Antibiotics and antifungals Flashcards

1
Q

Bacteria

A
  • single cell microorganisms (cell wall and cell membrane included)
  • entire phylogenetic domain
  • ~ one third are pathogenic
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2
Q

Gram positive bacteria membrane properties

A
  • prominent thick peptidoglycan cell wall

- EG: Staphylococcus Aureus

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3
Q

Gram negative bacteria membrane properties

A
  • outer membrane with lipopolysaccharide

- EG: Escherichia Coli

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4
Q

Mycolic bacteria membrane properties

A
  • outer mycolic acid layer

- EG: Mycobacterium Tuberculosis

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5
Q

Prokaryotic protein synthesis

A

1) Nucleic Acid synthesis
2) DNA replication
3) RNA synthesis
4) Protein synthesis

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6
Q

Nucleic acid synthesis

A

1) Dihydropteroate (DHOp)
- produced from paraaminobenzoate (PABA)
- converted into dihydrofolate (DHF)
- sulphonamides inhibit DHOp synthase
2) Tetrahydrofolate (THF)
- produced from DHF by DHF reductase
- important in DNA synthesis
- Trimethoprim inhibits DHF reductase

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7
Q

DNA replication

A

1) DNA gyrase
- Toposimerase which releases tension in DNA
- Fluoroquinolones (eg: Ciprofloxacin) inhibits DNA gyrase and topoisomerase IV

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8
Q

RNA synthesis

A

1) RNA polymerase
- produces RNA from DNA template
- differs from eukaryotic RNA polymerase
- rifamycins (eg: Rifampicin) inhibits bacterial RNA polymerase

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9
Q

Protein synthesis

A

1) Ribosomes
- produces protein from RNA templates
- prokaryotic ribosomes (70S) differ from eukaryotic ribosomes (80S)
- ribosomes inhibited by aminoglycosides (eg: Gentamicin), chloramphenicol, macrolides (eg: erythromycin) and tetracylcines

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10
Q

Bacterial wall synthesis

A

1) Peptidoglycan synthesis
2) Peptidoglycan transportation
3) Peptidoglycan incorporation

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11
Q

Peptidoglycan synthesis

A
  • pentapeptide is created on N-acetyl muramic acid (NAM)
  • N-acetyl glucosamine (NAG) associates with NAM forming peptidoglycan
  • Glycopeptides (eg: vancomycin) binds to pentapeptide to prevent peptidoglycan synthesis
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12
Q

Peptidoglycan transportation

A
  • peptidoglycan transported across membrane by bactoprenol

- Bacitracin inhibits bactoprenol regeneration preventing peptidoglycan transportation

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13
Q

Peptidoglycan incorporation

A
  • peptidoglycan incorporated into cell wall when transpeptidase enzyme cross-links peptidoglycan pentapeptides
  • Beta-lactams bind covalently to transpeptidase to inhibit peptidoglycan incorporation into cell wall (eg: carbapenems, cephalosporins, penicillins etc)
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14
Q

Cell wall stability

A
  • Lipopeptide (eg: Daptomycin) disrupts gram positive cell walls
  • Polymyxins bind to lipopolysaccharides and disrupts gram negative cell membranes
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15
Q

Threat of antibiotic resistance

A

0~70% of bacteria developed resistance

-25,000 yearly death rate in Europe and the US

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16
Q

Causes of antibiotic resistance

A
  • Unnecessary prescription (~50% of antibiotic prescriptions are not required)
  • Livestock farming (~30% of UK antibiotic use in livestock farming)
  • Lack of regulation (over the counter availability in Russia, China and India)
  • Lack of development (very few antibiotics in recent years)
17
Q

Production of destruction enzymes (resistance mechanism)

A

-Beta-lactamases hydrolyse C-N bond of the drug’s beta-lactam ring

Examples:

  • Penicillins G and V=gram positive bacteria (beta-lactamase non-resistant)
  • Flucloxacillin and Temocillin=beta-lactamase resistant
  • Amoxicillin (broad spectrum antibiotic)=gram negative bacteria activity and often co-adminstered with Clavulanic acid
18
Q

Additional targets (resistance mechanism)

A

-bacteria produce another target that is unaffected by drug (different DHF reductase enzyme)

Example:
-E. Coli produces a different DHF reductase enzyme to make them resistant to trimethoprim

19
Q

Alteration in target enzymes (resistance mechanism)

A
  • alteration/mutation to enzyme targeted by drug
  • enzyme still effective but drug now ineffective

Example:
-Staphylococcus Aureus=mutations in ParC region of topoisomerase IV confers quinolone resistance

20
Q

Hyperproduction (resistance mechanism)

A

-bacteria significantly increase DHF reductase levels (overproduction)

Example:
-E. Coli=produces additional DHF reductase enzymes making trimethoprim less effective

21
Q

Alterations in drug permeation (resistance mechanism)

A

-reductions in aquaporins (decreased drug influx) and increased efflux systems

Example:
-important in gram negative bacteria

22
Q

Fungal infection classification

A
  • Classified in terms of tissue/organs
    1) Superficial (outermost skin layers)
    2) Dermatophyte (skin, hair or nails)
    3) Subcutaneous (innermost skin layers)
    4) Systemic (primarily respiratory tract)
23
Q

Antifungals

A

-15 anti-fungal drugs licensed in UK

Two most common categories:

  • Azoles
  • Polyenes
24
Q

Azoles

A

-inhibits cytochrome P450-dependent enzymes involved in membrane sterol synthesis (ergosterol synthesis)

Example:
-Fluconazole (oral admin)=treats candidiasis and systemic infections

25
Q

Polyenes

A

-interacts with cell membrane sterols (ergosterols) forming membrane channels/pores

Example:
-Amphotericin (I.V. admin)=treats systemic infections