antifungals Flashcards
immunocompetent fungal infections
Blastomycosis, Chromoblastomycosis, Coccidioidomycosis, Histoplasmosis, Paracoccidioidomycosis and Sporotrichosis.
infection in immunocompromised
(eg. leukemic, neutropenic, debilitated patients- burns, surgery, etc.):
Aspergillosis, Candidiasis, Cryptococcosis, Mucormycosis, Pseudallescheriasis. These are termed opportunistic pathogens.
fungal infections in AIDs pts
Candidiasis
Crypto
Histoplasmosis, Coccidiodomycosis
Antifungal Therapy for subcutaneous and systemic mycosis.
Amphotericin B [AmphotecR, AmbisomeR, AbelcetR]
- Ketoconazole [Nizoral®]
- Miconazole [MonistatR]
- Fluconazole [DiflucanR]
- Itraconazole [SporanoxR]
Empiric Antifungal Therapy
for ??
Common element ??
antifungals of choice??
consider prophylaxis for what fungal infections?
neutropenic pts who do NOT respond to broad spectrum antibacterial tx (4-7 days), seriously ill patients (e.g. cancer, diabetes).
- impairment of normal phagocyte response to fungal infection
- use broad-spectrum: AmpB, miconazole
-candidiasis, Aspergillosis: use Nystantin, ampB, and -azoles
Drugs used for Superficial Fungal Infections: Dermatophytic infections:
- mild-moderate: Miconazole [MonistatR], Tolnaftate [TinactinR]
- moderately severe: the “azoles”, Terbinafine
- severe: Griseofulvin
- Tinea Versicolor: “azoles” esp. ketoconazole
for all drugs don’t need to know specific use except
know MOA, SEs
Capsofugin KNOW USE (later card)
Moderately severe Tinea infections (* oral administration)??
- cutaneous: ampB, azoles, nystatin, terbinafine
- vulvovag: azoles, nystatin
- oropharyngeal: azoles, nystatin
targets of certain antifungals (Figure 1)
- ampB, nystatin (Polyenes): alter membrane function
- Echinocandins: alter cell wall synthesis
- Allyamines/thiocarbamates/azoles: inhibit ergosterol synthesis
- Griseofulvin: inhibit nuclear division
remember ergosterol synthesis (Figure 2)
squalene–>lanosterol via squalene monooxygenase (inhibited by terbinafine and tolnaftate: squalene accumulates)
lanosterol–>ergosterol (via C-14 demethylase: cytP450 enzyme, inhibited by azoles-lanosterol accumulates))
amphotericin B
- insoluble in water: challenge, used parenterally, fungistatic,
- Binds to sterols (ergosterol) in fungal cell membrane
- pores or channels are formed in the cell membrane, permeability increases–>lose cell contents
ampB: selective or not??
not very, sterol selectivity also accounts for drugs toxicity, Mammalian cells, e. g. kidney cells and erythrocytes contain sterols (cholesterol)–>ampB alters cell perm
ampB SEs
- Frequent infusion-related reactions: fever, chills, ha, hypotension, tachy, muscle/ joint pain, N/V
- Nephrotoxicity*
- Anemia: Hypochromic and normocytic* reversible anemia is usual. Decreased production of erythropoietin is the probable mechanism.
ampB nephrotoxicity
Azotemia (nitrogen retention) (80% of pts). Toxicity is transient and increases by concurrent therapy with other nephrotoxic agents (aminoglycosides, cyclosporine). Damage to renal tubules occurs, but permanent functional deficits are uncommon. Renal function should be monitored frequently.
ampB uses: not going to test us on specifically
systemic (IV, intrathecal) and superficial infections (topical)