Artificial Synthetic Antimicrobial Drugs-Sulphonamide.,HISTORY,bacteriostatic.Prontosil Red Trimethoprim (Cotrimoxazole) as antiBacterial Pyrimethamine (Cotrimazine) as anti-Malarial ANTIMICROBIAL ACTIVITY,BROAD-SPECTRUM,G+ bacteria: group A Streptococcus pyogenes Streptococcus pneumoniae. G- bacteria: meningococcus, Gonococcus, Escherichia coli, shigella Others: bacillus anthracis, Nocardia actinomyces, Chlamydia trachomatis, and some protozoa. Sulphonamides (Members),SYSTEMIC USE i.Short Acting (4-8hrs) sulpha methizole sulpha salazine Sulpha cytine Sulfisoxazole Sulfa diazine Less protein bound, Penetrates BBB- Meningitis Acetylated product is less soluble and cause for crystalluria Intermediate acting (8-12 hrs) Sulphapyridine Sulphamethoxazole ,Long acting (> 12 hrs) Sulphadoxine - Sulphamethoxypyrazine Mechanisms of action,Pharmacokinetics CLINICAL USES 1.SYSTEMIC INFECTIONS Cerebral meningitis Tympanitis Uncomplicated urinary tract infections urinary tract infections, respiratory infections, GI infections (2) INTESTINAL INFECTIONS Ulcerative colitis, enteritis, other inflammatory bowel disease sulfasalazine (3) INFECTIONS OF BURN AND WOUND Sulfadiazine sliver

1. Vijay Salvekar
Department
of
Pharmacology

2. HISTORY
1932 Gerhard Domagk
• Discovered protective aspects of Prontosil (azo dye)
– 1933 Prontosil given to 10 month old girl who
survived
– 1935 Sulfa first used in US unsuccessfully
– Late 1930’s sulfanilamide derivatives synthesized
• Increase efficacy and decrease side effects
– 1968 Sulfa combined with Trimethoprim
Suphonamides (Sulfonamides)
[F=USA, Ph=UK]

4.  1st chemotherapeutic agent effectively used to treat
general infections.
Also called sulfa drugs. bacteriostatic.
Prontosil Red (sulfonamide chrysoidine dye) –
 by- Domagk – for – streptococcal infection.
 Broken down in body –
 into- Sulfanilamide(Active against bacteria)

5. Use increased –Overuse- Development-
Resistance
Rarely used (alone) today due to
◦ Availability of safer and effective antibiotics
At present, most sulfonamides have been
substituted by other new antimicrobial drugs.

6. Sulfonamides today used as combination
 Trimethoprim (Cotrimoxazole) as antiBacterial
Pyrimethamine (Cotrimazine) as anti-Malarial.
TB in PM

7. ANTIMICROBIALACTIVITY
Spectrum of activity: BROAD-SPECTRUM
G+ bacteria: group A
Streptococcus pyogenes
Streptococcus pneumoniae.
G- bacteria:
 meningococcus,
Gonococcus, Escherichia coli, shigella
 Others: bacillus anthracis, Nocardia
actinomyces, Chlamydia trachomatis, and
some protozoa.

8. Sulphonamides (Members)
SYSTEMIC USE
i.Short Acting (4-8hrs)
•sulpha methizole
• sulpha salazine
•Sulpha cytine
•Sulfisoxazole
•Sulfa diazine
•Less protein bound,
•Penetrates BBB- Meningitis
•Acetylated product is less soluble and cause for
crystalluria

9. Intermediate acting (8-12 hrs)
•Sulphapyridine
•Sulphamethoxazole –
•Combination with Trimethoprim,
( Cotrimoxazole)
• High fraction is acetylated and may lead
to Crystalluria

10. Long acting (> 12 hrs)
•Sulphadoxine -
•Very high plasma protein binding and slow
renal excretion,
•Longest acting,
•Used in malaria, Toxoplasmosis,
Pneumocystis,
•Sulphamethoxypyrazine

11. Special purpose Sulfonamides
II.LOCAL USE
1.opthelmic
Sulphacetamide-
• ex. Ocular drops

12. 2.TOPICAL
Mafenide –
•Active in presence of
•Pus and Pseudomonas
•Produces severe burning
•Can alkalinize urine,
•Produce Acidosis, & Hyperventilation

13. Silver sulfadiazine –
•Releases silver ions (antimicrobial)
•Burn dressing,
•May be absorbed

14. Mechanisms of action
Sulfonamides could compete for
dihydrofolic acid synthetase with PABA
(para aminobenzoic acid)and affect the
synthesis of dihydrofolic acid.
Susceptible bacteria need PABA because
they are incapable of using folic acid directly
Human cells use exogenous folic acid
exclusively and thus a lack of PABA does not
affect them.

15. Sulfonamides (MOA)
Dihydropteridine + PABA
Sulfonamides (PABA analogues)
Sulfomethoxazole (Bacterial)
Sulfadiazine (Bacterial)
Sulfodoxine (Malarial)
Dihydropteroic acid Synthetase
Dihydropteroic acid
Glutamate
Dihydrofolic Acid
Timethoprim (Bacterial) /
Pyrimethamine (Malarial)
Dihydrofolate Reductase
Tetrahydrofolic Acid
Nucleic Bases
Amino Acids
RNA
DNA
Proteins
Folic
Acid
Dihydrofolate
Reductase
(Mammalian)
+ Cotrimoxazole
Cotrimazine
Static
Cidal
Static

16. Sulphonamides
Spectrum
•Primarily bacteriostatic
•Both Gram positive and gram negative
Resistance is due to
•Increased production of PABA
•Folate synthetase affinity Less
•Adoption of alternate pathway in folate
metabolism

17. Pharmacokinetics
1.ABSORPTION:
 Orally absorbed
 Absorbed from the stomach and small intestine
 Found in serum and urine 30 min after ingestion
 Peak plasma level obtain in 2 – 6 hr

18. 2. Distribution:
 Distributed widely to tissues
 body fluids (CSF), placenta, and fetus.
 Plasma protein bound 20 -95%
 Half lives range -2.5 to 17 hr
 Sulfadiazine and sulfisoxazole may be effective
in meningeal infections .

19. •3) METABOLISM:
Metabolized in the liver by acetylation
By microsomal acetyl transferase
Acetylated metabolites inactive but
Produce Crystalluria

20. 4.EXCRETION:-
Eliminated mainly in the urine as the unchanged
drug and metabolic product
In acid urine, the eliminated are insoluble and may
precipitate, thus induce renal disturbance.

21. 1.SYSTEMIC INFECTIONS
 Cerebral meningitis
Tympanitis
 Uncomplicated urinary tract infections
 urinary tract infections, respiratory infections, GI
infections
(2) INTESTINAL INFECTIONS
Ulcerative colitis, enteritis, other inflammatory bowel
disease
 sulfasalazine
(3) INFECTIONS OF BURN AND WOUND
Sulfadiazine sliver
CLINICAL USES

22. ADVERSE REACTIONS
1. HYPERSENSITIVITY
Skin rash and fever is common
Stevens-Johnson syndrome is rare, but is a serious and
potentially fatal type of skin and mucous membrane
eruption
2. GASTROINTESTINAL EFFECTS
Nausea, vomiting, and diarrhea is common
Mild hepatic dysfunction, hepatitis is uncommon

23. ADVERSE REACTIONS CONT.
3. URINARY TRACT DISTURBANCES
May precipitate in acid urineCrystalluria and hematuria
4. HEMATOPOIETIC DISTURBANCES
Rare
Granulocytopenia, thrombocytopenia, and aplastic anemia
Acute hemolysis in G-6PD
Kernicterus in newborn