Quinolones Flashcards
What is this?
quinolone
What is this?
cinnolone
What is this?
1,8-Napthyridone
What is this?
pyridopyrimidone
Which drugs are first gen quinolones?
- oxolinic acid
- nalidixic acid
discontinued
What are the characteristics of first generation quinolones?
oxolinic acid, nalidixic acid
- narrow gram-negative spectrum
- didn’t achieve useful concentrations
- only useful for UTI
Which drug is a second gen quinolone?
ciprofloxacin
What are the characteristics of the second generation quinolones?
ciprofloxacin
- fluorine substituent at C6
- heterocyclic ring at C7
- broader spectrum
Which drugs are third and fourth gen quinolones?
- levofloxacin
- moxifloxacin
What are the characteristics of the third and fourth generation quinolones?
levofloxacin, moxifloxacin
- improved activity against gram-positive
- none of them are as potent as cipro against gram-negative
What is the mechanism of action of quinolones?
- Bind to the cleavage complex that forms during DNA replication
- This stabilizes the complex and inhibits the religation reaction
- This blocks the progression of the replication fork and the double-strand breaks eventually lead to apoptosis
topo II
What are the therapeutic uses for the quinolones?
- UTI
- prostatitis
- STDs
- diabetic foot infections
What are the resistance mechanisms against quinolones?
- decreased cellular permeability
- efflux pumps
- mutation of the target enzymes
- incidence of resistance is low relative to other abx agents
- point mutations can occur at A subunit of DNA gyrase for B subunit of DNA gyrase
- mutations at both sites give rise to more highly resistant strains
Describe the absorption of quinolones:
The quinolones are all readily absorbed orally and have a high degree of bioavailability.
How well are quinolones distributed?
Quinolones are widely distributed
How are quinolones eliminated?
renal and hepatic clearance
Why shouldn’t quinolones be administered with food and drugs that contain heavy metals?
Quinolones form insoluble chelates with heavy metals
How is ciprofloxacin metabolized?
Glucuronidation that attacks the hydroxyl on the left side of the molecule.
The major inactive metabolite is the glucuronide at the 3-carboxyl position, and this is excreted in the urine
What are the common adverse effects of the quinolones?
- GI
- peripheral neuropathy
- hallucinations
- damage to growing cartilage
What adverse effects has gatifloxacin been associated with?
hyperglycemia and hypoglycemia in diabetic patients
