Antibiotics and bacteria Flashcards

1
Q

Which antibiotics target cell wall synthesis?

A

B-lactam

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2
Q

Which drugs disrupt the DNA structure?

A

Metronidazoles
Quinolones
Nitroimidazoles

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3
Q

Which drugs inhibit protein synthesis?

A

Chloramphenicol

Tetracylines

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4
Q

Which class of drugs interfere with the other pathways?

A

Sulphonamides

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5
Q

Describe a unique feature of the bacterial cell wall that is a common drug target

A

Peptidoglycan

  • Polymer of sugars and Aa
  • Serves structural role
  • Counteracts osmotic pressure of the cytoplasm
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6
Q

List some cell wall targeting antibiotics and describe how they work

A
  • Penicillin (type of beta lactam antibiotic) (binding protein A transpeptidase stops peptide cross link forming in the wall)
  • Peptide antibiotics: directly interact with cell wall preventing synthesis of the polymers (e.g. vancomycin)
  • Bacitracin: cyclic peptides that affect transporters in the celll wall synthesis process
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7
Q

What are the 2 classes of beta lactam antibiotics?

A

Penicillins and Cephalosporins

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8
Q

Give examples of narrow/ broad spectrum beta lactam antibiotics

A

Penicillin and Methicillin don’t penetrate the outer membrane well so are narrow spectrum, but Ampicillin and Amoxicillin do so are broad spectrum

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9
Q

Give an example of a beta lactamase resistant beta lactam

A

Methicilin

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10
Q

Describe how beta lactams work

A
  • Gram +ve haave direct acess to the wall but gram -ve require a porin to access the wall through the outer membrane
  • PBP (Penicillin binding protein) inhibits transpeptidation in cell walls peptidoglycan, the accumulation of peptide precursors causes autolysin activity.
    (the autolysin activity breaks bonds to try and rebuild extra blocks but the PBP is affected by the B lactam drug so this can’t happen and this affects cell wall synthesis)
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11
Q

Describe Penicillins

A
  • Organic acids
  • Ionised in serum so spread well in extracellular fluids BUT are poor at crossing membranes
  • eliminated at the kidney so high conc in urine
  • Broad spec drugs e.g. Ampicillin have an altered R group allowing them to cross membranes more easily
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12
Q

Describe Cephalosporins

A
  • Inhibits same as the penicillins
  • Can be used on patients hypersensitive to penicillin
  • Resistant to B lactamases produced by Staphylococcus
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13
Q

Describe Bacitacin

A
  • The are cell wall precursor carrier targeting
  • Gram +ve
  • Narrow spectrum
  • Limited to topical/ opthalmic use due to causing nephrotoxicity
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14
Q

Describe Vancomycin

A
  • Cell wall peptide blocking action
  • Prevent cross linking of peptide chains (think of it as capping the end of the chains)
  • Resistance can occur by the Aa at the end of the chains being altered so vancomycin can’t bind)
  • Protected group
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15
Q

What are the impacts of cell membrane disruption?

A
  • Lead to leakage of ions
  • Remove proton motive force
  • Damages cytoplasmic conditions
    (essentially messes up cell homeostasis)
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16
Q

Describe the reason why inhibiting the protein synthesis of bacteria is beneficial as a drug target?

A
  • It is selective because of different structures between the 80S ribosome (eukaryotic) and the 70S ribosome (prokaryotic)
  • Most antibiotics bind to either the 30S or 50S (this is because the 70S consists of a 30 and a 50)
17
Q

What is the impact of changes in ribosome sequence on antibiotic binding?

A

-The changes can lead to resistance

18
Q

Give examples of ribosomal binding antibiotics

A
  • Aminoglycosides (Bacteriocidal)

- Tertracylines, Chloramphenicol, Macrolides (Bacteriostatic)

19
Q

Describe resistance to ribosome binding antibiotics

A

Can alter be cause by alteration of target (intrinsic due to lack of correct receptor domain in ribosome or due to methylation of binding site)
Or it can be alteration of the drug (extrinsic resistance may be due to acquisition of degredative enzymes or drug modifying enzymes)

20
Q

How do Sulphonamides work?

A

Competitive inhibition of THF an enzyme needed for DNA synthesis= they stop PABA incrporation

21
Q

How to Quinolones work?

A

Bind to and stop DNA gyrase - stops DNA supercoiling (DNA synthesis). (single point mutation results in resistance- mutated gyrase means quinolones won’t work)
-Not effective on ut anaerobes

22
Q

How do Nitroimidazoles work? (e.g. Metronidazle)

A

Reduction products react with DNA causing the strands to break.

  • Don’t work on aerobes
  • Resistance is rare
23
Q

How does Rifampicin work?

A

Blocks initiation of protein synthesis

24
Q

What can combined therapy result in?

A
  • Additive effect (purely summative)
  • Synergistic effect (greater than summative)
  • Indifference (no effect either way
  • Antagonistic (reduced effectiveness)
25
Q

What is the results of giving penicillin with claevulanic acid?

A

Inhibits B lactamase activity reducing resistance

26
Q

What is the result of giving sulphonamides and trimethoprim together?

A

they work at two different sites on the DHF pathway so are syngergistic

27
Q

Highly lipid soluble drugs:

A
  • Can penetrate cells (e.g. tetracylines/ macrolides/ quinolones)
  • Have a large Vd
28
Q

Polar water soluble drugs:

A

Remain confined to blood and extracellular fluids (e.g. aminoglycosides)

29
Q

Weak acids drugs:

A

Affected like other weak acid drugs by local pH

30
Q

Aerobic/ anaerobic drugs:

A

Impact on expression of factors in the bacteria which can alter activation of or uptake of drugs

31
Q

Which group of antibiotics work in anaeorbic conditions?

A

Nitromidazoles

32
Q

Which group of antibiotics work in aerobic conditions?

A

Aminoglycosides (drug re-uptake requires aerobic respiration/ functional ECT)

33
Q

Give examples of 1s5 line, 2nd line, 3rd line an restricted antibiotics

A

1st: Penicillins, Tetracylins
2nd: Metronidazoles, Flouroquinolones
3rd: Rifampicin
RestrictedVancomycin (glycopeptides)