II. Mechanism
- Sulfonamide Antibiotics are natural or synthetic Sulfanilamide derivatives
- Sulfonamide Antibiotics are antimetabolites, agents that inhibit DNA, RNA and Protein synthesis via Tetrahydrofolate path blockade
- Sulfonamides are structural analogs of para-aminobenzoic acid (PABA) which is key to microbial Tetrahydrofolate synthesis
- Sulfonamides competitively inhibit PABA at the dihydropteroate synthase enzyme in production of Dihydropteric acid
- Dihydropteric acid is a Tetrahydrofolate precursor, and blocking its synthesis, blocks Bacterial DNA, RNA and Protein synthesis
- Trimethoprim also inhibits Bacterial Tetrahydrofolate synthesis (blocks dihydrofolate reductase at tetrahydofolic acid generation)
- Sulfonamides precipitate in the urine at therapeutic doses
- Limits Sulfonamides alone to subtherapeutic doses
- Combining Sulfonamides with other agents (e.g. trimethoprim) allows them to reach therapeutic levels without urine precipitation
III. Medications
-
Trimethoprim Sulfamethoxazole (Bactrim, Septra)
- Covers enteric Gram Negative Bacteria (Urinary Tract Infections) and some Gram Positive organisms
- Also used in PCP Pneumonia treatment and prophylaxis (AIDS) and MRSA Skin Infections
-
Sulfadiazine
- Broad spectrum activity against both Gram Positive and Gram Negative organisms
- Use limited to Toxoplasmosis Prevention and management (combined with Pyrimethamine and leucovorin)
- Silver Sulfadiazine Topical Cream (Silvadene, SSD) has a limited role in Burn Injury
- Sulfisoxazole (Gantrisin)
- Primarily indicated in Urinary Tract Infection prophylaxis
- Higher urine solubility than other Sulfonamides (lower precipitation risk)
IV. Contraindications
- Avoid in infant under age 2 months
- Sulfonamide Allergy
- G6PD Deficiency
V. Adverse Effects: General
- Allergic Reaction or Anaphylaxis
- Bone Marrow suppression (Agranulocytosis)
- Steven's Johnson Syndrome
- Toxic Epidermal Necrolysis
- Hepatotoxicity
- Hemolysis (in G6PD Deficiency)
-
Neonatal Hyperbilirubinemia and Kernicterus
- Sulfonamides compete with Bilirubin for albumin binding
- Results in increased free Bilirubin, with risk of Neonatal Hyperbilirubinemia and Kernicterus
VI. References
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 111
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Definition (NCI) | An organic sulfur compound structurally similar to p-aminobenzoic acid (PABA) with antibacterial property. Sulfanilamide competes with PABA for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. This leads to an inhibition of bacterial folic acid synthesis and de novo synthesis of purines and pyrimidines, ultimately resulting in cell growth arrest and cell death. |
Definition (CSP) | potent antibacterial agent, the first of the sulfonamides discovered. |
Concepts | Antibiotic (T195) , Organic Chemical (T109) |
MSH | C036944 |
SnomedCT | 255972004, 386569003, 56436005 |
English | 4-aminobenzenesulfonamide, sulfanilamide, Sulfanilamide, 4-Aminobenzenesulfonamide, 4-Sulfamoylaniline, sulfanilamide (vaginal) (medication), vaginal preparations sulfanilamide, sulfanilamide (vaginal), sulfanilamide [Chemical/Ingredient], SULFANILAMIDE, sulphanilamide, Sulphanilamide, Sulfanilamide (product), Sulfanilamide (substance), Sulfanilamide [dup] (substance) |
Spanish | sulfanilamida (producto), sulfanilamida (sustancia), sulfanilamida |
Ontology: Sulfonamide Anti-Infective Agents (C0599503)
Definition (NCI) | A class of natural or synthetic sulfanilamide derivatives with antibacterial activity. Sulfonamides are structural analogs of para-aminobenzoic acid (essential for microbial folate synthesis). Sulfonamides inhibit bacterial metabolism by competing with PABA for dihydropteroate synthase, thereby resulting in disruption of folic acid metabolism and ultimately DNA synthesis. |
Definition (NCI_NCI-GLOSS) | A type of antibiotic used to treat infection. |
Concepts | Organic Chemical (T109) , Antibiotic (T195) |
SnomedCT | 387406002, 59255006, 372788003 |
LNC | LP16283-1, MTHU007722 |
English | sulfonamides (medication), sulfonamides, drugs sulfa, drug sulfa, sulfa drugs, sulfa drug, Sulfonamide Anti-Infective Agent, Sulfonamide Anti-Infective Agents, sulfonamide, Sulfonamide, Sulphonamide, Sulfonamide (substance), Sulfonamide -class of antibiotic- (product), Sulfonamide -class of antibiotic- (substance), Sulfonamide -class of antibiotic-, Sulfonilamide, Sulphonamide -class of antibiotic-, Sulphonilamide, sulfonamide agent, Sulfonamide, NOS, Sulfonilamide, NOS, Sulfonamides |
Spanish | sulfonamida (clase de antibiótico) (producto), sulfonamida (clase de antibiótico) (sustancia), sulfonamida (clase de antibiótico), sulfonilamida, sulfonamida (sustancia), sulfonamida |