Sulfonamides
Objectives
• Differentiate between short-acting and intermediate-acting sulfonamides.
• Compare the similarities and differences between the sulfonamides and sulfadiazine.
• Explain the pharmacokinetics of the sulfonamides.
• Apply the nursing process to the patient taking trimethoprim-sulfamethoxazole.
Key Terms
bacteriostatic, p. 429
cross-sensitivity, p. 430
crystalluria, p. 430
erythema multiforme, p. 432
exfoliative dermatitis, p. 432
photosensitivity, p. 430
synergistic effect, p. 431
Sulfonamides are one of the oldest antibacterial agents used to combat infection. When penicillin was initially marketed, the sulfonamide drugs were not widely prescribed, because penicillin was considered the “miracle drug.” However, use of sulfonamides has increased as a result of new sulfonamides and the combination drug of sulfonamide with an antibacterial agent in preparations such as trimethoprim-sulfamethoxazole (Bactrim, Septra).
Sulfonamides
Sulfonamides were first isolated from a coal tar derivative compound in the early 1900s and were produced for clinical use against coccal infections in 1935. It was the first group of drugs used against bacteria. Sulfonamides are not classified as an antibiotic, because they were not obtained from biologic substances. The sulfonamides are bacteriostatic because they inhibit bacterial synthesis of folic acid, which is essential for bacterial growth. Humans do not synthesize folic acid but acquire it through the diet; therefore, sulfonamides selectively inhibit bacterial growth without affecting normal cells. Folic acid (folate) is required by cells for biosynthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and proteins.
The clinical usefulness of sulfonamides alone, not in combination, has decreased for several reasons. The availability and effectiveness of penicillin and other antibiotics has increased, and bacterial resistance to some sulfonamides can develop. Sulfonamides may be used as an alternative drug for patients who are allergic to penicillin. They are still used to treat urinary tract and ear infections and may be used for newborn eye prophylaxis. Sulfonamides are approximately 90% effective against Escherichia coli; therefore they are frequently a preferred treatment for urinary tract infections, which are often caused by E. coli. They are also useful in the treatment of meningococcal meningitis and against the organisms Chlamydia and Toxoplasma gondii. Sulfonamides are not effective against viruses and fungi.
Pharmacokinetics
Sulfonamide drugs are well absorbed by the gastrointestinal (GI) tract and are well distributed to body tissues and the brain. The liver metabolizes the sulfonamide drug, and the kidneys excrete it.
Pharmacodynamics
Many sulfonamides are for oral administration, because they are absorbed readily by the GI tract. They are also available in solution and ointment for ophthalmic use and in cream form (silver sulfadiazine [Silvadene] and mafenide acetate [Sulfamylon]) for burns. Most of the early sulfonamides were highly protein-bound and displaced other drugs by competing for protein sites. The following are two categories of sulfonamides, classified according to their duration of action: (1) short-acting sulfonamides (rapid absorption and excretion rate) and (2) intermediate-acting sulfonamides (moderate to slow absorption and slow excretion rate).
Sulfadiazine is useful in prophylactic treatment of streptococcal infections in patients with rheumatic fever who are hypersensitive to penicillin. Sulfadiazine is poorly soluble in urine and can cause crystallization, which could damage the kidneys if there is insufficient fluid and water intake. Table 31-1 lists the protein-binding, half-life, and solubility in urine of most drugs in the sulfonamide group.
TABLE 31-1
PHARMACOKINETICS OF SELECTED SULFONAMIDES
| DRUG | PROTEIN-BINDING (%) | HALF-LIFE (HOURS) | SOLUBILITY IN URINE |
| Short-Acting | |||
| sulfadiazine (Microsulfon) | 20-60 | 17 | +1 |
| Intermediate-Acting | |||
| sulfasalazine (Azulfidine) | 99 | 5-10 | +1 |
| trimethoprim-sulfamethoxazole (Bactrim) | 50-65 | 8-12 | +1-2 |
Older sulfonamides (e.g., sulfadiazine) have low solubility and may cause crystallization in the urine. The current sulfonamides have greater water solubility; therefore, crystal formations in the urine and renal damage are unlikely. Table 31-2 describes the sulfonamides.
TABLE 31-2
| GENERIC (BRAND) | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| Short-Acting | ||
| sulfadiazine (Microsulfon) | A: PO: LD: 2-4 g; then 2-4 g/d in 4-6 divided doses C >2 mo: PO: LD: 75 mg/kg; then 150 mg/kg/d in 4-6 divided doses; max: 6 g/d | For systemic infections. Could be classified as a short- to immediate-acting sulfonamide. When taking this drug, increase fluid intake to >2000 mL/d. Pregnancy category: C; PB: 38%-48%;  : 17 h |
| Intermediate-Acting | ||
| sulfasalazine (Azulfidine) | A: PO: Initially: 1 g q6-8h; maint: 500 mg q6h C >6 y: PO: Initially: 40-60 mg/kg/d in 4-6 divided doses; maint: 30 mg/kg/d in 4 divided doses; max: 2 g/d | For ulcerative colitis, Crohn’s disease, rheumatoid arthritis (some cases), and reduces Clostridium and E. coli in stools. Take after eating. Side effects include nausea, vomiting, bloody diarrhea. Pregnancy category: B (near term: D); PB: 99%;  : 6 h |
| trimethoprim-sulfamethoxazole (Bactrim, Septra) | See Prototype Drug Chart 31-1. | |
, half- life; y, year; >, greater than; ≥, greater than or equal to.Side Effects and Adverse Reactions
Side effects of sulfonamides may include an allergic response such as skin rash and itching. Anaphylaxis is not common. Blood disorders such as hemolytic anemia, aplastic anemia, and low white blood cell and platelet counts could result from prolonged use and high dosages. GI disturbances (anorexia, nausea, vomiting) may also occur. The early sulfonamides were insoluble in acid urine, and crystalluria (crystals in urine) and hematuria were common problems. Increasing fluid intake dilutes the drug, helping prevent crystalluria from occurring. Photosensitivity (excessive reaction to direct sunlight or ultraviolet light leading to redness and burning of skin) can occur, so the patient should avoid sunbathing and excess ultraviolet light. Cross-sensitivity (a sensitivity or allergy to one sulfonamide may lead to sensitivity to another sulfonamide) might occur with the different sulfonamides but does not occur with other antibacterial drugs. Sulfonamides should be avoided during the third trimester of pregnancy.
Safety
Preventing Medication Errors
Do not confuse…
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