Drugs that inhibit Nucleic acid synthesis Flashcards
Rifampin
Mech: Binds bacterial RNA pol at active center
Spec: Extended Mycobacteria tuberculosis
Resistance: Some strains drug is unable to bind to Beta subunit of RNA, Acquired= mutations in probe gene prevents drug binding
Side-effects: GI, turns body fluids red-orange, increases liver enzymes
Fidaxomicin
Mech: Inhibits RNA pol
Spec: narrow (spares gut flora), Gram+ anaerobes (C. diff)
Resistance: point mutation in RNA pol in vitro
Side effects: Few due to low absorption
Note: only used for C. diff
Fluoroquinolones (Ciprofloxacin, levofloxacin, moxifloxacin)
Mech: Binds bacterial topoisomerase II and IV
spec: broad, Gram+, Gram- and Mycoplasma, hospital acquired pneumonia and UTIs
Resistance: overprescribed for UTI, Active efflux of drug, mutations in topoisomerase
Side effects: GI, confusion, photosensitivity, C. diff colitis, Candida vaginitis, chelates heavy metals
Notes: Ciprofloxacin is used during biological warfare
Sulfonamides
Mech: folate antagonist, PABA analog prevent folate synthesis, competes with PABA
Spec: bacteria and fungi that synthesize their own FH2
Resistance: Bacteria that uptake their own FH2 are resistant, change in target enzyme, increased efflux, increased PABA to compete
Side effects: Hypersensitivity, kernicterus and jaundice, hemolysis if G-5-Phosphate DH is mutated
Trimethoprim
Mech: Folate antagonist, inhibits final step in FH2 synthesis
Resistance: Altered enzyme, increased amt of enzyme, alternative metabolic pathways
Side effects: GI upset
Note: can use in conjunction with sulfonamides, broad treatment for UTIs
Metronidazole, Tinadazole
Mech: Becomes e- sink and generates free radicals damaging DNA
Spec: protozoa, anaerobic bacteria (C. diff)
Nitrofurantoin
Mech: reduced by bacterial flavoproteins to reactive intermediate
Spec: Broad, rapidly secreted in urine (used for UTIs)
Resistance: very little
Side effects: vomiting and rash
Note: not useful for treating anything systemic because it is excreted so quickly
