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What type of drugs are quinolones?
What type of drugs are quinolones?
Synthetic antibacterials
What was the first quinolone drug?
What was the first quinolone drug?
Nalidixic acid
What are the primary targets of fluoroquinolones?
What are the primary targets of fluoroquinolones?
DNA gyrase (topoisomerase 2) and topoisomerase 4
What is the mechanism of action of fluoroquinolones?
What is the mechanism of action of fluoroquinolones?
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What is the role of DNA gyrase in DNA replication?
What is the role of DNA gyrase in DNA replication?
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What is the role of topoisomerase IV in DNA replication?
What is the role of topoisomerase IV in DNA replication?
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Fluoroquinolones have a high affinity for mammalian topoisomerase II.
Fluoroquinolones have a high affinity for mammalian topoisomerase II.
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Which of the following fluoroquinolones is a first-generation drug?
Which of the following fluoroquinolones is a first-generation drug?
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Which of the following fluoroquinolones is a second-generation drug?
Which of the following fluoroquinolones is a second-generation drug?
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What is the primary route of administration for most fluoroquinolones?
What is the primary route of administration for most fluoroquinolones?
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What are some factors that can interfere with the absorption of fluoroquinolones?
What are some factors that can interfere with the absorption of fluoroquinolones?
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Dosage adjustments are always required for fluoroquinolones in patients with renal dysfunction.
Dosage adjustments are always required for fluoroquinolones in patients with renal dysfunction.
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Where do fluoroquinolones accumulate in the body?
Where do fluoroquinolones accumulate in the body?
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Which of the following is NOT a common adverse effect of fluoroquinolones?
Which of the following is NOT a common adverse effect of fluoroquinolones?
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What are some common connective tissue problems associated with fluoroquinolones?
What are some common connective tissue problems associated with fluoroquinolones?
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What are some common superinfections associated with fluoroquinolones?
What are some common superinfections associated with fluoroquinolones?
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What are two common drug-drug interactions associated with fluoroquinolones?
What are two common drug-drug interactions associated with fluoroquinolones?
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Folic acid is essential for the synthesis of DNA, RNA, and certain amino acids.
Folic acid is essential for the synthesis of DNA, RNA, and certain amino acids.
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What is the critical folate derivative synthesized by humans?
What is the critical folate derivative synthesized by humans?
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Bacteria are generally permeable to folate derivatives.
Bacteria are generally permeable to folate derivatives.
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When were sulfa drugs first used in clinical practice?
When were sulfa drugs first used in clinical practice?
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Why are sulfa drugs seldom prescribed alone today?
Why are sulfa drugs seldom prescribed alone today?
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What is the primary mechanism of action of sulfonamides?
What is the primary mechanism of action of sulfonamides?
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What is the metabolic pathway that sulfonamides interfere with?
What is the metabolic pathway that sulfonamides interfere with?
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Sulfonamides can be given by intravenous injection.
Sulfonamides can be given by intravenous injection.
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What is the primary route of excretion of sulfonamides?
What is the primary route of excretion of sulfonamides?
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What is a common adverse effect of sulfonamides?
What is a common adverse effect of sulfonamides?
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Which of the following is a common superinfection associated with sulfonamides?
Which of the following is a common superinfection associated with sulfonamides?
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What drug interacts with sulfonamides to cause crystalluria?
What drug interacts with sulfonamides to cause crystalluria?
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What drug is often combined with trimethoprim?
What drug is often combined with trimethoprim?
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Trimethoprim is concentrated in the prostate and urine.
Trimethoprim is concentrated in the prostate and urine.
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Trimethoprim can cause megaloblastic anemia.
Trimethoprim can cause megaloblastic anemia.
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What can reverse the effects of trimethoprim-induced folic acid deficiency?
What can reverse the effects of trimethoprim-induced folic acid deficiency?
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Trimethoprim can cause hyperkalemia.
Trimethoprim can cause hyperkalemia.
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What medication class is contraindicated with trimethoprim due to its potassium-sparing effect?
What medication class is contraindicated with trimethoprim due to its potassium-sparing effect?
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What is the combination of trimethoprim and sulfamethoxazole called?
What is the combination of trimethoprim and sulfamethoxazole called?
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Co-trimoxazole has greater antimicrobial activity than equivalent amounts of either drug used alone.
Co-trimoxazole has greater antimicrobial activity than equivalent amounts of either drug used alone.
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What is a common opportunistic infection that co-trimoxazole is effective against?
What is a common opportunistic infection that co-trimoxazole is effective against?
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What are some alternative urinary tract antiseptics that can be used when fluoroquinolones and co-trimoxazole are ineffective due to resistance?
What are some alternative urinary tract antiseptics that can be used when fluoroquinolones and co-trimoxazole are ineffective due to resistance?
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What are the two main reasons why these alternative urinary tract antiseptics are effective?
What are the two main reasons why these alternative urinary tract antiseptics are effective?
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What is the mechanism of action of methenamine?
What is the mechanism of action of methenamine?
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Methenamine is contraindicated in patients with hepatic insufficiency.
Methenamine is contraindicated in patients with hepatic insufficiency.
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What is the mechanism of action of nitrofurantoin?
What is the mechanism of action of nitrofurantoin?
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Nitrofurantoin can cause pulmonary fibrosis.
Nitrofurantoin can cause pulmonary fibrosis.
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What formulation of nitrofurantoin can reduce gastrointestinal toxicity?
What formulation of nitrofurantoin can reduce gastrointestinal toxicity?
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Study Notes
Fluoroquinolones
- Quinolones are synthetic antibacterial drugs
- Nalidixic acid, developed in the early 1960s, led to modifications of the quinolone nucleus, expanding the spectrum of activity, improving pharmacokinetics, and increasing resistance to common drug resistance mechanisms.
- Quinolone antimicrobials quickly integrated into human and agricultural medicine.
- However, overuse led to rising resistance rates in both gram-negative and gram-positive organisms.
- Fluoroquinolones inhibit DNA gyrase (topoisomerase II) and topoisomerase IV, causing DNA replication failure and cell lysis.
- DNA gyrase reduces torsional stress ahead of replicating DNA forks. Topoisomerase IV helps separate replicated chromosomes.
- Fluoroquinolones bind to these enzymes, interrupting DNA ligation. This increases permanent chromosomal breaks, triggering cell lysis.
- Gram-negative organisms are targeted by DNA gyrase inhibition. Gram-positive organisms are targeted by topoisomerase IV inhibition.
- Mammalian cells have topoisomerase II, which has very low affinity for fluoroquinolones, decreasing toxicity to host cells.
- Fluoroquinolones are available in various generations each showing different antimicrobial spectra and applications.
- Fluoroquinolones have good oral bioavailability
- Fluoroquinolones distribute well in tissues, including bone.
- Iron, zinc, and calcium interfere with fluoroquinolone absorption.
- Dosage adjustments are required in renal dysfunction, except for moxifloxacin.
- Accumulation in macrophages and polymorphonuclear leukocytes results in activity against intracellular organisms like Listeria, Chlamydia, and Mycobacteria.
Adverse Effects
- Gastrointestinal distress
- Central nervous system (CNS) effects like rashes and photosensitivity
- Connective tissue problems, avoid during pregnancy, breastfeeding, and in individuals under 18.
- QT prolongation (moxifloxacin, gemifloxacin, levofloxacin)
- High risk of causing superinfections (C. difficile, candida albicans, streptococci)
Drug Interactions
- First-generation quinolones and theophylline
- Second-generation quinolones and warfarin
Folic Acid Antagonists
- Folic acid is crucial for the synthesis of RNA, DNA, and amino acids.
- Humans obtain folic acid from their diet and convert it to tetrahydrofolic acid.
- Many bacteria synthesize folic acid independently (de novo).
Sulfonamides
- Sulfa drugs are among the first antibiotics.
- Currently, they are less frequently prescribed due to drug resistance.
- Developing countries often use them due to their low cost and efficacy.
- Sulfonamides act by inhibiting bacterial dihydrofolate synthesis.
- Inhibition of bacterial folic acid synthesis prevents DNA and RNA production, hindering cell growth and replication.
- They are well absorbed after oral administration, except for sulfasalazine.
- They are widely distributed in body tissues, including the cerebrospinal fluid. They cross the placental barrier.
- They are primarily metabolized in the liver and become devoid of antimicrobial activity. Acetylated products retain some toxicity.
Adverse Effects of Sulfonamides
- Crystalluria and potential kidney damage due to precipitation at specific pHs. This can be addressed by adequate hydration and alkalinization of urine.
- Hypersensitivity reactions, including rashes, angioedema, and Stevens-Johnson syndrome.
- Hemolytic anaemia (in patients with G6PD deficiency); granulocytopenia and thrombocytopenia; aplastic anaemia; and other blood dyscrasias.
- Kernicterus (Bilirubin-associated brain damage in newborns) due to bilirubin displacement from serum albumin.
Drug Interactions
- CYP2C9, plasma protein binding level of warfarin, phenytoin, and methotrexate.
Contraindications
- Avoid sulfonamides in newborns and infants under 2 months of age as well as in pregnant women at term.
Trimethoprim
- Trimethoprim concentrates in the prostate and urine.
- Causes megaloblastic anaemia, granulocytopenia (folate-deficiency issues) and Hyperkalemia.
- Folate deficiency effects are reversible with simultaneous folinic acid administration, which does not affect bacteria.
- Avoid in cases of ACEI use due to hyperkalemia risk
Co-trimoxazole
- Trimethoprim and sulfamethoxazole combination with potent antimicrobial activity.
- Used in gastrointestinal infections (shigellosis, non-typhoid salmonella), urinary tract infections (including prostate and vaginal infections), and respiratory infections (influenzae), including Pneumocystis carinii pneumonia (opportunistic infection related to AIDS).
Urinary Tract Antiseptics
- Fluoroquinolones and cotrimoxazole were initial choices for urinary tract infections.
- Resistance has increased. Methenamine, nitrofurantoin, and fosfomycin are alternative agents.
- These alternatives are often used due to their efficacy against common pathogens and high concentrations in urine.
Methenamine
- Methenamine (hexamine/urotropine) is hydrolysed to ammonia and formaldehyde in acidic urine (pH ≤ 5.5).
- Formaldehyde denatures microbial proteins and nucleic acids, leading to bacterial cell death.
- Use is restricted in hepatic insufficiency.
Nitrofurantoin
- Inhibits DNA and RNA synthesis.
- Effective against E. coli, Klebsiella spp., Enterococcus spp., and Staphylococcus spp.
- Common side effects include nausea, vomiting, and diarrhea.
- Microcrystalline formulation reduces gastrointestinal toxicity.
- Prolonged exposure can cause pulmonary fibrosis, neuropathy, and autoimmune hepatitis. Especially, in patients with impaired renal function.
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Description
Explore the world of fluoroquinolones, synthetic antibacterial drugs that have revolutionized medicine since the 1960s. Learn how these drugs work by inhibiting key enzymes involved in DNA replication, and understand the implications of their overuse in medicine and agriculture. This quiz covers the mechanisms, applications, and resistance issues associated with fluoroquinolones.
