PHARM: Fungal Infections Flashcards
Presentation of candida albicans (yeast) in lung infection.
Fever, tachycardia, patchy infiltrates on chest film
Characteristics of candida albicans lung infection.
Uncommon cause of pneumonia; hematogenous spread seen in immunocompromised patients
Treatment of candida albicans lung infection.
Amphotericin B IV and Fluconazole
Presentation of cryptococcus neoformans (cryptococcus) lung infection.
Often asymptomatic
May have productive cough, fever, and weight loss
Characteristics of cryptococcus neoformans (cryptococcus) lung infection.
Associated with pigeon droppings
Can cause cryptococcal meningitis
Treatment of cryptococcus neoformans (cryptococcus) lung infection.
CNS: Amphotericin B IV + flucytosine PO
Non-CNS: fluconazole PO
Presentation of aspergillus (mold) in lung infection.
Wheezing, dyspnea, and cough with allergic bronchopulmonary aspergillosis (ABPA)
Fever, cough, dyspnea, pleuritic chest pain, and hemophysis seen in invasive forms (in immunocompromised patients)
Characteristics of aspergillus (mold) in lung infection.
Aspergillomas (fungal balls) can form in pre-existing cavities
The invasive form spreads hematogeneously
Treatment of aspergillus (mold) in lung infection.
1st line: Voriconazole IV then step down to PO
2nd line: Amphotericin B IV then step down to PO
Presentation of blastomyces dermatitidis (dimorphic) in lung infection.
Fever, chills, productive cough
May also present with skin/bone lesions or GI involvement
Characteristics of blastomyces dermatitidis (dimorphic) in lung infection.
Causes pneumonia-like disease and may progress to disseminated disease
Treatment of blastomyces dermatitidis (dimorphic) in lung infection.
1st line: Fluconazole IV (or Amphotericin B IV if severe) step down to Voriconazole/Itraconazole/Fluconazole
2nd line: Amphotericin B IV step down to Voriconazole or Fluconazole PO
Presentation of histoplasma capsulatum (dimorphic) in lung infection.
Often asymptomatic
Young or immunocompromised may have disseminated or chronic disease with fever, fatigue, and weight loss
Characteristics of histoplasma capsulatum (dimorphic) in lung infection.
Caseating granuloma formation in tissue (like Tb)
Disseminated form is marked by multi-system involvement with macrophage infiltrates filled with intracellular fungi
Treatment of histoplasma capsulatum (dimorphic) in lung infection.
SEVERE: Amphotericin B IV followed by Itraconazole PO
MILD: Voriconazole or posaconazole/fluconazole PO
Presentation of coccidioides immitis (dimorphic) in lung infection.
Fever, cough, headache, Chest pain
Disseminate or chronic disease produces systemic symptoms
Characteristics of coccidioides immitis (dimorphic) in lung infection.
May have acute, disseminated or chronic course. Fungal spheres containing endospores are found in granulomas.
Treatment of coccidioides immitis (dimorphic) in lung infection.
SEVERE: Amphotericin B IV followed by Itraconazole PO or Fluconazole PO
MILD: Voriconazole or posaconazole PO
What is the only fungal infection to use flucytosine?
cryptococcal infections
Why do physicians want to use lipid formulations or stop using Amphotericin B in general?
it has nephrotoxicity associated iwth the deoxycholate form
Aspergillus species is devleoping a resistant to what drug class? How?
Azoles. The resistance is associated iwth mutations in the promoter region of CYP51A (encodes lanosterol-14-alpha demethylase activity)
Which azole has low and variable oral absorption and is beginning to fall out of favor?
itraconazole
Which is the ONLY azole that can penetrate the BBB?
Fluconazole
How are azoles metabolized?
hepatic CYP metabolism (2C9, 2C19, 3A4)
Which types of antifungals do NOT undergo hepatic metabolism?
Amphotericin B
Flucytosine
What agents interact with amphotericin B?
nephrotoxic agents
Drugs producing hypokalemia
What agents should be avoided when using flucytosine? Why?
Hematoxic drugs, because flucytosine can produce anemia and blood dyscrasias (like agranulocytosis)
MOA of Amphotericin B
Binds to ergosterol (in fungal membrane) and forms pores that allow leakage (leading to cell death
AE of Amphotericin B
Infusion related reactions
Renal toxicity, anemia, abnormal liver function tests, seizures
Which azole has the most CYP interactions?
Voriconazole
Which azole has the least CYP interactions?
posaconazole
The highest incidence of GI discomfort, weight loss, and side effects occurs with what azoles?
itraconazole
posaconazole
Which azoles are contraindicated in pregnancy?
voriconazole
Fluconazole
Which azole has severe liver side effects?
ketoconazole
What are the adverse effects of voriconazole?
photosensitive dermatitis
elevated liver enzymes
temporary visual disturbances upon IV
neurologic symptoms (hallucinations)
Which azole is orally administered and has activity against mucomycosis?
posaconazole
What is the MOA of Flucytosine?
enters fungal cell via enzyme cytosine permease, converted to 5-FU, becomes incorporated into intermediary metabolism (eventual inhibition of DNA and RNA synthesis).
Where is flucytosine converted to 5-FU?
intestines (needs flora)
What are the side effects of flucytosine?
renal toxicity in impairment
Anemia, leukopenia, thrombocytopenia
NARROW THERAPEUTIC WINDOW
What is the MOA of azoles?
inhibits ergosterol formation
