Inhibitors of NA Synthesis Flashcards
How do you increase Rifampin’s excretion in the feces?
Deacetylate it
Fidaxomicin
Mechanism: Bactericidal- Inhibits RNA polymerase
Spectrum: Narrow spectrum sparing many of the gut flora,
Gram positive anaerobes- C. difficile
Side effects: Few due to low absorption
Resistance: Point mutation in RNA polymerase has been observed in vitro
Fluoroquinolones: Ciprofloxacin, levofloxacin, moxifloxacin
Mechanism: Bactericidal- Inhibit DNA replication by binding bacterial DNA topoisomerase II (gyrase) and IV
Spectrum: Broad spectrum- Gram+, Gram-, and atypical organisms like Mycoplasma Hospital acquired pneumonia and UTIs
Resistance: Overprescribed for UTI, respiratory, and acute GI infections, Active efflux of the drug, Mutations in topoisomerases
What is the difference between inhibiting Topo-II vs. Topo-IV?
Inhibition of topoisomerase II (DNA gyrase) prevents relaxation of positively supercoiled DNA that is required for normal transcription and replication. Gram –
Inhibition of topoisomerase IV interferes with separation of replicated chromosomal DNA (decatenation) into the respective daughter cells during cell division
Floroquinalones are fine to take along with Calcium and other cations. (T/F)
F, they chelate cations
Sulfonamides and Trimethoprim are what?
Folate antagonists. Block production of THF = Block DNA synthesis indirectly.
Sulfamethoxazole
It’s a sulfamethoxazole
Mechanism:
Bacteriostatic- drug is a para-aminobenzoic acid analog and acts as a competitive inhibitor of Dihydropteroate synthetase (upstream of THF production)
Resistance: change in dihydropteroate synthetase, increased efflux, increased production of PABA
What are some adverse affects of sulfonamides?
Hypersensitivity- Rash, Stevens-Johnson syndrome
Cross reaction to other drugs containing sulfonamide moieties
Crystalluria leading to acute renal failure
Hemolysis if Glucose-6-phosphate dehydrogenase deficient
Kernicterus- neurologic condition occurring in severely jaundiced newborns
Trimethoprim
Mechanism: Bacteriostatic- Inhibits bacterial dihydrofolate reductase. Has low affinity for the mammalian enzyme.
Resistance:Altered dihydrofolate reductase
Increased amounts of dihydrofolate reductase.
Alternative metabolic pathways
Adverse effects:GI upset
Trimethoprim and sulfamethoxazole [TMP-SMX] (Bactrin)
Bacterialcidal
Mechanism: Sequential blockage of the folate synthesis pathway but if sulfa-allergy can use trimethoprim alone
Spectrum: broad treatment of UTIs, Pneumocystis
Metronidazole
Mechanism: Bactericidal- when metronidazole is reduced (electron sink) it generates free radicals leading to DNA strand breaks and cell death.
Spectrum: Anaerobic bacteria including Clostridium difficil, Protozoa
Resistance: Rare
Adverse effects: Nausea, diarrhea, headache, and metallic taste. Avoid during pregnancy
Disulfiram-like reaction with alcohol (blocks aldehyde dehydrogenase)
Nitrofurantoin
Mechanism: Bactericidal- reduced by bacterial flavoproteins to reactive intermediates, which inactivate or alter bacterial ribosomal proteins to inhibit the synthesis of DNA, RNA, cell wall, and protein.
Spectrum:Broad Spectrum, Rapidly excreted in the urine in an active form- used for UTIs
Resistance: Lack of bacterial resistance since the drug interferes with a variety of processes.
Adverse effects: Vomiting and rash
Sulfonamides can compete for binding to albumin leading to free bilirubin and complications with drugs like warfarin (T/F)
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