Sulphonamide

CLASSIFICATION:
  • Short acting: Sulfadiazine(oral), Sulfadimidine, Sulfacetamide
  • Intermediate acting: Sulfamethoxazole
  • Long acting: Sulfadoxine, Sulfamethoxypyrazine, Sulfadimethoxine etc.
  • Topically used: Mafenide, Silver sulfadiazine and Sulfacetamide
  • Ulcerative colitis: Sulfasalazine
ANTIBACTERIAL PROPERTY:
  • Bacteriostatic against gm +ve and gm –ve bacteria
  • Bactericidal in urine
  • Susceptible organisms: 
  1. Str. pyogens, H. influenzae, H. ducreyi, Callymatobacterium grannulomatosis, V. cholerae, Chlamydia, Actinomyces etc.
  2. Few strains of Staph aureus, gonococci, meningococci, pneumococci, E. coli and Shigella
  • Chlamydiae: trachoma, lymphogrnuloma venereum., inclusion conjunctivitis. Also Actinomyces and Nocardia
  • Protozoa:
  1. Plasmodium (Sulfadoxine + Pyrimethamine)
  2. Toxoplasmosis (Sulfadiazine + Pyrimethamine)
  3. PCP (Sulfamethoxazole + Trimethoprim = SXT)
MOA:
  • Woods and Fielde`s Theory:
  • Bacteriae normally picks up PABA from surroundings to synthesize folic acid
  • Inhibition of bacterial folic acid synthesis from PABA (enzyme folate synthase) – competitive
  • Essential metabolic reactions suffer
RESISTANCE:
  • Mechanism:
  1. Production of increased amounts of PABA (Staph, Neisseria)
  2. Folate synthase enzyme has low affinity to sulfonamides
  3. Adopt alternative pathway of folate synthesis – structural changes in folate synthase (E coli) – encoded chromosomally and plasmid mediated
  • Resistant to one sulfonamide – resistant to all
  • Acetazolamide, Dorzolamide and Brinzolamide are sulfonamide derivatives which act by inhibiting carbonic anhydrase (carbonic anhydrase inhibitor).
  • Being sulphonamide derivatives they are contraindicated in patients with allergy to sulphonamides.
  • No cross resistance
PHARMACOKINETICS:
  • Rapidly and completely absorbed from GIT
  • Widely distributed – enters in serous cavity easily
  • Metabolized by non microsomal acetyl transferase in liver – slow and fast acetylators
  • Acetylated product – inactive excreted in urine (but, more toxic than parent) – crystalluria
  • Acetylated form accumulates in blood – toxic in renal faiure
  • Reabsorbed in tubule
USES:
  • UTI: caused by E. coli and P. mirabilis: Sulfisoxazole – 1 gm 4 times daily
  • Malaria: sulfadoxine and pyrimethamine combination
  • Toxoplasmosis: sulfadiazine + pyrimethamine
  • In Combination with Trimethoprim: Cotrimoxazole
  • Ulcerative colitis: Sulfasalazine(Salazopyrin) – 1-4 gm initially and 500 mg 6 Hrly.
  • Locally:
  • Sodium sulfacetamide: 10-30% ophthalmic solution in bacterial conjunctivitis, trachoma etc.
  • Mafenide acetate (1% cream) and Silver sulfadiazine 1% cream): Burn dressing and chronic ulcers
ADVERSE EFFECT:
  • Nausea, vomiting and epigastric pain
  • Crystalluria – alkanization of urine
  • Hypersensitivity (2 – 5%) – rashes, urticaria, drug fever. 
  • Exfoliative dermatitis, SJ syndrome (long acting ones)
  • Hepatitis
  • Haemolysis – G-6-PD deficiency
  • Erythema multiformis 
  • Kernicterus – displacement of bilirubin
  • Acute intermittent porphyria:Abdominal pain is the most common symptom in Acute intermittent porphyria and is usually steady and poorly localized but may be cramping. Seizures can be due to neurologic effects or to hyponatremia.
INDIVIDUAL SULFONAMIDES:
  • Sulfadiazine: General purpose use – absorbed orally and rapidly excreted. More crystalluria. Preferred in meningitis.
  • Sulfamethoxazole: slower absorption and lower excretion. 10 Hrs. half life. Combination with Trimethop
  • Sulfadoxine:Ultra-long acting >1 week. High protein bound – long excretion. Not suitable for Pyogenic infections – low plasma conc.. Used in Malaria, Pneumocystis jiroveci and toxoplasmosis
  • Sulfacetamide: Ophthalmic use – infections by bacteria, chlamydia, ophthalmia neonatorum etc
  • Mafendie: Atypical sulfonamide. Local application – inhibits variety of bacteria – active in presence of pus – pseudomonas and clostridia
  • Silver sulfadiazine: Bacteria, fungi, Pseudomonas. In burn case
Exam Question
  • Brinzolamide is contraindicated in patients with allergy to sulphonamides
  • Sulphonamides precipitate attacks of acute intermittent porphyria
  • Sulfadiazine is a sulfonamide which can used orally, as it is rapidly absorbed & rapidly excreted.
  • Sulphonamides can precipitate kernicterus in the new born
  • Longest acting sulphonamide is Sulphadoxine
  • Sulphonamide injection causes decrease in folic acid by Competitive inhibition
  • Topical Sulfonamides - Sulfacetamide sodium, Mafenide, silver sulfadiazine.
  • Due to sulphonamide erythema multiformis may occur
  • Salazopyrin is used for the treatment of ulcerative colitis
Don't Forget to Solve all the previous Year Question asked on Sulphonamide