- Sulfonamide is a class of antibacterial medications derived from p-aminobenzene sulfonamide. They act as competitive inhibitors of p-amino benzoic acid in the bacterial folic acid synthesis pathway. - Sulfonamide was the first antibacterial discovered in the 1930s and ushered in the "sulfur drug era". It works by interfering with the production of folic acid which is essential for bacterial cell division and growth. - Cotrimoxazole is a fixed-dose combination of sulfamethoxazole and trimethoprim that provides broad-spectrum antibacterial activity. It is commonly used to treat urinary tract infections, respiratory infections, and Pneumoc

1. -: PRESENTED BY :-
ASSISTANT PROF. NATHANI ZEESHAN MUNAF
(M.Pharm)
DEPT. OF PHARMACOLOGY
PROF. RAVINDRA NIKAM COLLEGE OF
PHARMACY Morane – Gondur By-Pass Road, Near
Punam Petrol Pump, Gondur, Tal. dist. Dhule- 424001
SULFONAMIDE
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2. INDEX
• Sulfonamide
• Classification
• MOA
• Pharmacokinetics
• Adverse effect
• Cotrimoxazole
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3.  Sulfonamide is anti-bacterial medications; also called sulfa-
related group of drugs.
 Sulfonamides derived from p-aminobeneznesulfonamide
 They are competitive inhibitors of p- amino benzoic acid in the
folic acid metabolism cycle in the organisms
 Which are used to treat bacterial infection and some fungal
infections.
 They are synthetic antibacterial agents where in all sorts of drug
design strategies have been applied successfully.
 It was developed as life saving drugs called era of sulfa drugs.
SULFONAMIDE
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4.  Sulfonamide was firstly noted as anti-bacterial in 1900’s by Gerhard
Domagk; a Nobel Prize winner in 1939.
 In his attempt to save his daughter from streptococci killing
infection, he observed that prontosil; a sulfonamide dye, is able to
selectively restrain the infectious bacteria cells.
 In 1936, Ernest Fourneau found out prontosil pathway in human
body.
 He discovered that this dye was a pro-drug.
 It, actually changes in human body to sulfanilamide which is the
anti-bacterial active agent.
HISTORY
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5.  his invention triggered the discoveries of other anti-bacterial
members derived from this chemical group such as sulfapyridine in
1938 against pneumonia.
 sulfacetamide in 1941 against urinary tract infections.
 succinoylsulfathiazole in 1942 against gastrointestinal tract
infections.
 Sulfathiazole was commonly used during World War II to cure
soldier wounds’ infections.
 On the contrary, sulfanilamide was not very used due to its greater
human toxicity.
 Later on, sulfisoxaide, sulfamethoxazole, sulfacetamide, mafenide
and sulfadiazine silver were discovered, and those four agents are
the sulfonamide anti-bacterial agents have been in the clinical use
so far.
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7. PRONTOSIL RED
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9. Prontosil Rubrum metabolization
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10. Structure Components
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11. Structure Analogue of PABA
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12. Classification
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13. Classification
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14. MOA
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15. Sulfonamides
The sulfonamides are bacteriostatic inhibitors of
folic acid synthesis.
As antimetabolites of PABA, they are competitive
inhibitors of dihydropteroate synthase. (It is an
enzyme use for folic synthesis)
The selective toxicity of sulfonamides results from
the inability of mammalian cells to synthesize folic
acid; they must use preformed folic acid that is
present in the diet.
MOA
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16. PABA
The structure of Folic acid
Folic acid, another form of which is known as folate, is
one of the B vitamins. Folate is essential for the body to
make DNA, RNA, and metabolize amino acids which are
required for cell division.
Humans cannot make folic acid, it is required from the diet.
MOA ( Wood-Fields Theory)
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17. MOA
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18. MOA
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19. PHARMACOKINETICS
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20. ADVERSE EFFECT
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21. COTRIMOXAZOLE
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23. COTRIMOXAZOLE
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24. COTRIMOXAZOLE
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25. COTRIMOXAZOLE
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26.  Sulfamethoxazole was selected for combining with trimethoprim because both
have nearly the same t½ (~ 10 hr).
 Optimal synergy in case of most organisms is exhibited at a concentration ratio of
sulfamethoxazole 20 : trimethoprim 1, the MIC of each component may be
reduced by 3–6 times. This ratio is obtained in the plasma when the two are given
in a dose ratio of 5 : 1, because trimethoprim enters many tissues, has a larger
volume of distribution than sulfamethoxazole and attains lower plasma
concentration.
 However, the concentration ratio in many tissues is less than 20 : 1.
 Trimethoprim adequately crosses blood-brain barrier and placenta, while
sulfamethoxazole has a poorer entry. Moreover, trimethoprim is more rapidly
absorbed than sulfamethoxazole concentration ratios may vary with time.
 Trimethoprim is 40% plasma protein bound, while sulfamethoxazole is 65%
bound. Trimethoprim is partly metabolized in liver and excreted in urine.
Sulfamethoxazole
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27. Trimethoprim
It has been argued that in certain situations trimethoprim alone may be as effective as
the combination, while majority of adverse effects are due to the sulfonamide. Thus,
wherever shown effective, trimethoprim alone may be preferred.
However, comparable efficacy of trimethoprim alone has been demonstrated only in:
1. Urinary tract infections: treatment of acute cases, suppressive treatment of
chronic and recurrent cases— especially in females.
2. Prostatitis: Trimethoprim is concentrated in prostate, but not sulfonamide.
Dose: 100–200 mg BD (children 6 mg/kg/day).
Trimethoprim
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28. COTRIMOXAZOLE MOA
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29. Spectrum of Action
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30. Resistance
 Bacteria are capable of acquiring resistance to
trimethoprim mostly through mutational or
plasmid mediated acquisition of a DHF Rase
having lower affinity for the inhibitor.
 However, resistance to the combination has been
slow to develop compared to either drug alone.
Widespread use of the combination has resulted in
reduced responsiveness of over 20% originally
sensitive strains.
Resistance
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31. Preparations SEPTRAN, SEPMAX, BACTRIM, CIPLIN, ORIPRIM, SUPRISTOL,
FORTRIM
Trimethoprim Sulfamethoxazole
8 0 mg + 400 mg tab: 2 BD for 2 days then 1 BD.
160 mg + 800 mg tab: double strength (DS); 1 BD.
2 0 mg + 100 mg pediatric tab.
4 0 mg + 200 mg per 5 ml susp; infant 2.5 ml (not to be used in newborns), children 1–5
yr 5 ml, 6–12 year 10 ml (all BD).
160 mg + 800 mg per 3 ml for i.m. injection 12 hourly. (CIPLIN, ORIPRIM-IM)
8 0 mg + 400 mg per 5 ml for i.v. injection (WK-TRIM, ORIPRIM-IV) 10–15 ml BD.
Cotrimazine It is a combination of trimethoprim with sulfadiazine. Its utility is similar to that
of cotrimoxazole.
Trimethoprim Sulfadiazine
90 mg + 410 mg: TRIGLOBE, ULTROX tab and per 10 ml susp.; 2 tab BD
for 2 days, then 1 BD.
180 mg + 820 mg: TRIGLOBE FORTE, ULTROX DS tabs.
Preparations
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32. 1. Urinary Tract Infections
Most acute uncomplicated infections respond rapidly. Single dose therapy with 4 tablets of cotrimoxazole has been recommended for acute
cystitis. Courses of 3–10 days have been advised for lower and upper urinary tract infections, according to associated features. It is specially
valuable for chronic and recurrent cases and in prostatitis, because trimethoprim is concentrated in prostate.
2. Respiratory Tract Infections
Both upper and lower respiratory tract infections, including chronic bronchitis and faciomaxillary infections, otitis media caused by gram
positive cocci and H. influenzae respond well.
3. Typhoid
Initially cotrimoxazole was an effective alternative to chloramphenicol. However, in many areas resistant S. typhi have appeared, and now it is
seldom used. Sensitive strains of S. typhi respond to one DS tab BD for 2 weeks.
4. Bacterial Diarrhoeas And Dysentery
Cotrimoxazole may be used for severe and invasive infections by Campylobacter, E. coli, Shigella and Y. enterocolitica (see p. 661). Though
response rate is lower than previously, and fluoroquinolones are more commonly used, it is effective in ampicillin resistant cases.
5. Pneumocystis jiroveci
Pneumocystis jiroveci causes severe pneumonia in neutropenic and AIDS patients. Cotrimoxazole has prophylactic as well as therapeutic value,
but high doses are needed. One DS tablet 4–6 times/day for 2–3 weeks may be curative, but adverse effects necessitate discontinuation in upto
20% cases. One DS tab. daily has been used for prophylaxis and is better tolerated.
6. Chancroid Cotrimoxazole (800 + 160 mg) BD for 7 days is a 3rd choice inexpensive alternative to ceftriaxone, erythromycin or ciprofloxacin.
USES
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33. Adverse effects
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