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Antibiotics Flashcards

1
Q

What are the three classes of synthetic antibiotics in current clinical use?

A
  1. Sulfa drugs
  2. Fluoroquinolones
  3. Oxazolidinone
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2
Q

What is a broad-spectrum antibiotic?

A

Effective against wide range of Gram-positive and Gram-negative bacteria

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3
Q

What is a narrow-spectrum antibiotic?

A

Effective mainly against Gram-positive or Gram-negative bacteria

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4
Q

What is a limited-spectrum antibiotic?

A

Effective against a single organism or disease

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5
Q

What is an extended-spectrum antibiotic?

A

Semi-synthetic antibiotic that has been modified to have a broader spectrum of activity

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6
Q

What do the cephalosporins treat?

A
  1. Pneumonia
  2. Bronchitis
  3. Meningitis
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7
Q

What do the macrolides treat?

A
  1. Toxic shock syndrome

2. Meningitis

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8
Q

What do the beta-lactamase inhibitors treat?

A
  1. Pneumonia
  2. Bronchitis
  3. Septicaemia
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9
Q

What do the penicillins treat?

A
  1. Pneumonia
  2. Bronchitis
  3. Septicaemia
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10
Q

What do the quinolones treat?

A
  1. Toxic shock syndrome

2. Meningitis

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11
Q

What are the extended spectrum macrolides?

A
  1. Clarithromycin

2. Azithromycin

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12
Q

What kind of antibiotics are used when the immune system is compromised?

A

Bactericidal drugs because bacteriostatic drugs require the immune system to eliminate the infection

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13
Q

What is the minimal inhibitory concentration?

A

Lowest concentration of a drug that inhibits growth of a bacterium

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14
Q

What is the minimal bactericidal concentration?

A

Lowest concentration of a drug that kills a bacterium

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15
Q

What is the therapeutic ratio?

A

Maximum non-toxic dose over minimum effective dose

Higher is better

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16
Q

What are the five major targets in bacterial pathogens?

A
  1. Cell wall biosynthesis
  2. Protein biosynthesis
  3. DNA replication, repair and expression
  4. Folate coenzyme biosynthesis
  5. Membrane
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17
Q

What is the tonicity of the bacterium relative to its environment?

A

Hyptertonic

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18
Q

What is the role of the bacterial cell wall?

A

Prevent rupture of cell membrane by osmotic shock

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19
Q

How does the peptidoglycan cell wall in Gram-positive organisms differ?

A
  1. Thicker
  2. Substantially layered
  3. Polymers of teichoic acids associated with it
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20
Q

What does the peptidoglycan cell wall consist of?

A
  1. Orthogonal glycan and peptide strands
  2. Glycan strands cross-linked by transglycosylase
  3. Peptide strands cross-linked by transpeptidase
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21
Q

What is the role of the peptide cross-links in the cell wall?

A
  1. Covalent connectivity to meshwork
  2. Mechanical strength
  3. Major structural barrier to prevent osmotic forces
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22
Q

What is the basic cell building block of PG synthesis?

A

UDP N-acetylmuramylpentapeptide

23
Q

Where does production of UDP N-acetylmuramylpentapeptide take place?

A

Inside cell

Inner leaflet of phospholipid bilayer

24
Q

Which enzyme converts L-alanine to D-alanine?

A

L-alanine racemase

25
What is the role of pyruvyl transferase?
Catalyses transfer of phosphoenolpyruvate group to N-acetylglucosamine in the production of UDP N-acetyl muramyl tripeptide
26
What is bactoprenol phosphate?
Lipid anchor also referred to as C55 undecaprenyl phosphate
27
What type of enzymes are transpeptidases?
Serine hydrolases Active-site serine nucleophile Side-chain that functions as general base
28
What is the transiently-linked acyl group of the acyl-O-Ser enzyme intermediate?
Glycan-tetrapeptidyl moiety
29
What induces cell death when penicillin antibiotics act?
Cell wall autolytic enzymes
30
What kind of cells are sensitive to beta-lactam antibiotics?
Proliferating cells in which autolysins are active only
31
What is the first N-terminal amino acid for bacterial proteins?
Formyl-methionine
32
Which protein is required Required to attach mRNA to 30S subunit in bacteria?
Initiation factor 3
33
Which factors are required to combine tRNA with mRNA-30S subunit in initiation step?
1. Initiation factors 1 and 2 | 2. GTP
34
What is the function of initiation factor Tu?
Hydrolysis of GTP
35
What do macrolide antibiotics compete with?
Lincosamide antibiotics
36
How do lincosamide antibiotics work?
Direct peptidyltransferase inhibitors
37
What is the effect of decreased fidelity in translation in growing bacteria?
1. Inserting more incorrect amino acids 2. Alteration of proteins 3. If membrane proteins, permeability is affected 4. Death by cell leakage
38
What is the role of DNA topoisomerases?
Change linking number in supercoiled DNA by making transient cuts and passing DNA through the breaks
39
How does DNA topoisomerase I work?
Passes one strand through the cut in DNA
40
How does DNA topoisomerase II work?
Passes two strands at the same time through the cut in DNA
41
What type of enzyme is DNA gyrase?
DNA topoisomerase II
42
What is the intracellular target of quinolones?
1. DNA gyrase | 2. DNA topoisomerase IV
43
How does DNA topoisomerase IV differ from DNA gyrase?
1. Cannot supercoil DNA 2. Carries out ATP-dependent relaxation of DNA 3. More potent decatenase
44
What kind of intermediate do DNA gyrase and topo IV form?
Covalent intermediate with target DNA
45
How does rifampin bind?
Tight but non-covalent manner to allosteric site of beta subunit of DNA-dependent RNA polymerase
46
What is unaffected by rifampin?
Protein synthesis in progress at time of drug exposure because only initiation is affected, not later steps of protein synthesis
47
How do rigid planar polycyclic antibiotics intercalate into DNA?
Preliminary local unwinding of DNA double helix to produce spaces
48
How does intercalation inhibit normal replication and transcription?
Partial unwinding affects molecular dimensions of major and minor grooves of DNA preventing DNA replication and transcription machinery from binding and acting
49
How do bleomycins cause damage to DNA?
Interaction between oxygen and bound iron Generates superoxide and hydroxyl radicals Causes single and double stranded breaks
50
Why are eukaryotes less affected by drugs that inhibit synthesis of folate?
Bacteria must make folate de novo but eukaryotes can scavenge dietary folate
51
How do folate synthesis enzymes differ between mammals and bacteria?
1. DHPS totally absent in mammals | 2. DHFR sufficiently structurally different to be selectively inhibited
52
How fast do folate enzyme inhibitors act?
Slowly because folate pools persist for several bacterial generations
53
Why are antibiotics that disrupt membrane permeability toxic?
1. Dissipation of transmembrane ion gradients 2. Disturb ion homeostasis 3. Induce leakage of macromolecules

MODA Questions (7 decks)

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