Sulphonamides were the first effective AMAs used in the treatment of bacterial infections in humans. They are derivatives of sulphanilamide (para-aminobenzene sulphonamide) and are synthetic compounds. pk: All systemic-acting sulphonamides are well absorbed from the gut. They are bound to plasma proteins, particularly albumin. Sulphonamides are distributed in almost all tissues of the body including CSF. They cross placental barrier and reach fetal circulation; they are metabolized in liver mainly by acetylation. The acetylated prod ucts have no antibacterial activity but retain the toxic potential of the parent compound. Sulphonamides are excreted partly unchanged and partly as metabolic products.

1. SULPHONAMIDES
P Harshitha Reddy

2. Sulphonamides
Sulphonamides were the first effective AMAs used in the
treatment of bacterial infections in humans. They are derivatives of
sulphanilamide (para-aminobenzene sulphonamide) and are
synthetic compounds.

3. Classification

4. Mechanism of Action
• Para-Aminobenzoic acid (PABA) is a precursor of folic acid which is
essential for growth and multiplication of many bacteria.
• Sulphonamides, being structurally similar to PABA, competitively
inhibit folate synthase enzyme and prevent the formation of folic
acid, thereby producing bacteriostatic effect.
• They are not effective in the presence of pus as it is rich in PABA,
purines and thymidine.
• Mammalian cells do not synthesize folic acid, but utilize folic acid
present in diet, hence are unaffected by sulphonamides.

5. MOA:

6. Bacterial Resistance to Sulphonamides
Most of the bacteria have developed resis tance to sulphonamides.
It could be due to:
1. Decreased affinity of folate synthetase for the drug
2. Efflux of the drug by bacteria
3. Development of alternate metabolic pathway for folate synthesis

7. Pharmacokinetics
• All systemic-acting sulphonamides are well absorbed from the gut.
• They are bound to plasma proteins, particularly albumin.
• Sulphonamides are distributed in almost all tissues of the body
including CSF.
• They cross placental barrier and reach fetal circulation; they are
metabolized in liver mainly by acetylation.
• The acetylated prod ucts have no antibacterial activity but retain the
toxic potential of the parent compound.
• Sulphonamides are excreted partly unchanged and partly as
metabolic products.

8. Adverse Effects
1. The acetylated products of sulphonamides are poorly soluble in
acidic urine and may cause crystalluria, haematuria or even
obstruction to urinary tract. This may be avoided by taking plenty
of water and alkalinizing the urine.
2. Hypersensitivity reactions include skin rashes, itching, drug fever
and exfoliative dermatitis. Stevens–Johnson syndrome is the most
severe type of hypersensitivity reaction characterized by fever,
erythema multiforme and ulceration of mucous membranes.
3. In patients with glucose-6-phosphate dehydrogenase deficiency,
sulphonamides may cause acute haemolytic anaemia.

9. 4. Rarely cause hepatitis and suppression of bone marrow.
5. Use of sulphonamides in neonates, especially in premature babies,
may cause displacement of bilirubin from plasma proteins. The free
bilirubin can cross BBB and get deposited in the basal ganglia
resulting in kernicterus.

10. Drug Interactions
• Sulphonamides potentiate the effect of phenytoin, methotrexate
(MTX), oral anticoagulants and oral hypoglycaemic agents
(sulfonylureas) by inhibiting their metabolism and displacing them
from plasma protein binding sites.

11. Therapeutic Uses
Sulphonamides alone are rarely used now for systemic
infections. They are used in combination with other AMAs.
1. Sulphadoxine and pyrimethamine are used in combination with
artesunate in the treatment of chloroquine-resistant Plasmodium
falciparum malaria.
2. Sulphadiazine and pyrimethamine combination is the drug of choice
for toxoplasmosis.
3. Nocardiosis: Sulphamethoxazole in combination with trimethoprim is
used.

12. 4. Sulphamethoxazole in combination with trimethoprim is used in the
treatment of P. jiroveci infection in patients with AIDS.
5 . Sodium salt of sulphacetamide is used exclusively for the treatment
of ophthalmic infections. It is administered as eye drops or eye
ointment. It is preferred because of:
• High aqueous solubility
• Neutral pH and nonirritant nature of the drug
• Good penetrability on topical administration
• Low incidence of hypersensitivity reactions
• Low cost

13. 6. Silver sulfadiazine and mafenide are used topically for preventing
infection of burn wound. Silver sulfadiazine slowly releases silver ions
which are toxic to microorganisms. It is not effective in the presence
of pus and tissue fluid.
7. Sulphasalazine is useful in the treatment of inflammatory bowel
disease and rheumatoid arthritis.
8. Rheumatic fever: Sulphadiazine can be used for prophylaxis of
rheumatic fever.