DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1466 readily than the free fraction, and the administration of alkali accelerates
the renal clearance of both forms by further diminishing their
Table 52–1
Classes of Sulfonamides
tubular reabsorption.
In adults and children who are being treated with sulfadiazine,
every precaution must be taken to ensure fluid intake adequate
SERUM t 1/2
CLASS SULFONAMIDE (hours) to produce a urine output of at least 1200 mL in adults and a corresponding
Absorbed and
excreted rapidly
Sulfisoxazole
Sulfamethoxazole
5-6
11
quantity in children. If this cannot be accomplished,
sodium bicarbonate may be given to reduce the risk of crystalluria.
Sulfadiazine 10
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Poorly absorbed– Sulfasalazine —
active in bowel
lumen
Topically used Sulfacetamide —
Silver sulfadiazine —
Long-acting Sulfadoxine 100-230
Sulfisoxazole acetyl is tasteless and hence preferred for oral
use in children. Sulfisoxazole acetyl is marketed in combination with
erythromycin ethylsuccinate for use in children with otitis media.
Fewer than 0.1% of patients receiving sulfisoxazole suffer
serious toxic reactions. The untoward effects produced by this agent
are similar to those which follow the administration of other sulfonamides,
as discussed later. Because of its relatively high solubility in
the urine as compared with sulfadiazine, sulfisoxazole only infrequently
produces hematuria or crystalluria (0.2-0.3%). Despite this,
patients taking this drug should ingest an adequate quantity of water.
Sulfisoxazole and all sulfonamides that are absorbed must be used
with caution in patients with impaired renal function. Like all sulfonamides,
sulfisoxazole may produce hypersensitivity reactions, some
of which are potentially lethal. Sulfisoxazole currently is preferred
over other sulfonamides by most clinicians when a rapidly absorbed
and rapidly excreted sulfonamide is indicated.
Sulfamethoxazole. Sulfamethoxazole is a close congener of sulfisoxazole,
but its rates of enteric absorption and urinary excretion are
slower. It is administered orally and employed for both systemic and
urinary tract infections. Precautions must be observed to avoid sulfamethoxazole
crystalluria because of the high percentage of the
acetylated, relatively insoluble form of the drug in the urine. The
clinical uses of sulfamethoxazole are the same as those for sulfisoxazole.
In the U.S., it is marketed only in fixed-dose combinations
with trimethoprim.
Sulfadiazine. Sulfadiazine given orally is absorbed rapidly from the
GI tract, and peak blood concentrations are reached within 3-6 hours
after a single dose. Following an oral dose of 3 g, peak concentrations
in plasma are 50 μg/mL. About 55% of the drug is bound to
plasma protein at a concentration of 100 μg/mL when plasma protein
levels are normal. Therapeutic concentrations are attained in cerebrospinal
fluid within 4 hours of a single oral dose of 60 mg/kg.
Sulfadiazine is excreted quite readily by the kidney in both
the free and acetylated forms, rapidly at first and then more slowly
over a period of 2-3 days. It can be detected in the urine within
30 minutes of oral ingestion. About 15-40% of the excreted sulfadiazine
is in acetylated form. This form of the drug is excreted more
Poorly Absorbed Sulfonamides
Sulfasalazine. Sulfasalazine (AZULFIDINE, others) is very poorly
absorbed from the GI tract. It is used in the therapy of ulcerative colitis
and regional enteritis (Chapter 47). Intestinal bacteria break sulfasalazine
down to sulfapyridine, an active sulfonamide that is
absorbed and eventually excreted in the urine, and 5-aminosalicylate
(5-ASA, mesalamine; Figures 47–2 through 47–4), which reaches
high levels in the feces. Whereas sulfapyridine is responsible for most
of the toxicity 5-ASA is the effective agent in inflammatory bowel
disease. Toxic reactions include Heinz-body anemia, acute hemolysis
in patients with glucose-6-phosphate dehydrogenase deficiency,
and agranulocytosis. Nausea, fever, arthralgias, and rashes occur in up
to 20% of patients treated with the drug; desensitization has been an
effective treatment. Sulfasalazine can cause a reversible infertility in
males owing to changes in sperm number and morphology.
Sulfonamides for Topical Use
Sulfacetamide. Sulfacetamide is the N1-acetyl-substituted derivative
of sulfanilamide. Its aqueous solubility (1:140) is ~90 times that of
sulfadiazine. Solutions of the sodium salt of the drug are employed
extensively in the management of ophthalmic infections. Although
topical sulfonamide for most purposes is discouraged because of
lack of efficacy and a high risk of sensitization, sulfacetamide has
certain advantages. Very high aqueous concentrations are not irritating
to the eye and are effective against susceptible microorganisms.
A 30% solution of the sodium salt has a pH of 7.4, whereas the solutions
of sodium salts of other sulfonamides are highly alkaline. The
drug penetrates into ocular fluids and tissues in high concentration.
Sensitivity reactions to sulfacetamide are rare, but the drug should
not be used in patients with known hypersensitivity to sulfonamides.
See Chapters 64 and 65 for ocular and dermatogical uses.
Silver Sulfadiazine. Silver sulfadiazine (SILVADENE, others) inhibits
the growth in vitro of nearly all pathogenic bacteria and fungi,
including some species resistant to sulfonamides. The compound is
used topically to reduce microbial colonization and the incidence of
infections from burns. It should not be used to treat an established
deep infection. Silver is released slowly from the preparation in concentrations
that are selectively toxic to the microorganisms.
However, bacteria may develop resistance to silver sulfadiazine.
Although little silver is absorbed, the plasma concentration of sulfadiazine
may approach therapeutic levels if a large surface area is
involved. Adverse reactions—burning, rash, and itching—are infrequent.
Silver sulfadiazine is considered by most authorities to be an
agent of choice for the prevention of burn infections.
Mafenide. This sulfonamide (α-amino-p-toluene-sulfonamide) is
marketed as mafenide acetate (SULFAMYLON). When applied topically,
it effectively prevents colonization of burns by a large variety of
gram-negative and gram-positive bacteria. It should not be used in