folate snthesis inhibitor

Folate synthesis inhibitor
Required for DNA synthesis


PABA
dihydropetroate synthase Sulfonamide



Dihydrofolat

dihydrofolate reductase Trimethoprim


Tetrahydrofolif acid

Sulfonamide
sulfadiazine , Silver sulfadiazine, sulfamethoxazole sulfacetamide, sulfasalazine, sulfisoxazole succinylsulfathiazole, Mafenid
-static
-compete with PABA for dihydropetroate synthase so inhibit dihydrofolic acid
-against nocardia, enterobacteria in UT
- Bind to plasma Protein
-Given orally (except Sulfasalazine)
-i/v used in patient unable to taken oral preparation
-Silver sulfadiazine used in burning with sepses
-Mafenid used in burn ( painfull, acid base imbalance),
-Pass CSF, placenta
SE:
1- Crystal urea due to acidity of urine
Sulfisoxazole, sulfamethoxazole are more soluble in urinary PH
2-Hypersensitivity
3-Hemolytic anemia in G-6-PD deficiency
4-Kernicterus (in newborn) due displacement of bilirubin from albumin
DIA:
displacement of tolbutamide, warfarin, methotrexate
CI:
-newborns
-infant less than 2 month
-pregnancy
-sulfonamide react with formaldehyde (metabolite of Methenamide)
Trimethoprim
-inhibit dihydrofolate reductase enzyme so inhibit tetrahydrofolate
-same spectrum of sulfonamide
-Pyrimethamine (used with sulfonamide in parasitic infection), methotrexate also inhibit this enzyme
-reach CSF, prostate
SE:
-symptoms of folic acid deficiency
-megaloblastic anemia, leucopenia
Cotrimoxazole: 1/5
- Is combination of trimethoprim with sulfamethoxazole
-have grater antimicrobial activity
MOA:
synergistic antimicrobial effect due to inhibition of 2steps in THFA synthesis
Uses:
-treating prostat, UTI, respiratory , GI infection , pneumonia, Ampicillin or chloramphenicol-resistant salmonella infection
SE:
-Dermatological
-GI upset
-Megaloblastic anemia, leukopenia which treated by folinic acid
DIA:
Prolong prothrombin times with warfirin
Inhibit metabolism of phenytoin
Displace Methotrexate by sulfamethoxazole