Sulfonamides and Cotrimoxazole

Sulfonamides and Cotrimoxazole


Sulfonamides and Cotrimoxazole


       Mechanism of action


       Drug interactions

       Clinical uses


At the end of this session, students will be able to:

       Classify sulfonamides

       Describe the mechanism of action of sulfonamide and cotrimoxazole

       Outline the adverse effects of sulfonamides and cotrimoxazole

       Discuss the therapeutic uses of sulfonamide and cotrimoxazole

Sulfonamides and Cotrimoxazole

       Sulfonamides are structural analogues of p-amino benzoic acid (PABA)

       Obtained from sulphanilamide

       -NH2 group is responsible for antibacterial property

Classification of sulfonamides

Orally absorbable agents

       Short acting sulfonamides (t1/2 6-9 h)

      Sulfacystine, Sulfadiazine, Sulfisoxazole and Sulfamethizole

       Intermediate acting sulfonamides (t1/2 10-12 h)

      Sulfamethoxazole and Sulfamoxole

       Long acting sulfonamides (t1/2 7-8 days)


Orally non absorbable agents




Topical agents

       Silver sulphadiazine



Mechanism of action

       Bacterium synthesizing its own folic acid are more susceptible

       Inhibits formation of tetra hydro folic acid

       Sulfonamides are structurally similar to PABA

       May lead to synthesis of false folic acid

       False folic acid metabolically injurious to bacteria

Mechanism of action of sulfonamides 

       Antibacterial effect of sulfonamides can be overcome if excess of PABA is present (Puss)

       Puss contains tissue breakdown product thymidine

       Thymidine could be used by bacteria to bypass the need of folic acid


       Combination of sulfamethoxazole + trimethoprim (5:1)

       Has wider spectrum of activity

       Delays development of bacterial resistance

       Synergistic action is due to blockade of folic acid syntheis at two sites

       Sulfonamides inhibits dihydropteric acid synthase

       Trimethoprim inhibits dihydrofolate reductase

Antimicrobial spectrum

       Bacteriostatic to gram positive and gram negative

       Attain bactericidal concentration in urine than in body fluids

Susceptible organisms

E. coli, Shigella, Salmonella, Haemophillus influenzae, Vibrio cholerae, Proteus, Neisseria gonorrhoeae, N. meiningitidis, Actinomycetes, Rickettsiae, Toxoplasma gondii


Mutations leading to

       Overproduction of PABA

       Alteration in the nature of DHP synthase enzyme

       Increased capacity to inactivate the drug

       Inhibition of drug accumulation

       Alternate metabolic pathway for the synthesis of essential nutrients


       Well absorbed when given orally

       Peak plasma concentration attained in 4-6 hours


       well distributed

      10-95% plasma protein bound

      In unbound form enters into body fluids like pleural, peritoneal and synovial

      Sulphdiazine & Sulfisoxazole – enters CSF


       In liver

       By acetylation

       Acetylated derivative responsible for side effects

       Accumulates in acidic urine – crystalluria

Excretion – Kidneys

Pharmacokinetics of cotrimoxazole

       Attains plasma concentration ratio of 20:1

       Trimethoprim – high entry into tissues ; less available in plasma

       Metabolised in liver

       Excreted through kidneys

       Half-life is 10 h

       Peak plasma level – Trimethoprim – 2 h and Sulphamethoxazole – 4 h

Adverse effects

       Nausea, Vomiting, epigastric pain, crystalluria

       Haemolytic anaemia, Agranulocytosis and aplastic anaemia

       Hypersensitivity reactions

       Kernicterus – bilirubin deposited in brain- encephalopathy (new born)

       Contraindicated in pregnant women and lactating mothers

Drug interactions

       Sulfonamides are enzyme inhibitors

       Inhibit the metabolism of certain drugs

       Increases activity of

      Oral anticoagulants

      Sulfonyl ureas (Antidiabetics)


Clinical uses

Orally absorbable sulfonamides

       Acute uncomplicated UTI – sulfisoxazole

       Gum infection

       Streptococcal pharyngitis


       Sodium sulfacetamide – eye drops in conjuctivitis

       Silver sulfadiazine – infection – in burn cases

       Mefanide – effective against gram positive and gram negative bacteria

Sulfasalazine – Ulcerative colitis


       Chronic UT infection

       Bacterial respiratory infection – chronic bronchitis

       GI infections- Typhoid, bacterial dysentry, diarrhoea 

       Prostrate inflammation




       Sulfonamides are structural analogues of p-amino benzoic acid (PABA) obtained from sulphanilamide

       Sulfonamides show antibacterial action via inhibition of THFA formation

       Sulfonamides are classified based on duration of action into short acting, Intermediate acting and long acting sulfonamides

       Cotrimoxazole is a synergistic combination of sulfanethoxazole and trimethoprim - used in the treatment of many infectious diseases


For PDF Notes Click on Download Button

For PPT Notes Click on Download Button

Post a Comment