Quinolones and urinary tract antiseptics Flashcards Preview

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Flashcards in Quinolones and urinary tract antiseptics Deck (15):
1

UTI usual organisms

gram - 

- E.Coli

- other enterobacteriaceae and pseudomonas

Gram +

- interococci

- group B strep

- coagulase - staph

2

DNA gyrase:

Topoisomerase iV:

gyrase: primary target in gram - bacteria

top: primary target in gram + bacteria

 

alter the topology of bacterial DNA by introduring or removing supercoils

3

Resistance to fluoroquinolones

- decreased permeability

-efflux pump

- mutation of the enzymes

4

first generation fluoroquinolones

- fluorine at position 6 enhances activity

- norfloxacin, ciprofloxacin, ofloxacin

- improved gram - activity

- GI and urinary infections

- Bactericidal

5

2nd gen and later fluoroquinolones

gatifloxacin- only opthalmic formulation

Levo, moxifloxcin, gemifloxacin- once daliy use for respiratory infections including CA pneumonia

Moxifloxacin- anaerobic

6

fluoroquinolones

absorption:

distribution:

metabolism:

excretion:

absorption: well absorbed orally but bound by divlaent cations that inhibit absorption

distribution: widely distributed, most concentrate in urine

metabolism: hepatic metabolism dimishes activity of norfloxacin and ciprofloxacin

excretion: urinary excretion predominated for first gen FQs

7

Fluoroquinolones 

clinical uses

UTI

GI infections

CA/nosocomial pneumonia

osteomyelitis

STI: neisseria gonorrhea and chlamydia

prophylaxis against B. anthracis, N. meningitidis exposure

 

8

Nitrofurantoin

well absorbed orally

for cystitis only

mech: REduced within bacteria, bind to proteinsand DNA, causing bacterial death

distribution: only active in bladder, not for upper UTI, systemic infection, no tissue penetration

adverse effects:

- GI distress

-acute pneumonitis

-neurological symtoms: neuropathy, nystagmus, headache

- hemolysis in those with G6PD deficiency

9

Fluoroquinolones

adverse effects:

GI: nausea, vomiting common

Hepatotoxicity: severe hepatitis seen with trovafloxacin and removed from market by FDA

hyper  and hypoglycermia: especially with gatifloxacin (fomrulation for ystemis use removed from US market in 2006)

- gatifloxacin stimulated insulin secretion and suppresses sysnthesis

- less commonly reported with other FQ

 

Tendinopathy: rare but black box warning, achilles

10

FQ musculosckeletal toxicity

cartilage concerns

- artropathy reported in animals

 

tendinopathy

- achilles

-black box

11

FQs and Tx of STIs

Oflaxacin, levofloxacin are alternative drugs for:

- chlamydia- urethritis, cervicitis

- Chancroid- haemophilus durcreyi

- Granuloma inguinale

- Neisseria gonorrheae often reisitent- not recomended

 

12

FQ summary

very broad antimicrobial spectrum

resistace develops rapidly when used widely

- no longer recommended for gonoccocal infections

Ciprofloxacin- IV and PO. better pseudomonas

Levofloxacin- IV and Po. bettter S. pneumoniae

Moxifloxacin- IV and PO. better S. pneumoniae, anaerobes, 

Norfloxacin- PO only, poor systemic activity

CLMC

13

Methenamine

mech:

pharmacokinetics:

drug interactions:

mech action: froms formaldehyde in the bladder

- decomposes at acidic pH below 4.5 from urine

- ineffective for pylonephritis

- ineffective if organisms are urea splitting (proteus)

pharmacokinetics:

- some degraded by gastric acid, most absorbed

- most enter urine via glomerular filtration

formulation:

tablet or oral suspension

14

Methenamine

adverse effects:

drug interactions:

adverse effects:

- GI distress is the major side effect

- high does can cause albuminemia, hematuria and rashes

- overdose associated with hematuria

- contraindicated for: renal dyfunction (mandelis acid may precipitate), hepatic dysfunction (ammonia ions accumulate to cause CNS toxicity)

Drug interactions:

Sulfonamides react chemically with formaldehyde and inactivate both agents

15

Daptomycin

mech:

spectrum:

uses:

administration:

toxicity:

 

naturally occuring lipopeptide isolated from mold

Mech: inserts into bacterial cell membrane as a polymer, creates K+ channel, disrupting e- gradient, macromolecular synthesis

Rapidly bactericidil

Spectrum:

gram + (staph, strep, enterococcus)

Active against MRSA, VRE.

No gram -

Uses:

skin infections, bacteremia and right sided endocarditis

Inactivated by surfactant in alveoli, not used for pneumonia

administration:

IV only, dosed by weight, once daily

Toxicity:

skeletal myopathy with elevated creatine kinase

Rare eosinophilic pneumonia