Sweatman - Anti-Fungals Flashcards
(23 cards)
What are the presentation and characteristics of Candida albicans (yeast)?
- Fever, tachycardia, patchy infiltrates on chest film
- Uncommon cause of pneumonia; hematogenous spread seen in immuncompromised patients
What are the presentation and characteristics of Cryptococcus neoformans (yeast)?
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Cyptococcosis
1. Often asymptomatic; may have productive cough, fever and weight loss
2. Associated with pigeon droppings; can produce cryptococcal meningitis
What are the presentation and characteristics of Aspergillus (mold) aspergillosis?
- Wheezing, dyspnea and cough w/allergic broncho-pulmonary aspergillosis (ABPA): fever, cough, dyspnea, pleuritic chest pain, and hemoptysis seen in invasive forms, usually in immuno-compromised patients
- Aspergillomas (fungal balls) can form in pre- existing cavities; the invasive form spreads hematogeneously
What are the presentation and characteristics of Blastomyces dermatidis (dimorphic) blastomycosis?
- Fever, chills, productive cough. May also present with skin or bone lesions, or genitourinary involvement
- Causes pneumonia-like lung disease and may progress to disseminated disease
What are the presentation and characteristics of Histoplasma capsulatum (dimorphic) histoplasmosis?
- Often asymptomatic; young or immuno-compromised may have disseminated or chronic disease with fever, fatigue and weight loss
- Caseating granuloma formation in tissue; the disseminated form is marked by multi-system involvement with macrophage infiltrates filled with intracellular fungi
What are the presentation and characteristics of Coccidoides immitis (dimorphic) coccidioidomycosis?
- Fever, cough, headache, chest pain; disseminated or chronic disease produces systemic symptoms
- May have acute, disseminated or chronic course
1. Fungal spheres containing endospores are found in granulomas
What is the treatment for Candida albicans (yeast)?
Amphotericin B IV and fluconazole
What is the treatment for Cryptococcus neoformans (yeast) - cryptoccosis?
- CNS: Amphotericin B IV + flucytosine PO
- Non-CNS: fluconazole PO
What is the treatment for Aspergillus (mold) aspergillosis?
Amphotericin B IV or itraconazole
- 1st line: Voriconazole IV
1. Step down: Voriconazole PO - 2nd line: Amphotericin B IV
1. Step down: Posaconazole PO
What is the treatment for Blastomyces dermatitidis (dimorphic) blastomycosis?
Amphotericin B IV or itraconazole
- 1st line: Fluconazole IV or Amph B IV if severe
1. Step down: Voriconazole or Itraconazole or Fluconazole - 2nd line: Amph B IV
1. Step down: Voriconazole or Fluconazole PO
What is the treatment for Histoplasma capsulatum (dimorphic) histoplasmosis?
- Severe or immunocompromised: Amphotericin B IV followed by itraconazole PO
- Mild-moderate: Itraconazole PO
- Updated Rx: Voriconazole, or posaconazole, fluconazole PO
What is the treatment for Coccidioides immitis (dimorphic) coccidioidomycosis?
- Severe or immunocompromised: Amphotericin B IV followed by itraconazole or fluconazole PO
- Mild-moderate: Itraconazole or fluconazole PO
- Updated Rx: Voriconazole or posaconazole PO
What is the primary indication for flucytosine?
Cryptococcal infections
How has treatment for Aspergillus and Blastomyces shifted gears?
- There is a move to employ one of the newer azole drugs, which are effective against theses species, rather than Amphotericin B (which remains a second-line treatment option)
Why are most physicians using lipid formulations of Ampho B now?
- To try and avoid the nephrotoxicity associated with the deoxycholate form of the drug
- Modest improvement, at best, in toxicity profile, and very expensive
- 3 alternatives: AmBisome, Amphotec, and Abelcet
Why is azole resistance by Asperigillus on the rise?
- Possibly due to increased clinical use, but also to increased agricultural use of azole-like compounds
- Resistance seems to be associated with mutations in the promotor region of CYP51A, which encodes lanosterol-14α-sterol demethylase activity (the drug target of the azoles)
Why is there a trend towards moving away from Itraconazole to the newer azole drugs?
- Oral absorption of itraconazole is low and variable from patient to patient
- Drug levels achieved with the newer azoles (fluconazole, voriconazole, posaconazole) are much more consistent BUT only fluconazole is able to penetrate the blood-brain barrier
What are some potential drug interactions of the anti-fungals?
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Azoles: undergo hepatic CYP metabolism and interact with concurrent drugs metabolized via CYP2C9, 2C19 & 3A4
1. Neither Amphotericin B nor Flucytosine undergoes hepatic metabolism - Amphotericin B: possible interxn w/other nephro-toxic agents and drugs producing hypokelmia
- Flucytosine: caution advised w/other hematotoxic drugs bc Flucyto can produce anemia and blood dyscrasias, including agranulocytosis
What is the MOA of Amphotericin B?
- Binds to ergosterol, the prominent sterol in fungal cell membranes -> forms pores
1. Amphipathic: combines avidly with ergosterol along the double bond-rich side of its structure and associates with H2O molecules along the hydroxyl-rich side - Pore allows leakage, leading to cell death
- Highly effective in many serious infections, but can also be very toxic
Why (and how) does Ampho B affect the kidney?
- Binds to human membrane sterols, probably accounting for the drug’s prominent renal effects
1. 80% of pts on original formulation experience renal damage -> azotemia, hypokalemia (risk of arrhythmia), reduced GFR, and frank renal failure
What are the common AE’s associated with Ampho B?
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Immediate: infusion-related reactions
1. Fever, chills, muscle spasms, vomiting, headache, and hypotension
2. Test dose often used to gauge pt rxn
3. Premedicate: antipyretics, antihistamines, meperidine, or corticosteroids -
Delayed: renal toxicity
1. Sometimes necessitates dialysis
2. Na+ loading often used to reduce pre-renal toxicity (decreased renal perfusion)
3. Anemia: 2o to renal damage (EPO)
4. Abnormal liver function tests (LFT’s)
5. Seizures after intrathecal drug admin
What is the MOA of the azoles?
- Prevent the conversion of lanosterol to ergosterol, interrupting cell membrane synthesis -> mediated by CYP 450 enzymes
- Issue of specificity of drug action on fungal CYP versus mammalian is important
- Named after the azole ring structure (all of the ones covered in this block are triazoles -> 3 nitrogens)
Which CYP’s are affected by the azoles (table)?
- All of them are capable of inhibiting CYP3A4, the major metabolic pathway for prescription meds
- Can inhibit concurrent meds and can also experience a change in their own metabolism when they are processed through the same metabolic route
