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Abhinav Sawhney
M. Pharmacy (Pharmacology)
A10654913001
Amity Institute of Pharmacy
Amity University
NOIDA

2.  Sulfonamides
 Trimethoprim
 Trimethoprim & Sulfamethoxazole mixture
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3.  The discovery of sulfonamides is a significant
milestone event in the human chemotherapeutic
history. Sulfonamides are synthetic compounds
that have activity against both gram-positive and
gram- negative bacteria.
 Originally, sulfonamides were synthesized in
Germany as azodyes. In an attempt to expand on
earlier ideas of using dyes as antimicrobial agents,
a man by the name of Domagk

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6. Mechanism of Action (Wood-fields Theory)
Folic aicd Dihydrofolic acid Tetrahydrofolic acid
Coezyme F
Folate Raductase Dihydrofolate Raductase
The biosynthesis of DNA/RNA
The structure of folic acid
N
N
N
N
Pteridine
H2N
O
H
N
H
N
O
COOH
COOH
PABA Glutamic acid
Folic acid

7. HN
N N
N
H2N
O
O P
O
OH
O P
O
OH
OH
H
HN2
COOH
PABA
Dihydropteroate synthase
HN
N N
N
H2N
O
NH
COOH
Dihdropteroic acid
HN
N N
N
H2N
O
NH
CONHCHCH2CH2COOH
COOH
H
Glutamic acid
Dihydrofolic acid (DHFA)
H2N
SO2NH2
HN
N N
N
H2N
O
NH
SO2NH2
H
False Dihdropteroic acid
HN
N N
N
H2N
O
NH
CONHCHCH2CH2COOH
COOH
H
H
Tetrahydrofolic acid (THFA)
Dihydrofolate Reductase
(DHFR)
TMP

8.  Gram positive and negative bacteria
 Nocardia, chlamydia trachomatis
 Some protoza
 Some enteric bacteria
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9.  Overproduction of PABA
 Low affinity dihydropteroate synthase
 Loss of permeability to sulfonamides
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10.  Oral absorbable
 Short
 Medium
 Long
 Oral, nonabsorbable
 Serum protein bind
 20 ~ 90%
 Excreted into urine
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Drug Half-Life Oral Absorption
Sulfonamides
Sulfacytine Short Prompt (peak levels in 1–4 hours)
Sulfisoxazole Short (6 hours) Prompt
Sulfamethizole Short (9 hours) Prompt
Sulfadiazine Intermediate (10–17 hours) Slow (peak levels in 4–8 hours)
Sulfamethoxazole Intermediate (10–12 hours) Slow
Sulfapyridine Intermediate (17 hours) Slow
Sulfadoxine Long (7–9 days) Intermediate
Pyrimidines
Trimethoprim Intermediate (11 hours) Prompt

12.  Oral absorbable agents
 Sulfamethoxazole (GANTANLOL 0.5gm tab.)
 To treat urinary tract infection
 Sulfadiazine (0.5 gm QID): toxoplasmosis
 Sulfadoxine: long acting, in a combination for treatment of
malaria
 Oral nonabsorbable agents
 Ulcerative colitis, enteritis, other inflammatory bowel disease
 Topical agents
 Sulfacetamide (LOCULA 10% eye drops.): ophthalemic
 Mafenide (SULFAMYLON 1% cream): topical
 Silver sulfadiazine ( SILVIRIN 15% cream): topically
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13.  Cross allergenic sulfonamide drugs:
 Thiazide, furosemide, diazoxide, sulfonylurea
hypoglycemic agents, and others
 Fever, skin rashes, exfoliative dermatitis,photosensivity,
urticaria, nausea, vomiting, diarrhoea
 Stevens-Johnson syndrom
 Urinary tract disturbances
 Crystalluria, hemturia
 Hematopoietic disturbance
 Hemolytic or aplastic anemia
 Granulocytopenia, thrombocytopenia, leukmoid reaction
 Hemolysis in G-6PDH deficient patients
 Kernicterus in newborn of mothers have taken near the end
of pergnancy
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15.  Reduced cell permeability
 Overproduction of DHF reductase
 Altered affinity of reductase
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16.  Usually given orally alone or in combination
with sulfamethoxazole
 Mainly excreted into urine
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17.  Oral trimethoprim
 Acute urinary infection
 Oral trimethoprim-sulfamethoxazole
 Pjiroveci pneumonia, shigellosis, systemic salmonella infection,
complicated urinary tract infection,
 Active against many respiratory pathogens
 Intravenous trimethoprim-sulfamethoxazole
 Gram negative sepsis, pneumocystis pneumonia
 Shigllosis, typhoid fever
 Oral pryrimethamine with sulfanamide
 With sulfadiazine in Leishmaniasis, toxoplasmosis
 With sulfadoxine in malaria
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18.  Megaloblastic anemia
 Leukopenia, granulocytopenia
 Can be prevented by folinic acid
 The AIDS patients have high frequency of
unwanted reactions
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19.  Optimal ratio of the two drugs is 5:1 sulfa
:trimethoprim.
 Septran, Sepmax, Bactrim, Ciplin
 80mg + 400mg tab: 2 BD for 2 days
 160mg + 800mg tab (DS): 1 BD

20. Synergism

21.  Expanded number of organisms inhibited.
 Bactericidal .
 Decreased resistance.
 Decreased toxicity.

22.  SILVEZ ( silver sulfadiazine 1% w/w ) Topical
used, Laborate
 ALBUCID(Sulphacetamide 10% ointment, 10-30%
eye drop ) opthalmic , Allergan
 AUBRIL ( Sulphadiazine 410 mg + Trimethoprim
90 mg) Tablet, Novartis Pharma
 AMALAR ( Sulfadoxine 500 mg + Pyrimethamine
25 mg) tablet, Micro
 SEPTRAN ( Sulfamethoxazole + Trimethoprim 80
mg) tablet, GSK
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23.  Rang H.P; Dale M.M; etal “ Rang and Dale’s
Pharmacology, 7th edition, p.no 622-625
 Tripathi K.D. “Essentials of Molecular
Pharmacology” 6th Edn. P.no 682-687
 Goodman & Gillman, “ The Pharmacological
Basis of Therapeutics”, 12th edn
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