Pharm 125 OTSA 1

• chloramphenicol, macrolides, and lincosamides

  • binds to the 50s ribosomal subunit
  • prevent peptide bond formation
  • stop protein synthesis
• aminoglycosides

  • binds to the 30s subunit
  • impair proofreading, resulting in production of faulty proteins
• tetracyclines

  • binds to the 30s ribosomal subunit
  • block the binding of tRNAs, thereby inhibiting protein synthesis
• 30 s subunit

  • mechanism of action - causes mismatches between codons and anticodons, leading to faulty proteins that insert into and disrupt cytoplasmic membrane
  • drug class - aminoglycosides
  • specific drugs - streptomycin, gentamicin, neomycin, kanamycin
  • bacteriostatic or bactericidal? - bactericidal
  • spectrum of activity - broad spectrum
• 30 s subunit

  • mechanism of action - blocks association of tRNAs with ribosome
  • drug class - tetracyclines
  • specific drugs - tetracycline, doxycycline, tigecycline
  • bacteriostatic or bactericidal? bacteriostatic
  • spectrum of activity - broad
• 50s subunit

  • mechanism of action - blocks peptide bond formation between amino acids
  • drug class - lincosamides
  • specific drugs - lincomycin, clindamycin
  • bacteriostatic or bactericidal? bacteriostatic
  • spectrum of activity - narrow
• 50s subunit

  • mechanism of action - blocks peptide bond formation between amino acids
  • drug class - macrolides
  • specific drugs - erythromycin, azithromycin, telithromycin
  • bacteriostatic or bactericidal? bacteriostatic
  • spectrum of activity - broad
• 50s subunit

  • mechanism of action - blocks peptide bond formation between amino acids
  • drug class - N/a
  • specific drugs -chloramphenicol
  • bacteriostatic or bactericidal? bacteriostatic
  • spectrum of activity - broad
• 50s subunit

  • mechanism of action - interferes with the formation of the initiation complex between 50s and 30s sbunits and other factors
  • drug class - oxazolidinones
  • specific drugs -linezolid
  • bacteriostatic or bactericidal? bacteriostatic
  • spectrum of activity - broad
• mechanism of action - interacts with lipopolysaccharide in the outer membrane of gram nega bacteria, killing the cell through the eventual disruption of the outer membrane and cytoplasmic membran

  drug class - polymyxins

  specific drugs- polymyxins B

  spectrum - narrow spectrum against gram nega, including multidrug resistant strains

  clinical use - topical preparations to prevent infections in wounds
• mechanism of action - interacts with lipopolysaccharide in the outer membrane of gram nega bacteria, killing the cell through the eventual disruption of the outer membrane and cytoplasmic membran

  drug class - polymyxins E (colistin)

  specific drugs - narrow spectrum against gram nega, including multidrug resistant strains

  clinical use - oral dosing to decontaminate bowels to prevent infections in immunocompromised or patients undergone surgery/procedure

  IV dosing to treat serious systemic infections caused by multidrug resistant pathogens
• mechanism of action - inserts into the cytoplasmic membrane of gram-positive bacteria, disrupting the membrane and killing the cell

  drug class - lipopeptide

  specific drugs - daptomycin

  spectrum of activity - narrow spectrum against gram posi, including multidrug resistant strains

  clinical use - complicated skin and skin-structure infections and bacteremia caused by gram positive pathogens, including mrsa
• mechanism of action - inhibits bacterial RNA polymerase activity and blocks transcription, killing the cell

  drug class - rifamycin

  specific drugs - rifampin

  spectrum of activity - narrow against gram posi and limited gram nega also against mycobacterium tuberculosis

  clinical use - combination therapy for treatment of tuberculosis
• mechanism of action - inhibits the activity of DNA gyrase and blocks DNA replication, killing the cell

  drug class - fluoroquinolines

  specific drugs - ciprofloxacin, ofloxacin, moxifloxacin

  spectrum of activity - broad against gram posi andgram nega

  clinical use - wide variety of kin and systemic infections
• metabolic pathway target- folic acid synthesis

  mechanism of action - inhibits the enzyme involved in production of dihydrofolic acid

  drug class - sulfonamides; sulfamethoxazole, sulfones; dapsone

  spectrum of activity - broad against gram posi and gram nega against mycobacterium tuberculosis
• metabolic pathway target- folic acid synthesis

  mechanism of action - inhibits the enzyme involved in the production of THF

  drug class - N/A

  specific drugs - trimethoprim

  spectrum of activity - broad against gram posi and gram nega against mycobacterium tuberculosis
• metabolic pathway target- mycolic acid synthesis

  mechanism of action -interferes with the synthesis of mycolic acid

  drug class -N/A

  specific dug - isoniazid

  spectrum of activity - narrow against mycobacterium spp., including mycobacterium tuberculosis
• metronidazole is a semisynthetic member of the nitroimidazole family that is also an antiprotozoan. it interferes with the DNA replication in target cells
• rifampin is a semiisynthetic member of the rifamycin family and functions by blocking RNA plymerase activity in bacteria. the RNA polumerase enzymes in bacteria is structurally different from those in eukaryotes providing selective toxicity
• rifampin is used often in a cocktail with other antibacterial drugs and is against mycobacteria that cause tuberculosis
• rifampin can casue heaptoxicity and negatively influence the bioavailability and therapeutic effect of companion drugs
• Nalidixic acid


  Selectively inhibits the activity of bacterial DNA gyrase, blocking DNA replication
• Nalidixic acid was discovered in 1962 and is a byproduct during the synthesis of chloroquine, an antimalarial drug
• Fluoroquinolones


  Chemical modification to the original quinolone backbone
• Fluoroquinolones

  • Inhibit DNA gyrase
  • Effective against a broad spectrum of gram negative and gram positive bacteria
  • Used to treat UTI, respiratory infections, abdominal infections, and skin infections
• Fluoroquinolones


  • Ciprofloxacin
  • Levofloxacin
• Synthesis of chloroquine


  Nalidixic acid is a byproduct
• the sulfonamides (sulfa drugs) are the oldest synthetic antibacterial agents and are structural analogues of PABA, an early intermediate in folic acid synthesis
• by inhibiting the enzyme involved in the production of dihydrofolic acid, dihydropteroate synthase, sulfonamides block bacterial biosynthesis of folic acid and subsequently pyrimidines, and purines required for nucleic acid synthesis
• sulfonamides provides bacteriostatic inhibition of growth against a wide spectrum of gram nega and gram posi
• because human obtain folic acid from food instead of synthesizing it intracellularly, sulfonamides are selectively toxic for bacteria
• allergic reactions to sulfa drugs are common
• the sulfones are structurally similar to sulfonamides but are not commonly used today except for the treatment of hansen's disease (leprosy)
• trimethoprim is a structural analogue of dihydrofolic acid and inhibits a later step in the metabolic pathway
• trimethoprim is used in combination with the sulfa drug sulfamethoxazole to treat urinary tract infections, ear infections, bronchitis an example of antibacterial synergy
• when used alone, each antimetabolite decreases production of folic acid to a level where bacteriostatic inhibition of growth occurs
• when used in combination, inhibition of both steps in the metabolic pathway shows bactericidal inhibition
• sulfa drugs and trimetoprim use shpuld be carefully considered during early pregnancy as it may cause congenital anomalies
• isoniazid is administered as a prodrug requiring activation through the action of an intracellular bacterial peroxidase enzyme, forming isoniazid-NAD and isoniazid-NADP ultimately preventing the synthesis of mycolic acid, which is essential for mycobacterial cell walls
• possible side effects of isoniazid include hepatoxicity, neurotoxicity, and hematologic toxicity