Synthetic Antibacterial

• Quinolones:

  • MOA: Inhibition of DNA gyrase (Topoisomerase II); Antagonize GABA receptors
• Quinolones SAR:

  • R1 - Addition of alkyl and aryl = Increase potency
  • R2 - Inhibits substitution, otherwise = No activity
  • R5 - Addition of X, OH, NH2, Methoxy = Decrease phototoxicity
  • R6 - Addition of fluoroquinolone = Increase spectrum
  • R7 - Addition of piperazine = Basic = Presence of crystalluria
  • R8 - addition of X, Alkyl, Methoxy = Increase phototoxicity
• Nalidixic acid "NegGam, Wintomylon" - active against gram (-) bacteria but not for pseudomonas; its 7-hydroxy metabolite is more active
• Ciprofloxacin + Doxycycline = gonococcal urethritis
• Ofloxacin - better than ciprofloxacin, not effective in syphilis and supplied as a racemate
• Lomefloxacin - for exacerbations of chronic bronchitis by H. influenzae or Moraxella catarrhalis; once-daily dosing
• Isonicotinic hydrazide - a synthetic antibacterial agent which is bactericidal against replicating organisms, but bacteriostatic against nonreplicating organisms; mycolic acid synthesis
• Ethionamide - is used in the treatment of isoniazid resistant tuberculosis; blocks mycolic acid synthesis
• Pyrazinamide - prodrug converted to pyrazinoic acid via pyrazinamidase
• Ethambutol - active against dividing mycobacteria; not recommended for use alone
• P-aminosalicylic acid - this agent was once quite popular, until significant resistance to the drug developed
• Rifabutin - inferior to rifampin for the short-term therapy of tuberculosis