ANTI-MICROBIALS: DNA GYRASE INHIBITORS AND DNA STRAND BREAKERS Flashcards
What type of enzyme is DNA gyrase?
Topoisomerase II
What does DNA gyrase do?
Induces left-handed supercoiling in bacterial DNA by a process of cutting and rejoining using ATP, so that the DNA can fit into the cell
Why is DNA gyrase a good antibacterial target?
Only bacteria supercoil their DNA
How do Quinolones work?
- Quinolones bind to A subunit of DNA gyrase
- This interferes with DNA breakage and re-joining, so this prevents the supercoiling of DNA
What type of Gram bacteria is Quinolones effective against?
- Quinolones are broad-sprectrum (active against gram +ve and gram -ve)
Quinolones are effective against gram negative bacteria which are resistant to penicillins. True or false?
True
What is a first generation quinolone and what is it used to treat?
- Nalidixic acid
- Treats uncomplicated urinary tract infections
What are fluoroquinolones and how do they differ from first generation quinolones?
- Second generation quinolones
- Have increased for gram +ve infections and systemic activity
- Fluorine substitutes hydrogen in an aromatic ring, difference in electronegativity alters properties
What are some examples of fluroquinolones? (3)
- Norfloxacin
- Ciprofloxacin
- Ofloxacin
What are the indications of Ciprofloxacin? (5)
- Infections of the respiratory tract (NOT pneumococcal pneumonia)
- Urinary-tract infections
- Gonorrhoea.
- Prophylaxis of meningococcal meningitis.
- ANTHRAX (treatment and post-exposure prophylaxis).
What cytochrome metabolizes ciprofloxacin and why is this problematic?
- CYP450 1A2
- Can lead to overdose of caffeine, warfarin and other drugs
What drugs should ciprofloxacin not be taken with?
- Magnesium or aluminium antacids = absorption reduced
- NSAIDs = leads to CNS disturbances
Why is Ciprofloxacin cautioned in young and older patients?
Can cause damage to cartilage, especially in young and old patients.
Ciprofloxacin is contraindicated in pregnancy. True or false?
True
Why are third generation quinolones different from first/ second generation quinolones?
- Third generation quinolones are active against streptococci, inc. S. pneumoniae (1st/ 2nd quinolones are not)
What are third generation quinolones used to treat?
- Streptococci infections
- Pneumonia
- Urinary tract infections
Give the name of a third generation quinolone?
Levofloxacin (brand name Tavanic)
Give some examples of DNA strand breakers:
Nitrofurans (e.g. nitrofurantoin, nitroimadazoles such as metronidazole)
How do nitrofurans work?
- Nitrofurans become radicals anions in anaerobic conditions
- These radical anions extract a H from DNA causing cleavage of the sugar-phosphate backbone
What is Nitrofurantoin used for?
UTIs (anaerobic bacterial infections only)
- Includes gram +ve and -ve
What are nitroimidazoles used for?
- anaerobic bacterial infections (BV, C. difficile, and acute oral infections)
- protozoal infections (amoebiasis, Trichomoniasis, Giardiasis)
What are the problems with using nitroimidazoles?
- Can cause alcohol intolerance
Who is suspecitible to a C. difficile infections?
- Patients in hospitals
- Patients that are using broad-spectrum antibiotic (oral penicillins e.g.ampicillin, cephalosporins, clindamycin, quinolones)
- this eliminates much of the normal microflora = promotes overgrowth of C. difficile
What are the symptoms of C. difficile? (3)
- Diarrhoea
- Abdominal pain and tenderness
- Fever and nausea
