What are the functions of fluoroquinolones?
Inhibit 2 key enzymes in bacterial DNA synthesis (gyrase and topoisomerase IV)
What is the function of helicase?
Breaks H-bonds btwn nucleotide bases and unwinds DNA for replication to proceed
What does the process of helicase induce?
Positive supercoiling on the unwound portion of the DNA helix; eventually this strain will prevent the DNA strand from unwinding and stop replication
What is the function of topoisomerase IV and gyrase?
- Produce reversible single-strand breaks in DNA during replication
- Gyrase re-ligates the strands in a way that produces negative supercoiling to counteract the positive supercoiling
- Topoisomerase IV in a similar way relaxes the strain and re-ligates the strands
What is similar about gyrase and helicase?
Both work by covalently attaching the DNA phosphate backbone of the cut strand to a tyrosine residue
What do fluoroquinolones bind to?
Gyrase, forming pi stacking interactions w/ DNA where strand break happens
What is the spectrum of ciprofloxacin?
- Some GM+ including MSSA and staph epidermidis
- Many GM- including E coli and pseudomonas aeruginosa
What is ciprofloxacin used to treat?
- Sometimes uncomplicated UTI’s and traveler’s diarrhea
- Can be used to treat mycoplasma pneumoniae and legionella pneumophila
Which is the only fluoroquinolone that treats pseudomonas aeruginosa?
Ciprofloxacin
What is the spectrum of levofloxacin?
- Very broad spectrum
- Many GM+ including MSSA, staph epidermidis, and strep pneumonia and pyogenes
- Many GM- including E coli
- Some anaerobes
What is levofloxacin used to treat?
- Complicated or uncomplicated community-acquired pneumonia
- UTI’s, depending on severity
- 1st line agent to treat legionella pneumophila
- Can be used for mycoplasma pneumoniae
What is the spectrum of moxifloxacin?
- Very broad spectrum GM+ except MRSA
- Very broad GM-
- Many anaerobes
What is moxifloxacin used to treat?
- 1st line for legionella pneumophila
- Used for community acquired pneumonia
- Can be used for mycoplasma pneumoniae
What is the spectrum of gatifloxacin?
- Very broad spectrum GM+ except MRSA
- Very broad GM-
- Many anaerobes
What do fluoroquinolones form? And what effect does this have for contraindications?
- Form stable chelation complexes w/ many metals (Ca, Mg, Fe, Al, Zn)
- Chelates are not absorbed very well b/c of very poor water solubility
- Should avoid dairy products, antacids, Zn-containing cough and cold products, and supplements w/ these ions 1 h before and 2 h after dose
What are some other contraindications for fluoroquinolones besides metal ions?
- Children 16 and under b/c can cause joint cartilage injury (eye drops are fine)
- Pregnant or breast feeding
- NSAIDs increase CNS toxicity
- Any drug that prolongs QT interval
- Warfarin
What are some side effects of fluoroquinolones?
- Tendinopathy
- QT prolongation
- CNS toxicity
- Photosensitivity
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Lecture 1 - Intro115
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Lecture 2 - Drug Solubility68
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Lecture 3 - Drug Absorption/Isomers68
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Lecture 4 - Drug Metabolism88
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Lecture 5 - Drug Receptor Interactions57
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Lecture 6 - Drug Targets63
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Lecture 7 - Nicotinic and Muscarinic Receptors67
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Lectures 8, 9, 10, and 11138
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Lectures 12, 13, 14, and 15170
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Lectures 16, 17, 18, and 19141
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Lecture 20, 21, and 22127
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Lecture 2368
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Lecture 2446
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Lecture 2517
