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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
what enzyme does trimethoprim target?
DHF reductase
26
how can Ptg synthesis be targeted by ABx?
Glycopeptides (e.g. vancomycin) binds to pentapeptide and prevents PtG synthesis.
27
what Abx targets Ptg synthesis in bacteria?
Glycopeptides (e.g. vancomycin)
28
what occurs in Ptg transportation in bacteria?
Bactoprenol transports the PtG across the membrane.
29
how can Ptg transportation be targetted?
Bacitracin inhibits Bactoprenol regeneration bactoprenol transfers Ptg across the membrane
30
what ABx targets Ptg transportation?
Bacitracin
31
what is required for Ptg transportation to occur in bacteria?
Bactoprenol (a hydrophobic alcohol, lipid)
32
what occurs in Ptg incorporation into the wall in bacteria?
Transpeptidase enzyme cross-links PtGs and creates wall.
33
how can Ptg incorporation be targetted by Abx?
beta-lactams (e.g. Carbapenems, Cephalosporins, Penicillins) bind covalently to Transpeptidase and inhibit its action.
34
what is required by bacteria for Ptg incorporation into the wall?
transpeptidase
35
what ABx target Ptg incorporation?
beta-lactams | e.g. Carbapenems, Cephalosporins, Penicillins
36
what drugs target the cell wall stability? name one for G+ve and G-ve
Lipopeptide (e.g. Daptomycin) – disrupt gram +ve walls. Polymyxin – binds to LPS and disrupts gram –ve membranes.
37
what are the causes of antibiotic resistance?
``` o Unnecessary prescription. o Livestock farming. o Lack of regulation – OTC in some countries. o Lack of development – no new ABs. ```
38
what are the 5 mechanism that leads to antibiotic resistance?
1) Additional targets 2) Hyperproduction 3) Alterations in target enzymes 4) Alterations in drug permeation 5) Production of destruction enzymes
39
how do additional targets produced by bacteria leads to ABx resistance?
- different DHF reductase enzyme produced - another target that is then unaffected by the drug e.g. e.coli --> trimethoprim resistance
40
how does hyperproduction by bacteria lead to ABx resistance?
more DHF reductase enzyme bacteria significantly increase levels of an enzyme to overwhelm the Abx e.g. e.coli--> trimethoprim resistance
41
why is hyperproduction the least effective method of a bacteria gaining Abx resistance?
this is resource expending for the bacteria
42
how does alteration of target enzymes by bacteria lead to ABx resistance?
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
how does alteration of drug permeation by bacteria lead to ABx resistance?
- reductions in AQPs - increased efflux systems so reduced ABx entry Important in GRAM –VE bacteria.
44
what mechanism of resistance is particularly used by gram -ve bacteria?
alteration of drug permeation
45
how does the production of destructive enzymes by bacteria lead to ABx resistance? name a destructive enzyme
beta-lactamases (bacterial enzymes) hydrolyse C-N bonds of the beta-lactam ring
46
what Abx can be used against bacteria that produce beta lactamases?
- Flucloxacillin & Temocillin. these are beta-lactamase resistant (have a steric shield around Beta lactam ring) - Amoxicillin (for G-ve) with clavulanic acid
47
which Abx is not resistant to beta lactamase?
penicillins (for G+ve)
48
when is amoxicillin "beta-lactamase resistant"?
resistant to beta-lactamases only when co-administered with Clavulanic acid.
49
what are the classifications of fungal infections?
``` 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
what are the 2 main classes of drugs used for fungal infections?
azoles and polyenes
51
what do azoles do?
Inhibit CYP450 enzymes (CYP51p) involved in membrane Ergosterol synthesis.
52
name an example of an azole
Fluconazole
53
what do polyenes do?
Binds to Ergosterol and creates channel pores "puncture" holes in the cell membrane so to distrupt cell homeostasis e.g amphotercin
54
name an example of a polyene
Amphotericin
55
which infections can be treated by the azole ,fluconazole?
candidiasis | systemic infections
56
what infections can be treated by the polyene amphotericin?
systemic infections

LCRS Pharma (32 decks)

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