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
 SilverSulfadiazine
 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