Antibiotics and Anti-fungals Flashcards

1
Q

Describe the membrane properties of the gram -ve and +ve bacteria

A

Gram Positive Bacteria
- Prominent peptidoglycan cell wall
E.g. Staphylococcus Aureus

Gram Negative Bacteria
- Outer membrane with lipopolysaccharide
E.g. Escherichia Coli

Mycolic Bacteria (pretty much gram +ve)
- Outer mycolic acid layer
E.g. Mycobacterium Tuberculosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the process of prokaryotic protein synthesis

A
1. Nucleic Acid Synthesis
Dihydropteroate (DHOp)
 - Produced from paraaminobenzoate (PABA)
 - Converted into dihydrofolate (DHF)
Tetrahydrofolate (THF)
 - Produced from DHF by DHF reductase
 - THF --> Important in DNA synthesis
  1. DNA replication
    DNA gyrase
    - Topoisomerase –> releases tension (unwinds the DNA)
  2. RNA synthesis
    RNA polymerase
    - Produces RNA from DNA template
    - Differ from eukaryotic RNA polymerase
  3. Protein synthesis
    Ribosomes (40s and 60s vs 30s and 50s)
    - Produce protein from RNA templates
    - Differ from eukaryotic ribosomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List the protein synthesis inhibitors and which protein synthesis mechanism it inhibits?

A
1. Nucleic Acid Synthesis
Dihydropteroate (DHOp)
 - Sulphonamides inhibit DHOp synthase
Tetrahydrofolate (THF)
 - Trimethoprim inhibits DHF reductase
  1. DNA replication
    DNA gyrase
    - Fluoroquinolones (e.g. Ciprofloxacin) inhibit DNA gyrase & topoisomerase IV
  2. RNA synthesis
    RNA polymerase
    - The rifamycins (e.g. Rifampicin) inhibits bacterial RNA polymerase
4. Protein synthesis
Ribosomes
Inhibited by:
 - Aminoglycosides (e.g. Gentamicin)
 - Chloramphenicol
 - Macrolides (e.g. Erythromycin)
 - Tetracyclines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is the bacterial cell wall synthesised?

A
  1. Peptidoglycan (PtG) synthesis (occurs within the cytoplasm)
    - 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 into the periplasm
  3. PtG incorporation
    - PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the bacterial wall inhibitors and which mechanism it inhibits?

A
  1. PtG synthesis
    - Glycopeptides (e.g. Vancomycin) bind to the pentapeptide preventing PtG synthesis
  2. PtG transportation
    - Bacitracin inhibits bactoprenol regeneration preventing PtG transportation
  3. PtG incorporation
    - beta-lactams bind covalently to transpeptidase inhibiting PtG incorporation into cell wall
    - beta-lactams include:
    1) Carbapenems
    2) Cephalosporins
    3) Penicillins
  4. Cell wall stability
    - Lipopeptide - (e.g. daptomycin) disrupt Gram +ve cell membranes
    - Polymyxins - binds to LPS and disrupts Gram -ve cell membranes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

List the 5 mechanisms which cause antibiotic resistance

A

Destruction enzymes
- Production of beta-lactamase

Additional target
- Different DHF reductase enzyme produced

Enzyme alteration
- Mutations in DNA gyrase enzyme

Hyperproduction
- Over-production of DHF reductase

Drug Permeation
- decrease drug influx, increase efflux systems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe mechanism 1 of antibiotic resistance

A

Production of destruction enzymes
beta-lactamases hydrolyse C-N bond of the beta-lactam ring

Examples of beta-lactamases

  • Penicillins G and V –> Gram +ve (destroyed by beta-lactamases)
  • Flucloxacillin and Temocillin –> beta-lactamase resistant
  • Amoxicillin –> Broad spectrum
    1) Gram -ve activity
    2) Co-administered with Clavulanic acid otherwise destroyed by beta-lactamases.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe mechanism 2 of antibiotic resistance

A

Additional target
- Bacteria produce another target that is unaffected by the drug

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe mechanism 3 of antibiotic resistance

A

Alterations in target enzymes
- Alteration to the enzyme targeted by the drug. Enzyme still effective but drug now ineffective

Example
- S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe mechanism 4 of antibiotic resistance

A

Hyperproduction
- Bacteria significantly increase levels of DHF reductase. The drugs work but there not able to remove all the reductase enzymes

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe mechanism 5 of antibiotic resistance

A

Alterations in drug permeation

  • Reductions in aquaporins and increased efflux systems
  • Together they reduce the drugs being able to get into the cell.

Examples
Primarily of importance in gram –ve bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the two main classes of anti-fungals

A

Azoles

  • Inhibit cytochrome P450-dependent enzymes involved in membrane sterol synthesis. Prevents conversion of lanosterol to ergosterol
  • Fluconazole (oral) –> candidiasis and systemic infections

Polyenes

  • Interact with cell membrane sterols forming membrane channels. (punches holes in the cell wall - making it permeable)
  • Amphotericin (I-V) –> systemic infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly