4. Introduction
Folic acid enzymes are necessary for the synthesis of Amino
acids, hence necessary for bacterial protein synthesis.
We shall be discussing some drugs which interfere with the
synthesis of folic acid at different levels and prevent /
inhibit growth of micro-organisms
5. Sulfonamides
Sulfonamide = Sulfone + amide
Sulfonamides derivative of p-amino-benzene sulfonamide
Are commonly referred as sulfa drugs.
Are folic acid synthesis inhibitor
6. Sulfonamides Classification
Rapidly Absorbed from GIT:
i) Sulfisoxazole
ii) Sulfamethoxazole
iii) Sulfadiazine
Poorly absorbed – Active in Bowel:
i) Sulfasalazine
Topically used:
i) Sulfacetamide
ii) Silver Sulphadiazine
iii) Mafenide
Long Acting:
i) Sulfadoxine
Diaminopyrimidines
i) Trimethoprim
ii) Pyrimethamine
7. Sulfonamides can be divided into three
major groups:
1. oral, absorbable
2. oral, non absorbable
3. topical.
The oral, absorbable sulfonamides can
be classified as
1. Short acting (4-8 h): Sulfadiazine
2. Intermediate acting (8-12 h):
Sulfamethoxazole
3. Long acting ( ~ 7 days):
Sulfadoxine, Sulfamethopyrazine
Special purpose sulfonamides:
Sulfacetamide sodium,
Mafenide,
Silver sulfadiazine,
Sulfasalazine
8. Pharmacokinetics
● Sulfonamides are readily absorbed in the G.I.T and intestine and reach
maximum concentrations in the plasma in 4-6 h
● Distributed widely to tissues and body fluids (including the central
nervous system placenta, and fetus.
● metabolized in liver by acetylation (N-acetylation)
● excreted by the kidney through glomerular filtration
(Metabolites are insoluble in urine, hence crystalluriacan occur)
● In significant renal failure, the dosage of sulfonamide must be reduced.
● Therapeutic concentrations are in the range of 40–100 mcg/mL of blood.
9. Indications of sulfonamides:
1. Urinary tract infections: Sulfisoxazole and sulfamethoxazole
The usual adult dosage is 1 g of sulfisoxazole four times daily or
1 g of sulfamethoxazole two or three times daily.
2. Nocardiosis
3. Toxoplasmosis
10. Clinical Uses
● Sulfonamides are infrequently used as single agents.
● Many strains of formerly susceptible species, including
meningococci, pneumococci, streptococci, staphylococci,and
gonococci, are now resistant.
● The fixed-drug combination of trimethoprim-
sulfamethoxazole is the drug of choice for infections
such as Pneumocystis jiroveci (formerly P carinii)
pneumonia,toxoplasmosis, nocardiosis, and occasionally other
bacterial infections.
11. Effects of Sulfonamides
1. Wide range of antimicrobial
2. Activity against both Gram +ve and Gram –ve
bacteria
3. Resistant strains are produced
4. Bacteriostatic
12. Contraindications of Sulfonamides
1. Hypersensitivity
2. In patients with impaired renal functions
3. In patients with impaired hepatic functions
4. Pregnancy
5. Lactation
13. Drug Interactions
1. Oral anticoagulants
2. Sulfonylurea
3. Hydantoin anticonvulsants
( sulfonamides potentiate their effect)
Therefore Dose adjustment is required
14.
15.
16. Trimethoprim
•Bacteriostatic antibiotics.
•Diaminopyrimidine related pyrimethamine
(folate antagonist), which is selectively inhibits bacterial
dihydrofolate reducates (DHFRase).
• Trimethoprim, a trimethoxybenzylpyrimidine, selectively
inhibits bacterial dihydrofolic acid reductase, which
converts dihydrofolic acid to tetrahydrofolic acid, a step
leading to the synthesis of purines and ultimately to DNA
17. Pharmacokinetics
• Trimethoprim is well absorbed from the gut and distributed
widely in body fluids and tissues, including cerebrospinal
fluid.
Because trimethoprim is more lipid-soluble than
sulfamethoxazole, it has a larger volume of distribution
than the latter drug.
• About 30-50% of the sulfonamide and 50-60% of the
trimethoprim (or their respective metabolites) are excreted
in the urine within 24 hours.
• The dose should be reduced by half for patients with
creatinine clearances of 15-30 mL/min.
18. ADR
1. Megaloblastic anemia
2. Leukopenia,
3. Granulocytopenia
The combination trimethoprim-sulfamethoxazole
may cause all of the untoward reactions associated with sulfonamides.
Nausea and vomiting, drug fever, vasculitis, renal damage, and central nervous system
disturbances occasionally occur also.
19. Combinations
Inhibitors of Folate synthesis and reduction:
Sulfamethoxazole + Trimethoprim = Co-Trimoxazole
The introduction of trimethoprim with combination of sulfamethoxazole is a
clinically effective antimicrobial agent.
The combination is SYNERGISTIC and the drug becomes Bactericidal.
21. Summary
● Folic Acid Synthesis Inhibitors or Folate Antagonist drugs are Sulfonamides and
Trimethoprims
● They are used in combinations or alone e.g (Sulfamethoxazole + Trimethoprim =
Co-Trimoxazole)
