Sulphonamides

Question 1

What is the first antimicrobial agents used in the treatment of bacterial infection in man?

Answer 1

Sulphonamides

Question 2

Sulphonamides are derivatives of?

Answer 2

Sulphanilamide(para-aminobenzene sulphonamide)

Question 3

Classification of sulphonamide?

Answer 3

A. SYSTEMIC ACTING AGENTS
1. Short acting (4-8h) : Sulphadiazine
2. Intermediate acting (8-12h) : Sulphamethoxazole
3. Long acting ( >7 days) : Sulphadoxine
B. LOCAL ACTING AGENTS :
-Sulphacetamide
-Silver sulphadiazine
-mafenide
C. OTHERS
-sulphasalazine(locally and systemically)

Question 4

Mechanism of action?

Answer 4

Para-aminobenzoic acid (PABA) is a precursor of frolic acid which is essential for growth and multiplication of bacteria. Sulphonamides, being structurally similar to PABA, competitively inhibit folate synthase enzyme and prevent the formation of frolic acid, thereby produce bacteriostatic effect.

Sulphonamides are not effective in the presence of pus because it is rich with PABA, purines and thymidine.

Mammalian cells do not synthesise frolic acid, but utilise frolic acid present in diet, hence are unaffected by sulphonamides.

Para-amino benzoin acid
                                |
-sulphonamid.    |folate synthase
                                |
             Dihydrofolic acid
                                |
                                |folate reductase
                                |
          Tetrahydrofolic acid

Question 5

Causes of bacterial resistances to sulphonamides?

Answer 5

1. Decrease affinity of folate synthase for the drug
2. Effluent of the drug by bacteria
3. Development of alternate metabolic pathway for folate synthesis

Question 6

Pharmacokinetics of sulphonamides?

Answer 6

All systemic acting sulphonamides are well absorbed from the gut. They bound to plasma protein, particularly albumin. Sulphonamides are distributed in almost tissue of the body including CSF. They cross placental barrier and reach feral circulation. They are metabolised in the liver mainly by acetylation. The acetylated product have no antibacterial activity but retain the toxic potential of the parent compound. The sulphonamides are excreted partly unchanged and partly as metabolic products.

Question 7

Adverse effects of sulphonamides?

Answer 7

1. The acetylated product of sulphonamides are poorly soluble in acidic urine and may cause crystalluria, haematuria, or even obsrtuction of urinary tract.
2. Hypersensitivity reactions including skin rashes, itching, drug fever, and exfoliative dermititis.
3. May cause acute haemolytic anaemia to patient with glucose 6 phosphate dehydrogenase deficiency.
4. Rarely cause hepatitis and suppression of bone marrow
5. Cause displacement of bilirubin from plasma protein in neonates .

Question 8

What is Stevens-JOhnson syndrome?

Answer 8

Most severe type of hypersensitivity reaction characterised by fever , erythema, multiforme and ulceration of mucous membranes.

Question 9

Drug interaction of sulphonamides?

Answer 9

Sulphonamides potentiates the effect of phenytoin, methotrexate, oral anticoagulant and oral hypoglycaemic agents (sulphonylureas) by inhibiting their metabolism and displacing them from plasma protein binding sites.

Question 10

Therapeutic uses of sulphonamides?

Answer 10

• Sulphonamides alone are rarely used now for systemic infection. They are used in combination of other antimicrobial agents
  1. Sulphodoxine and pyrimethamine are used in combination with artesunate in the treatment of chloroquine -resistance Plasmodium falciparum malaria
  2. Sulphadiazine and pyrimethamine for toxoplasmosis
  3. Sulphamethoxazole with trimethoprim for nocardiosis
  4. Sulphamethoxazole with trimethoprim for treatment of P. jiroveci infection in AIDS patients
  5. Sodium salt of sulphacetamide for ophthalmic infection.
  6. Rheumatic fever : sulphadiazine for prophylaxis of rheumatic fever
  7. Sulphasalazine for inflammatory bowel disease and rheumatoid arthritis .
  8. Silver sulfadiazine and mafenide for preventing infection of burn wound.