Sulfonamides

One of the oldest - broad spectrum antibiotic.

Bacteriostatic - inhibits bacterial synthesis of

folic acid, essential for bacterial growth since
Bacteria for the synthesis of purines and
pyramidines need co-enzyme containing folic
acid.

Can cross BBB and Placenta.

ANTIFOLATE DRUGS
CLASSIFICATION
 Inhibitors Of  Inhibitors of
Folate synthesis: Folate reduction
(Sulfonamides) i) Trimethoprim
i) Sulfisoxazole ii) Pyrimethamine
ii) Sulfamethoxazole  Inhibitors of
iii) Sulfadiazine Folate synthesis
iv) Sulfasalazine and reduction:
v) Sulfacetamide i) Co-trimoxazole
vi) Silver
Sulphadiazine
vii) Mafenide
viii) Sulfadoxine
Classification of Sulfonamides:
USED FOR THE Used topically in eye:
TREATMENT OF Sulfacetamide*
LOCAL INFECTIONS
Used topically on skin
in burns:
Gastrointestinal
Infections: Silver Sulfadiazine.*
 Sulfasalazine* Used topically in skin
 Sulfaguanidine & ENT infections:
 Sulfapyridine Mafenide*
 Saccinyl sulfathiazole
Classification of Sulfonamides:
FOR TREATMENT OF SYSTEMIC
INFECTIONS

SHORT ACTING:
 • Sulfadiazine
 • Sulfadimidine
 • Sulfanilamide
INTERMEDIATE ACTING:
 • Sulfamethoxazole
 • Sulfafenazole
LONG ACTING:
 • Sulfamethoxy-pyridazine
 • Sulfadimethoxine
 • Sulfadoxine
 Mechanism Of Action of
Sulfonamides
Competitive antagonists of PABA. Hence they
interfere and prevent the normal utilization of
PABA for the synthesis of Folic Acid
(Pteroylglutamic Acid).

More Specific: Pteridine + PABA

Sulfonamides
Dihydroptero
ate
Synthetase

Dihydropteroic
Acid
Mechanism Of Action of Trimethoprim

Selectively inhibits bacterial dihydrofolate reductase

which converts dihydro folic acid to tetrahydro folic
acid.
Mechanism Of Action of trimethoprim
Pteridine + PABA

Blocked By
Sulfonamides

Dihydropteroic Acid
glutamate

Dihydrofolic acid
NADPH
Blocked By
NADP
Trimethoprim
Tetrahydrofolic Acid
 Inhibited by
SULFONAMIDES Dihydropteroate
synthase

Folic Acid
Synthesis in
Bacteria
 Mechanism of Resistance of sulfonamides
Natural Resistance:
 Bacteria which do not produce their folic acid are
resistant. Bacteria which utilize exogenous folic
acid are resistant to sulfonamides.

Acquired resistance:
Alteration in site of dihydropteroate
synthase
Decrease in cellular permeability
Enhance production of natural substrate
(PABA)
 Mechanism of Resistance of Trimethoprim
Resistance:
 Reduced cell membrane permeability
 Overproduction of dihydro folate reductase
 Production of altered dihydro folate reductase
with decreases drug binding affinity.
& Trimethoprim
 Some Sulfonamides used alone:
 Sulfasalazine:
This drug is poorly absorbed from GIT, hence used in
treatment of IBD ( Ulcerative Colitis) and regional
enteritis.
Note: sulfasalazine can cause reversible infertility in
males due to change in sperm number and
morphology.
Silver sulfadiazine:
This drug inhibits nearly all pathogenic
bacteria and fungi including those resistant to
other sulfonamides.

Indications:
used topically to reduce microbial colonization and
incidence of infections of wounds from burns.
(Mafenide is an alternative)

Contraindication:
Should not be used in deep infection and known
hypersensitivity.
Sulfacetamide:
This drug is usually used in ophthalmic
preparations.Because of its water solubility
it has very high aqueous concentrations are
less irritant than other sulfonamides.
 Adverse effects of sulfonamides & Trimethoprim
Hypersensitivity: allergic reactions including skin
rashes and fever , exfoliative dermatitis. Cross allergy
may occur wit chemically related drugs
(thiazides,sulfonylureas).
Stevenson’s Johnson syndrome: Fatal skin and mucous
membrane eruption.
Adverse effects of sulfonamides & Trimethoprim

Stomatitis, Conjunctivitis, arthritis, Hepatitis,

Polyarthritis nodosa and psychosis.

Nephrotoxicity: they may precipitate in the urine

at acidic pH, causing crystalluria and
hematuria.adequate hydration and alkalinazation
of urine may prevent this problem.

Hematotoxicity: they are rare. Haemolytic anemia

.(G6PDdeficiency) Granulocytopenia,
thrombocytopenia and aplastic anemia
 Kernicterus: displacement of bilirubin from plasma
In New Born:

albumin, due to deposition of bilirubin in basal

ganglia and substantia nigra.
 Should not be given to pregnant ladies and new
borns.
 Rare:
Focal or diffuse hepatic necrosis (1%)
 GIT: nausea, vomiting and diarrhea.
Contraindications of Sulfonamides
 Hypersensitivity
 In patients with impaired renal functions
 In patients with impaired hepatic functions
 Pregnancy
 Lactation
 New borns < 2 months age.
 The Combinations
Inhibitors of Folate synthesis and reduction:

Sulfamethoxazole+Trimethoprim=CoTrimoxazole

The introduction of trimethoprim with combination

of sulfamethoxazole is a clinically effective
antimicrobial agent. The combination is
SYNERGISTIC and the drug becomes Bactericidal.
 Clinical indications of CoTrimoxazole
 TMP-SMX is also the drug of choice in
 cholera
 typhoid fever
 UTIs
 Pneumonia in HIV patients
 treatment of infections caused by methicillin-
resistant staphylococci (MRSA) and Listeria
monocytogenes.
 Sexually transmitted diseases(STDs)