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Flashcards in Quinolones Lecture 25 Deck (24):
1

Quinolones Structure and chemistry

strucually related to nalidixic acid

all agents besides nalidixic acid have been fluorinated, making these compounds less susceptible to resistance

2

Quinolones MoA

DNA gyrase is essential for supercoiling of cellular DNA by a nicking, pass thorugh, and resealing process

quinolones inhibit the enzymatic activity of bacterial DNA gyrase and promote the cleavage of DNA within the enzyme DNA complex

Bactericidal

3

Quinolones names and proerpties

ciprofloxacin: 3.2 Hour half life. 70% Bioavail. 29% renal excretion

oflaoxacin: 5 hour half life. 95% bio. 73 renal

levofloxacin: 6-7 hours half life. 100% bio. 61-86% renal

moxifloxacin: 9-16 hours. ~90% bioavialble. 15-21 renal excretion

gemifloxacin: 7 hour. ~70% bioavilablity. 36% renal

4

Quinolones absorption

food decreases rate, but not extent, of absorption

magnesium, aluminum, and/or calcium containing antacids ecrease the oral bioavailability

bioavailability varies with agents

5

Drug interactions quinolones

theophylline: decreased theophylline metabolism. Ciprofloxacin can double theophilline levels. Levofloxacin but no well documented effects.

antacids/iron/sucralfate: interfere with absorption of quinolones. Do not give within 2 hours of quinolone dose.

warfarin: increased anticoagulant effect possibly due to metabolism or protein binding changes. Levofloxacin: no well documeted effects, should monitor.

6

AE: Quinolones

Hypersensitivity: maculopapular rash, urticaria, pruritis, anaphylaxis/angioedema, photosensitivity.

gastrointestinal reactions: abnormal liver function tests. Dia/N/V

nephrotoxicity

CNS: HA/D

muscoloskeltal: arthropathy (not indicated for under 18 years of age; however debates occuring). Tendon rupture

7

SoA quinolones

G+: s. pneumonia, s. pyogenes, s. agalactiae, s. aureus, e. faecalis?

G-: salmonella, shigella, neisseria gon, H flu, M. cat, M. Morganii, proteus mirabilis/vulgaris, e coli, K. pneumonia, P. aeruginosa, enterbacter.

8

Summary or other quinolones

ciprofloxacin: excellent gram negative coverage

levofloxacin, gemifloxacin, moxifloxacin: gram + (staph and strep) and gram negative coverage.

9

Quinolones indications

UTI, Uncomplicated urethral or endocervical gonorrhea, chlamydia, mild to moderate lower respiratory tract infections caused by susceptible organisms. PID, prostatitis, gastroenteritis/infectious diarrhea,

Skin/ Skin structure infections caused by susceptible organisms (ciprofloxacin ofloxacin. Levofoxacin and gemifloxacin, and moxifloxacin better gram+ coverage, Moxifloxacin covers anaerobes well)

Bone and joint infections caused by susceptible organisms. (ciprofloxacin and ofloxacin)

complicated intra abdominal infections: cirpofloxaci/metronidazole or moxifloxacin

10

Quinolones: Ciprofloxacin

Widest range of FDA approved indications

cirploxacin is most potent of the quinolones against gram -. 4x more potent against pseudomonas

due to excellent biavailability oral form should be used in patients with functioning GI tracts or severely ill where absorption may be impaired

gram + activity very variable

11

Quinolones: Levofoxacin, gemifloxacin, moxifloxacin

gram + coverage, including resistant pneumoccous

g-: not as potent as ciprofloxacin

atypical respiratory pathogens: mycoplasma, legionella

due to excellent bioavailability oral form should be used in patients with functioning GI tracts or severely ILL where absorption my be impaired.

MOxifloxacin covers intrabdominal infections (anaerobes) but not UTI.

G+, G-, atypicals

12

tetracycline members:

doxycycline, minocycline, demecyocyline, oxytetracycline, chloratetracycline, tetracycline

13

Tetracycline: MoA

reversibly bins to 30s ribosomal subunit: decreases protein syntehsis

bacteriostatic

absorption decreased by food: variable from 20-50% for various TCN

14

characteristics of tetracyline. Bioavailbility

Bioavailability varies dependt on products.

doxy and mino: 90-100

tetracycline, demeclocyline, oxytetracycline: 58-75%

15

Tetracycline: elimination

renally: tetracycline, oxytetracycline, demeclocycline

hepatobiliary: doxycycline, minocycline

16

AE: tetracycline

photosensitivity

discoloration of developing teeth: bones and teeth developing during pregnancy and in children through 8 years old.

reversible diabetes insipidus associated with demeclocycline. Ue this side effect to treat SIADH

Vestibular AE with minocycline: dizziness, ataxia, vertigo.

fanconi like syndrome: N/V, lethargy, polydipsia, polyuria, proteinuria, acidosis, hypkalemia

associated with use of outdated citric acid formulation of tetracycline.

17

Tetracycline: drug interactions

decreased absorption of TCN agents when coadminister via chelation. Di and trivalent cations (Ca, Mg, Z, Al, Fe). Medications such as antacids. Diary prodcuts

potential antagonism effect since these agetns are static and many cidal agents require active growth
enhances anticoagulation of warfarin: increases PT/INR.

18

SoA Tetracycline

Broad spectrum coverage: G+, G-, Atypicals, Rickettsia

19

Clinical use: tetracycline

rickettsia infections (parasites): rocky mountain spotted fever

mycoplasma pneumonia

chlamydia infections: urogenital 7 days of doxy

acne

H. pylori in combination with other agents: bismuth, Metro, PPI. QID dosing: less patient compliance.

20

Clinical use for brucellosis: tetracycline

Brucellosis: unpasturized cheeses, milk.

humans become infected by coming in contact with animals or animal products that are contaminated with brucella.

In humans brucellosis can cause a range of symptoms that are similar to the flu and may include fever, sweats, headaches, back pains, and physical weakness.

Severe infections of the CNS or lining of the heart may occur.

Brucellosis can also cause long lasting or chronic symptoms that include recurrent fevers, joint pain, and fatigue.

21

Clinical use for vibrio cholera/vulnificus: tetracyline

V. Vibrio is an acute diarrheal disease endemic in india and southeast asia whose causative agent is vibrio cholerae.

this condition can lead to severe dehydrtion in a matter of hours unless quickly treated

v. vulnificus can cause disease in those who eat contaminated seafood or have an open wound that is exposed to seawater.

22

Clinical use for borrelia burgdorferi: tetracyline

Lyme disease

lyme disease is a bacterial disease caused by borrelia brugdorferi.

within 1 to 2 weeks of being infected, people may have a bull's eye rash with fever, HA, and muscle or joint pain.

SXS: some people have lyme disease and do not have any early symptoms while others have a fever and other flu like symptoms without a rash
after several days or weeks, the bacteria may spread throughout the body of an infected person. These people can get symptoms such as rashes in other parts of the body, pain that seems to move from joint to joint, and signs of inflammation of the heart or nerves

if the disease is not treated, a few patients can get additional symptoms, such as swelling and pain in major joints or mental changes, months after getting infected.

23

Tetracycline others

SIADH. Demeclocycline only!!!

24

Tetracycline summary

do not use in pregnancy/kids under 8

photosensitivity

fanconi like syndrome: outdated tetracycline

divalent and trivalent cations will chelate antibiotic

treatment of SIADH: demeclocycline