nalidixic Acid

Answer 2

discovered while synthesizing the malaria drug (Chloroquine)

Question 3

Spectrum of Nalidixic Acid

Answer 3

Narrow:
gram -ve

Question 4

Indications of Nalidixic Acid

Answer 4

No longer used; due to resistance, it WAS used to treat UTIs

Question 5

Spectrum of Ciprofloxacin

Answer 5

Broad:
→ gram +ve
S. aureus / B. anthracis
→ gram -ve
→ P. aeruginosa

Question 6

A.D.M.E of Ciprofloxacin

Answer 6

D: it achieves high therapeutic conc. in bone & prostate

Question 7

Indications of Ciprofloxacin

Answer 7

“CrAP TOP”

1. Cystitis (Bladder infection) → E. coli
2. Traveler’s diarrhea → E. coli, S. typhi
3. Pneumonia in cystic fibrosis → P. aeruginosa
4. Prostatitis → E. coli
5. Osteomyelitis → S. aureus
6. Anthrax → B. anthracis

Question 8

Properties of Ofloxacin

Answer 8

Ofloxacin is an isomer for Ciprofloxacin

Question 9

Spectrum of Ofloxacin

Answer 9

Broad:
→ gram +ve
S. aureus / B. anthracis
→ gram -ve
→ P. aeruginosa

Question 10

Indications of Ofloxacin

Answer 10

Cervicitis and Urethritis → C. trachomatis - alternative for Azithromycin

Question 11

Properties of Levofloxacin

Answer 11

called a Respiratory Fluoroquinolone; it is given as an inhaler

Question 12

Spectrum of Levofloxacin

Answer 12

Extended:
→ gram +ve
→ atypical:
Mycobacteria / Chlamydia

Question 13

Indications of Levofloxacin

Answer 13

1. CAP → S. pneumonia
2. TB as a 2nd line drug → M. tuberculosis
3. Cervicitis and Urethritis → C. trachomatis
   - alternative for Azithromycin

Question 14

Properties of Moxifloxacin

Answer 14

called a Respiratory Fluoroquinolone; it is given as an inhaler

Question 15

Spectrum of Moxifloxacin

Answer 15

Extended:
→ gram +ve
→ atypical:
Mycobacteria

Question 16

A.D.M.E. of Moxifloxacin

Answer 16

E: excreted in bile

Question 17

Indications of Moxifloxacin

Answer 17

1. CAP → S. pneumonia
2. TB as a 2nd line drug → M. tuberculosis
3. Anthrax → B. anthracis

Question 18

Spectrum of Delafloxacin

Answer 18

Narrow:
→ P. aeruginosa

Question 19

MoA of Fluoro/Quinolones

Answer 19

These drugs will interfere with the DNA replication by inhibiting the Topoisomerase:
* in gram +ve → Topoisomerase II (Gyrase)
* in gram -ve → Topoisomerase IV
This inhibits the release of supercoils & DNA replication

Question 20

Adverse Effects of Fluoro/Quinolones

Answer 20

• Photosensitivity
• Peripheral neuropathy
  — due to the F atom in fluoroquinolones
• Seizures when given with NSAIDs
  — contraindicated with epileptic patients
• CYP P450 inhibition [Ciprofloxacin]
  — combining Ciprofloxacin with the muscle relaxant (Tizanidine) will decrease its
  metabolism, resulting in dizziness, weakness, and slurred speech
• Hyperkalemia, used with caution in:
  — DM → to avoid hypoglycemia
  — Arrhythmia → due to TdP
• Arthropathy
  — it is the damaging of the growing cartilages during pregnancy (Category C) and in children younger than 18 years old
• Myasthenia Gravis
  — these drugs exacerbate the symptoms of Myasthenia gravis
• Tendinitis
  — the risk of tendon rupture in adults with renal failure and are using fluoroquinolones
  — the most common tendon to rupture is Achilles tendon
  — fluoroquinolones are labelled with “FDA Blackbox” to indicate severe side effects