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Pharmacology Block III > Fluoroquinones (FQ) + Metronidazole: 9/11/15 > Flashcards

Fluoroquinones (FQ) + Metronidazole: 9/11/15 Flashcards

1
Q

What is the mechanism of action for the FQs?

A

DNA destruction and inhibition of DNA synthesis

They act by targeting & inactivating bacterial topoisomerase II (gyrase) and IV

gram negative: top II

gram positive: top IV (THINK FOUR is more positive than TWO)

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2
Q

Name the four main FQs that are commonly used today

A
  • ciprofloxacin (cipro)
  • levofloxacin (levo)
  • moxifloxacin (moxi)
  • gentifloxacin (she mentioned randomly but wasn’t main focus)
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3
Q

Are FQs bacteriostatic of bactericidal?

A

Bactericidal

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4
Q

What are the main clinical illnesses that FQs target?

A
  • Pneumonia: nosocomial and community acquired (P. aeruginosa, MSSA and PRSP)
  • UTIs and Prostatitis (entero)
  • Respiratory infections: sinusitis and bronchitis (Strep)
  • STIs, osteomyelitis, TB (atypical)
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5
Q

Describe the spectrum of activity of: ciprofloxacin

A

gram negative: enterrobacteria and P. aeruginosa*

atypical bacteria: all

anaerobes: none

gram positive: NONE

Good penetration in urinary tract

No CNS penetration

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6
Q

Describe the spectrum of activity of: levofloxacin

A

gram positive: MSSA and S. pneumo [PRSP]

gram negative: enterrobacteria and P. aeruginosa

anaerobes: none

atypical bacteria: all

Good penetration in urinary tract and CNS too!*

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7
Q

Describe the spectrum of activity of: moxifloxacin

A

gram positive: MSSA and S. pneumo [PRSP]

gram negative: enterrobacteria and NO P. aeruginosa*

anaerobes: YES.

atypical bacteria: all

gram negative: cipro = levo > moxi

Good penetration in the CNS

NO penetration in the urinary tract*

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8
Q

Which FQs are able to target UTIs, CNS infections, and hospital acquired pneumonia?

A

UTIs: cipro and levo

CNS/meningitis: moxi and levo

Hospital acquired pneumonia: levo and cipro

**Think about which the spectrum of activity for each drug

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9
Q

Name three adverse effects of taking FQs

A
  • GI: C. diff, nausea, vomiting
  • CNS: headaches & agitation (esp in the elderly)
  • Cardiac: prolonged QT syndrome*
  • Peds: articular cartilage damage* (contraindicated in children)
  • Tendon rupture*
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10
Q

For which patient population of FQs contraindicated?

A
  • Pregnant women
  • Children: articular cartilage damage
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11
Q

What are the major adverse drug reactions with FQs?

A

-divalent and trivalent cations from supplements and food: diminish absorption of FQ by binding them -warfarin: increased anti-coag effects -theophyline/cyclosporine + cipro = increased toxicity of both drugs

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12
Q

Name the three mechanisms of resistance

A
  • Chromosomal mutations in topoisomerase II or IV
  • Efflux pumps
  • Plasmid mediated resistance
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13
Q

What is the MOA of Metronidazole (IV/PO), and what makes it selectively toxic against certain bacteria?

A

Inhibits DNA synthesis

Ferredoxins in these bacteria = Metronidazole toxicity against anaerobic and microaerophilic bacteria

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14
Q

Which of the following 2 words describe Metronidazole:

  • Bactericidal
  • Bacteriostatic
  • Time dependent
  • Concentration dependent
A

Bactericidal

Concentration dependent

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15
Q

List 2 methods of resistance for Metronidazole.

A
  1. Altered growth requirements
  2. Altered ferredoxin levels

Both are relatively uncommon

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16
Q

List the most common bacteria targeted by Metronidazole.

A

Anaerobic Bacteria:

  • Bacteroides spp (ALL)
  • Clostridium spp (ALL

Anaerobic Protozoa:

  • Trichomonas vaginalis
  • Giardia lamblia
17
Q

Describe A, D and E of Metronidazole.

A

Absorption:

IV/PO

Rapidly/completely

Distribution:

Good serum concentrations via both routes

DOES penetrate the CSF

Elimination:

Metabolized by liver, excreted in urine/feces

IS removed during HD

18
Q

What are the major clinical uses of Metronidazole?

A

Anaerobic Infections (including CNS):

  • Intraabdominal
  • Pelvic
  • Diabetic foot ulcers

Pseudomembranous colitis (C. diff):

-DOC for mild to moderate C. diff infection

Other:

  • Trichomonas
  • Bacterial Vaginosis
  • H. pylori
19
Q

What are the major AEs of Metronidazole?

A

GI = MOST COMMON

N&V, Stomatitis, Metallic taste

CNS = MOST SERIOUS

Peripheral neuropathy, seizures, encephalopathy

Mutagenicity, carcinogenicity

Avoid during pregnancy/breastfeeding

20
Q

What major drug interactions may occur with Metronidazole?

A

Warfarin = increase anti-coagulant effect

Alcohol = Disulfiram reaction = Systemic effects + Circulatory Collapse

Phenytoin = Increase Phenytoin Concentration

Pharmacology Block III (8 decks)

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