Sulfonamide

• What is the chemical structure of sulfonamides?

  (SO2-Aromatic ring- SO₂NH2)
• Who discovered the effectiveness of Prontosil in preventing Streptococcal infections?

  Gerhard Domagk
• What was the significance of Prontosil in medical history?

  It was used to treat puerperal sepsis and was the first synthetic antimicrobial agent.
• What does sulfanilamide inhibit?

  It inhibits microbes.
• What is the role of folic acid in cells?

  Folic acid is used by cells to synthesize DNA and RNA.
• How do mammals obtain folic acid?

  Mammals obtain folic acid through their diet.
• Why are microbes more susceptible to sulfonamides compared to mammals?

  Microbial Dihydropteroate Synthase is more active than Mammalian Dihydropteroate Synthase.
• What is the mechanism of action (MoA) of sulfonamides?

  Sulfonamides are structural analogs of PABA and interfere with folic acid synthesis, reducing DNA synthesis.
• What are the components required to synthesize folic acid?

  Pteridine, PABA, and Glutamic acid.
• What is the role of Dihydropteroate Synthase in folic acid synthesis?

  It catalyzes the reaction of Glutamic acid, PABA, and Pteridine to form Dihydropteroic acid.
• What is the effect of Trimethoprim in folic acid synthesis?

  It inhibits Dihydrofolate Reductase, affecting the conversion to Tetrahydrofolic acid.
• What are the mechanisms of resistance (MoR) to sulfonamides?

  1. Increased synthesis of PABA, 2. Altered bacterial dihydropteroate synthase, 3. Bacteria bypassing 1-Carbon synthesis pathway.
• What is the absorption characteristic of sulfonamides?

  Sulfonamides are readily absorbed and usually given orally or topically.
• How do sulfonamides distribute in the body?

  They distribute in bodily water, enter the CNS, synovial fluid, milk, ocular fluids, and fetal circulation.
• What caution should be taken when administering sulfonamides to pregnant women or neonates?

  They should not be given to near-term pregnant women or neonates due to the risk of bilirubin encephalopathy or kernicterus.
• What is the metabolism process of sulfonamides?

  Sulfonamides are metabolized hepatically with acetylation of the amino group and oxidation of the aromatic ring/side chain.
• How are sulfonamides eliminated from the body?

  They are eliminated renally, mostly unchanged, and are useful in treating UTIs.
• What issue can arise from the crystallization of older sulfonamide drugs?

  Crystallization in urine can occur due to the increased pKa of older drugs.
• What are the characteristics of short-acting and intermediate/long-acting sulfonamides?

  Short-acting:

  • Examples: Sulfisoxazole, Sulfamethoxazole, Sulfadiazine
  • T½ = short (6-9 h)
  • Rapidly absorbed & excreted

  
  

  Intermediate/Long-acting:

  • Examples: Sulfadimethoxine, Sulfadoxine, Sulfadiazine (topical), Sulfacetamide
  • T½ = long (10-17 h; 7-9 days)
  • Poorly excreted, useful in protozoal infections, especially in AIDS patients
• What is the antimicrobial spectrum of sulfonamides?

  Sulfonamides have a broad antimicrobial spectrum, effective against G+ve & G-ve bacteria, Chlamydia, Toxoplasma gondii, and chloroquine-resistant Plasmodium falciparum.
• What is the combination of sulfonamides with trimethoprim used for?

  It is effective against Pneumocystis carinii in AIDS patients.
• What is the half-life (T½) of sulfonamides?

  10-17 hours; 7-9 days
• Why are sulfonamides considered useful in protozoal infections, especially in AIDS patients?

  They are poorly excreted, making them effective in treating such infections
• What is the antimicrobial spectrum of sulfonamides?

  • Broad spectrum
  • Effective against G+ve and G-ve bacteria
  • Microbiostatic/bacteriostatic
  • Targets Chlamydia, Toxoplasma gondii, and chloroquine-resistant Plasmodium falciparum
• What is the combination of sulfonamides and trimethoprim used for?

  It increases the usefulness of sulfonamides, especially in treating Pneumocystis carinii infections
• What is the ratio of sulfamethoxazole to trimethoprim in their combination?

  1. 1
• In which conditions are sulfonamides particularly effective?

  UTIs caused by E. coli and GI infections by E. coli, Yersinia, and Salmonella sp.
• What limits the therapeutic use of sulfonamides?

  Resistance problems
• What are the therapeutic uses of sulfonamides?

  • Protozoal and fungal infections
  • Chlamydia, nocardia, toxoplasma
  • Chloroquine-resistant P. falciparum
  • Pneumocystis carinii in AIDS patients
• What is a significant toxicity associated with older sulfonamides?

  They can crystallize in urine, leading to renal issues
• What should be advised to mitigate renal toxicity from sulfonamides?

  Increase fluid intake or alkalinize urine
• What blood dyscrasias can occur with sulfonamide use?

  Hemolytic anemia, agranulocytosis, aplastic anemia, thrombocytopenia
• What hypersensitivity reactions can occur with sulfonamides?

  Rash, pruritus, erythema, exfoliative dermatitis, and Stevens-Johnson syndrome
• What is Stevens-Johnson syndrome and its symptoms related to sulfonamide use?

  It is a severe reaction causing blisters on skin, mouth, eyes, and genitalia, and can lead to kidney failure
• What is the cross-reactivity of sulfonamides in terms of hypersensitivity?

  All sulfonamides are cross-allergenic with other S-containing drugs
• What are some examples of S-containing drugs that can cause hypersensitivity reactions with sulfonamides?

  • Carbonic anhydrase inhibitors
  • Thiazides
  • Furosemide
  • Sulfonylureas
• When was trimethoprim introduced and what is its purpose?

  Introduced in 1969 to synergize with sulfonamides and reduce resistance
• What is the ratio of trimethoprim to sulfamethoxazole in cotrimoxazole?

  1. 5
• What are the therapeutic uses of cotrimoxazole?

  • Respiratory infections (e.g., bronchitis)
  • Pneumocystis carinii infections
  • Gonorrhea
  • Nocardial infections
  • GI infections due to G-ve bacteria (salmonellosis)
• What are the common toxicities associated with trimethoprim?

  GI upset, bone marrow depression leading to megaloblastic anemia, and renal toxicity