This document provides information on sulfonamides, which were the first antimicrobial agents effective against pyogenic bacterial infections. It discusses how sulfonamides work by competitively inhibiting the bacterial enzyme dihydropteroate synthetase, blocking the synthesis of folic acid. Various sulfonamides are described based on their absorption, duration of action, and clinical uses for infections like UTIs, respiratory infections, and travelers' diarrhea. Adverse effects include crystalluria, blood disorders, and hypersensitivity reactions. Sulfonamides remain important oral antibiotics but require monitoring for toxicity.

1. SULFONAMIDES

2. chemotherapy
A science of treating diseases with the help of
drugs.
The term gradually came in to use in reference to
treatment of infections, infestations, and cancers.

3. • Treatment of systemic/topical infection with
drugs that have selective toxicity for an invading
pathogens with out harming the host cells.
• Due to analogy between the pathogenic organism
and malignant cells the treatment of neoplastic
diseases with drugs is also called as Chemotherapy
»Contd.,

4. landmarks
• 1877 – Louis Pasteur – “LIFE DESTROYS LIFE”Bacteria prevented growth of anthrax bacillus in
urine
• 1891 – Paul Erlich (FATHER OF MODERN
CHEMOTHERAPY- NOBEL 1909) - methylene blue
inhibited growth of bacteria
• 1928 – Alexander Fleming: The fungus
penicillium notatum could inhibit staphylococci in
a culture plate
• 1938 – Domagk – Prontosil – a dye inhibited
micro-organisms – sulfonamides- sulfanilamide
• 1941 – Penicillin – Fleming, Florey, Chain- Nobel

5. organisms
•
•
•
•
•
•
•
•
•
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Bacteria
Fungi
Viruses
Spirochetes (Treponemes, Borrelia )
Actinomyces
Rickettsiae
Chlamydiae
Mycoplasma
Nocardia
Protozoa/parasites(ameba,giardia,trichomonas, toxoplasma)
worms (Helminths)
• Prions

6. • Obtain MO (Antibiotics)
• Antimicorbials  Syn in Lab,
• Semisenthetic antibiotics
»Contd.,

7. Mechanism of Action
• Antibiotic action can be split into 2
mechanisms:
Bacteriostatic
Bacteriocidal

8. STATIC - implications
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NO KILLING EFFECT – long period of treatment
Infection MAY NOT BE totally eradicated
ORGANISMS MAY REMAIN IN A DORMANT STAGE
MAY MULTIPLY LATER
RELAPSE
E.g. chloramphenicol for enteric fever
• COMBINATION – static drug may reduce the rate of growth – a
cidal agent cannot work effectively.

9. CIDAL - IMPLICATIONS
•
•
•
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•
KILLING EFFECT
Infection totally eradicated
Less chances of relapse
Example : ENTERIC FEVER (TYPHOID)
Chloramphenicol (static)
Cotrimoxazole, Ampi/amoxicillin, Ciprofloxacin, Ceftriaxone
(cidal)
• CIDAL drugs produce rapid effect – shortening of length of
treatment – tuberculosis (streptomycin, INH, rifampicin,
pyrazinamide)
010613
mmm

10. • Bacteriostatic Drugs arrest the growth and
replication of bacteria and limits the spread of
infection
• Bacteriostatic antibiotics hamper the growth
of bacteria by interfering with bacterial:
Protein production
DNA replication
Cellular metabolism
• Macrolids ,Broad spectrum antibiotics ,Sulfanamides
• Trimethroprim, Clindamycin, Ethambutol

11. • Bacteriocidal kill or irrverisible damage the
multiplying bacteria
• Microbe death is usually achieved by
disruption of the bacterial cell membrane
leading to lysis.
•
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Betalactum antibiotics
Cotrimoxazole, Aminoglycoside
Fluroquinolones, Vancomycin, Polymixins
Rifampicin, INH, Bacitracin

12. Spectrum of activity
• Spectrum = range of micro-organisms
inhibited
• Narrow spectrum
• Penicillin G (Benzyl penicillin) Mainly Gm +ve
• Aminoglycosides, Metronidazole – Mainly Gm
–ve
• Broad Spectrum Antibiotics: (BSA)
• TETRACYCLINES, CHLORAMPHENICOL

13. Extended spectrum
• Broader than NARROW SPECTRUM
• Narrower than BROAD SPECTRUM
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Extended spectrum penicillins
II and III generation cephalosporins
Co-trimoxazole
Sulfa drugs, trimethoprim
Quinolones
Macrolides

14. Mech
• Usually it take advantage of the biochemical
and physiological differences that exist betn
MO and human beings.

15. PROKARYOTIC
EUKARYOTIC
Size 1-10µm
10-100m
Envelope by rigid cell wall
Flexible plasma membrane
Sub cellular organs absent
present
Ill- defined nucleus
Well defined nucleus
Energy metabolism bounded to cell
membrane
Located in mitochondria
Division -- fission
mitosis
Ribosomes-70s– 30s & 50s
80s– 60s & 40s

16. Site and Mechanism of action of
Antibiotics

17. Combination therapy
• To make broaden spectrum activity
(Pulmonary, Aerobic, anaerobic)
• Increase antibacterial activity (Synergism)
• To prevent resistance (TB, leprosy)
• To reduce duration of therapy (MDT, leprosy)
• Reduce adverse effects

18. 1. As result of mutation or by plasmid mediated
1.
2.
3.
Conjugation
Transduction
Transformation
2. Producing an enzyme that inactivate antibiotic
1.
2.
3.
Betalactmase
Chloramphenicol acetyltransferase
Acetyl transferase, phosphotrans, adenyltransferase (aminoglycosides)
3. Decreased bacterial permeability or active efflux of drug.
4. An appearance of alternative pathway
5. Decreased affinity for target : Penicillin binding proteins

19. Prevention of drug resistance
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Right drug
Right dose
Right period
Prefer rapidly acting selective spectrum
Combination of AMAs whenever prolong
therapy

20. Factors affecting choice of
antimicrobial agents
Age:
– Chloramphenicol – Gray baby syndrome
– Half life amino glycosides is prolonged in elderly
– Tetracyclines – CI in below 6 years it accumulates in developing bone
and teeth
Pregnancy:
–
All antibiotics produce risk to the fetus . Penicillins, Macrolids &
Cephalosproins
Impaired host defenses
– Bactericidal drugs are must in immunocompromised patients

21. • Renal function:
CI in renal disease
Dose reduction in renal failure
cephalothin
Aminoglycosides
Cephaloridine
Amphotericin B
Nalidixic acid
Vancomycin
Nitrofurantoin
Ethambutol
• Liver function
CI in liver disease
Dose reduction in liver failure
Tetracycline
Chloramphenicol
Pyrazinamide
Isoniazid
Pefloxacin
Rifampicin
Erythromycin
Clindamycin

22. SULFONAMIDES
•Sulfonamide were the first antimicrobial agents effective against
pyogenic bacterial infections
•Anti metabolites
•Bacteriostatic agents
•GELMO 1908 – Synthesized
•Prontosil was first drug active in vivo
•In liver it converting to Sulfonamide
•These are synthetic agents(Antimicrobials)
•Originally, sulfonamides were synthesized in Germany as azodyes.

23. Gerhard Domagk (1895-1964)
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.

24. The process of discovery for sulfonamides
SO2NH2
SO2NH2
NH
2
N N
CH3CONH
N
N
NaO3S
SO3Na
H2N
Prontosil Soluble
Prontosil
NH2
SO2NH2
N
N
H2N
inactive (in vitro)
SO2NH2
Liver
[H]
H2N
active(in vivo)

25. SULFONAMIDES
• The antimicrobial containing a sulfonamido (sulfanilamide, SO4NH2)
group are called sulfonamides.
H2N
SO4-NH2
• Structurally related to p-aminobenzoic acid (PABA).
SINCE THEN :
* 5000 SYNTHESISED.
* 150 MARKETED.
* 20 IN COMMON USE.
• This group is also present in other non-antibacterial compounds like
-Sulphonureas
-Benzothiazids
-Furosemide
-Acetazolamide

26. Mechanism of action
• Folic acid - synthesized from PABA, pteridine and
glutamate.
• All sulfonamides are analogs of PABA.
• SA compete with this substrate for the bacterial
enzyme, dihydropteroate synthetase.
• All sulfa drugs are bacteriostatic.

27. Folic acid synthesis inhibitors
pterdine + para-amino benzoic acid
Dihydropteroate
synthetase
dihydropterate
Sulphamethoxazole
(Sulphonamides)
Structural analogues of
PABA
dihydrofolate
Dihydrofolate
reductase
tetrahydrofolate (folinic acid)
Trimethoprim
(Diaminopyrimidines)
Binding
DNA/RNA

29. Antimicrobial effects
Both G+ & G- bacteria, nocardia,
chlamydia trachomatis, some
protozoa, some enteric bacteria (E coli,
klebsiella, salmonella, shigella, &
enterobacter)
Sulfonamides stimulate rickettsiae in
their growth.

30. CLASSIFICATION
Orally absorbable agents
• Short acting(6-9hrs.)-
Sulfadiazine
Sulfacytine
Sulfamethizole
Sulfisoxazole
• Intermidiate acting(10-12hrs.)Sulfamethaxazole
Sulfamoxole
• Long acting(7days)Sulfadoxine
sulfamethopyrazine
Orally non absorbable agents
Sulfasalazine
Olsalazine
Topical agents
Silver sulfadiazine
Sulfacetamide
Mafenide

31. Pharmacokinetics
• Absorbed rapidly from the gastrointestinal tract (except topically
used ).
Peak plasma levels are achieved in 2-6hrs.
• widely distributed and pass through BBB as well as placental barrier.
• Never administered SC & IM (Very painful)
• Metabolized as acetylated conjugates in liver.
Acetylated metabolites are inactive and low soluble in acidic urine,
leads to ppt. of crystaluria and renal toxicity.
• Excreted through the glomerular filtration in urine.

32. COTRIMOXAZOLE
COMBINATION OF : Fixed dose combination
SULPHAMETHAXAZOLE : TRIMETHOPRIM.
5
:
1
400 mg. 800mg
:
80 mg. 160mg
M. A. O.
PABA
F.A. SYNT.
SULPHA
FOLIC ACID
D. H. F. R. THFA
TRIMETHOPRIM
- SEQUENTIAL BLOCK.
- Broad spectrum bactericidal combination.
- Delays the development of bacterial resistance

33. Clinical use
Oral sulfonamides
• Cotrimoxazole
UTIs –Actue uncomplicated
• E.coli, Proteus
• 5 -10 days cotrimaxozole DS BD
Prostatis• concentrated in prostatic fluid
• Acute prostatis – DS tablet BD- 3weeks
• Chronic – 6-12 week

34. Respiratory tract infections- DS tablet BD
• Frequent choice for acute sinusitis, bronchitis,
otitis media due to Pneumococcus and
Haemophilus
Thyphoid- (Ciprofloxacin DOC)
• Alternative drug
• DS tablet BD- 2week
• 10-12 week course eradicate carrier state
Salmonella typhi

35. Bacterial diarrhoea and Dysentery (Ds tablet Bd 7
days)
Gastroenteritis
- Shigella & Yersinia entrocolitica
Traveler's diarrhoea - E.coli
Cholera
- Vibrio cholerae
Nocardiosis (Sulfadiazine)
Pulmonary lesions or Brain abscess -DOC

36. STD DS tablet BD for 7-10days
– Chancoroid- Haemophilus ducreyi
(Chancoroiod – highly infectious nonsyphilitic venereal ulcer)
– Lymphomagranuloma – Chalamydia
– Gonorrhoea- Neisseria gonorrhoea
Pneumonia
• Prophylactic DS tablet OD
• Curative – DS 4 times a day for 2-3 week
Sulfadiazine + Pyrimethamine
• 1st line Acute Toxoplasmosis
• Folinic acid 10mg each day to minimize bone marrow
suppression

37. • IV cotrimoxazole - 80mg Trimetho + 500mg
Sulfamethoxazole in 5ml diluted in 125ml of
5% dextrose infusion over period 60-90min
• Preferred for moderate to severe
– Pneumocytis carinii-pneumonia
– Shigellosus
– Thyoid fever
– Nocardiosis
– Gram –ve bacterial sepsis

38. Sulfadoxine + Pyrimethamine
combination
• Sequential block in protozoal folic acid synthesis
• Clinical curative for choloro qunine resistance P.
Falciparum (1500mg sulfadoxine+ 75mg Pyri)
sulfadoxine 500mg + Pyrimethamine 25mg (1:20)
• Pyrimethamine + sulfadoxine in toxoplasmosis

39. Oral non absorbable
• Sulfaslazine
Poorly absorbed by GIT
Bacterial flora
5 Aminosalicyclic acid + sulfapyridine
Anti inflammatory activity
Ulcerative colitis
Anti bacterial agent
Carrier moiety for 5AMA
to reach bowel
Rheumatoid arthritis

40. Topical agents
Sodium sulfacetamide- 10%, 20%, 30%
• Ophthalmic solution or ointment – conjunctivitis
Mafenide acetate
Prevent bacterial colonization and infection
of burn wounds,
Silver sulfadiazine
For prevention of infection of burn wounds

41. Adverse effects
Crystalluria and renal toxicityAdequate intake of water
By making urine alkaline
Blood
Hemolytic and aplastic anemia (G6PD def.)
Thrombocytopenia
Hypersensitivity
Photosensitivity
Exfoliative dermatitis
Eosinophelia

42. • Kernicterus in neonates– Sulfonamides displace bilirubin from protein binding
– Free bilirubin gets diposited in basal anglia, subthalamic
nuclei - toxic encephalopathy
– Avoided in neonates & pregnancy (last trimi)
• GI Nausea, vomiting, diarrhea, pancreatitis

43. •
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R- Rash
A- Acetylation
S- Systemic lupus erythromatus
H- Heamolysis in G6PD
A- Aplastic, Megaloblastic anemia
B- Bilirubin displace
C- Crystalluria

44. Resistance to Sulfonamides
① Over-production of PABA
② Produce dihydropteroate synthase with
low sulfonamide affinity
③ Loss permeability to the sulfonamide
④ Use exogenous sources of folate;

45. CONTRAINDICATIONS
• Pregnancy (full term)
• Newborn and infant (<2months)
• Patients on Methenamine, Tolbutamide, oral
anticoagulants.

46. THANK Q