SULFONAMIDES AND TRIMETHOPRIM

Sulfonamides and trimethoprim are antifolate drugs.
that means, they inhibit the synthesis of folate acid..

they have similar structure to p-aminobenzoic acid (PABA)

SULFONAMIDES

Mechanism of action

• Inhibit dihydroteroate synthase enzyme in bacteria

• Inhibit bacterial growth by reversibly block folic acid synthesis(bacteriosatatic)
• Microorganisms need PABA to form dihydrofolic acid which is essential in production of purine and synthesis of DNA
• Sulfonamides compete with PABA for enzyme and eventually inhibit the enzyme

Spectrum of activity

• Broad spectrum-effective against gram +ve and gram -ve bacteria
• inhibit Chlamydia trachomatis, enteric bacteria, toxoplasma and nocardia sp.

Pharmacokinetics

• Distrubuted widely(CNS and CSF)
• Cross placenta
• Bound to plasma protein
• Exretion by urine so need to reduce dosage in renal failure patients

Clinical uses

• Sulfisoxazole + Sulfamathoxazole = treat urinary track infection
• Sulfadiazine + Pyrimethamine = treat toxoplasmosis
• Sulfadoxine + Pyrimethamine = second line agent for antimalaria
  

Adverse effects

• Hypersensitivity-fever,skin rashes, Steven-Johnson syndrome
• Nausea, vomitting and diarrhea
• Uritary tract disturbances
• Hematopoietic disturbances-can cause kernicterus in newborn baby..be aware!!

TRIMETHOPRIM

Mechanism of action

• Inhibit dihydrofolate reductase enzyme

Clinical used

• oral combination with sulfonamides produces synergistic effect
• Salmonella infection
• Traveller's diarrhea

Adverse effect

• Megaloblastic anemia
• leukopenia
• granulocytopenia
• p/s- to avaoid antifolate adverse effect;administer folinic acid