Anti-microbial (protein synthesis)

Question 1

Protein synthesis inhibitors

Specific target smaller bacterial ribosome (70S, made of 30S and 50S subunits), leaving human ribosome (80S) unaffected.

Buy AT30, CCEL at 50

Define the types of inhibitors and determine if they are bactericidal or bacteriostatic.

Answer 1

• 30S inhibitors
  
  • Aminoglycosides (bactericidal)
  • Tetracyclines (bacertiostatic)
• 50S inhibitors
  
  • Chloramphenicl, Clindamycin (bacteriostatic)
  • Eryhtromycin (macrolides) bacteriostatic
  • Linezolid (variable

Question 2

Clincial use

Sever gram - rod infrecitons, synergisitc w/B-lactam antibiotics. _ _ for bowel surgery.

Drug, MOA, toxicity, Resistance

‘Mean GNATS caNNOT kill anaerobes’

Answer 2

• Tobramycin, Amikacin, Neomycin, Gentamicin, Streptomycin.
• MOA:
  
  • bactericidial; inhibit formation of initiation complex and cause misreading of mRNA. Also block translocation.
  • Require O₂ for uptake, therefore ineffective against anareobes
• Toxicity:
  
  • Nephrotoxicity (especially when used with cephalosporins)
  • Neuromuscular blockade
  • Ototoxicity (especially when used w/loop diuretics)
  • Teratogen
• Resistance
  
  • Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation or adenylation.

Question 3

Clincial use

Borrelia burgdorferi, M penuominae. Drugs ability to accumulate intracellularly makes it very effective against richettsia and Chlamydia. Also used to treat acne.

Drug, MOA, toxicity, Resistance

Answer 3

• Tetracycline
  
  • Tetracycline, doxycycline, minocycline
• MOA
  
  • _{Bacteriostatic;}
  • _{bind 30S and prevent attachment of aminoacyl-tRNA;}
  • _{limited CNS pentration. Doxycycline is fecally eliminated and can be used in pts with renal failure.}
  • _{Do not take with milk (Ca2), antacids (Ca or Mg) or iron containing preparations b/c divalent cations inhibit its absorption in the gut.}
• _​Toxicity:
  
  • GI distress, discoloration of teeth and ihibition of bone growth in children, photosensitivity, contraindicaetd in pregnancy.
• ​Resistance:
  
  • dec uptake or inc efflux of bacterial cells by plasmid encoded transport pumps.

Question 4

Clincial use

Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STD (Chlamydia) and G+ cocci (Streptococcal infectios in pt allergic to penicillin)

Drug, MOA (slides), toxicity (MACRO), Resistance

Answer 4

• Macrolides
  
  • Azithromycin, Clarithromycin, erythromycin
• MOA:
  
  • inhibits protein syn by blocking translocation (macroslides); binds to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.
• Toxicity:
  
  • Gastrointestinal Motility issues
  • Arrhythmia caused by prolonged QT
  • acute Cholestatic hepatitis
  • Rash
  • eOsinophilia.
• Resistance
  
  • ethylation of 23S rRNA-binding site prevents binding of drug.

Question 5

Clincial use

Meningiits (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and Rocky mountian spotted fever (Richettsia richettsii)

Limited use owing to toxicities but often still used in developing countries bc of low cost

Drug, MOA, toxicity, Resistance

Answer 5

• Chloramphenicol
• MOA:
  
  • blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.
• toxicity:
  
  • Anemia (dose dependent)
  • aplastic anemia (dose independent)
  • gray baby syndrome (in premature infants bc they lack liver UDP-glucuronyl transferase)
• Resistance:
  
  • Plasmid-encoded acetyltransferase inactivates the drug

Question 6

Clincial use

Anaerobic infections (e.g. Bacteroides spp, Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive Groupd A streptococcal (GAS) infection.

Drug, MOA, toxicity, Resistance

Treat anareobes above the diaphragm vs metronidazole (anaerobic infections below the diaphragm)

Answer 6

• Clindamycin
• MOA: blocks peptide transfer (translocation at 50 ribosomal subunit. bacteriostatic
• toxicity: pseudomembranous colitis (C. difficile overgrowth) fever diarrhea.