Sulfonamides

Sulfonamides are a group of antibiotics that work by decreasing the synthesis of purines and pyrimidines by competing with PABA (p-aminobenzoic acid) in the production of dihydrofolic acid, which is used in the synthesis of proteins and DNA.  Blood dyscrasias, hypersensitivity syndromes including Stevens-Johnson syndrome, crystalluria and nephrotoxicity, and drug-drug reactions can occur.

Trimethoprim is combined with sulfamethoxazole in a single form and works by inhibition of dihydrofolate reductase, which is an enzyme in the production of purines, thymidine, and amino acids.  Resistance from altered dihydrofolate reductase can occur. Toxicity occurs from folic acid deficiency and includes megaloblastic anemia and granulocytopenia.  

Class Drugs

• Trimethoprim/Sulfamethoxazole

• Sulfasalazine

• Silver sulfadiazine

Class Mechanism of Action

Sulfonamide Mechanism:

• Decreases synthesis of purines and pyrimidines by competing with PABA (p-aminobenzoic acid), which is used by bacteria in the production of dihydrofolic acid. Dihydrofolic acid is used for the next step of production of proteins, DNA precursors, etc.

Trimethoprim Mechanism:

• Inhibits dihydrofolate reductase, which is the next step in production of purines, thymidine, and amino acid synthesis after the production of dihydrofolic acid

Dihydrofolate reductase converts dihydrofolic acid to tetrahydrofolic acid, which is used in the production of proteins, DNA precursors, etc.

Bacteriostatic

Class Applications

See individual drugs

Class Adverse Effects

Resistance

• Altered dihydrofolate reductase decreases affinity for trimethoprim

• Efflux pumps

• Decreased uptake

Sulfonamide specific adverse effects:

• Crystalluria

Prevention with adequate hydration and alkalinized urine

• May lead to nephrotoxicity

• Hypersensitivity

Stevens-Johnson syndrome

• Angioedema, rash

• Hemolytic anemia

Increased risk in patients with glucose-6-phosphate deficiency (G6PD)

• Blood dyscrasias

Aplastic anemia

• Agranulocytosis

• Thrombocytopenia

• Granulocytopenia

• Drug-drug interactions

Displaces warfarin and methotrexate from albumin binding site leading to increased serum levels

• Kernicterus

Avoid in pregnant women near term and newborns

Trimethoprim specific adverse effects

• Signs of folic acid deficiency

Megaloblastic anemia

• Granulocytopenia

• Avoided by co-administration of folinic acid, which does not go into the bacteria

Drug Table

Drug Name	Application	Comments	Image
Trimethoprim/Sulfamethoxazole	MRSA skin infections; Respiratory infections; -H. influenzae; -Pneumocystis jirovecii pneumonia (formerly PCP pneumonia); Opportunistic infection in AIDS; Prophylaxis initiated with CD4 count less than 200; Listeria monocytogenes; Urinary tract infections; GI infections; Nontyphoid salmonella; Shigellosis		"Triangle" "Meth" "Sulfur" "Meth" "Ox"
Sulfasalazine	Chronic inflammatory bowel disease (Ulcerative colitis, Crohn's)	Not an orally absorbed drug; Metabolized by gut flora; Metabolite exerts anti-inflammatory effect	"Sulfur" "Salamander"
Silver Sulfadiazine	Prevents topical infection in burns		"Silver" "Sulfur" "Die"