Fluoroquinolones

Question 1

Nalidixic acid was a byproduct of

Answer 1

chloroquine synthesis

Question 2

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

Answer 2

UTI

Question 3

Nalidixic acid spectrum of activity included

Answer 3

gram - but not pseudomonas

Question 4

Quinolone pharmacophore at position 6

Answer 4

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

Question 5

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

Answer 5

PK

Question 6

Fluoroquinolone MOA

Answer 6

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

Question 7

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

Answer 7

DNA gyrase and topoisomerase IV

Question 8

DNA gyrase is the primary target in

Answer 8

Gram -

Question 9

Topoisomerase IV is the primary target in

Answer 9

Gram +

Question 10

Fluoroquinolones include

Answer 10

ciprofloxacin
levofloxacin
moxifloxacin
delafloxacin

Question 11

Ciprofloxacin oral absorption

Answer 11

high

Question 12

Ciprofloxacin 1/2 life

Answer 12

4 hours

Question 13

Ciprofloxacin elimination

Answer 13

50% renal

Question 14

Levofloxacin oral absorption

Answer 14

high (IV:PO)

Question 15

Levofloxacin 1/2 life

Answer 15

7 hours

Question 16

Levofloxacin elimination

Answer 16

87% renal

Question 17

Moxifloxacin oral absorption

Answer 17

high (IV:PO)

Question 18

Moxifloxacin 1/2 life

Answer 18

12 hours

Question 19

Moxifloxacin elimination

Answer 19

20% renal; low

Question 20

Delafloxacin oral absorption

Answer 20

high but lowest out of FQ

Question 21

Delafloxacin 1/2 life

Answer 21

4 hours

Question 22

Delafloxacin elimination

Answer 22

65% renal

Question 23

FQs distribute _____ into tissues including _____

Answer 23

well; CNS

Question 24

FQ’s are mostly _______ eliminated

Answer 24

renally

Question 25

Moxifloxacin is mostly metabolized by the

Answer 25

liver

Question 26

Moxifloxacin needs/does not need a renal adjustment

Answer 26

does not

Question 27

Ciprofloxacin spectrum coverage

Answer 27

GRAM - ONLY dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, p. aeriginosa light red: E. coli

Question 28

Levofloxacin spectrum coverage

Answer 28

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

Question 29

Levofloxacin and moxifloxacin are

Answer 29

respiratory agents

Question 30

Moxifloxacin spectrum coverage

Answer 30

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

Question 31

Delafloxacin spectrum coverage

Answer 31

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

Question 32

Which FQ covers MRSA?

Answer 32

Delafloxacin

Question 33

Which organisms do FQ not cover at all

Answer 33

e. faecium and acinetobacter

Question 34

FQ cover atypicals:

Answer 34

++ (oral and gut) chlamydia mycoplasma legionella

Question 35

FQ also cover

Answer 35

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

Question 36

There is a high frequency of FQ resistance in

Answer 36

ESBL-producing gram - bacteria

Question 37

Dosing is dependent on

Answer 37

indication

Question 38

Levofloxacin and Moxifloxacin dosing is

Answer 38

QD

Question 39

Mechanisms of resistance for FQ

Answer 39

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

Question 40

Adverse effects with FQ

Answer 40

``` nausea diarrhea dizziness rash headache vaginitis ```

Question 41

FQ use is associated with higher risk of

Answer 41

C. difficile infection

Question 42

FDA warnings for FQ

Answer 42

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

Question 43

Quinolone-induced arthropathy/tendinopathy is a

Answer 43

class effect

Question 44

In peds we worry about FQ causing

Answer 44

developmental issues in cartilage and joints

Question 45

In adult patients ____ is most common musculoskeletal disorder

Answer 45

Achille's tendon rupture

Question 46

FQ musculoskeletal disorders potential mechanism may involve

Answer 46

chelating properties- interact with regulating proteins of tenocytes

Question 47

Magnesium deficient has a

Answer 47

synergistic effect on tendonopathy

Question 48

FQ have been associated with

Answer 48

aortic aneurysm and rupture of aortic aneurysm

Question 49

Risk factors for aortic aneurysm associated with FQ use

Answer 49

age > 70 and course >14 days

Question 50

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

Answer 50

aortic aneurysms

Question 51

FQ can cause ___prolongation

Answer 51

QTc/QT

Question 52

QT prolongation is a risk factors for

Answer 52

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

Question 53

Avoid FQ with other _____ medications

Answer 53

QT prolonging

Question 54

FQ have also been associated with disturbances of blood glucose causing

Answer 54

hyperglycemia and hypoglycemia

Question 55

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

Answer 55

hypoglycemia

Question 56

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

Answer 56

hyperglycemia

Question 57

FQ drug-drug interactions

Answer 57

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

Question 58

FQ indications

Answer 58

``` 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)

Question 59

Fluoroquinolones are bactericidal/bacteriostatic

Answer 59

bactericidal