Folic Acid Antag Bpt

FOLIC ACID ANTAGONISTS Dr. SYED SHEHNAZ ILYAS, M.B.B.S,M.D.

CLASSIFICATION Inhibit Folate synthesis: sulfonamides Inhibit Folate reduction:  Trimethoprim  Pyrimethamine

Inhibit Folate synthesis & reduction  Cotrimoxazole

SULFONAMIDES SHORT ACTING: (4-8 Hrs)  Sulfadiazine

INTERMEDIATE ACTING: (8-12 Hrs)  Sulfamethoxazole

LONG ACTING:(7 Days)  Sulfadoxine

SPECIAL PURPOSE  Silver

Sulfadiazine  Sulfacetamide  Sulfasalazine  Mafenide

MECHANISM OF ACTION

Sulfonamides,chemical analogs of PABA, competitive inhibit dihydropteroate synthetase. Reversibly inhibit folic acid synthesis

ANTIBACTERIAL SPECTRUM &USES Bacterostatic TOXOPLASMA : sulfadiazine + Pyrimethamine Urinary Tract Infections Eye infections: conjunctivitis, trachoma Burns Ulcerative colitis

ADVERSE EFFECTS GIT: nausea, vomiting diarrhea, HYPERSENSITIVITY REACTIONS: fever, rash, dermatitis, photosensitivity NEPHROTOXICITY :↓ by hydration & alkalinization of urine HEMOPOIETIC DISTURBANCES: hemolytic or aplastic anemia, granulcytopenia, thrombocytopenia KERNICTERUS: sulfonamides displace bilirubin from albumin

PYRIMETHAMINE M.O.A.; Inhibitor of dihydrofolic acid reductase(DHFR) in protozoa

USES ;Pyrimethamine + Sulfadiazine used for toxoplasmosis and chloroquine resistant malaria

TRIMETHOPRIM M.O.A : Inhibit Bacterial DHFR USES: Acute urinary tract infections

ADVERSE: Folic acid deficiency: Megaloblastic anemia, leukopenia granulcytopenia,(avoided by coadminstration of folinic acid)

COTRIMOXAZOLE Fixed dose combination of SULFAMETHOXAZO LE: TRIMETHOPRIM=5:1 ratio M.O.A: Sequential block of folate metabolism Combination bacteriocidal

USES GIT ,R.S. infections I.V. Moderate to severe infections with Pneumocystis carinii pneumonia, especially in patients with HIV.

ADVERSE EFFECTS GIT: Nausea, vomiting SKIN: Rashes esp. in elderly HEMATOLOGIC: Folic acid deficiency: Megaloblastic anemia, leukopenia granulcytopenia,(avoided by coadminstration of folinic acid) AIDS PATIENTS: High frequency of fever, rash, leucopenia, diarrhea. DRUG INTERACTIONS: +

diuretics: ↓platelets  +methotrexate :↑plas.conc. methotrexate

SUMMARY Folic acid inhibitors Sulfonamides:Toxoplasmosis,Ulcera tive colitis , burns Trimethoprim:not used alone Pyrimethamine +SULFADIAZINE : toxoplasmosis and chloroquine resistant malaria Cotrimoxazole:R.T.I,G.I.T Infections, Pneumocystis carinii pneumonia Sulfamethoxazole