DD- Fungal Infections/Rx Flashcards
Factors that allow overgrowth of opportunistic organisms
Alteration in oral flora
Immunosuppression
Systemic diseases
Binds ergosterol in fungal membrane
opens pores
leakage of cellular constituents
cell death [fungicidal]
Amphotericin B - Mechanism of Action
Similar mechanism to Amphotericin B - toxicity limits systemic use
No appreciable absorption from GI tract
Safe and effective for topical treatment of candidal infections of skin, mucous membranes, and GI tract
Nystatin
- Myelosuppression with chemotherapy agents
- Long-term use of steroid anti-inflammatory agents
- Inhaled steroids use in asthma
Can cause immunosupression
Deep candidiasis
Aspergillosis
Mucormycosis
Cryptococcosis
Extracutaneous sporotrichosis
life-threatening systemic fungal infections (esp. in immunosuppressed patients)
Inhibits the synthesis of β (1,3)-D-glucan - essential component of fungal cell walls. disruption of cell wall
Higher level of selective toxicity due to absence of these enzymes in mammalian cells
Echinocandins - Micafungin
Drug of choice for nearly all life-threatening systemic fungal infections (esp. in immunosuppressed patients)
Amphotericin B - Clinical Uses
- AIDS, diabetes
- Long-term xerostomia (anticholinergic agents)
- Adrenal suppression (steroid anti-inflammatory agents)
- Anemia
Systemic diseases examples
Selective inhibition of fungal cytochrome P450 (14α-demethylase) ↓ ergosterol synthesis fungistatic-cidal
Greater selectivity for fungal vs mammalian cytochrome
Triazoles
Fluconazole - Itraconazole
Inhibits P450-dependent enzyme (14α-demethylase) resulting in decreased levels of ergosterol
Disruption in synthesis of cell membrane sterols, alterations in membrane permeability
Fungistatic / fungicidal depending on concentration
Imidazoles
Ketoconazole - Clotrimazole - Miconazole
Inhibits squalene oxidase, dec ergosterol synthesis (plus accumulation of squalene is toxic), fungicidal
Concentrates in keratin (like griseofulvin)
Terbinafine
Converted in fungal cell into 5-fluorouracil (via cytosine deaminase)
5-FU interferes with DNA synthesis, cell death
High selective toxicity - host cells lack deaminase
Resistance occurs in fungi that lack cytosine deaminase
Flucytosine
Binds to microtubules inhibiting fungal mitosis - interferes with processing of new cell wall components - fungistatic
Griseofulvin
Inhibits protein and nucleic acid synthesis
Effective against wide variety of protozoa (concentrated in organisms)
Pentamidine
Dermatophytes
Infections deeper in the epidermis and its integuments - hair and nails
