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Questions and Answers
What is the role of DNA gyrase in bacterial DNA synthesis?
Why is Folinic acid (leucovorin) administered to patients receiving a combination of medications?
How do fluoroquinolones affect bacterial cells during DNA replication?
Which statement is true about the mechanism of resistance to fluoroquinolones in bacteria?
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What is the primary function of topoisomerases in bacterial cells?
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What is the primary mechanism of action of Pyrimethamine?
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How does Pyrimethamine affect the bone marrow?
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What is the significance of folinic acid when using Pyrimethamine to treat toxoplasmosis?
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Which bacteria are affected by Trimethoprim according to the text?
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What is the pharmacological effect of Trimethoprim?
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What kind of mutation is required for high-level fluoroquinolone resistance according to the text?
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How did the later fluoroquinolones address the issue of bacteria developing resistance?
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What was the initial assumption regarding bacteria's ability to develop resistance to later fluoroquinolones?
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Which type of mutation characterized older fluoroquinolones' resistance development?
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Why do high-level fluoroquinolones require multiple mutations for resistance according to the text?
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Why is it mentioned that in the early generations of fluoroquinolones bacteria only needed to be smart once?
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What common adverse reactions are associated with systemic fluoroquinolones?
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Why is besifloxacin highlighted as a unique drug among fluoroquinolones?
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Why are runners specifically advised against using fluoroquinolones?
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What factor mentioned in the text increases the expression of MMP9 in tendons when taking Ciprofloxacin?
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Which of the following antibiotics is commonly used in the treatment of toxoplasmosis by inhibiting dihydrofolic acid reductase?
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What is the mechanism of action of sulfadiazine in the treatment of toxoplasmosis?
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Which drug combination is effective for treating MRSA and dacryocystitis?
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Which enzyme is inhibited by pyrimethamine in the treatment of toxoplasmosis?
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Fluoroquinolones primarily target which bacterial enzyme to exert their antibacterial effects?
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What is the proposed reason for the effect of levofloxacin and ciprofloxacin on tendons when a ligament is torn?
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Which type of antibiotics are associated with a controversy regarding retinal detachments?
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Which Ocular Fluoroquinolone has the highest aqueous concentration among the 2nd Generation ones?
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What is the clinical indication for Levofloxacin 0.5% (Quixin)?
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In terms of Gram-positive bacteria activity, which of the following statements is correct regarding 2nd and 3rd Generation Fluoroquinolones?
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Why is it essential for humans to consume Folic acid in their diet?
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What is the primary purpose of Folinic acid (leucovorin) when combined with pyrimethamine?
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How is Folic acid different from Folinic acid?
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What is the reason behind the combined use of Folinic acid with antimicrobial dihydrofolate reductase inhibitors like trimethoprim and pyrimethamine?
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In bacterial cells, what is the primary impact of Folic acid antagonists like trimethoprim and pyrimethamine?
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How do fluoroquinolones affect bacterial cells during DNA replication?
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Which statement best describes the role of topoisomerases in bacterial cells?
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What effect do Folic acid antagonists like pyrimethamine have on red blood cell production?
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Why is Folinic acid also known as leucovorin?
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Which cellular process is directly impacted by folic acid deficiency in humans?
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Study Notes
Folate, Folic Acid, and Folinic Acid
- Folate is a B-vitamin (Vitamin B9) naturally found in some foods and essential for making DNA, RNA, and healthy cells.
- Humans cannot produce it, so it's required in the diet.
- Folic acid is the synthetic form of Vitamin B9, used as a dietary supplement, and added to processed foods.
- Folinic acid (leucovorin) is a medication used to decrease the toxic effects of certain medications, and prescribed to treat toxoplasmosis retinitis, often in combination with pyrimethamine and sulfadiazine.
Fluoroquinolones
- Fluoroquinolones are a type of antibiotic that affects bacterial DNA synthesis.
- They inhibit the enzyme DNA gyrase (topoisomerase II) and topoisomerase IV, preventing bacterial DNA replication.
- This leads to cell death (bactericidal) and the loss of the ability to replicate.
- Fluoroquinolones have a broad spectrum, are bactericidal, and have a rapid killing effect on organisms.
Mechanisms of Resistance
- Reduced cellular accumulation of quinolones through decreased passive transport and increased active transport out of cells.
- Efflux pumps can also contribute to resistance.
- Single-step mutations in topoisomerase IV (involved in bacterial chromosome replication) can lead to resistance.
- Multi-step mutations are required for resistance to newer fluoroquinolones.
2nd Generation Ocular Fluoroquinolones
- Examples: ofloxacin (Ocuflox), ciprofloxacin (Ciloxan), and norfloxacin (Chibroxin).
- Better activity against common ocular pathogens compared to aminoglycosides, chloramphenicol, tetracycline, and erythromycin.
- Can form corneal precipitates, which may not affect vision.
3rd Generation Ocular Fluoroquinolones
- Examples: levofloxacin (Quixin, Iquix).
- Maintained excellent gram-negative coverage and improved gram-positive activity.
- Less resistance compared to 2nd generation fluoroquinolones.
- Levofloxacin is the L-isomer of ofloxacin.
4th Generation Ocular Fluoroquinolones
- Examples: moxifloxacin (Vigamox, Moxeza), gatifloxacin (Zymar, Zymaxid), and besifloxacin (Besivance).
- Require a two-step mutation process for bacterial resistance.
Systemic Fluoroquinolones
- Examples: norfloxacin, ofloxacin, ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin.
- Adverse reactions: gastrointestinal effects, CNS effects, increased risk of tendon rupture, and prolongation of QT interval.
Pyrimethamine and Trimethoprim
- Pyrimethamine is a folic acid antagonist, inhibiting the enzyme dihydrofolic acid reductase.
- Trimethoprim is a bacteriostatic antibiotic, inhibiting the synthesis of folic acid.
- Both are used to treat toxoplasmosis, and pyrimethamine requires concurrent administration of folinic acid (leucovorin) to mitigate bone marrow suppression.
Toxoplasmosis Treatment
- Pyrimethamine and sulfadiazine are used to treat toxoplasmosis, with folinic acid (leucovorin) to mitigate bone marrow suppression.
- Trimethoprim/sulfamethoxazole (Bactrim) is used to treat MRSA, and dacrocystitis.
- Folinic acid (leucovorin) is used to reduce the toxic effects of pyrimethamine.
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Description
Test your knowledge on the potential side effects of fluoroquinolone antibiotics including levofloxacin and ciprofloxacin. Explore the impact on tendon health and the risk of retinal detachments. Written by Diane T.Adamczyk, OD, FAAO in 2024.
