McKenna's Pharmacology for Nursing, 2e

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P A R T 2  Chemotherapeutic agents

SULFONAMIDES The sulfonamides, or sulpha drugs (Table 9.6), are drugs that inhibit folic acid synthesis. Sulfonamides include sulfadiazine (generic), sulfacetamide ( Bleph-10 ), sul- fasalazine ( Salazopyrin ) and sulfamethoxazole ( Septrin , Bactrim ). Therapeutic actions and indications Folic acid is necessary for the synthesis of purines and pyrimidines, which are precursors of RNA and DNA. For cells to grow and reproduce, they require folic acid. Humans cannot synthesise folic acid and depend on the folate in their diet to obtain this essential substance. Bacteria are impermeable to folic acid and must synthe- sise it inside the cell. The sulfonamides competitively block para -aminobenzoic acid (PABA) to prevent the synthesis of folic acid in susceptible bacteria that syn- thesise their own folates for the production of RNA and DNA (see Figure 9.2). This includes gram-negative and gram-positive bacteria such as Chlamydia trachomatis and Nocardia and some strains of H. influenzae , E. coli and P. mirabilis. Because of the emergence of resistant bacterial strains and the development of newer antibiotics, the sulpha drugs are no longer commonly used. However, they remain an inexpensive and effective treatment for UTIs and trachoma, especially in developing countries and when cost is an issue. These drugs are used to treat trachoma (a leading cause of blindness), nocardiosis (which causes pneumonias, as well as brain abscesses and inflammation), UTIs and sexually transmitted diseases. See Table 9.6 for usual indications for each of these agents.

Pharmacokinetics The sulfonamides are teratogenic; they are distributed into breast milk (see contraindications and cautions). These drugs, given orally, are absorbed from the GI tract, metabolised in the liver and excreted in the urine. The time to peak level and the half-life of the individual drug vary. Sulfadiazine is an oral agent slowly absorbed from the GI tract, reaching peak levels in 3 to 6 hours. Sulfasalazine is a sulfapyridine that is carried by aminosalicylic acids (aspirin), which release the amino- salicylic acid in the colon. In a delayed-release form, this sulpha drug is also used to treat rheumatoid arthritis that does not respond to other treatments. It is rapidly absorbed from the GI tract, reaching peak levels in 2 to 6 hours. After being metabolised in the liver, it is excreted in the urine with a half-life of 5 to 10 hours. Sulfamethoxazole is a combination drug with tri- methoprim, another antibacterial drug. It is rapidly absorbed from the GI tract, reaching peak levels in 2 hours. After being metabolised in the liver, it is excreted in the urine with a half-life of 7 to 12 hours. Contraindications and cautions The sulfonamides are contraindicated with any known allergy to any sulfonamide, to sulfonylureas or to thiazide diuretics because cross-sensitivities occur ; during pregnancy because the drugs can cause birth defects, as well as kernicterus ; and during breastfeeding because of a risk of kernicterus, diarrhoea and rash in the infant. They should be used with caution in people with renal disease or a history of kidney stones because of the possibility of increased toxic effects of the drugs.

TABLE 9.6

DRUGS IN FOCUS Sulfonamides

Drug name

Dosage/route

Usual indications

sulfacetamide (Bleph-10)

1–2 drops into the affected eye q 2–3 hours Adult: 2–4 g PO loading dose, then 2–4 g/day PO in 4–6 divided doses Paediatric: 75 mg/kg PO, then 120–150 mg/kg/ day PO in 4–6 divided doses Adult: 3–4 g/day PO in evenly divided doses, then 500 mg PO q.i.d.; 500 mg PO q.i.d. (arthritis) Paediatric: 40–60 mg/kg/day PO in divided doses, then 20–30 mg/kg/day PO in four equally divided doses Adult: 2 tablets PO q 12 hours; reduce dose with renal impairment Paediatric: 8 mg/kg/day trimethoprim plus 40 mg sulfamethoxazole PO q 12 hours

Treatment of superficial eye infections Treatment of a broad spectrum of infections

sulfadiazine (generic)

sulfasalazine (Salazopyrin)

Treatment of ulcerative colitis and Crohn’s disease; rheumatoid arthritis

sulfamethoxazole (Bactrim)

Treatment of otitis media, bronchitis, urinary tract infections, and pneumonitis caused by Pneumocystis carinii