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Sulphonamides

Sulfonamides or "sulfa drugs" is the first class of antibacterial preparations approved for widespread use. For the recent years the use of sulphonamides in medical practice became limited because of lower bacteriostatic activity and higher toxicity in comparison with other up-to-date antibacterial remedies. Due to the fact that sulphonamides are used in medical practice for a long period of time, many of microorganisms developed resistance to the majority of "sulfa drugs".

Action mechanism
Sulfonamides possess bacteriostatic effects. The chemical structure of sulphonamides is very close to p-aminobenzoic acid. They work by inhibiting bacterial enzyme responsible for the synthesis of dihydrofolic acid-predecessor of folic acid. Folic acid is one of the main component in synthesis of nucleic acid, purine and pyrimidine bases.

Some sulphonamides for local use contain silver (sulfadiazine, sulphathiazole). As a result of dissociation silver ions are slowly released providing bactericidal activity (due to binding to DNA).

Spectrum of activity
Originally sulfonamides were active against a broad spectrum of gram-positive (S.aureus, S.pneumoniae, etc.) and gram-negative (gonococci, meningococci, H.influenzae, E.coli, Proteus spp., Salmonella, Shigella, etc.) bacteria. More over, they act on chlamydia, nocardia, pneumocystis, actinomycetes, malaria parasite, Toxoplasma.
Currently, many strains of staphylococci, streptococci, pneumococci, gonococci, meningococci, enterobacteria are characterized by high levels of acquired resistance. Enterococci, Pseudomonas aeruginosa and most anaerobes have natural resistance to "sulfa drugs".
Preparations containing silver are active against many pathogens of wound infections-Staphylococcus spp., P.aeruginosa, E.coli, Proteus spp., Klebsiella spp., Candida strains.

Indications
Systemic preparations:

  • Nocardiosis
  • Toxoplasmosis (sulfadiazine in combination with pyrimethamine)
  • Malaria caused by susceptible to chloroquine P.falciparum (in combination with pyrimethamine)
  • Plague prophylaxis

Cotrimoxazole (Bactrim) is a combined sulfa drug for oral administration. It contains sulfonamide sulfamethoxazole and trimethoprim. It is used in the treatment of:

  • Intestinal infections (shigellosis, salmonellosis, traveler's diarrhea)
  • Community-acquired infections of urogenital system: acute cystitis, chronic recurrent cystitis, pyelonephritis
  • Staphylococcal infections
  • Infections caused by S.maltophilia and B.cepacia
  • Nocardiosis
  • Brucellosis
  • Toxoplasmosis
  • Pneumocystis pneumonia

Preparations for local use:

  • Burns
  • Trophic ulcers
  • Bed sores

Ophtalmological preparations (sulfacetamide)

  • Purulent corneal ulcers
  • Conjunctivitis
  • Blepharitis
  • Blennorrhea prophylaxis in children

Contraindications
Sulphonamides are contraindicated for use in the following conditions:

  • Allergic reactions to sulphonamides, furosemide, thiazide diuretics, sulfonylurea drugs
  • It is not recommended to use sulfa drugs in children for the exception of inborn toxoplasmosis
  • Renal failure
  • Severe liver diseases

Cautions

  • Allergy is crossed for all sulfa drugs because of similarity of chemical structure
  • Pregnancy. Because sulfonamides pass through placenta their use should be limited. Sulfonamides may cause teratogenic and embryotoxic effects
  • Breastfeeding. Sulfonamides pass through breast milk and may cause nuclear jaundice and hemolytic anemia in children with deficiency of G6PD
  • Pediatric use. Sulfonamides should be used with caution because of high risk of nuclear jaundice. That is why oral and parenteral forms of sulfa drugs are contraindicated for use in children under 6 months
  • Geriatric use. Sulfonamides should be used with caution in elderly patients because of high risk of side effects, suppression of hematopoiesis, thrombocytopenic purpura. It is recommended not to use the medication in patients over 65 years of age

Kidney dysfunction. Decreasing in renal excretion leads to accumulation of sulfonamides and their metabolites in the organism and this significantly increases the risk of their nephrotoxic action up to severe interstitial nephritis and necrosis of renal tubules. Therefore sulfonamide should not be used in patients with renal failure. Liver dysfunction. Liver diseases impair metabolism of sulfa drugs and increase the risk of hepatotoxicity. Sulfonamides are contraindicated for use in hepatic pathology.

  • Hemopoietic system: there is an increased risk of side effects
  • Deficiency of G6PD: there is an increased risk of hemolytic anemia
  • Porphyria. There is an increased risk of porphyria attacks
  • Local application. In prolonged use it is necessary to control kidney and liver function, peripheral blood picture

Sulfonamides side effects
Preparations for systemic use:

  • Allergic reactions: fever, skin rash, itching, Stevens Johnson's syndrome
  • Hematologic reactions: leukopenia, agranulocytosis, hypoplastic anemia, thrombocytopenia, pancytopenia
  • Liver: hepatitis, toxic dystrophy
  • CNS: headache, dizziness, weakness, confusion, hallucination, depression
  • Digestive system: stomach pain, anorexia, nausea, vomiting, diarrhea, pseudomembranous colitis.
  • Kidney: crystalluria, hematuria, interstitial nephritis, necrosis of renal tubules.
  • Thyroid: dysfunction of thyroid gland
  • Other: photosensibilisation

Preparations for local use:

  • Local reactions: itching, redness and pain at application area
  • Systemic reactions: allergic reactions, hyperemia, rhinitis, bronchospasm, leukopenia

Drug interactions

  • Sulfonamides may enhance the effects of indirect blood thinners, antiepileptics (derivative of hydantoin), oral diabetes drugs and methotrexate
  • Sulfonamides may increase the risk of toxic effects when are used in combination with preparations that inhibit bone marrow, cause hepatotoxic action
  • Sulfonamides may decrease the effectiveness of estrogen-containing birth control pills and increase the risk of uterine bleedings
  • Sulfonamides may enhance metabolism of cyclosporine and increase its concentration in the blood. Also the risk of nephrotoxicity is increased is well.
  • It is not recommended to use Sulfonamides in combination with methenamine because of high risk of crystalluria
  • Phenylbutazone, salicylates and indomethacin may increase blood levels of sulfonamides

Information for patients

  • Oral forms of Sulfonamides should be taken on empty stomach washing down with sufficient amount of water.
  • The medications should be taken strictly according to doctors prescription.
Avoid direct sunlight and ultraviolet rays during the treatment with sulfonamides