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Pharmacology and Therapeutics 2 Y2 > Antibiotics and Anti-Fungals > Flashcards

Antibiotics and Anti-Fungals Flashcards

1
Q

antibiotic intracellular process targets? (4)

A

nucleic acid synthesis, DNA replication, RNA synthesis and protein synthesis

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2
Q

antibiotic cell membrane targets? (3)

A

peptidoglycan synthesis
peptidoglycan incorporation
membrane stability

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3
Q

antibiotic resistance mechanisms? (5)

A 
destruction enzymes
additional target
hyper-production
changes to target
alterations in permeation
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4
Q

2 types of anti-fungals?

A

azoles and polyenes

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5
Q

3 types of bacteria? example of each

A

gram +ve staph. aureus, gram -ve e. coli and mycolic mycobacterium tuberculosis

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6
Q

Describe the 4 stages for DNA synthesis in bacteria

A
  1. NUCLEIC ACID SYNTHESIS:
    paraaminobenzoate (PABA) -> [DHOp synthase] -> dihydropteroate (DHOp) -> dihydrofolate (DHF) -> [DHF reductase] -> tetrahydrofolate (THF)
    - THF is Important in DNA synthesis
  2. DNA REPLICATION:
    DNA gyrase
    - Topoisomerase unwinds bacteria DNA, releases tension and provides access for enzymes
  3. RNA SYNTHESIS:
    RNA polymerase
    - Produces RNA from DNA template
    - Differ from eukaryotic RNA polymerase
  4. PROTEIN SYNTHESIS:
    Ribosomes
    - Produce protein from RNA templates
    - Differ from eukaryotic ribosomes
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7
Q

Describe the pathway for synthesis of tetrahydrofolate

A

paraaminobenzoate (PABA) -> [DHOp synthase] -> dihydropteroate (DHOp) -> dihydrofolate (DHF) -> [DHF reductase] -> tetrahydrofolate (THF)

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8
Q

What is the use of tetrahydrofolate

A

important in DNA synthesis

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9
Q

What inhibits DHOp synthase

A

sulphonamides

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10
Q

what inhibits DHF reductase

A

Trimethoprim

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11
Q

Target of sulphonamides

A

Inhibits DHOp synthase

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12
Q

Target of Trimethoprim

A

inhibits DHF reductase

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13
Q

drugs that target bacterial DNA synthesis pathway?

A

sulphonamides

Trimethoprim

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14
Q

Target of Fluoroquinolones

A

inhibit DNA gyrase & topoisomerase IV

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15
Q

Drug that targets DNA gyrase

A

Fluoroquinolones

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16
Q

Drug that targets topoisomerase IV

A

Fluoroquinolones

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17
Q

What enzymes are involved in unwinding DNA in bacterial DNA replication

A

DNA gyrase & topoisomerase IV

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18
Q

Target of Aminoglycosides

A

bacterial Ribosomes

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19
Q

Target of Chloramphenicol

A

bacterial Ribosomes

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20
Q

Target of rifamycins

A

bacterial RNA polymerase

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21
Q

Target of Macrolides

A

bacterial Ribosomes

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22
Q

Target of Tetracyclines

A

bacterial Ribosomes

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23
Q

Drug that targets bacterial Ribosomes

A

Macrolides
(Aminoglycosides
Chloramphenicol
Tetracyclines)

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24
Q

Drug that targets bacterial RNA polymerase

A

rifamycins

25
Q

Describe three stages of bacterial wall synthesis

A
  1. PEPTIDOGLYCAN (PtG) SYNTHESIS:
    - A pentapeptide is created on N-acetyl muramic acid (NAM)
    - N-acetyl glucosamine (NAG) associates with NAM forming PtG
  2. PtG TRANSPORTATION:
    - PtG is transported across the membrane by bactoprenol
  3. PtG INCORPORATION:
    - PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides
26
Q

how do we inhibit PtG synthesis

A
  • Glycopeptides (e.g. Vancomycin) bind to the pentapeptide preventing PtG synthesis
27
Q

how do we inhibit PtG transportation

A

• Bacitracin inhibits bactoprenol regeneration preventing PtG transportation

28
Q

how do we inhibit PtG incorporation

A
  • b-lactams bind covalently to transpeptidase inhibiting PtG incorporation into cell wall
  • b-lactams include Carbapenems, cephalosporins and penicillins
29
Q

how do we inhibit CELL WALL STABILITY

A
  • Lipopeptide - (e.g. daptomycin) disrupt Gram +ve cell walls
  • Polymyxins - binds to LPS & disrupts Gram -ve cell membranes
30
Q

What do Glycopeptides do

A

bind to the pentapeptide preventing PtG synthesis

31
Q

What binds to the pentapeptide preventing PtG synthesis

A

Glycopeptides

32
Q

What does Bacitracin do

A

inhibits bactoprenol regeneration preventing PtG transportation

33
Q

What do b-lactams do

A

bind covalently to transpeptidase inhibiting PtG incorporation into cell wall

34
Q

What does Lipopeptide do

A

disrupt Gram +ve cell walls

35
Q

What do Polymyxins do

A

binds to LPS & disrupts Gram -ve cell membranes

36
Q

Common example of a beta lactam?

A

Penicillin

37
Q

what inhibits bactoprenol regeneration preventing PtG transportation

A

Bacitracin

38
Q

what binds covalently to transpeptidase inhibiting PtG incorporation into cell wall

A

beta-lactam

39
Q

what disrupts Gram +ve cell walls

A

lipopeptide

40
Q

what binds to LPS & disrupts Gram -ve cell membranes

A

polymyxins

41
Q

What 2 things come together to form PtG

A
  • N-acetyl glucosamine (NAG)

on N-acetyl muramic acid (NAM)

42
Q

what transports PtG across the bacterial membrane

A

bactoprenol

43
Q

what enzyme incorporates PtG into the cell wall

A

transpeptidase

44
Q

what does transpeptidase do

A

incorporates PtG into the cell wall by cross linking PtG pentapeptides

45
Q

what does bactoprenol do

A

transports PtG across the bacterial membrane

46
Q

4 causes of AB resistance?

A
  1. Unnecessary prescription ~ 50% of antibiotic prescriptions not required
  2. Livestock farming ~ 30% of UK antibiotic use in livestock farming
  3. Lack of regulation OTC availability in Russia, China, India
  4. Lack of development Very few antibiotics in recent years
47
Q

Difference between gram +ve and gram -ve bacteria and mycolic?

A

Gram Positive Bacteria:
- Prominent peptidoglycan cell wall

Gram Negative Bacteria:
- Outer membrane with lipopolysaccharide

Mycolic Bacteria:
- Outer mycolic acid layer

48
Q

Give an example of AB resistance via Production of destruction enzymes

A

b-lactamases hydrolyse C-N bond of the b-lactam ring

49
Q

Example of AB resistance via Additional target

A

E Coli produce different DHF reductase enzyme making them resistant to trimethoprim

50
Q

Explain and give example of AB resistance via Alterations in target enzymes

A

Alteration to the enzyme targeted by the drug. Enzyme still effective but drug now ineffective
S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones

51
Q

give example of AB resistance via hyperproduction

A

Bacteria significantly increase levels of DHF reductase

Example E Coli produce additional DHF reductase enzymes making trimethoprim less effective

52
Q

Explain AB resistance via Alterations in drug permeation

A

Reductions in aquaporins which are needed for the drug to get into the cell & increased efflux systems

53
Q

What resistance do e coli show

A

E Coli produce different and additional DHF reductase enzymes making them resistant to trimethoprim

54
Q

What resistance do S Aureus show

A

Mutations in the ParC region of topoisomerase IV confers resistance to quinolones

55
Q

4 classifications of antifungals?

A
  1. Superficial - Outermost layers of skin
  2. Dermatophyte - Skin, hair or nails
  3. Subcutaneous - Innermost skin layers
  4. Systemic - Primarily respiratory tract
56
Q

2 types of antifungals?

A
  1. Azoles: Fluconazole

2. Polyenes: Amphotericin

57
Q

MOA azoles?

A
  • Inhibit cytochrome P450-dependent enzymes involved in membrane ergosterol synthesis
  • Fluconazole (oral) candidiasis & systemic infections
58
Q

MOA polyenes

A
  • Interact with cell membrane ergosterolsforming membrane channels
  • Amphotericin (I-V) systemic infections

Pharmacology and Therapeutics 2 Y2 (24 decks)

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