sulphonamides and their classification

1. SULPHONAMIDES
UTTARA JOSHI

2. DESCRIPTION
• One of the oldest antibacterial agents
used to combat infection
• Used for coccal infection in 1935
• They are bacteriostatic because it
inhibits bacterial synthesis of folic acid
• Clinical usefulness has decreased
because of the effectiveness of other
antibiotics and penicillin

3. Antimicrobial activity
1) Sulfonamides have a wide range of antimicrobial
activity.
G+,G- bacteria, Nocardia, Chlamydia trachomatis,
etc.
Enteric bacteria etc. less effective
2) Sulfonamides exert only bacteriostatic effect.

4. PRONTOSIL
Building on Ehrlichs early work, Gerhard
Domagk, a medical doctor employed by a
German dye manufacturer made a
breakthrough discovery by finding that a
dye known as prontosil, dosed orally, was
effective in curing life threatening
streptococci infections in humans. He
made the discovery in a desperate, but
successful attempt to save his daughter
who was dying of a streptococci infection.
German bacteriologist and pathologist who was awarded the
1939 Nobel Prize for Physiology or Medicine for his
discovery (announced in 1932) of the antibacterial effects of
Prontosil, the first of the sulfonamide drugs.

5. CHEMISTRY OF SULFONAMIDE
4- Recognized since 1932.
4- In clinical usage since 1935.
4- First compounds found to be effective antibacterial
agents in safe dose ranges.
4- Chemically, it is a molecule containing the sulfonamido
(sulfanilamide, SO ,NH2) functional group attached to an
aniline.
I Structurally related to p-amino benzoic acid (PABA).
4- This group is also present in other non-antibacterial
compounds like
-Sulphon ureas -Benzothiazids
-Furosemide They act as antimicrobial agents by inhibiting
-Acetazolamide bacterial growth and activity and commonly
called sulfa drugs.

6. MECHANISM OF SULFONAMIDE
4- Sulfonamide molecular structure is similar to p-Amino
benzoic acid (PABA) which is needed in bacteria organisms as
a substrate of the enzyme dihydric prorate synthetize for the
synthesis of Tetra Hydro Folic acid (THF).
4- Folic acid - synthesized from PABA, pteridine and
glutamate.
4- All sulfonamides are analogs of PABA.
4- All sulfa drugs are bacteriostatic.

8. Mechanism of action
Structural analogs of para-amino benzoic acid
(PABA)
Inhibit dihydropteroate synthase - needed for
folic acid synthesis
Prevent normal bacterial utilization of
PABA for the synthesis of folic acid
Sulfanilamide

9. Mechanism of action
• Sulfonamides are a competitive inhibitors of
dihydropteroate synthetize which is a vital enzyme for the
synthesis of tetrahydrofolate ( Coenzyme F).
• Tetrahydrofolate is important for pyrimidine nucleic acid
synthesis so the bacteria can no longer grow and divide
which gives time for the host immune system to destroy the
bacterial cells.
• Sulfonamide is not recommended in patients with weak or
impaired immune system.
• This binding is reversible.
• Because of that sulfonamides have bacteriostatic effect not
bactericidal.

10. Mechanism of action
Sulfonamides mimic P-aminobenzoic acid (PABA) which is
the normal substrate for dihydropteroate synthetase. This
means that sulfonamide will bind in the same
manner as PABA:
PABA in the active site Sulfonamide in the active site

11. Mechanism of action
• Because sulfonamides are competitive inhibitors
for the enzyme, the bacteria can increase the
production of PABA to compete with sulfonamide
at the active site and become resistant to sulfa
drugs.
• In such case, the dose of sulfonamide agents
should be increased to overcome this resistant
mechanism. But this high dose is accompanied
with an increase in side effects especially the
crystalluria.

12. Mechanism of action
• In human, the cell synthesized tetrahydrofolate
from folic acid that obtained from food sources.
This folic acid is normally transported to inside
the cell by special transport system.
• Bacterial cell does not have such transport
system and they should synthesize
tetrahydrofolate using PABA.
• For that reason, human cells do not need
dihydropteroate synthetaze enzyme which means
sulfonamides have selective antibacterial activity.

13. Structural Similarity :

14. Mammalian Folate
biosynthesis
Dihydrofolate
reductase
i Tetrahydrofolate
DNA synthesis

16. Sulphonamides-
 Sulphadiazine,
Sulphaguanidine,
Phthalylsulphathaizole,
Succinylsulphathiazol,
 Sulphadimethoxine,
Sulphamethoxypyridie,
Co-trimoxazole,
sulfacetamide*

17. Properties:
1. It is a white or whitish-yellowish crystalline powder.
2. It is having characteristic odour.
3. It is having bitter taste.
4. It is practically insoluble in water
5. It is soluble in solutions of alkali hydroxides &carbonates,& in
dilute solutions of mineral acids.
Storage:
It should be stored in well closed container at cool place away
from direct sunlight
N1- (pyrimidine-2yl) sulphanilamide
SULPHADIAZINE

18. Use:
1. It is as anti microbial agent.
2. It is used for treatment of Meningitis
3. It is used in the treatment of Urinary tract
infection.
4. It is in Toxoplasmosis.
5. It is used for the treatment Burn Therapy.
Official preparation:
 Sulphadiazine I.P, B.P, U.S.P
 Sulphadiazine tablet I.P, B.P
 Sulphadiazine injection I.P
 Sulphadiazine sodium I.P
Brand name:
Atrina, Cotrizine, Trimozin

19. SULPHAGUANIDINE
N-guanidyl sulphanilamide OR N-guanidyl sulphanilamide
Properties:
1. It is a white crystalline powder.
2. It is having characteristic odour.
3. It is sparingly soluble in water
4. It is dissolves in boiling water.
5. It is darken slowly on exposure to light.

20. Storage:
It should be stored in well closed light
resistant container at cool place away from
direct sunlight.
Use:
1. It is as anti microbial agent.
2. It is used for treatment of local GIT infection
3. It is is used in the treatment of bacillary
dysentery.
Official preparation:
Sulphaguanidine I.P
Sulphaguanidine tablet I.P
Brand name:
Ganidan, Gaunimycin,
Entrogen.

21. PHTHALYL SULPHATHIAZOLE
Properties:
1. It is a white powder.
2. It is having bitter taste.
3. It is insoluble in water.
4. It is slightly soluble in alcohol
5. It is soluble in aqueous solutions of alkali
hydroxides
and mineral acids.
6. It darkens slowly on exposure to light.
Storage:
It should be stored in well closed light resistant
container at cool place away from direct sunlight.

22. Use:
1. It is as anti microbial agent.
2. It is used for treatment of intestinal
infections.
3. It is used mainly in the preparation of
bowel surgery.
4. It is in chronic ulcerative colus.
5. It is used for the treatmentintestinal
amoebiasis.
Official preparation:
Phthalyl Sulphathiazole I.P, B.P
Phthalyl Sulphathiazole tablet I.P, B.P
Brand name:
Collicitina, Talidine

23. SUCCINYL SULPHATHIAZOLE
Properties:
1. It is a white to yellowish white crystalline powder.
2. It is having characteristic odour.
3. It is very slightly soluble in water.
4. It is soluble in aqueous solutions of alkali
hydroxides
and carbonates.
5. It is slowly darkens on exposure to light.
Storage:
It should be stored in well closed light resistant
container at cool place away from direct sunlight.

24. Use:
1. It is as anti microbial agent.
2. It is used for treatment of intestinal infections.
3. It is used mainly in the preparation of bowel surgery.
4. It is in chronic ulcerative colus.
5. It is used for the treatment intestinal amoebiasis.
Official preparation:
Succinyl Sulphathiazole I.P, B.P
Succinyl Sulphathiazole tablet I.P, B.P
Brand name:
SS Thiazole, Cremomycin, Cremostep, Sulphmycin.

25. SULPHADIMETHOXINE
Properties:
1. It is a creamy white crystalline powder.
2. It is having characteristic odour.
3. It is insoluble in water
4. It is moderately soluble in alcohol.
5. It is soluble in solutions of alkali hydroxides and
mineral acids.
Storage:
It should be stored in well closed container at cool
place away from direct sunlight.

26. Use:
1. It is as anti microbial agent.
2. It is used for treatment of systemic infection.
3. It is is used in the treatment of urinary tract
infections.
Official preparation:
Sulphadimethoxine I.P, B.P
Sulphadimethoxine tablet I.P, B.P
Brand name:
Bensulfa, Sulfadren, K-prim

27. SULPHAMETHOXYPYRIDAZINE
Properties:
1. It is a white to yellowish white crystalline powder.
2. It is having characteristic odor.
3. It is having bitter taste.
4. It is very slightly soluble in water and alcohol.
5. It is soluble solutions of alkali hydroxides and
mineral acids.
Storage:
It should be stored in well closed container at cool
place away from direct sunlight.

28. Use:
1. It is as anti microbial agent.
2. It is used for treatment of systemic infection
3. It is is used in the treatment of Conjunctivitis,
Trachoma.
4. It is in urinary tract infections.
5. It is topically used for the treatment of acne and
seborrhic
dermatitis.
Official preparation:
Sulphamethoxypyridazine I.P, B.P
Sulphamethoxypyridazine tablet I.P, B.P
Brand name:
Dyrasul, Confin

29. CO-TRIMOXAZOLE
Introduction:
Cotrimoxazole is the combination of two drugs i.e.
Sulphamethoxazole and Trimethoprim
Co-trimoxazole mixture contains 5 parts of sulphamethoxazole
and 1 part of trimethoprim.
These two drugs produce overtly similar effects; will sometimes
produce increased effects when used concurrently.
Sulphonamides block the biosynthesis of folic acid from p-
amino
benzoic acid.
Trimethoprim inhibits the enzyme folate reductase and blocks
the
conversion of folic acid to tetrahydofolic acid (THF).
THF is the form required for coenzyme synthesis.
Combination of Sulphamethoxazole and Trimethoprim by
synergism produces bactericidal effect.

31. Use:
1. It is as anti microbial agent.
2. It is mainly used in treatment of;
Urinary tract infection
Upper and Lower respiratory infection (URTI and LRTI)
Skin and wound infection Septicemias
In systemic infection.
Official preparation:
Cotrimoxazole Tablets I.P., B.P.C.
Cotrimoxazole Mixture B.P.C.
Cotrimoxazole Injection B.P.C.
Cotrimoxazole Dispersible tablets B.P.C.
Pediatric Cotrimoxazole mixture B.P.C.
Cotrimoxazole Oral suspension I.P.
Brand name:
Bactrim, Bactrimel, Co-trimoxazole, Cotrim, Septra, Sulfatrim,
Biseptol, Trisul, Bactrom, Septram, Vactrim, Bibactin

32. SULPHACETAMIDE
N-acetyl sulphanilamide
or
N1-acetyl sulphanilamide
Properties:
1. It is a white crystalline powder.
2. It is having characteristic odor.
3. It is having bitter taste.
4. It is soluble in water and alcohol.
5. It is very soluble in hot water and solutions of
alkali
hydroxides and mineral acids.
Storage:
It should be stored in well closed container at
cool
place away from direct sunlight.

33. Use:
1. It is as anti microbial agent.
2. It is used for treatment of eye infection
3. It is is used in the treatment of Conjunctivitis, Trachoma.
4. It is in urinary tract infections.
5. It is topically used for the treatment of acne and seborrhic
dermatitis.
Official preparation:
Sulfacetamide I.P, B.P
Sulfacetamide sodium I.P, B.P
Sulfacetamide sodium eye ointment I.P, B.P
Brand name:
Albucid, Locula, Ne-Ba-sulf, Eycula, Cetamide, Isopto Cetamide,
Sodium Sulamyd, Sulf-10