SULFONAMIDES
Prof. Amol B. Deore
Department of Pharmacology
MVPs Institute of Pharmaceutical Sciences, Nashik

Introduction
•Sulfonamides were the first
antimicrobial agents effective against
bacterial infections. A large number of
sulfonamides were produced and used
extensively in the subsequent years.

But because of rapid development
of bacterial resistance and adverse
reactions, the more effective
antibiotics are preferred.
All sulfonamides may be
considered to be derivatives of
sulfanilamide.

CLASSIFICATION OF SULFA DRUGS
[1] Short-acting
Sulfacetamide, Sulfadiazine, Sulfadimidine, Sulfafurazole, Sulfisomidine
[2] Intermediate-acting
Sulfadoxine, Sulfamethoxazole, Sulfamoxole,
[3] Long-acting
Sulfadimethoxine, Sulfamethoxypyridazine, Sulfametoxydiazine,
[4] Ultra long-acting
Sulfadoxine, Sulfametopyrazine
[5] Local use
Silver sulfadiazine
[6] Ophthalmic use
Sulfacetamide

Mechanism of action of sulpha drugs
• Many bacteria synthesize their own folic acid for protein synthesis.
• Sulfa drugs are structurally similar to PABA and folic acid, but
inhibit bacterial folic acid synthesis.
• Sulfa drugs act as competitive antagonist of the enzyme
dihydropteroate synthetase (DHPS), an enzyme involved in folate
synthesis.
• Sulfonamides are therefore bacteriostatic and inhibit growth and
multiplication of bacteria, but do not kill them.
• Humans, in contrast to bacteria, acquire folic acid (vitamin B9)
through the diet.

Therapeutic uses
• Urinary tract infections
• Ulcerative colitis
• Plaque
• Respiratory tract infections
• Meningococcal meningitis
• Venereal diseases
• Chlamydial infections
• Conjunctivitis
• Protozoal infections: malaria
• Burns and skin disorders
• Vaginitis

Adverse drug reactions
• Renal damage:
• Crystalluria can cause blockade in the kidney tubules,
ureters, urinary bladder due to deposition of crystalline
aggregates of sulfa drugs or their metabolites.
• Due to deposition of crystals, haematuria, oligouria,
anuria, and uremia may occur.
• Crystalluria and obstruction can be avoided by high
fluid intake; ensuring good urine output and maintains
alkalization in the urine.

Hypersensitivity reactions: allergic skin
reactions, Stevens-Johnson syndrome,
Blood dyscarias: haemolytic anemia,
thrombocytopenia, aplastic anemia
Glucose 6 phosphate dehydrogenase
deficiency (G-6-PD)

CONTRAINDICATIONS
•In Pregnancy, liver disease impaired
renal functioning.

Sulphonamides are not used
nowadays?
•Sulphonamides are broad spectrum
bacteriostatic agents. Most of bacteria develop
resistance to Sulphonamides. Sulphonamides
are not effective in controlling infections.

Sulphonamides and their metabolites are poorly
water soluble hence produce crystalluria and
urinary obstruction.
They show hyper sensitivity reactions, such as
intolerance, fever, severe skin rashes, joint pain,
bronchospasm, toxic hepatitis, toxic nephritis,
acute haemolytic anemia.

It causes renal irritation, crystalluria, haematuria and
obstruction of urine flow, skin rashes, aplastic anemia, bone
marrow depression, Steven Johnson syndrome. Since better
drugs are available with fewer side effects for the treatment of
diseases, Hence

Sulfonamides are ineffective in presence of Pus.
• Bacteria utilize PABA for Folic acid synthesis. But sulfonamides
are competitive antagonist of PABA and folic acid synthesis.
The Pus contains large amount of PABA, hence Pus resists the
antibacterial activity of sulfonamides.

Higher doses of sulfonamides cannot be given as
it causes crystalluria and renal damage. Hence
Sulfonamides are ineffective in presence of pus.

Patients on sulfonamide therapy are advised
to drink plenty of water. Why?
• Sulfa drugs are weekly acidic and lipid soluble
molecules. They metabolize in liver to be converted into
acetylated metabolites. These acetylated metabolites
are poorly water soluble and remain unionized. Hence
they get slowly excreted through kidney.

They get precipitated in acidic PH of urine to form crystals.
These crystals form blockade in the kidney tubules,
ureters, and in urinary bladder due to deposition of
crystalline aggregates of sulfa drugs or their acetylated
metabolites. Hence Crystalluria can occur,

Due to deposition of crystals, haematuria, oligouria,
anuria, and uremia may occur. Crystalluria and renal
obstruction can be avoided by high fluid intake; ensuring
good urine output and maintains alkalinization in the
urine.

COTRIMOXAZOLE

COTRIMOXAZOLE
• Cotrimoxazole is an antibacterial drug used in treatment
of variety of bacterial, fungal and protozoal infections. It
consists of combination of one part of Trimethoprim to
five parts of Sulphamethoxazole (1:5).

Trimethoprim (TMP) is an antimalarial agent where as
Sulphamethoxazole (SMX) is sulfa drug. Both these
drugs are intermediate acting.
Combination of both drugs at 5:1 ratio (SMX 400 mg+
TMP 80 mg) shows synergistic effect 10,000 times
greater than their individual actions.

Mechanism of Action
•Sulphamethoxazole inhibits dihydropteroic acid
synthetase and trimethoprim inhibits
dihydrofolic acid reductase.
•Both these enzymes are required for conversion
of PABA into folic acid in bacterial cell.

Brand name: Septra R, Bactrim R

Therapeutic uses:
• Urinary tract infections
• Ulcerative colitis
• Plaque
• Respiratory tract infections
• Meningococcal meningitis
• Venereal diseases
• Chlamydial infections
• Conjunctivitis
• Protozoal infections: malaria
• Burns and skin disorders
• Vaginitis

Sulphamethoxazole is given in
combination with Trimethoprim. Why?
•Sulphamethoxazole is sulfa drug and trimethoprim
is an antimalarial drug. Sulphamethoxazole inhibits
dihydropteroic acid synthetase and trimethoprim
inhibits dihydrofolic acid reductase.
•Both these enzymes are required for conversion of
PABA into folic acid in bacterial cell.

Combination of both drugs at 5:1 ratio (SMX 400 mg+
TMP 80 mg) shows synergistic effect 1000 times greater
than their individual actions.
Hence Trimethoprim is given in combination with
Sulphamethoxazole.

Thanking You