Anti-microbial (DNA synthesis)

Question 1

Clincial use

G- rods of urinary and GI tracts (include Pseudomonas), Neisseria, some G+ organisms

Drug, MOA, toxicity, Resistance

Answer 1

• Fluoroquinolones
  
  • Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfloxacin, moxifloxacin, gemifloxacin, enoxacin (fluoroquiolones), nalidixic acid (fluoroquiolones)
• MOA: inhibits DNA gyrase (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken w/antacids.
• Toxicity:
  
  • GI upset, superinfections, skin rashes, headache, dizziness.
  • Less comonly can cause tendonitis, tendon rupture, leg cramps, and myalgias,
  • Contraindicated in pregnant women, nursing mothers, and children under 18 yo due to possible damage to cartilage.
  • some may cause prolonged QT interval, may cause tendon rupture in people >60 and in pts taking prednisone.
• resistance
  
  • Chromosome-encoded mutation in DNA gyrase, plasmid mediated resistance efflux pumps.

Question 2

Clincial use

G+, G- Nocardia, Chlamydia. Triple sulfa or SMX for simple UTI.

Drug, MOA, toxicity, Resistance

Answer 2

• Sulamethoxazole (SMX), sulfisoxazole, sulfadiazine
• MOA
  
  • _{inhibit folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihdryopteroate synthase. Bacteriostatic.}
  • _{(paba +pteridine –> dihydropteroic acid)}
• Toxicity
  
  • _{Hypersenstivity rxn, hemolysis if G6D def, nephrotoxicity (tubulointersitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. warfarin)}
• Resistance:
  
  • _{Altered enzyme (bacterial dihrdopteroate synthase) dec uptake or inc PABA synthesis.}

Question 3

Clincial use

Used in combination with sulfonamides (_ _-sulfamethoxazole (TMP-SMX), causing sequential block of folate synthesis.

Combo used for UTI, Shigella, Salmonella, Pneumocystis jirovecii, pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis.

Drug, MOA, toxicity, Resistance

Treats Marrow Poorly

Answer 3

• Trimethoprim
• MOA: inhibits bacterial dihydrofolate reducatse. bacteriostatic.
• toxicity: megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic acid).

Question 4

Clincial use

Treats Giardia, Entamoeba, Trichomaons, Gardenerella vaginalis, Anaerobes (Bacteroides, C. difficle).

Used w/a PPI and clarithromycin for triple therapy against H. pylori

Drug, MOA, toxicity, Resistance

Answer 4

• Metronidazole
• MOA:
  
  • Forms free radical toxic metabolites in the bacterial cell that damage DNA.
  • Bactericidal antiprotozoal
• Toxicity
  
  • Disulfiram-like rxn (severe flushing tachycardia, hypotension) w/Alcohol
  • Headache metallic taste

*GET GAP on the Metro with metronidazole: *

Treats anaerobic infections below the diaphragm vs clindamycin (anaerobic infections above diaphragm)