112
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
Treatment of superficial eye infections
sulfadiazine (generic)
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
Treatment of a broad spectrum of
infections
sulfasalazine (Salazopyrin)
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
Treatment of ulcerative colitis and Crohn’s
disease; rheumatoid arthritis
sulfamethoxazole (Bactrim)
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 otitis media, bronchitis,
urinary tract infections, and pneumonitis
caused by Pneumocystis carinii
