Lecture 15 - Antibiotics 2 Flashcards
What are the most commonly prescribed antibiotics?
30% cell wall inhibitors -penicillins, cephalosporins 34% protein synthesis inhibitors -tetracyclines, macrolides 12% DNA synthesis inhibitors -fluoroquinolones
Describe cell wall inhibitors
- bacteria have cell walls
- mammalian cells do not have cell walls
- targeting the synthesis of bacterial cell walls is one of the most widely effective and least toxic antibiotic strategies
- only effective against actively growing bacteria
Examples of cell wall inhibitors
- penicillins
- cephalosporins
Describe Penicillin
- Blocks the last step of bacterial cell wall synthesis
- Inhibits “transpeptidases” that form cross-links between peptidoglycan chains that are essential for cell wall integrity
- Causes osmotic pressure on the cells resulting in cell lysis
- Gram positive bacteria produce enzymes called “autolysis” that break down the cell wall
- Without active cell wall synthesis autolysis can damage the cell
*Blocks the cross-links, allows things to penetrate through the cell wall and kill the microbe
List the types of Penicillins
- Penicillin G, Penicillin V
- Penicillinase-resistant penicillins
- Methicillin, cloxacillin
- Extended spectrum penicillins
- Ampicillin, amoxicillin
List 3 important facts about Penicillins
Bactericidal
Cross resistance
Cross allergic potential
Administration of penicillins
Route is determined by stability of the medicine to gastric acid and the severity of the infection:
- Penicillin V, Amoxicillin only available as oral preparations
- Piperacillin must be by the IV/IM route
- Others available as oral, IV, IM preparations
Absorption of penicillins
Most penicillins are incompletely absorbed so they affect the composition of the intestinal flora
-Absorption of penicillinase Resistant antibiotics are reduced by food in the stomach and must be administered before a meal or 2-3 h after
Distribution of penicillins
Distribution is throughout the body
-crosses the placenta but does not penetrate bone or CNS
Excretion of penicillins
in the urine and breast milk
Adverse Effects of Penicillins
- GI effects relatively common but seldom severe due to disruption of normal intestinal microflora
- Allergy to its metabolite penicillin acid relatively common (rash, swelling of tongue/lips, anaphylaxis)
- Cross allergy within penicillin class
- Hematological: reduced coagulation a concern in patients receiving anticoagulants
- No teratogenicity
Cephalosporins have a similar ____ and ______ to penicillins
structure
mechanism
List some cephalosporins
cephalexin
cephalothin
cepazolin
cefepime
Administration of cephalosporins?
Most must be administered IV/IM due to poor oral absorption:
-Cephalexin and Cefixime are administered orally
Distribution of cephalosporins?
Throughout the body
- Cefazolin penetrates the bone
- Cefuroxime crosses the BBB
- Cefotaxime, Ceftriaxone penetrate the cerebrospinal fluid
Excretion of cephalosporins?
- Most are eliminated in the urine
- Ceftriaxone is excreted in the bile, longest half-life of all cephalosporins (6-8 hours) permits once a day dosing
Cephalosporins have cross resistance and cross allergic potential with ?
each other and with penicillins
Other adverse effects?
Allergy and GI effects less common than with penicillins
Describe Protein Synthesis Inhibitors
- Mammalian cells have 80S ribosomes (60S and 40S subunits)
- Bacteria have smaller 70S ribosomes (50S and 30S subunits)
- Protein synthesis inhibitors bind to 70S ribosomes (as opposed to 80S ribosomes)
- Effective against gram positive and gram negative bacteria as well as other microorganisms (very broad spectrum)
*they inhibit peptide synthesis
Examples of Protein Synthesis Inhibitors
- Tetracyclines
- Aminoglycosides
- Macrolides
- Chloramphenicol
- Clindamycin
Describe Tetracyclines
- Binds irreversibly to the 30S ribosome
- Blocks acyl-tRNAaccess to the ribosome
- Broad spectrum
- Bacteriostatic
What is the naturally occurring tetracycline?
Tetracycline
What is the semi-synthetic tetracyclines?
- Doxycycline
- Methacycline
- Minocycline
Administration of Tetracyclines?
Oral route is determined by stability of the medicine to gastric acid and the severity of infection
