antibacterial MoA

• what is antimicrobial

  chemicals which kill/inhibit imicrobialcrobial growth
• what is antibacterial

  chemically that specifically targets bacteria and kills/inhibits growth
• what is antibiotic

  a drug used to treat bacterial infections
• can microorganisms naturally produce antibiotics

  yes
• give a bacterial that produces antibibiotic

  penicillin
• give a semi synthesised antibitoic

  amoxicillin
• give a fully synthesised antibiotic

  chloramphenicol
• antibacterials only kill actively growing bacteria, it is hard to treat dormant infections e.g TB
• what is meant if the antibiotic is bactericidal

  kills the bacteria
• what if an antibiotic is bacteriostatic

  it only slows down or stalls bacterial growth, this gives the immune system time to kill
• what is meant by selective toxicity

  selectively kills/inhibits that target organism without causing harm to host
• why is it hard to find selective toxicity in antifungals

  they are also eukaryotic so it is hard to find a unique target
• why is it hard to find selective toxicity in antivirals

  they don't have much to them so it is hard to find a target
• what are the ideal antimicrobial properties

  1. specific - ability of the drug to interact with specific target
  2. selective - selectively kills/inhibits the target organism without causing harm to the host, less selective means more adverse effects
  3. bactericidal
  4. minimal chances of resistance to the drug
• what are the pharmacological activities of antibacterials

  1. non toxic
  2. long plasma half life - effective for a longer time
  3. good tissue distribution - gets to site of infection, hard to treat brain infections since antibiotics cant cross blood brain barrier
  4. low plasma protein binding - needs to be free
  5. oral and prenteral administration
  6. no interference with other drugs
• what are the 4 main sites of action for antibacterial

  cell wall, protein synthesis, cell membrane, nucleic acid
• why do we have few drugs that target the bacteria cell membrane

  bacterial cell membrane and human cell membrane are similar so its harder to find a unique target
• the cell wall is a major target for antibacterials since it is unique to procaryotes and it provides a selective target

  most antibacterials targeting the cell wall are bactericidal
• protien synthesis is a target for antibacterials, however it is a bit hard since we both have ribosomes which make proteins and so we need to find the differences between prokaryotic and eukaryotic ribosomes to have a selective target

  a lot of the antibiotics that target protein synthesis are bacteriostatic
• nucleic acid synthesis can be targeted by antibiotics since they have different cellular machinery, so has a selective target.

  mainly bactericidal
• cell membrane can also be targetted by antibiotics however only a few drugs that do this since there is high similarity to eukaryotic cell membrane.

  mostly bactericidal antibiotics
• name the inhibitors of cell wall synthesis

  B-lactams

  glycopeptides
• whats the difference between a gram negative and gram positive bacteria

  gram negative:

  • thin peptidoglycan layer
  • outer membrane
  • has liposaccharides
  • has porin channels

  gram positive:

  • thick peptidoglycan layer that contains techoic acids and lipotechoic acids
  • no outer membrane
• name 5 gram-negative bacteria

  1. Escherichia coli
  2. pseudomonas areuginosa
  3. Klebsiella pneumonia
  4. Neisseria meningitis
  5. Haemophilus influenzae
• name 4 gram positive bacteria

  1. staphylococcus
  2. streptococcus
  3. enterococcus
  4. C.diff
• why is it important to know if a bacteria is gram + or gram - for antibiotic use

  to know which antibiotic will be more effective

  its easier to treat gram positive bacteria since gram negative has an outer membrane and it is difficult for antibiotics to pass through porin channel
• describe the bacteria cell wall

  it is made of peptidoglycan which is a chain of alternating amino sugars bound by glycosidic bonds (NAG, NAM)

  NAM has a peptide chain which cross links the sugars together
• peptidoglycan biosynthesis

  peptidoglycan monomer has 2 amino sugars, NAG and NAM, with a 5 amino acid long chain, the end 2 being alinine coming from NAM.

  alinine gets cleaved off when transported outside the cell

  2 enzymes attach onto the monomer - glycosylases joins by glycosidic bonds to existing glycan back bone, transpeptidases cross links the peptidoglycan amino acid side chains
• what are the 4 major classes of B-lactams

  1. penicillin
  2. cephalosporin
  3. monobactam
  4. carbapenem
• B-lactams all contain B-lactam ring

  differences in structure of ring attached to B-lactam and side chains
• how many modes of action do B-lactams have

  3
• what are the direct modes of actions for B-lactams

  1. binds to and inhibits the action of transpeptidases usually known as penicillin binding proteins. this prevents the cross linking leading to unstable formation of peptidoglycan causing cell lysis
  2. they can get incorporated into peptide side chains. this prevents cross linking which prevents stable formation of peptidoglycan leading to cell lysis
• what is the indirect mode of action for B-lactams

  they stimulate the bacteria to produce autolysins which breaks down the cell wall and leads to cell lysis
• give an example of penicillin B-lactam

  amoxicillin
• all B-lactams can treat gram-positive and gram-negative bacteria

  false

  only some can pass through the porin channels therefore not all can treat gram negative bacteria
• name examples of glycopeptides

  vancomycin

  teicoplanin
• what bacteria do glycopeptides work on

  gram positive only since they are too big to get through porin channels of gram negative bacteria
• what is the mode of action for glycopeptides

  it binds to the terminal amino acids on the peptide sidechain of the monomer, this prevents cross linking of peptide side chains and prevents glycosylase enzyme from adding PG monomer onto PG chain
• name inhibitors acting on cell membrane and give and example of each

  polymyxins e.g polymyxin E

  lipopeptides e.g daptomycin
• what are ploymyxins used for

  severe gram negative infections