Inhibitors of nucleic acid synthesis

Question 1

Name the classes of drugs that inhibit nucleic acid synthesis

Answer 1

• Sulphonamides
• Quinolones
• Azoles

Question 2

List drugs that fall part of non-fluoroquinolones and fluoroquinolones

Answer 2

Non-fluoroquinolones – nalidixic acid
Fluoroquinolones – all other quinolones
Norfloxacin , ciprofloxacin , levofloxacin

Question 3

Explain the generations of quinolones, giving examples and clinical uses. Are quinolones effective against MRSA?

Answer 3

1st Generation:
-Limited gram -ve activity
- Nalidixic acid and cinofloxacin
- Use limited to GIT, UTI and bladder infections

2nd generation
Ciproflaxin has the greatest gram -ve activity
Anti-pseudomonal activity

3rd generation
Levofloxacin (greatest gram + activity)

4th generation
gemifloxacin

No!!

Question 4

Explain the MOA of quinolones

Answer 4

• DNA gyrase inhibitors

Block bacterial DNA synthesis

• Inhibit topoisomerase II (DNA gyrase)
  Prevents relaxation of positively supercoiled DNA, Prevents DNA transcription and replication

Inhibits topoisomerase IV
interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division.

Question 5

What are the adverse effects of quionolones. What are the contraindications?

Answer 5

PPSHT Quiet Calm

Photosensitivity
Peripheral neuropathy
Super infections with Strep, C. difficle and canida
Headaches, dizziness, skin rashes
Tendonitis
QTc prolongation
Chondrotoxicity

Not recommended for patients under 18 yrs
Avoided in pregnancy
May be given to children with serious infections

Question 6

How to bacteria resist Quinolones

Answer 6

1. Mutation in the quinolone binding region of target enzyme (DNA gyrase)
2. Altered permeability
3. Active efflux pump

Question 7

Discuss Sulphonamides and Trimethroprim
- Antibacterial activity
- Analogues (sulfonamides)
- MOA
- Adverse reactions of sulfonamides
- Resistance

Answer 7

• Inhibit both gram +ve and gram –ve bacteria
• Nocardia, chlamydia, and some protozoa
• Sulfonamides= no inhibitory activity against pseudomonas
• Not effective against MRSA
• Bacteriostatic in monotherapy
• Bactericidal in combination

** Cortrimoxazole

• Structural analogues of p-amino-benzoic acid (PABA

Sulphonamides inhibit the enzyme which converts PABA into folate
Trimethoprim inhibits the dihydrofolate reductase

• Allergic reactions:
  Stevens-Johnson Syndrome
  Fever, skin rashes, photosensitivity, urticaria
  -Precipitate in urine causing obstruction
  -Hemolytic and anaplastic anaemia and thrombocytopenia
• Kernicterus in new borns
• Exogenous sources of folic acid
• Over-production of PABA
• Loss of permeability
• Overproduction of dihydrofolate reductase

Question 8

Discuss Metronidazole:
MOA
Antibacterial activity
Dental usage
Adverse effects
Drug interactions

Answer 8

• Reduction of nitro groups producing metabolites that damage DNA
• reacts with DNA = inhibit replication and fragments DNA

Protozoal infections
Clostridia
Bacteriodes fragilis
H pylori infections
Bacterial vaginosis

NPD
gum disease caused by spirochetes or other commensals (oral hygiene poor)
Chronic periodontits
Often combined with omoxycillin in management of periodontitis

Metallic taste
Dark/red-brown urine
peripheral neuropathy
vaginal burning sensation
CNS toxicity

Barbiturates reduce the efficacy of metronidazole
Cimetidine inhibits its metabolism
- reaction when used together with alcohol (disulfiram)
Flushing, tachycardia, nausea, vomiting