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PHAR20400 > ANTI-MICROBIALS: DNA GYRASE INHIBITORS AND DNA STRAND BREAKERS > Flashcards

ANTI-MICROBIALS: DNA GYRASE INHIBITORS AND DNA STRAND BREAKERS Flashcards

1
Q

What type of enzyme is DNA gyrase?

A

Topoisomerase II

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2
Q

What does DNA gyrase do?

A

Induces left-handed supercoiling in bacterial DNA by a process of cutting and rejoining using ATP, so that the DNA can fit into the cell

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3
Q

Why is DNA gyrase a good antibacterial target?

A

Only bacteria supercoil their DNA

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4
Q

How do Quinolones work?

A
  • Quinolones bind to A subunit of DNA gyrase
  • This interferes with DNA breakage and re-joining, so this prevents the supercoiling of DNA
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5
Q

What type of Gram bacteria is Quinolones effective against?

A
  • Quinolones are broad-sprectrum (active against gram +ve and gram -ve)
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6
Q

Quinolones are effective against gram negative bacteria which are resistant to penicillins. True or false?

A

True

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7
Q

What is a first generation quinolone and what is it used to treat?

A
  • Nalidixic acid
  • Treats uncomplicated urinary tract infections
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8
Q

What are fluoroquinolones and how do they differ from first generation quinolones?

A
  • Second generation quinolones
  • Have increased for gram +ve infections and systemic activity
  • Fluorine substitutes hydrogen in an aromatic ring, difference in electronegativity alters properties
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9
Q

What are some examples of fluroquinolones? (3)

A
  • Norfloxacin
  • Ciprofloxacin
  • Ofloxacin
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10
Q

What are the indications of Ciprofloxacin? (5)

A
  • Infections of the respiratory tract (NOT pneumococcal pneumonia)
  • Urinary-tract infections
  • Gonorrhoea.
  • Prophylaxis of meningococcal meningitis.
  • ANTHRAX (treatment and post-exposure prophylaxis).
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11
Q

What cytochrome metabolizes ciprofloxacin and why is this problematic?

A
  • CYP450 1A2
  • Can lead to overdose of caffeine, warfarin and other drugs
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12
Q

What drugs should ciprofloxacin not be taken with?

A
  • Magnesium or aluminium antacids = absorption reduced
  • NSAIDs = leads to CNS disturbances
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13
Q

Why is Ciprofloxacin cautioned in young and older patients?

A

Can cause damage to cartilage, especially in young and old patients.

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14
Q

Ciprofloxacin is contraindicated in pregnancy. True or false?

A

True

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15
Q

Why are third generation quinolones different from first/ second generation quinolones?

A
  • Third generation quinolones are active against streptococci, inc. S. pneumoniae (1st/ 2nd quinolones are not)
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16
Q

What are third generation quinolones used to treat?

A
  • Streptococci infections
  • Pneumonia
  • Urinary tract infections
17
Q

Give the name of a third generation quinolone?

A

Levofloxacin (brand name Tavanic)

18
Q

Give some examples of DNA strand breakers:

A

Nitrofurans (e.g. nitrofurantoin, nitroimadazoles such as metronidazole)

19
Q

How do nitrofurans work?

A
  • Nitrofurans become radicals anions in anaerobic conditions
  • These radical anions extract a H from DNA causing cleavage of the sugar-phosphate backbone
20
Q

What is Nitrofurantoin used for?

A

UTIs (anaerobic bacterial infections only)

  • Includes gram +ve and -ve
21
Q

What are nitroimidazoles used for?

A
  • anaerobic bacterial infections (BV, C. difficile, and acute oral infections)
  • protozoal infections (amoebiasis, Trichomoniasis, Giardiasis)
22
Q

What are the problems with using nitroimidazoles?

A
  • Can cause alcohol intolerance
23
Q

Who is suspecitible to a C. difficile infections?

A
  • Patients in hospitals
  • Patients that are using broad-spectrum antibiotic (oral penicillins e.g.ampicillin, cephalosporins, clindamycin, quinolones)
    • this eliminates much of the normal microflora = promotes overgrowth of C. difficile
24
Q

What are the symptoms of C. difficile? (3)

A
  • Diarrhoea
  • Abdominal pain and tenderness
  • Fever and nausea
25
Q

How is C.diff treated?

A
  • Discontinue using broad-spectrum antibiotic
  • Rehydration
  • 1st line = oral metronidazole 400mg every 8 h for 7-10 days).
  • 2nd line = oral Vancomycin (125mg every 6 h for 7-10 days).
26
Q

Spores are resistant to alcohol handwash. True or false?

A

True

27
Q

How are C. difficile infections prevented?

A
  • Use of narrow spectrum antibiotics
  • Use of antibiotic for the minimum amount of time
  • Patient isolation if suspected C. difficile
  • Good hygiene
28
Q

What is a new drug that has proven to be successful against C.diff?

A

Fidaxomicin

29
Q

Name this structure

A

double-ring structure (benzene and a pyridine ring fused) with a nitrogen atom = basic quinolone

30
Q

Name the structure

A

Nitrofurans

31
Q

Name the structure

A

NITROIMIDAZOLES

PHAR20400 (20 decks)

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