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MODA Questions > Antibiotics > Flashcards

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
Q

What is the role of pyruvyl transferase?

A

Catalyses transfer of phosphoenolpyruvate group to N-acetylglucosamine in the production of UDP N-acetyl muramyl tripeptide

26
Q

What is bactoprenol phosphate?

A

Lipid anchor also referred to as C55 undecaprenyl phosphate

27
Q

What type of enzymes are transpeptidases?

A

Serine hydrolases

Active-site serine nucleophile

Side-chain that functions as general base

28
Q

What is the transiently-linked acyl group of the acyl-O-Ser enzyme intermediate?

A

Glycan-tetrapeptidyl moiety

29
Q

What induces cell death when penicillin antibiotics act?

A

Cell wall autolytic enzymes

30
Q

What kind of cells are sensitive to beta-lactam antibiotics?

A

Proliferating cells in which autolysins are active only

31
Q

What is the first N-terminal amino acid for bacterial proteins?

A

Formyl-methionine

32
Q

Which protein is required Required to attach mRNA to 30S subunit in bacteria?

A

Initiation factor 3

33
Q

Which factors are required to combine tRNA with mRNA-30S subunit in initiation step?

A
  1. Initiation factors 1 and 2

2. GTP

34
Q

What is the function of initiation factor Tu?

A

Hydrolysis of GTP

35
Q

What do macrolide antibiotics compete with?

A

Lincosamide antibiotics

36
Q

How do lincosamide antibiotics work?

A

Direct peptidyltransferase inhibitors

37
Q

What is the effect of decreased fidelity in translation in growing bacteria?

A
  1. Inserting more incorrect amino acids
  2. Alteration of proteins
  3. If membrane proteins, permeability is affected
  4. Death by cell leakage
38
Q

What is the role of DNA topoisomerases?

A

Change linking number in supercoiled DNA by making transient cuts and passing DNA through the breaks

39
Q

How does DNA topoisomerase I work?

A

Passes one strand through the cut in DNA

40
Q

How does DNA topoisomerase II work?

A

Passes two strands at the same time through the cut in DNA

41
Q

What type of enzyme is DNA gyrase?

A

DNA topoisomerase II

42
Q

What is the intracellular target of quinolones?

A
  1. DNA gyrase

2. DNA topoisomerase IV

43
Q

How does DNA topoisomerase IV differ from DNA gyrase?

A
  1. Cannot supercoil DNA
  2. Carries out ATP-dependent relaxation of DNA
  3. More potent decatenase
44
Q

What kind of intermediate do DNA gyrase and topo IV form?

A

Covalent intermediate with target DNA

45
Q

How does rifampin bind?

A

Tight but non-covalent manner to allosteric site of beta subunit of DNA-dependent RNA polymerase

46
Q

What is unaffected by rifampin?

A

Protein synthesis in progress at time of drug exposure because only initiation is affected, not later steps of protein synthesis

47
Q

How do rigid planar polycyclic antibiotics intercalate into DNA?

A

Preliminary local unwinding of DNA double helix to produce spaces

48
Q

How does intercalation inhibit normal replication and transcription?

A

Partial unwinding affects molecular dimensions of major and minor grooves of DNA preventing DNA replication and transcription machinery from binding and acting

49
Q

How do bleomycins cause damage to DNA?

A

Interaction between oxygen and bound iron

Generates superoxide and hydroxyl radicals

Causes single and double stranded breaks

50
Q

Why are eukaryotes less affected by drugs that inhibit synthesis of folate?

A

Bacteria must make folate de novo but eukaryotes can scavenge dietary folate

51
Q

How do folate synthesis enzymes differ between mammals and bacteria?

A
  1. DHPS totally absent in mammals

2. DHFR sufficiently structurally different to be selectively inhibited

52
Q

How fast do folate enzyme inhibitors act?

A

Slowly because folate pools persist for several bacterial generations

53
Q

Why are antibiotics that disrupt membrane permeability toxic?

A
  1. Dissipation of transmembrane ion gradients
  2. Disturb ion homeostasis
  3. Induce leakage of macromolecules

MODA Questions (7 decks)

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