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Questions and Answers
Which of the following is a characteristic of 1,2,4-triazole?
Which of the following is a characteristic of 1,2,4-triazole?
1,2,4-triazole is a less expensive alternative to ketoconazole.
1,2,4-triazole is a less expensive alternative to ketoconazole.
False
What type of agent is 1,2,4-triazole classified as?
What type of agent is 1,2,4-triazole classified as?
antifungal
1,2,4-triazole is considered a more effective and better tolerated oral _____ agent.
1,2,4-triazole is considered a more effective and better tolerated oral _____ agent.
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Match the following compounds with their associated characteristics:
Match the following compounds with their associated characteristics:
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Which of the following is a key advantage of Itraconazole over Ketoconazole?
Which of the following is a key advantage of Itraconazole over Ketoconazole?
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Itraconazole has anti-androgenic effects.
Itraconazole has anti-androgenic effects.
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What is one health concern Itraconazole does not have compared to Ketoconazole?
What is one health concern Itraconazole does not have compared to Ketoconazole?
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Itraconazole is effective against _______ infections.
Itraconazole is effective against _______ infections.
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Match the following terms with their descriptions:
Match the following terms with their descriptions:
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Which of the following conditions are not treated with Ketoconazole and Itraconazole?
Which of the following conditions are not treated with Ketoconazole and Itraconazole?
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Ketoconazole and Itraconazole are used as treatments for fungal CNS infections.
Ketoconazole and Itraconazole are used as treatments for fungal CNS infections.
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What must be decreased when using Ketoconazole and Itraconazole due to their effect on CYP3A4?
What must be decreased when using Ketoconazole and Itraconazole due to their effect on CYP3A4?
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Ketoconazole and Itraconazole are potent inhibitors of _____ enzymes.
Ketoconazole and Itraconazole are potent inhibitors of _____ enzymes.
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Match the following medications with their respective actions:
Match the following medications with their respective actions:
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Which of the following is a primary use of Itraconazole?
Which of the following is a primary use of Itraconazole?
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Itraconazole is effective against both Candida and viral infections.
Itraconazole is effective against both Candida and viral infections.
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What metabolic process is associated with Itraconazole?
What metabolic process is associated with Itraconazole?
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Itraconazole is used to treat invasive infections caused by ______ species.
Itraconazole is used to treat invasive infections caused by ______ species.
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Match the following terms to their correct descriptions:
Match the following terms to their correct descriptions:
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What does the broader spectrum of activity refer to in comparison to fluconazole?
What does the broader spectrum of activity refer to in comparison to fluconazole?
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Fluconazole has a broader spectrum of activity than the alternative mentioned.
Fluconazole has a broader spectrum of activity than the alternative mentioned.
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What does 'N' represent in the context of activity spectrum?
What does 'N' represent in the context of activity spectrum?
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Fluconazole has a ______ spectrum of activity compared to other alternatives.
Fluconazole has a ______ spectrum of activity compared to other alternatives.
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What is the role of enzymes in relation to flucytosine?
What is the role of enzymes in relation to flucytosine?
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Chronic exposure to flucytosine does not affect enzyme activity in the intestinal microflora.
Chronic exposure to flucytosine does not affect enzyme activity in the intestinal microflora.
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What is the product of the deamination of flucytosine?
What is the product of the deamination of flucytosine?
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Flucytosine can be converted to ______ by intestinal microflora.
Flucytosine can be converted to ______ by intestinal microflora.
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Study Notes
Antifungal Drugs: Part 2
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Classification of Antifungal Drugs:
- Inhibitors of cell membrane function
- Polyenes (e.g., Amphotericin B, Nystatin): Affect cell membrane function.
- Inhibitors of ergosterol synthesis
- Azoles (Imidazoles and Triazoles).
- Imidazoles (e.g., Clotrimazole, Miconazole, Ketoconazole)
- Triazoles (e.g., Itraconazole, Posaconazole, Fluconazole, Voriconazole).
- Allylamines (e.g., Terbinafine, Tolnaftate).
- Morpholines.
- Azoles (Imidazoles and Triazoles).
- Inhibitors of cell wall synthesis: Echinocandins (e.g., Caspofungin)
- Inhibitors of RNA/DNA functions/mitosis inhibitors: Flucytosine, Griseofulvin.
- Inhibitors of cell membrane function
Inhibitors of Ergosterol Synthesis
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Three enzymes in pathway:
- Squalene epoxidase (inhibited by allylamines).
- Lanosterol 14α-demethylase (inhibited by azoles).
- Δ14-Reductase (inhibited by morpholines).
Mechanism of Action: Azoles (Imidazoles and Triazoles)
- Inhibition of CYP450 14α-demethylase: This enzyme is vital for ergosterol synthesis. Its inhibition leads to a lack of ergosterol, causing the fungal cell membrane to become damaged and dysfunctional.
- This results in fungal cell death.
- Reduced strength of inhibition for human cells: The drugs' ability to bind to the human equivalent enzyme is much less compared to fungal enzyme, thus minimizing effects on human cells.
- High binding affinity to Fungal enzyme: Ketoconazole demonstrates a significant increased affinity to human fungal enzyme compared to the human equivalent.
Selected Triazole Antimycotics
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Itraconazole: Structurally related to ketoconazole; more effective and better tolerated orally; broad-spectrum antifungal agent. More expensive than ketoconazole.
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Advantages over ketoconazole: Not hepatotoxic; effective against Aspergillus; longer half-life. Active hydroxy metabolite.
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Absorption issues: Requires acidic conditions for absorption; does not readily penetrate CNS and CSF.
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Drug interactions: Potent CYP3A4 inhibitor, so needs careful co-administration with other CYP3A4 substrates.
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Posaconazole: Novel itraconazole analog; designed after active 0-1 hydroxyl metabolite; mainly metabolized by phase II glucuronide conjugation; fewer drug interactions. Thus, better tolerability compared to ketoconazole or itraconazole.
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Fluconazole: Two triazole rings + hydroxy group; water-soluble; suitable for oral and IV administration. Excellent oral bioavailability; long half-life; used to treat candidiasis and cryptococcosis; penetrates CNS and CSF; highly potent drug of choice for treating cryptococcal meningitis
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Voriconazole: Fluorinated pyrimidine analog of fluconazole; broader spectrum; good oral absorption and penetration; extensive CYP450 biotransformation. Active against Aspergillus and Candida; significant drug interactions.
Inhibitors of Cell Wall Synthesis: Echinocandins
- Caspofungin: Semi-synthetic cyclic peptide; long lipophilic side chain; used in treating life-threatening infections; effective against Candida species resistant to other drugs and azole-resistant Aspergillus; not effective against Cryptococcus neoformans.
- Mode of action: Inhibits 1,3-β-glucan synthase, crucial for cell wall synthesis; no oral bioavailability.
Inhibitors of RNA/DNA Functions:
- Flucytosine: 5-fluorocytosine; inhibits RNA/DNA function thus inducing cell death; pyrimidine analog that gets misincorporated. It's orally active, and works on Candida or Cryptococcus.
- Griseofulvin: Antifungal antibiotic from Penicillium griseofulvum; incorporated in newly synthesized keratin. Mode of action involves binding to tubulin, interfering with microtubule function & inhibiting mitosis (i.e, fungistatic).
Microtubule Structure
- Microtubules are polymers of α-and β-tubulin protein heterodimers; involved in cell division, cell motility and intracellular transport.
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Description
This quiz explores key characteristics and classifications of antifungal agents such as 1,2,4-triazole and Itraconazole. You'll match compounds with their properties, identify effective treatments, and understand the implications of using these medications. Test your knowledge on their health concerns and enzyme interactions.
