Nucleic Acid Synthesis Inhibitors

Question 0

Fidaxomicin

Answer 0

Mechanism: Inhibits RNA polymerase by binding to sigma subunit
Spectrum: Narrow spectrum. Gram + anaerobes, C diff
Resistance: Point mutation in RNA poly observed in vitro
Side effects: Low absorption, nausea, vomiting

Question 1

Rifampin

Answer 1

Mechanism: Binds RNA polymerase at active site
Spectrum: Gram + and -, good against mycobacteria tuberculosis
Resistance: Drug is unable to bind to beta subunit of RNA polymerase
Side Effects: GI side effects, hypersensitivity (fever), hepatotoxic thru cytochrome p450 enzymes that induce metabolism of other medicines
Body fluids turn orange red

Question 2

Fluoroquinolones: Ciprofloxacin, levofloxacin, moxifloxacin

Answer 2

Mechanism: Bactericidal- inhibit DNA replication by binding to topoisomerase
Spectrum: Broad. G+ and G-, as well as mycoplasma
Resistance: Was overprescribed. Mutations in topoisomerases, as well as active efflux of drug
Notes on Topoisomerase: If bound to topoisomerase II, Gram -. If bound to topoisomerase IV, Gram +
Side Effects: GI, confusion, photosensitivity, tendon rupture, not for pregnant women
Important facts: Do not consume with chelate cations like calcium

Question 3

Sulfonamides

Answer 3

Mechanism: inhibits folate synthesis through blocking dihydrofolic acid synth. Bacteriostatic!
Resistance: Change in dehydropterate synthetase
Side effects: Hypersensitivity: Rash. Cross reaction with other drugs that have sulfonamide moieties, Crystalluria leading to renal failure, Hemolysis if G6P dehydrogenase deficient, Kernicterus

Question 4

Trimethoprim

Answer 4

Mechanism: Inhibits bacterial dihydrofolate reductase. Bacteriostatic!
Resistance: Altered dihydrofolate reductase or increased amounts, alternative metabolic pathways
Side effects: Bone marrow suppression, hyperkalemia

Question 5

Metronidazole

Answer 5

Mechanism: Reduced form of metronidazole generates free radicals and leads to DNA strand breaks and cell death
Spectrum: Protozoa, anaerobic bacteria including C diff
Resistance: rare
Side effects: Nausea, diarrhea, headache, metallic taste. Avoid pregnancy use. Reacts with alcohol

Question 6

Nitrofurantoin

Answer 6

Mechanism: Reduced by flavoproteins which inactivate ribosomal proteins and other macromolecules. Inhibit DNA/RNA/Cell wall synth
Spectrum: Broad. Rapidly excreted in urine in active form
Resistance: Nope. Too versatile
Side effects: Vomiting and pulmonary toxicity
USE FOR UTI