31. Antibiotics and anti-fungals Flashcards Preview

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Flashcards in 31. Antibiotics and anti-fungals Deck (36)
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1
Q

outline the key features of bacteria

A
  • single-cell microorganisms
  • they have a cell wall and cell membrane
  • they have an entire phylogenetic domain
  • 1/3 are pathogenic
2
Q

describe the key features of gram + bacteria and give an example

A

prominent, thick peptidoglycan cell wall

e.g. staphylococcus aureus

3
Q

describe the key features of gram - bacteria and give an example

A

outer membrane with lipopolysaccharide

e.g. E-coli

4
Q

describe the key features of mycolic bacteria and give an example

A

outer mycolic acid layer

e.g. mycobacterium tuberculosis

5
Q

how is an important protein in prokaryotic nucleic acid synthesis made?

A

dihydropteroate (DHOp) is produced from paraaminobenzoate (PABA) by DHOp synthase and converted into dihydrofolate (DHF). DHF reductase then converts DHF into tetrahydrofolate (THF) which is important in DNA synthesis

6
Q

what important protein is involved in prokaryotic DNA replication?

A

DNA gyrase (topoisomerase) releases tension from the DNA molecules, allowing DNA replication to occur

7
Q

what important protein is involved in prokaryotic RNA synthesis?

A

RNA polymerase produces RNA from a DNA template

8
Q

what important structures are involved in prokaryotic protein synthesis?

A

ribosomes

RNA molecules go through prokaryotic ribosomes which produce protein from RNA templates

9
Q

what prevents dihydropteroate (DHOp) from being made? how successful is it?

A

sulphonamides inhibit DHOp synthase

the vast majority of bacteria are resistant to sulphonamides

10
Q

what prevents tetrahydrofolate (THF) from being made?

A

trimethoprim inhibits DHF reductase

11
Q

what interferes with DNA replication?

A

fluoroquinolones inhibit DNA gyrase and topoisomerase IV

12
Q

what inhibits RNA polymerase? what does this result in?

A

rifamycins

bacterial death because there is reduced production of proteins required for bacterial cell survival

13
Q

what are bacterial ribosomes inhibited by?

A
  • aminoglycosides (e.g. gentamicin)
  • chloramphenicol
  • macrolides (e.g. erythromycin)
  • tetracyclines
14
Q

what type of bacteria are most susceptible to drugs and why?

A

gram - bacteria because they don’t have a prominent cell wall like gram + bacteria

15
Q

what occurs in step 1 of bacterial wall synthesis - peptidoglycan synthesis?

A
  • a pentapeptide is created on N-acetyl muramic acid (NAM)

- N-acetyl glucosamine (NAG) associates with NAM forming peptidoglycan

16
Q

what occurs in step 2 of bacterial wall synthesis - peptidoglycan transportation?

A
  • peptidoglycan is transported across the cell membrane by a bactoprenol molecule
  • once it is in the periplasm, it undergoes a few steps before being incorporated into the bacterial wall
17
Q

what occurs in step 3 of bacterial wall synthesis - peptidoglycan incorporation?

A
  • it is incorporated into the cell wall

- transpeptidase enzyme cross-links peptidoglycan pentapeptides

18
Q

what inhibits peptidoglycan synthesis?

A

glycopeptides (e.g. vancomycin) which bind the pentapeptides and prevent synthesis

19
Q

what inhibits peptidoglycan transportation?

A

bacitracin inhibits bactoprenol regeneration

20
Q

what inhibits peptidoglycan incorporation?

A

b-lactams (e.g. carbapenems, cephalosporins, penicillins) bind covalently to transpeptidase, inhibiting peptidoglycan incorporation into cell wall

21
Q

what inhibits cell wall stability in gram + and gram - bacteria?

A

lipopeptides (e.g. daptomycin) disrupt gram-positive walls

polymyxins bind to lipolysaccharides (LPS) and disrupt gram-negative cell membranes

22
Q

what are the causes of antibiotic resistance?

A
  • unnecessary and inappropriate prescription
  • livestock farming
  • lack of regulation (available OTC in some countries)
  • lack of development (in recent years)
23
Q

what are beta-lactamases and what do they do?

A

they are destruction enzymes produced by bacteria

they hydrolyse the C-N bond of the beta-lactam ring in beta-lactam antibiotics

24
Q

what types of antibiotics are more effective in gram + bacteria?

A

penicillins G and V

25
Q

name 2 b-lactamase resistant antibiotics

A

flucloxacillin and temocillin

26
Q

what does amoxicillin do?

A

it has broad spectrum activity but is not b-lactamase resistant

  • it has gram - activity
  • it is coadministered with clavulanic acid which has b-lactamase resistance
27
Q

how do bacteria resist antibiotics by producing additional targets? give an example

A

they introduce an additional target that is unaffected by the drug

e.g. E Coli produces a different DHF reductase enzyme, which is resistant to trimethroprim

28
Q

how do bacteria resist antibiotics by altering their target enzymes? give an example

A

the alter the enzyme that is targeted by the drug so that the enzyme is still effective but the drug is now ineffective

e.g. S Aureus has mutations in the ParC region of topoisomerase IV which gives it resistance to quinolones

29
Q

how do bacteria resist antibiotics by hyper-production? give an example

A

bacteria significantly increase levels of DHF reductase

e.g. E Coli produces additional DHF reductase enzymes making trimethoprim less effective - the antibiotic is overwhelmed

30
Q

how do bacteria resist antibiotics by altering drug permeation?

A

they reduce the number of aquaporins and increase efflux systems

this reduces methods of influx and increases methods of efflux to limit drug interaction and is mostly done in gram - bacteria

31
Q

what does the fungal cell membrane contain?

A

ergosterol

32
Q

what can fungal infections be classified into?

A
  • superficial: outermost layers of skin
  • dermatophyte: skin, hair or nails
  • subcutaneous: innermost skin layers
  • systemic: primarily respiratory tract
33
Q

what are the 2 most common categories of anti-fungal drugs? give an example of each

A
  1. azoles e.g. fluconazole

2. polyenes e.g. amphotericin

34
Q

what do azoles do?

A

inhibit cytochrome P450-dependent enzymes involved in membrane sterol synthesis (preventing ergosterol production)

fluconazole is used to treat candidiasis and systemic infections

35
Q

what do polyenes do?

A

punch holes into the cell membrane of fungal cells by interacting with cell membrane sterols to form membrane channels –> cells burst

amphotericin is used to treat systemic infections

36
Q

what is a negative side effect of treatment using amphotericin?

A

it punches halls into the cell membranes of ALL cells which is bad (but still is more selective for fungal cells)