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PC2 > Fluoroquinolones > Flashcards

Fluoroquinolones Flashcards

1
Q

Nalidixic acid was a byproduct of

A

chloroquine synthesis

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2
Q

Nalidixic acid was used for treatment of ____ due to high urinary concentration but poor absorption

A

UTI

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3
Q

Nalidixic acid spectrum of activity included

A

gram - but not pseudomonas

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4
Q

Quinolone pharmacophore at position 6

A

fluorine was added leading to a 10 fold increase in DNA gyrase inhibition

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5
Q

Substitutions on the main quinolone core alter the____ properties and microbiologic activity

A

PK

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6
Q

Fluoroquinolone MOA

A
  1. separate the double helix
  2. As DNA helices pulls strands apart, positive supercoiling occurs, putting pressure on the strands
  3. DNA gyrase removes the supercoils to relieve torsional stress

Following complete replication the cells need to be separated

  1. topoisomerase IV is responsible for separating interlinked DNA and allows for the development of 2 daughter cells
  2. similar in structure to DNA gyros, topoIV is made of 4 sub its and encoded by ParC and ParE genes
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7
Q

Fluoroquinolones interfere with ______ to disrupt DNA development and daughter cell formation

A

DNA gyrase and topoisomerase IV

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8
Q

DNA gyrase is the primary target in

A

Gram -

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9
Q

Topoisomerase IV is the primary target in

A

Gram +

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10
Q

Fluoroquinolones include

A

ciprofloxacin
levofloxacin
moxifloxacin
delafloxacin

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11
Q

Ciprofloxacin oral absorption

A

high

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12
Q

Ciprofloxacin 1/2 life

A

4 hours

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13
Q

Ciprofloxacin elimination

A

50% renal

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14
Q

Levofloxacin oral absorption

A

high (IV:PO)

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15
Q

Levofloxacin 1/2 life

A

7 hours

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16
Q

Levofloxacin elimination

A

87% renal

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17
Q

Moxifloxacin oral absorption

A

high (IV:PO)

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18
Q

Moxifloxacin 1/2 life

A

12 hours

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19
Q

Moxifloxacin elimination

A

20% renal; low

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20
Q

Delafloxacin oral absorption

A

high but lowest out of FQ

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21
Q

Delafloxacin 1/2 life

A

4 hours

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22
Q

Delafloxacin elimination

A

65% renal

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23
Q

FQs distribute _____ into tissues including _____

A

well; CNS

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24
Q

FQ’s are mostly _______ eliminated

A

renally

25
Q

Moxifloxacin is mostly metabolized by the

A

liver

26
Q

Moxifloxacin needs/does not need a renal adjustment

A

does not

27
Q

Ciprofloxacin spectrum coverage

A

GRAM - ONLY

dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, p. aeriginosa

light red: E. coli

28
Q

Levofloxacin spectrum coverage

A

dark purple: streptococcus, s. pneumoniae, viridans, MSSA

dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia

light red: E. coli, p. aeruginosa

29
Q

Levofloxacin and moxifloxacin are

A

respiratory agents

30
Q

Moxifloxacin spectrum coverage

A

dark purple: streptococcus, s. pneumoniae, viridans, MSSA

light purple: MRSA

dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia

light red: E. coli

Misc: anaerobes

31
Q

Delafloxacin spectrum coverage

A

dark purple: streptococcus, s. pneumoniae, viridans, MSSA, MRSA

light purple: e. faecalis

dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia

light red: E. coli, p.aeruginosa

Misc: anaerobes

32
Q

Which FQ covers MRSA?

A

Delafloxacin

33
Q

Which organisms do FQ not cover at all

A

e. faecium and acinetobacter

34
Q

FQ cover atypicals:

A

++ (oral and gut)
chlamydia
mycoplasma
legionella

35
Q

FQ also cover

A

s. maltophilia, vibrio, yersinia, bacillus anthracis, mycobacterium, nocardia

36
Q

There is a high frequency of FQ resistance in

A

ESBL-producing gram - bacteria

37
Q

Dosing is dependent on

A

indication

38
Q

Levofloxacin and Moxifloxacin dosing is

A

QD

39
Q

Mechanisms of resistance for FQ

A

alterations to target sites DNA grease (gyrA or gryB) and topoIV (parC or parE)

primary mutation will occur at the drugs primary target
gram - is usually at DNA gyrase
gram + is usually at topoIV

reduction in intracellular concentrations (efflux pumps)
reduction in number of porin channels (decreased entry)
FQ/AG modifying enzymes

40
Q

Adverse effects with FQ

A 
nausea
diarrhea
dizziness
rash
headache
vaginitis
41
Q

FQ use is associated with higher risk of

A

C. difficile infection

42
Q

FDA warnings for FQ

A

tendinitis/tendon rupture
peripheral neuropathy
restricting use for sinusitis, bronchitis, uncomplicated UTI
decrease in blood sugar and entrain mental health side effects
aortic aneurysm and dissection

43
Q

Quinolone-induced arthropathy/tendinopathy is a

A

class effect

44
Q

In peds we worry about FQ causing

A

developmental issues in cartilage and joints

45
Q

In adult patients ____ is most common musculoskeletal disorder

A

Achille’s tendon rupture

46
Q

FQ musculoskeletal disorders potential mechanism may involve

A

chelating properties- interact with regulating proteins of tenocytes

47
Q

Magnesium deficient has a

A

synergistic effect on tendonopathy

48
Q

FQ have been associated with

A

aortic aneurysm and rupture of aortic aneurysm

49
Q

Risk factors for aortic aneurysm associated with FQ use

A

age > 70 and course >14 days

50
Q

FQ should be avoided in patients who have existing____unless no other options available

A

aortic aneurysms

51
Q

FQ can cause ___prolongation

A

QTc/QT

52
Q

QT prolongation is a risk factors for

A

arrhythmias
torsades de pointes (ventricular tachycardia)
can lead to ventricular fibrillation and death

53
Q

Avoid FQ with other _____ medications

A

QT prolonging

54
Q

FQ have also been associated with disturbances of blood glucose causing

A

hyperglycemia and hypoglycemia

55
Q

Risk of _____ is greater in diabetic patients, the elderly, and those with organ dysfunction

A

hypoglycemia

56
Q

____occurs more often although is still relatively infrequent. May occur in diabetic or non-diabetic patients and at any time in therapy

A

hyperglycemia

57
Q

FQ drug-drug interactions

A

warfarin-increased effect
anti diabetic agents
chelation agents: antacids, sucralfate, metal cations, multivitamins (separate by 2 hours before or 6 hours after FQ)
QT prolonging agents
NSAIDs (increase risk for seizures)
Ciprofloxacin specific (CYP1A2 inhibitor): theophylline, cyclosporine, methotrexate

58
Q

FQ indications

A 
CA pneumonia (moxi, levo, dela)
UTI, acute exacerbation of chronic bronchitis, sinusitis

decreasing use in many health systems but frequently prescribed despite warnings for UTI and intra-ab (caution with E. coli resistance)

59
Q

Fluoroquinolones are bactericidal/bacteriostatic

A

bactericidal

PC2 (18 decks)

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