1. Sulfonamides, Trimethoprim
and Fluoroquinolones
Dr. Muhammad Umair

2. Sulfonamides
Mechanism of Action:
Sulfonamides compete with PABA for the bacterial enzyme,
dihydropteroate synthetase.
They thus inhibit the synthesis of bacterial dihydrofolic acid and DNA.
These are bacteriostatic drugs.

3. PABA
Folic Acid
DNA Synthesis
Dihydropteroate synthetase Sulfonamides

4. Sulfonamides
Clinical uses:
1. Urinary tract infection
2. Nocardia infections
3. Sulfadiazine in combination with pyrimethamine for
toxoplasmosis.
4. Sulfadoxine in combination with pyrimethamine is used as an
antimalarial drug

5. Sulfonamides
Adverse effects:
1. Crystalluria
2. Hypersensitivity: Angioedema, Rashes, Steven Johnsons Syndrome
3. Hemolytic anemia in patients with G6PD deficiency,
Granulocytopenia and thrombocytopenia
4. Kernicterus
5. Drug interactions with Warfarin and Methotrexate

6. Trimethoprim
Mechanism of Action:
Inhibits reduction of dihydrofolic acid by dihydrofolate reductase
leading to a decreased availability of the tetrahydrofolate cofactors
required for purine, pyrimidine, and amino acid synthesis.
Clinical uses:
Trimethoprim is 20- to 50-fold more potent than the sulfonamides.
1. UTIs
2. Bacterial prostatitis

7. PABA
Folic Acid
DNA Synthesis
Dihydrofolate
reductase
Trimethoprim
Dihydrofolic acid
Tetrahydrofolic acid

8. Trimethoprim
Adverse effects:
Trimethoprim can produce the effects of folic acid deficiency
1. Megaloblastic anemia
2. Leukopenia
3. Granulocytopenia
especially in pregnant patients and those having very poor diets.
These blood disorders may be reversed by the simultaneous
administration of folinic acid, which does not enter bacteria.

9. Cotrimoxazole
The combination of trimethoprim with sulfamethoxazole is called
cotrimoxazole.
It shows greater antimicrobial activity than equivalent quantities of either
drug used alone.
Mechanism of Action:
The synergistic antimicrobial activity of cotrimoxazole results from its
inhibition of two sequential steps in the synthesis of tetrahydrofolic acid. Sulf
amethoxazole inhibits the incorporation of PABA into dihydrofolic acid
precursors, and trimethoprim prevents reduction of dihydrofolate to
tetrahydrofolate.

11. Cotrimoxazole
Clinical uses:
1. UTIs
2. Respiratory tract infections
3. Pneumocystis jirovecii pneumonia (PCP)
4. Toxoplasmosis
5. Ampicillin- or chloramphenicol-resistant salmonella infections.
6. MRSA
7. Nocardia species and Stenotrophomonas maltophilia

12. Cotrimoxazole
Adverse effects:
1. Skin rash
2. Nausea and vomiting
3. Glossitis and stomatitis
4. Hyperkalemia
5. Megaloblastic anemia, leukopenia, and thrombocytopenia
6. Hemolytic anemia in patients with G6PD deficiency
7. Drug interactions with Warfarin, Phenytoin, Methotrexate
The hematologic effects may be reversed by the concurrent administration of
folinic acid, which protects the patient and does not enter the microorganism.

13. Fluoroquinolones
1.Levofloxacin
2.Ciprofloxacin
3.Moxifloxacin
4.Norfloxacin
5.Gemifloxacin
6.Ofloxacin

14. Fluoroquinolones
Mechanism of Action:
1. Inhibition of DNA gyrase results in relaxation of supercoiled DNA,
promoting DNA strand breakage.
2. Inhibition of topoisomerase IV impacts chromosomal stabilization
during cell division.
These are bactericidal drugs.

15. Fluoroquinolones
Clinical indications:
Urinary tract infections (UTIs)
Prostatitis
Traveler’s diarrhea
Typhoid fever
Second-line agent in the treatment of tuberculosis.
Skin infections
Nosocomial pneumonia

16. Fluoroquinolones
Adverse effects:
1. Nausea, vomiting, and diarrhea
2. Headache and dizziness or lightheadedness
3. Peripheral neuropathy
4. Tendinitis or tendon rupture (< 18 year)
5. Articular cartilage erosion (arthropathy)
6. Glucose dysregulation
7. Phototoxicity
8. Arrhythmias