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What is the primary target of quinolones in terms of bacterial spectrum?
What is the primary target of quinolones in terms of bacterial spectrum?
What was the major limitation of Nalidixic acid when it was first introduced in the mid-1960s?
What was the major limitation of Nalidixic acid when it was first introduced in the mid-1960s?
What is the mechanism of action of Nalidixic acid?
What is the mechanism of action of Nalidixic acid?
What is the main reason for the limited usefulness of Nalidixic acid?
What is the main reason for the limited usefulness of Nalidixic acid?
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What is the consequence of fluorination of quinolone structure at position 6?
What is the consequence of fluorination of quinolone structure at position 6?
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What is the consequence of piperazine substitution at position 7 of quinolone structure?
What is the consequence of piperazine substitution at position 7 of quinolone structure?
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What is the reason for the high concentration of Nalidixic acid in urine?
What is the reason for the high concentration of Nalidixic acid in urine?
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What are the common adverse effects of Nalidixic acid?
What are the common adverse effects of Nalidixic acid?
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What is the primary mechanism of quinolones in inhibiting bacterial DNA replication?
What is the primary mechanism of quinolones in inhibiting bacterial DNA replication?
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Which of the following antibiotics works by inhibiting the synthesis of essential metabolites?
Which of the following antibiotics works by inhibiting the synthesis of essential metabolites?
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What is the primary mechanism of resistance to quinolones?
What is the primary mechanism of resistance to quinolones?
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Which of the following bacteria has shown increasing resistance to quinolones?
Which of the following bacteria has shown increasing resistance to quinolones?
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What is the second mechanism of action of quinolones?
What is the second mechanism of action of quinolones?
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Why do quinolones have a low risk of resistance?
Why do quinolones have a low risk of resistance?
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What is the effect of quinolones on bacterial DNA?
What is the effect of quinolones on bacterial DNA?
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How do quinolones differ from Nalidixic acid in terms of resistance?
How do quinolones differ from Nalidixic acid in terms of resistance?
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Why does pefloxacin need a dose reduction in certain cases?
Why does pefloxacin need a dose reduction in certain cases?
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What is ofloxacin effective against?
What is ofloxacin effective against?
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What is a characteristic of ofloxacin?
What is a characteristic of ofloxacin?
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What is levofloxacin?
What is levofloxacin?
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What is a characteristic of levofloxacin?
What is a characteristic of levofloxacin?
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What is not affected by levofloxacin treatment?
What is not affected by levofloxacin treatment?
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What is a difference between pefloxacin and ofloxacin?
What is a difference between pefloxacin and ofloxacin?
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What is a use of ofloxacin?
What is a use of ofloxacin?
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What is the primary use of Nalidixic acid?
What is the primary use of Nalidixic acid?
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What is a common adverse effect of Nalidixic acid in individuals with G-6-PD deficiency?
What is a common adverse effect of Nalidixic acid in individuals with G-6-PD deficiency?
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Which of the following fluoroquinolones is classified as a fourth generation?
Which of the following fluoroquinolones is classified as a fourth generation?
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What is the contraindication for using Nalidixic acid?
What is the contraindication for using Nalidixic acid?
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What is the reason for not giving Nitrofurantoin concurrently with Nalidixic acid?
What is the reason for not giving Nitrofurantoin concurrently with Nalidixic acid?
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What is a common side effect of fluoroquinolones?
What is a common side effect of fluoroquinolones?
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What is the characteristic of second generation fluoroquinolones?
What is the characteristic of second generation fluoroquinolones?
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What is the advantage of second generation fluoroquinolones over Nalidixic acid?
What is the advantage of second generation fluoroquinolones over Nalidixic acid?
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What is the primary target of action of Moxifloxacin?
What is the primary target of action of Moxifloxacin?
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Which of the following conditions is Moxifloxacin primarily used for?
Which of the following conditions is Moxifloxacin primarily used for?
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What is the metabolism of Moxifloxacin primarily done in?
What is the metabolism of Moxifloxacin primarily done in?
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What is Gemifloxacin active against?
What is Gemifloxacin active against?
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What should be done with the dose of Gemifloxacin for patients with creatinine clearance of 60 years age and those with kidney damage?
What should be done with the dose of Gemifloxacin for patients with creatinine clearance of 60 years age and those with kidney damage?
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What should not be mixed with any drug in the same syringe/infusion bottle?
What should not be mixed with any drug in the same syringe/infusion bottle?
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Study Notes
Quinolones and Fluoroquinolones
- Quinolones are synthetic antimicrobials with a quinolone structure, primarily active against gram-negative bacteria.
- The first quinolone, Nalidixic acid, was introduced in the mid-1960s, but had limited use due to low potency, modest blood and tissue levels, and high frequency of bacterial resistance.
- Fluoroquinolones were developed in the 1980s by fluorinating the quinolone structure at position 6 and introducing a piperazine substitution at position 7, resulting in high potency, expanded spectrum, and better tissue penetration.
Nalidixic Acid
- Nalidixic acid is active against gram-negative bacteria, especially coliforms, but not Pseudomonas.
- It acts by inhibiting bacterial DNA gyrase and is bactericidal.
- Resistance to nalidixic acid develops rapidly.
- Nalidixic acid is absorbed orally, highly plasma protein bound, and partly metabolized in the liver.
- It is excreted in urine with a plasma t½ of ~8 hours.
- Concentration of the free drug in plasma and most tissues is non-therapeutic for systemic infections.
- High concentration in urine and gut lumen is lethal to common urinary pathogens and diarrhoea-causing coliforms.
Adverse Effects of Nalidixic Acid
- Adverse effects are relatively infrequent and consist mostly of g.i. upset and rashes.
- Neurological toxicity is a major concern, including headache, drowsiness, vertigo, visual disturbances, and occasionally seizures.
- Photo toxicity is rare.
- Individuals with G-6-PD deficiency may develop hemolysis.
Use of Nalidixic Acid
- Nalidixic acid is primarily used as a urinary antiseptic, generally as a second-line drug in recurrent cases or on the basis of sensitivity reports.
- It is also used in diarrhoea caused by Proteus, E. coli, Shigella, or Salmonella.
Fluoroquinolones
- Fluoroquinolones are quinolone antimicrobials with one or more fluorine substitutions.
- The 'first generation' fluoroquinolones (FQs) introduced in the 1980s have one fluoro substitution.
- The 'second generation' FQs introduced in the 1990s have additional fluoro and other substitutions, extending antimicrobial activity to gram-positive cocci and anaerobics, and conferring stability.
Classification of Fluoroquinolones
- First generation: Nalidixic acid
- Second generation: Ciprofloxacin, Ofloxacin, Cinoxacin, Pefloxacin
- Third generation: Gatifloxacin, Levofloxacin, Sparfloxacin, Moxifloxacin
- Fourth generation: Tevofloxacin
Mechanism of Action
- Inhibition of bacterial DNA gyrase and topoisomerase IV
- Dual mechanism of action:
- Inhibition of bacterial DNA gyrase (Topoisomerase II)
- Inhibition of bacterial topoisomerase IV
Mechanism of Resistance
- Resistance is due to chromosomal mutation producing a DNA gyrase or topoisomerase IV with reduced affinity for FQs, or due to reduced permeability/increased efflux of these drugs across bacterial membranes.
- Plasmid-mediated transferable resistance is less likely.
- Resistance to FQs has been slow to develop, but increasing resistance has been reported among Salmonella, Pseudomonas, staphylococci, gonococci, and pneumococci.
Specific Fluoroquinolones
- Pefloxacin: has a longer t½, cumulates on repeated dosing, and is effective in many systemic infections.
- Ofloxacin: is somewhat less active than ciprofloxacin against gram-negative bacteria, but equally or more potent against gram-positive ones and certain anaerobes.
- Levofloxacin: is the active levo(s) isomer of ofloxacin, having improved activity against Streptococcus pneumoniae and some other gram-positive and gram-negative bacteria.
- Moxifloxacin: is a long-acting 2nd generation FQ, having high activity against Streptococcus pneumoniae, other gram-positive bacteria, and some anaerobes.
- Gemifloxacin: is another broad-spectrum FQ, active mainly against aerobic gram-positive bacteria, especially Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella.
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Description
This quiz covers the pharmacology of quinolones and fluoroquinolones, a class of synthetic antimicrobials active against gram-negative and gram-positive bacteria.
