Sulfonamides were the first effective antibacterial drugs, discovered in the 1930s. They work by inhibiting folic acid synthesis in bacteria. Potentiated sulfonamides combine sulfonamides with diaminopyrimidines like trimethoprim for increased efficacy. Sulfonamides are used to treat various bacterial and protozoal infections in animals. While generally safe, they can cause urinary tract disturbances and bone marrow depression if not properly administered and hydration maintained.

1. Antibiotic Groups
Sulfonamides

2. History
 The sulfonamides were the first effective chemotherapeutic
agents to be employed systemically for the prevention and
cure of bacterial infections in humans.

3. History
1933
 Foerster reported the first clinical case study of prontosil.
1935
 Prontosil was shown to be a pro-drug of sulfanilamide.
1939
 Domagk was awarded the Nobel Prize in Physiology or
Medicine for discovering the chemotherapeutic value of
prontosil.

4. Description
 The sulfonamide class contains a large number of
antibacterial drugs, including:
1. Sulfadiazine
2. Sulfamethazine (sulfadimidine)
3. Sulfathiazole
4. Sulfamethoxazole

5. Cont. …
 There are what is called “Potentiated sulfonamides” which
are combinations of sulfonamide and an antibacterial
diaminopyrimidine such as trimethoprim.
 Potentiated sulfonamides demonstrate improved efficacy
compared with sulfonamides alone.

6. Mechanism of Action
1. Sulfonamides are the structural
analogues of PABA
paraaminobenzoic acid.
1. Sulfonamides competitively
inhibit dihydropteroate
synthetase, which is an enzyme
that catalyzes the synthesis of
dihydrofolic acid (folic acid)

7. Mechanism of Action
3. The decreased synthesis of
dihydrofolic acid (folic acid)
lead to decreased synthesis of
tetrahydrofolic acid (folinic
acid), which is required for the
synthesis of DNA.

8. Cont. …
 A variety of effects may result in susceptible organisms,
including:
1. Suppression of protein synthesis.
2. Impairment of metabolic processes.
3. Inhibition of growth and multiplication.

9. Cont. …
Potentiated sulfonamides
 They inhibit dihydrofolate reductase which catalyzes the
synthesis of folic acid.
 This enzyme is present in both bacteria and mammals.
 The antibacterial diaminopyrimidines such as trimethoprim
and ormetoprim inhibit this enzyme more efficiently in
bacteria than in mammalian cells.

10. Cont. …
Notre that;
 Before such activity is exhibited, existing stores of folic acid,
folinic acid, purines, thymidine and amino acids are utilized
by bacteria.

11. Spectrum
 Organisms susceptible to sulfonamides must synthesize their
own folic acid, unlike mammalian cells, which utilize
preformed folic acid.
 Sulfonamides are not efficacious in the presence of purulent
material

12. Spectrum
 Sulfonamides are bacteriostatic
 Sulfonamides inhibit:
1. Gram positive
2. Gram negative
3. Some chlamydia, Nocardia, and Actinomyces species
4. Some protozoa including coccidia and Toxoplasma species

13. Cont. …
Potentiated sulfonamides
 Diaminopyrimidines such as trimethoprim and ormetoprim
are bacteriostatic when used alone.
 When combined with sulfonamides, the sequential blockade
of dihydropteroate synthetase and dihydrofolate reductase
elicits a bactericidal effect.

14. Cont. …
 Potentiated sulfonamide are active against Gram positive and
Gram negative organisms, including:
- Actinomyces - Bordetella
- Clostridium - Corynebacterium
- Fusobacterium - Haemophilus
- Klebsiella - Pasteurella
- Proteus - Salmonella
- Shigella - Campylobacter species
- E. coli - Streptococci
- Staphylococci

15. Resistance
 Organisms resistant to sulfonamides include:
1. Pseudomonas
2. Klebsiella
3. Proteus
4. Clostridium
5. Leptospira species
 Organisms resistant to potentiated sulfonamides include:
1. Pseudomonas
2. Mycobacterium species

16. Cont. …
 Resistance to sulfonamides is widespread in bacteria isolated
from animals, and may involve:
1. Chromosomal mutations
2. Plasmid-mediated mechanisms

17. Cont. …
Chromosomal mutations cause:
1. Impaired drug penetration.
2. production of altered forms of dihydropteroate synthetase for which
sulfonamides have a lowered affinity.
3. production of excessive PABA that overcomes the metabolic block
imposed by the inhibition of dihydropteroate synthetase.
Plasmid-mediated mechanisms, may result in;
1. Impaired drug penetration.
2. Synthesis of sulfonamide-resistant dihydropteroate synthetase.
 There is cross-resistance among sulfonamides.

18. Cont. …
 Resistance potentiated sulfonamides develops very rapidly
and results from:
1. Chromosomal mutations
• It allows bacteria to utilize exogenous sources of folinic acid or
thymidine, thereby overcoming the drug-imposed blockade.
2. Plasmid-mediated mechanisms
• It result in the synthesis of dihydrofolate reductase
characterized by a reduced affinity for antibacterial
diaminopyrimidines.

19. Indications
 Compared to most classes of antimicrobial drugs, the usage of
sulfonamides and potentiated sulfonamides in veterinary
medicine is high.

20. Cont. …
 Sulfonamides are used to treat or prevent acute systemic or
local infections, including:
1. Actinobacillosis
2. Coccidiosis
3. Mastitis
4. Metritis
5. Colibacillosis
6. Pododermatitis
7. Polyarthritis
8. Respiratory infections
9. Toxoplasmosis

21. Cont. …
 Sulfonamides in combination with pyrimethamine are used to
treat protozoal diseases such as leishmaniasis and
toxoplasmosis.

22. Administration
 Sulfonamides are most effective in the early stages of acute
infections when organisms are rapidly multiplying.
 Sulfonamides are administered as:
– Additives to feed
– In drinking water
– Controlled release oral boluses
– Intrauterine infusions
 Highly insoluble sulfonamides such as phthalylsulfathiazole
are absorbed from the gastrointestinal tract very slowly and
are used to treat enteric infections.

23. Side Effects
 The majority of adverse effects to sulfonamides are mild in
nature and reversible;
1. Urinary tract disturbances, including sulfonamide
crystalluria and hematuria which can be minimized by
maintaining an adequate water intake to maintain a high
urine flow.
2. Bone marrow depression and dermatologic.