Folate Flashcards
required for DNA synthesis in both bacteria and animals
folate
vitamin involved in rxns of transfer of one carbon unit
folic acid
antibiotics compete with ____ for active site dihydropteroate synthase
PABA
synthesis of THF requires?
dihydrofolate reductase
bacteria DHFR is more sensitive to?
trimethoprim
PABA analog that blocks dihydropteroate synthetase
Sulfamethoxazole
blocks dihydrofolate reductase
trimethoprim
activity against gram -, UTI bacteria, gram +, MRSA, Nocardia!
SMX
TMP
treat toxoplasmosis caused by toxoplasma gondii and treats leishmaniasis
pyramethamine + sulfadiazine
treats malaria
pyrimethamine + sulfadoxime
1st tri: anti folate effects cause neural tube defects
3rd tri: bilirubin displacement - kernicterus in fetus/baby; pre term labor
ADR of TMP/SMX
SE: G6PD def - hemolytic anemia, stevens johnson syndrome, photosensitivity, displace drugs from albumin, inhibits CYP450
SMX and TMP
Systemic sulfonamides
1) sulfamethoxale
2) sulfadiazine
3) sulfadoxine - malaria
4) dapsone - leprosy
5) sulfasalazine - ulcerative colitis
topical sulfonamides
1) silver sulfonamides - burns
2) sulfacetamide - trachoma
3) mefenide
sulfonamides compete competitively with
PABA
1) increase PABA synthesis can overcome inhibition of dihydropteroate synthesis
2) altered enzyme - bacterial dihydropteroate syn can undergo mutation
3) decrease uptake - permeability may be reduced
sulfonamides resistance
fixed dose combo (TMP + SMX)
produces seq. blockade of folate metabolism
bactericidal and synergistic
ratio 5:1
cotrimoxazole
used to tx: pneumocystis jiroveci, nocardia, g - UTI, listeria and g + MSSA and MRSA
cotrimoxazole
in oxidative stress, GSH is depleted - RBC mem. inflexible - hemolysis
G6PD def
trigger food - fava beans
trigger drugs
1) antimalarial - primaquine and chloroquine
2) anti tb - INH
3) sulfonamides - mafernide and cotrimoxazole
G6PD def
