Introduction:
Sulphonamides are a group of synthetic bacteriostatic antibiotics that has a broad spectrum of use with respect to gram positive and gram negative microorganisms. They were introduced into medical practice even before the discovery of penicillin. Sulphonamides are derivatives of sulphanilamide. The advent of penicillin and subsequent other antibiotics has diminished the usefulness of sulphonamides.
Classification:
Mechanism of action:
All sulfonamides are synthetic analogue of PABA (p. amino benzoic acid). Due to structural similarity to PABA, they compete with this substrate of bacterial enzyme dihydopteroate synthetase. It inhibits synthesis of bacterial dihydrofolic acid (which is further involve in bacterial amino acid synthesis, purine synthesis and thymidine synthesis).
Pharmacokinetics:
- Absorption: Most sulfa drugs are absorbed well via small intestine after oral administration.
* with exception of sulfasalazine which don’t get absorbed when taken orally or as a suppository; therefore it is reserved for diseases like chronic inflammatory bowel disease and ulcerative colitis.
** slow acetylators ,absorption of sulfapyridine can lead to toxicity. Sulfasalazine split into sulfapyridine and 5- aminosalicylate.
- Distribution: bound to serum albumin, extent of binding depends upon drug’s pKa.
*(smaller pKa grater binding).
Distributes throughout body tissue even in cerebrospinal fluid without inflammation.
Also cross placenta and penetrate in fetal tissue.
- Metabolism: acetylated primarily in liver. Once metabolized has no antimicrobial effect but is toxic and can precipitate (crystalluria (stone formation); damaging for kidney)
- Excretion: eliminates by glomerular filtration therefore requires dose adjustment for renal dysfunction. Sulfa metabolites may also get excreted in breast milk
Indications:
- Respiratory infection (gram –ve rods):
- Cotrimoxazole is effective against haemophilis influenza.
- Cotrimoxazole is an alternative treatment for legionella pneumophilia.
- Gastrointestinal infections
Cotrimoxazole useful in treatment of shigellosis and non typhoid salmonella.
- Pnemocystis jiroveci pneumonia
- It’s a common opportunistic infection complicating AIDS (cotrimoxazole is the most effective therapy).
- Prophylaxis with cotrimoxazole is recommended for HIV patients with fewer than 200 CD4+ cells/ml.
- Prostate and urinay tract infections
- Trimethoprim concentrates in prostatic and vaginal fluids rendering it effective in infections in these areas.
Chronic urinary tract infections respond to cotrimoxazole.
Contraindications:
Patients receiving Methenamine for UTI’s. (sulfonamides condense with formaldehydes).
Adverse effects:
- Crystalluria (prevention by adequate hydration or alkalinization of urine by sodium bicarbonate,
Sulphisoxazole and sulfamethoxazole are more soluble at urinary pH than sulfadiazine).
- Hypersensitivity (rashes, angioedema, stevens johnson syndrome)
- Hematological disturbances (hemolytic anemia in patients with G6PD deficiency , granulocytopenia, thrombocytopenia)
- Kernicterus (bilirubin induced neurological damage)
- Drug potentiation effect: transient potentiation of anticoagulants (warfarin) due to drug displacement at binding site or on serum albumin.
Sulphones:
Diamino diphenyl sulphones (Dapsone) used to treat infection caused by mycobacterium laprae.
Leprosy is caused by mycobacterium laprae.
However due to primary and secondary resistance due to prolonged use of this drug , it is now necessary to use it with certain combinations like currently, dapsone is used along rifampicin and clofazimine. Ethionamide can also be recommended.
Dapsone: 4, 4- Sulphonyl bis benzenamine.
It has mechanism of action similar to that of sulphonamides. It is used to treat both lepromatous and tuberculoid types of leprosy. Dapsone is a drug of choice for dermatitis herpetiformis, with pyrimethamine for the treatment of malaria, with trimethoprim for pneumocystis carinii pneumonia (PCP), and has been used for rheumatoid arthritis.