Quinolones

Question 1

MOA

Answer 1

Topoisomerase II is in bacteria to release stress on DNA strands that have supercoiling

how quinolones work is they stack at the base pairs that have been split which blocks the religation of the DNA strand. it also blocks the replication fork and the double stran break eventually leads to apoptosis

Question 2

First generation Quinolones

Answer 2

Oxolinic acid and Nalidixic acid
Mainly active against gram negative bacteria and only useful for treatment of lower UTi

Have been discontinues

Question 3

Second generation quinolones

Answer 3

Ciprofloxacin
fluorine substituent at C-6 and a heterocyclic ring (usually piperazine) at C-7.
broader specturm of bactericidal acitivty

Question 4

Third and fourth generation quinolones

Answer 4

Third gen - Levofloxacin
Fourth gen - moxifloxacin

Have improved acitivty against gram + organisms

Question 5

Ozenoxacin
therapeutic use and AE

Answer 5

Newest quinolone
oral or IV use for the treatment of skin infections
caused by a wide variety of Gram-positive and Gram-negative bacteria, including MRSA.

AE: Tendonitis, tendon rupture, peripheral neuropathy, CNS effects, exacerbation

Question 6

Therapeutic use

Answer 6

UTI
Prostatitis
Sexually transmitted disease
Travelers diarrhea
Respiratory tract infections
Bone joint and soft tissue infections

Question 7

Resistance mechanism

Answer 7

1. decreased cellular permeability
2. efflux pumps - increased expression of genes encoding efflux pumps occur in E. Coli and Pseudomonas aeuroginosa
3. mutation of the target enzyme - point mutation in the A-subunit of DNA gyrase (topoisomerase II)

incidence of resistance is low

Question 8

PK

Answer 8

Readily absorbed orally
renal and hepatic clearance

Can form insoluble chelates with heavy metals and should therefore not be administered with food and drugs that contain heavy metals

Question 9

Adverse effects

Answer 9

Can damage growing cartilage so do not give to patients 18 or younger

N/V, diarrhea, HA, dizziness, peripheral neuropathy
hallucinations, delirium and seizures occur, mainly in patients taking theophylline and nonsteroidal antiinflammatory drugs

Question 10

AE specific to fourth generation Gatifloxacin

Answer 10

hyperglycemia and hypoglycemia in diabetic patients