Antibiotics 1

Antibiotics 1

1. Antimetabolites

   • SULFONAMIDE
     • Synergy with trimethoprim leads to bacteriocidal effect
     • Competitively inhibits dihydropteroate synthetase
     • Pregnancy, nephrotox, hemolysis
       • Cross placenta
   • TRIMETHOPRIM
     • Synergy with sulfonamide often make bacteriocidal effect
     • Inhibits dihydrofolate reductase
   • Bacteriostatic

2. Cell Wall Synthesis Inhibitors

   • PENICILLINS, CEPHALOSPORINS
     • Block transpeptidase rxn
       • by binding penicillin binding proteins
     • Very safe!
       • We don't have these proteins in our cell walls
     • Penicillin G - neurotox
       • From non-specific irritation
     • Least toxic, most allergenic
   • VANCOMYCIN, BACITRACIN
     • Block early steps in synthesis
     • Toxic to kidneys
   • CYCLOSERINE
     • Blocks alanine racemase

3. Cell Membrane Affectors

   • POLYMYXINS
     • Form pores
     • Bind phosphatidyl ethanolamine-rich areas of membrane
     • Highly toxic to kidneys
       • We have phosphatidyl ethanolamine in our membranes Why these are toxic
     • CHOLISTINS
       • Currently being made

4. Protein Synthesis Inhibitors

   • Aminoglycosides
     • Bind to 30S
     • Bacteriocidal
     • STREPTOMYCIN
       • Pregnancy
         • 8th cranial nerve damage Skeletal defects
     • Nephrotox, neurotox
       • Neurotox in infants
   • TETRACYCLINES
     • Blocks tRNA binding 30S
     • Bacteriostatic
     • Pregnancy, liver tox, neurotox
       • Hypoplasia of fetal teeth & bones in fetus Cataracts in fetus Neurotox in infants
   • CHLORAMPHENICOL, ERYTHROMYCIN, CLINDAMYCIN
     • Bind 50S
     • Inhibit chain elongation
     • CHLOR - pregnancy, inhibits P450, toxic to marrow/hemolysis
       • Crosses placenta
     • CHLOR - phenytoin, coumadin
       • Inhibits their breakdown

5. Nucleic Acid Inhibitors

   • RIFAMPIN
     • Inhibits DNA-dependent RNA polymerase
       • Inhibits RNA synthesis
     • Birth control pills
       • Enhances breakdown
   • Quinolones
     • CIPROFLOXACIN
       • Blocks DNA gyrase
   • METRONIDAZOLE
     • Inhibits nucleic acid synthesis

6. Synergy

   • GOOD
     • Sulfonamide + trimethoprim
     • Isoniazid + rifampin
       • Treat TB
     • Penicillin + aminoglycoside
       • Penicillin stops cell wall formation Allows aminoglycosides to get inside
       • Mixed infections
       • Prophylaxis
     • Trimethoprim + sulfamethoxazole
       • Treat Pneumocystis carinii pneumonia
         • In people with AIDS
     • Bactericidal + bactericidal or bacteriostatic + bacteriostatic
   • BAD
     • Bactericidal + bacteriostatic
     • Penicillin + tetracycline

7. Side Effects

   • GI
     • C. diff -> fatal colitis Nausea & vomiting
   • Liver tox
     • Isoniazid

8. Cross-sensitivity can occur

   • Antibiotics act as haptens (give immune response when attached to large molecule)