Sulfonamides

Drugs
Sulfadiazine, silver sulfadiazine, sulfisoxazole, sulfamethoxazole,
sulfacetamide, and sulfasalazine.
Mechanism of action
Sulfonamides compete with para-aminobenzoic acid at the
first biosynthetic step of the folic acid pathway (see ig. !-"#.
$harmaco%inetics
Sulfonamides are highly protein bound, so drug interactions
may occur if sulfonamides displace other drugs from
plasma protein-binding sites. &his can lead to adverse effects
when used with drugs such as warfarin, nonsteroidal
antiinflammatory drugs, and sulfonylureas. Sulfonamides
are contraindicated in pregnant women near term and in infants
younger than ' months because these drugs displace
bilirubin from protein-binding sites in neonates. (yperbilirubinemia
in neonates may cause %ernicterus (central nervous
system disorders caused by elevated bilirubin#.
)linical use
*nitially, sulfonamides had a broad spectrum of activity
against gram-positive cocci and gram-negative bacilli+ however,
antimicrobial resistance is increasingly becoming problematic.
Sulfonamides are used to treat urinary tract
infections, con,unctivitis, and toxoplasmosis. &hey also are
used to prevent and treat burn-related infections and are used
ad,unctively with pyrimethamine for malaria. *ndications for
some sulfonamides are listed in -ox !-..
*ndividual sulfonamides have uni/ue actions. Sulfadiazine
distributes widely to the central nervous system. Sulfisoxazole
may be used to treat urinary tract infections and is also
an option for prophylaxis of rheumatic fever if the child is
allergic to penicillin. Sulfisoxazole is also administered in a
formulation that is combined with erythromycin. Sulfamethoxazole
is commonly used in con,unction with trimethoprim
for synergistic effects in the treatment of urinary tract infections.
Sulfacetamide is used topically in the eyes for treating con,unctivitis or corneal ulcers. Sulfasalazine is used
as a
treatment for inflammatory bowel disease. Silver sulfadiazine
is available as a topical cream for treating burn patients.
0esistance
-acteria develop resistance to sulfonamides in the following
ways1
l 0educed bacterial upta%e of the drugs
l Development of alternative metabolic pathways to synthesize
folic acid
l $roduction of excessive amounts of para-aminobenzoic
acid (up to "2 times normal# to compete with the sulfonamides
for folic acid synthesis
l 3lterations ormutations in dihydropteroate synthase, the enzyme
that catalyzes the rate-limiting step of folate synthesis
$harmaco%inetics
Sulfonamides are metabolized hepatically by acetylation, oxidation,
and4or glucuronidation. *ndividuals who are genetically
5slow acetylators6 may be at an increased ris% of
hypersensitivity reactions. 7xidation of sulfonamides li%ely
is responsible for many of the adverse effects associated with
sulfonamides. 3fter hepatic biotransformation, sulfonamide
metabolites are excreted renally.
3dverse effects
Sulfonamides predispose patients to photosensitivity. -one
marrow suppression, including hemolytic anemia, leu%openia,
and thrombocytopenia, may occur. &here is an increased
ris% of adverse hematologic effects in patients who are genetically
deficient in 89$D. Sulfonamides may precipitate in the
%idneys, causing renal stones+ good hydration prevents this.
7ther miscellaneous effects include hepatotoxicity, pseudomembranous
colitis, and hypersensitivity reactions, including
Stevens-:ohnson syndrome (&able !-'2#. -ecause of chemical
similarities, patients who are allergic to sulfonamides may
also be hypersensitive to sulfonylureas, thiazide diuretics,
and sunscreens that contain para-aminobenzoic acid.