Folate & DNA synthesis inhibitors Flashcards
What principle is used for Anti-folates?
Bacteria can’t produce folic acid exogenously; must be made from PABA
Sulfonamide - MOA
Inhibit dihydropteroate synthase
Trimethoprim - MOA
Inhibit dihydrofolate reductase
Cotrimoxazole - MOA
Combination of Sulfonamide & Trimethoprim
Are Sulfonamide & Trimethoprim bacteriostatic/cidal?
Both bacteriostatic, but if combine = bactericidal
Anti-folates - PK
Good oral
Good CSF - TMP > SMZ
Sulfonamide - Spectra
Gram +ve & -ve
Trimethoprim - Spectra
Same as sulfonamides; given when allergic to sulfonamides
Cotrimoxazole - Spectra
MRSA
Can be used in immunocompromised pts
Anti-folates - SE
GI Allergy (sulfa) Photosensitivity Renal Hyperkalemia BM suppression (give folinic acid if pregnant, malnourished)
Sulphonamides - DDI
1) Enhance oral anticoags
2) Potentiate sulfonylurea hypoglycemic agents & hydantoin anticonvulsants
Since 2) is via albumin displacement = cause Kernicterus
Trimethopirm - DDI
Enhance Warfarin
Increase Methotrexate
Increase half-life of Phenytoin
Name 2 groups of DNA synthesis inhibitors
Fluoroquinolones & Nirofurantoin
Fluoroquinolones - MOA
Inhibit DNA gyrase
High conc - inhibit Topoisomerase IV
Fluoroquinolones - PK
Good oral
Good CSF
Fluoroquinolones - Dosing
Can give OD if renal fx okay
Fluoroquinolones - Spectra
Broad spec Gram +ve - Strep pneu Anaerobe Atypical Gram -ve - P.aeruginosa
Fluoroquinolones - Clinical
2nd line - TB
Fluoroquinolones - SE
GI CNS - Seizures Hypersensitivity QT prolongation (Moxifloxacin > Ciprofloxacin, Levofloxacin Joint swelling Tendonitis & tendon rupture
Nitrofurantoin - MOA
Bacterial nitrofuran reductase -> reduce parent drug into reactive intermediate -> damage bacterial DNA
Nitrofurantoin - Spectra
Narrower than FQ
Gram +ve - MRSA
Gram -ve - E.coli
Nitrofurantoin - PK
Good oral
Alkaline urine reduces anti-microbial activity
Nitrofurantoin - SE
GI
Hypersensitivity
Pulmonary interstitial fibrosis - esp elderly
Blood dyscrasias, Hemolysis in infants & G6PD-deficient
Colors urine brown
Fluoroquinolones - DDI
Theophylline NSAIDs Warfarin Antacids - decr FQ absn CYP inhibitor - incr FQ
Nitrofurantoin - DDI
Antacids - decr absn of NF
Metronidazole - MOA
Nitroreductase -> Cytotoxic metabolites -> Bind to DNA
Metronidazole - Spectra
Cannot use on Aerobes bc they lack Nitroreductase
C.difficile
Amebiasis
H.pylori
Metronidazole - SE/CI
BM suppression
CI: 1st trimester
Metronidazole - DDI
Warfarin
Alcohol - disulfiram reaction