Sulfonamides were the first antibacterial agents discovered with prontosil. They are effective against many bacterial infections but resistance emerged quickly. Their current use is limited except in combination with trimethoprim or pyrimethamine. Sulfonamides work by inhibiting bacterial folate synthase. They have varied absorption and excretion profiles and are used for infections like pneumonia, UTIs, and toxoplasmosis when combined with other drugs. Adverse effects include nausea, rashes, and blood abnormalities.

1. Dr. R. Mirunalini
Asst. Professor
Dept. of Pharmacology

2. SULFONAMIDES
- First antibacterial agents- prontosil
- Effective against pyogenic bacterial infections.
- Rapid emergence of bacterial resistance and
the availability of many safer and more effective
antibiotics ,their current utility is limited except
in combination with trimethoprim[as
cotrimoxazole] or pyrimethamine [for malaria].

3.  Sulfonamides
 Trimethoprim/ Iclaprim
 Pyrimethamine

4. SULFONAMIDES
1.SHORT ACTING(4-8 hrs)
Sulfadiazine,sulfisoxazole
2. INTERMEDIATE ACTING(8-12 hrs):
Sulfamethoxazole ,sulfamoxole
3.LONG ACTING(7 days):
Sulfadoxine,sulfamethopyrazine
4.SPECIAL PURPOSE SULFONAMIDES:
Sulfacetamide,
Silver sulfadiazine,,Mafenide,
Sulfasalazine

5. ANTIBACTERIAL SPECTRUM
SENSITIVE ORGANISMS ARE:
Strepto pyogenes, Haemophilus influenzae,
Vibrio cholerae.
Staph.aureus, gonococci, meningococci,
Pneumococci, Escherichia coli, and Shigella but majority
resistant.
Anaerobic bacteria are not susceptable.

6. MECHANISM OF ACTION
Sulfonamide structural analogues of PABA,
Inhibit bacterial folate synthase to form folic
acid.
Sulfonamide competitively inhibit union of
PABA with PTERIDINE residue to form
dihydropteroic acid which conjugate with glutamic
acid to produce DIHYDROFOLIC ACID.

7. MECHANISM OF ACTION

8. PHARMACOKINETIC
ASPECTS:
 Most sulfonamides are readily absorbed in
the gastrointestinal tract and reach maximum
concentration in the plasma in 4-6 hours.
 risk of sensitization and allergic reactions.
 The drug pass into inflammatory exudate and
cross the placental and blood brain barriers.
 They are metabolized mainly in liver

9. SULFADIAZINE:
Rapidly absorbed orally and rapidly excreted in urine.
It is 50% plasma protein bound and 20-40% acetylated .
Good penetrability in brain and CSF
DOSE:0.5g QID to 2g TDS;SULFADIAZINE 0.5g tab.
SULFAMETHOXAZOLE:
Slower oral absorption and urinary excretion. t1/2 is 10
hrs.
used in combination with trimethoprim(septran)
because of similar half life period.
DOSE:1g BD for 2 days.then 0.5g BD.,GANTANOL 0.5g tab.
SULFADOXINE,SULFAMETHOPYRAZINE:
high plasma protein binding and slow renal excretion.
used in combination with pyrimethamine(laridox) for
malaria, Pneumocystis jiroveci pneumonia in AIDS and in
toxoplasmosis.

10. CONT…SULFACETAMIDE SOD:
highly soluble compound.
mild irritation to eye in concentration upto 30%.
used for occular infection by susceptable bacteria and
chlamydia,Including opthalmia neonatorum
MAFENIDE:
It is employed for burn dressing to prevent infection, but
not to treat already infected case.
it cause burning sensation and severe pain. when applied in
raw surface.
cause acidosis ,hyperventilation, allergic reactions.
SILVER SULFADIAZINE:
used as 1% cream active against many bacteria and fungi.e.g
Pseudomonas.
to prevent infection of burns and chronic ulcers.

11. CLINICAL USES OF
SULFONAMIDES:
 Combined with trimethoprim (co-
trimoxazole) for Pneumocystis carinii.
 Combined with pyrimethamine for drug
resistant malaria and for toxoplasmosis.
 In inflammatory bowel disease and as an
anti inflammatory drug-sulfasalazine
(sulfapyridine aminosalicylate combination)
is used.
 For infected burns silver sulfadiazine given
topically)
 For some sexually transmitted
infection(trachoma,chlamydia,chancroid)

12. CONT…
 For respiratory infections (e.g.infection
with Nocardia)
 For acute urinary tract infection.
 Ocular infection ; sulfacetamide sod.(10-
30%) a cheap alternative in trachoma
,inclusion conjunctivitis though additional
systemic azithromycin or tetracycline is
required for eradication of disease.
 For streptococcal pharyngitis and gum
infection .

13. ADVERSE EFFECTS
 Nausea ,vomiting, epigastric pain.
 Crystalluria-dose related.
 Hepatitis-unrelated to dose.
 Hypersensitivity-Stevens johnson
syndrome and exfoliative dermatitis.
 Neutropenia and other blood dyscrasias
are rare.
 Kernicterus-new born premature.

14. COTRIMOXAZOLE.
 The fixed dose combination of
trimethoprim and sulfamethoxazole is
called COTRIMOXAZOLE.
 same T1/2(~10hr)
 Concentation ratio of sulfmethoxazole
20:trimethoprim 1
 Trimethoprim is metobolised in liver and
excreted in urine.

15. SEQUENTIAL BLOCK IN
BACTERIAL FOLATE METABOLISM:
PABA
Folate synthase
SULFONAMIDE
DHFA
dihyrofolate reductase.
TRIMETHOPRIM
THFA

16. SPECTRUM OF ACTION.
ORGANISM WHICH ARE SENSITIVE:
Salmonella typhi,
klebsiella,
Staph aureus,
Strep pyogenes
shigella
Pneumocytis jiroveci
H.influenza
E.coli

17. Uses:
1.Urinary tract infection/ prostatitis
2.Respiratory tract infection.
3.In case of typhoid
4.bacterial diarrhoeas and dysentery
5.Used in case of severe pneumonia in
neutropenic and AIDS patients caused by
Pneumocystis jiroveci.
6.chancroid.
7.It s an alternative to penicillin.
8.Used in septicaemias.
9.Nocardiosis- DOC

18. ADVERSE EFFECTS
 Nausea,vomiting
 Headache
 Stomatitis
 Rashes
 Blood dyscrasias
 Folate deficiency
 neonatal haemolysis.

19. Summary
 Sulfanomides
 Trimethoprim
 Pyrimethamine