Antifungal agents

• What are antifungal agents used for?

  They are used to treat fungal infections.
• Why are systemic fungal infections significant in immunocompromised individuals?

  They are a major cause of death in immunocompromised individuals.
• What types of infections can fungi cause?

  Fungi can cause superficial infections of the skin and other soft tissue structures.
• What are the targets of antifungal agents?

  • Distinct components of fungal cell membrane
  • Alteration of cell wall synthesis
  • Alteration of nucleic acid synthesis
• What are the classifications of clinically important fungi?

  They are classified into yeasts, yeast-like fungi, filamentous fungi, and dimorphic fungi.
• Give an example of a yeast and a filamentous fungus.

  Yeast: Cryptococcus neoformans; Filamentous fungus: Aspergillus fumigatus.
• What are the types of fungal infections classified by their location?

  • Superficial infections
  • Cutaneous infections (e.g., dermatophytes, ringworm)
  • Subcutaneous infections
  • Deep mycosal infections (systemic)
• What is a major cause of morbidity and mortality in immunocompromised individuals related to fungal infections?

  Secondary systemic fungal infections due to the use of broad-spectrum antibiotics.
• What are the mechanisms of action of antifungal agents?

  • Direct killing of fungal cells
  • Preventing fungal cells from growing
  • Targeting distinct structures in fungal cells
• What is the composition of the fungal cell wall?

  The fungal cell wall is composed of chitin.
• What is the main sterol found in the fungal cell membrane?

  Ergosterol.
• What are the classes of antifungal drugs based on their mechanisms of action?

  1. Alteration of cell membrane/wall properties

  • Synthesis inhibitors (Azoles, Allylamines, Glucan synthesis inhibitors)
  • Porin formation (Polyene antibiotics)

  2. Nucleic acid synthesis blockade (Flucytosine)

  3. Microtubule function inhibition (Griseofulvin)
• What are polyene antibiotics used for?

  They are used to form artificial pores in fungal cell membranes.
• What is the role of azole antifungals?

  They inhibit fungal CYPs essential for ergosterol biosynthesis.
• Name two examples of azole antifungals.

  Imidazoles and triazoles.
• What are the adverse effects of ketoconazole?

  • Liver toxicity (rare but can be fatal)
  • Inhibition of adrenocortical steroid/testosterone synthesis (gynaecomastia)
• What is the significance of itraconazole's formulation?

  It lacks ketoconazole's corticosteroid suppresion
• What is the half-life of itraconazole?

  Approximately 30 hours.
• What are the common uses of fluconazole?

  Initial treatment of cryptococcal candidiasis and drug of choice for coccidioidal meningitis.
• What is the main route of elimination for fluconazole?

  Renal excretion accounts for 90% of elimination.
• What are the unwanted effects of voriconazole?

  Hepatotoxicity, QTc interval prolongation, and transient visual changes.
• What is miconazole primarily used for?

  Topical administration for oral and other infections.
• What are the characteristics of polyene antibiotics?

  • Broadest spectrum of activity
  • Effective against pathogenic fungi and protozoa
• What effect do NNRTIs have on voriconazole metabolism?

  They significantly increase voriconazole metabolism and slow the metabolism of NNRTIs.
• What should be done to the dose of voriconazole when given with Phenytoin?

  The dose should be doubled when given with Phenytoin.
• What are some unwanted effects of voriconazole?

  Unwanted effects include hepatotoxicity, QTc interval prolongation, and transient visual changes.
• What is the administration route for Miconazole?

  Miconazole is administered topically for oral and other infections.
• How often must Miconazole be administered due to its short plasma half-life?

  Miconazole must be administered every 8 hours.
• In which tissues does Miconazole attain therapeutic concentrations?

  Miconazole attains therapeutic concentrations in bone, joints, and lung tissue, but not in the CNS.
• What happens to Miconazole in the liver?

  Miconazole is inactivated in the liver.
• What are some unwanted effects of Miconazole?

  Unwanted effects may include blood dyscrasias and hyponatremia.
• What are the antifungal agents that are applied topically only?

  • Clotrimazole
  • Econazole
  • Tioconazole
  • Sulconazole
• What additional action does Clotrimazole perform besides being an antifungal?

  Clotrimazole interferes with amino acid transport into fungi by acting on the cell membrane.
• With what can Clotrimazole sometimes be combined?

  Clotrimazole can sometimes be combined with anti-inflammatory glucocorticoids.
• What are the characteristics of Polyene antibiotics like Amphotericin?

  • Broadest spectrum of activity against pathogenic fungi, protozoa, and Leishmania
  • Binds to sterol ergosterol in fungal cell membranes
  • Interferes with membrane permeability and transport functions
  • Forms large pores in fungal cell membranes
• What is the drug of choice for life-threatening systemic fungal infections?

  Amphotericin is the drug of choice for life-threatening systemic fungal infections.
• What is the mechanism of action of Amphotericin B?

  Amphotericin B interacts with ergosterol in the fungal cell wall, forming a pore that allows potassium and other small molecules to migrate through, causing cell death.
• What is the absorption characteristic of Amphotericin when administered orally?

  Amphotericin has negligible absorption when orally administered.
• How is Amphotericin B eliminated from the body?

  Amphotericin B is excreted very slowly via the kidneys, with traces found in urine for more than 2 months after administration.
• What is the most common unwanted side effect of Amphotericin?

  Renal toxicity is the most common unwanted side effect of Amphotericin.