Antibiotics & Antifungals Flashcards

1
Q

what is the main characteristic of gram +ve bacteria?

A

thick peptidoglycan cell wall

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2
Q

name a gram +ve bacteria

A

Staph. aureus

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3
Q

what is the main characteristic of gram -ve bacteria?

A

outer membrane with lipopolysaccharide (LPS)

smaller peptidoglycan wall

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4
Q

name a gram-ve bacteria

A

e.coli

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5
Q

what is the main characteristic of mycolic bacteria?

A

outer mycocolic acid layer

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6
Q

name a mycolic bacteria?

A

Mycobacterium tuberculosis

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7
Q

what are the 2 main types of target for antibiotics?

A

1- intracellular targets

2- extracellular targets (particularly for G+ve)

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8
Q

what are the intracellular targets for ABx?

A

1) nucleic acid synthesis
2) DNA replication
3) RNA synthesis
4) protein synthesis

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9
Q

what occurs in nucleic acid synthesis in bacteria?

A
  • Dihydropterate synthase converts PABA to DHOp.
  • DHOp becomes DHF
  • Dihydrofolate reductase converts DHF to THF.

THF can be use for DNA synthesis

PABA–>DHOp–>DHF–>THF–>DNA synthesis

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10
Q

how can nucleic acid synthesis be targeted by ABx?

A

1) Sulphonamide inhibits DHOp synthase so no DHOp is made

2) Trimethoprim inhibits DHF reductase so no THF is made

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11
Q

what ABx target nucleic acid synthesis?

A

Sulphonamide

Trimethoprim

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12
Q

what occurs in DNA replication in bacteria?

A

DNA gyrases (topoisomerases) release the tension in DNA

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13
Q

how can DNA replication be targeted by ABx?

A

Fluoroquinolones (e.g. Ciprofloxacin)

inhibits DNA gyrase and topoisomerase IV.

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14
Q

what ABx targets DNA replication?

A

Fluoroquinolones (e.g. Ciprofloxacin)

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15
Q

what occurs in RNA synthesis in bacteria?

A

RNA polymerase produces RNA from DNA template.

Prokaryotic RNA polymerase differs to eukaryotic RNA polyermase

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16
Q

how can RNA synthesis be targeted by ABx?

A

Rifamycins (e.g. Rifampicin) inhibits bacterial RNA polymerase.

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17
Q

what ABx targets RNA synthesis?

A

Rifamycins (e.g. Rifampicin)

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18
Q

what occurs in protein synthesis in bacteria?

A

Ribosomes produce the protein from RNA templates

Prokaryotic ribosomes differ to eukaryotic ribosomes

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19
Q

how do prokaryotic ribosomes differ to eukaryotic ribosomes?

A

prokaryotic –> 70s made of 30s and 50s

eukaryotic–> 80s made of 40s and 60s

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20
Q

what Abx targets protein synthesis in bacteria?

A
1) Macrolides
 – e.g. Erythromycin specially for myco. tuberculosis 
2) Aminoglycosides
 – e.g. Gentamycin
3) Chloramphenicol.			
4)Tetracyclines

all inhibit prokaryotic ribosome

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21
Q

what are extracellular targets that be be targetted by ABx?

A

particularly used in gram+ve bacteria

1) peptidoglycan wall (ptg) synthesis
2) ptg transportation
3) ptg incorporation
4) cell wall stability

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22
Q

what occurs in Ptg wall synthesis in bacteria?

A
  • occurs intracellularly in the cytoplasm

NAM+NAH+pentapeptide–> Ptg

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23
Q

which ABx is used particularly for mycobacterium tuberculosis?

A

erythromycin (a macrolide)

24
Q

what enzyme does sulphonamide target?

A

DHOp synthase

PABA–> DHOp

25
Q

what enzyme does trimethoprim target?

A

DHF reductase

26
Q

how can Ptg synthesis be targeted by ABx?

A

Glycopeptides (e.g. vancomycin) binds to pentapeptide and prevents PtG synthesis.

27
Q

what Abx targets Ptg synthesis in bacteria?

A

Glycopeptides (e.g. vancomycin)

28
Q

what occurs in Ptg transportation in bacteria?

A

Bactoprenol transports the PtG across the membrane.

29
Q

how can Ptg transportation be targetted?

A

Bacitracin inhibits Bactoprenol regeneration

bactoprenol transfers Ptg across the membrane

30
Q

what ABx targets Ptg transportation?

A

Bacitracin

31
Q

what is required for Ptg transportation to occur in bacteria?

A

Bactoprenol (a hydrophobic alcohol, lipid)

32
Q

what occurs in Ptg incorporation into the wall in bacteria?

A

Transpeptidase enzyme cross-links PtGs and creates wall.

33
Q

how can Ptg incorporation be targetted by Abx?

A

beta-lactams (e.g. Carbapenems, Cephalosporins, Penicillins)

bind covalently to Transpeptidase and inhibit its action.

34
Q

what is required by bacteria for Ptg incorporation into the wall?

A

transpeptidase

35
Q

what ABx target Ptg incorporation?

A

beta-lactams

e.g. Carbapenems, Cephalosporins, Penicillins

36
Q

what drugs target the cell wall stability? name one for G+ve and G-ve

A

Lipopeptide (e.g. Daptomycin) – disrupt gram +ve walls.

Polymyxin
– binds to LPS and disrupts gram –ve membranes.

37
Q

what are the causes of antibiotic resistance?

A
o Unnecessary prescription.
o Livestock farming.
o Lack of regulation 
– OTC in some countries.
o Lack of development 
– no new ABs.
38
Q

what are the 5 mechanism that leads to antibiotic resistance?

A

1) Additional targets
2) Hyperproduction
3) Alterations in target enzymes
4) Alterations in drug permeation
5) Production of destruction enzymes

39
Q

how do additional targets produced by bacteria leads to ABx resistance?

A
  • different DHF reductase enzyme produced
  • another target that is then unaffected by the drug

e.g. e.coli –> trimethoprim resistance

40
Q

how does hyperproduction by bacteria lead to ABx resistance?

A

more DHF reductase enzyme

bacteria significantly increase levels of an enzyme to overwhelm the Abx

e.g. e.coli–> trimethoprim resistance

41
Q

why is hyperproduction the least effective method of a bacteria gaining Abx resistance?

A

this is resource expending for the bacteria

42
Q

how does alteration of target enzymes by bacteria lead to ABx resistance?

A

alterations to enzyme to make the drug ineffective whilst the enzyme still works

e.g. S.aureus mutation in ParC region of topoisomerase IV–> quinolone resistance

43
Q

how does alteration of drug permeation by bacteria lead to ABx resistance?

A
  • reductions in AQPs
  • increased efflux systems

so reduced ABx entry

Important in GRAM –VE bacteria.

44
Q

what mechanism of resistance is particularly used by gram -ve bacteria?

A

alteration of drug permeation

45
Q

how does the production of destructive enzymes by bacteria lead to ABx resistance?

name a destructive enzyme

A

beta-lactamases (bacterial enzymes) hydrolyse C-N bonds of the beta-lactam ring

46
Q

what Abx can be used against bacteria that produce beta lactamases?

A
  • Flucloxacillin & Temocillin.

these are beta-lactamase resistant (have a steric shield around Beta lactam ring)

  • Amoxicillin (for G-ve) with clavulanic acid
47
Q

which Abx is not resistant to beta lactamase?

A

penicillins (for G+ve)

48
Q

when is amoxicillin “beta-lactamase resistant”?

A

resistant to beta-lactamases only when co-administered with Clavulanic acid.

49
Q

what are the classifications of fungal infections?

A
o Superficial 
– outermost layer of skin.
o Dermatophyte 
– skin, hair or nails.
o Subcutaneous 
– innermost skin layers.
o Systemic 
– primarily respiratory tract. 

the deeper the infection, the more serious

50
Q

what are the 2 main classes of drugs used for fungal infections?

A

azoles and polyenes

51
Q

what do azoles do?

A

Inhibit CYP450 enzymes (CYP51p) involved in membrane Ergosterol synthesis.

52
Q

name an example of an azole

A

Fluconazole

53
Q

what do polyenes do?

A

Binds to Ergosterol and creates channel pores

“puncture” holes in the cell membrane so to distrupt cell homeostasis
e.g amphotercin

54
Q

name an example of a polyene

A

Amphotericin

55
Q

which infections can be treated by the azole ,fluconazole?

A

candidiasis

systemic infections

56
Q

what infections can be treated by the polyene amphotericin?

A

systemic infections