Stauginger Fungal Flashcards
What drug contains 50 mg of amphotericin B intercalated into a liposomal
membrane consisting of:
- 213 mg hydrogenated soy phosphatidylcholine
- 2 mg cholesterol
- 84 mg distearoylphosphatidylglycerol
- 0.64 mg alpha tocopherol
- 900 mg sucrose
- 27 mg disodium succinate hexahydrate
AmBisome
A macrocyclic-polyenes-antifungal antibiotic drug produced from a strain of Streptomyces nodosus
Amphotericin B
This drug acts by binding to the sterol component of a cell membrane leading to alterations in cell permeability and cell death and has a high affinity for the ergosterol component of fungal cell membrane
Amphotericin B
This drug can bind to the cholesterol component of the mammalian cell and can leads to cytotoxicity
In particular, this drug can be very nephrotoxic!!!
Amphotericin B
What can be used to treat Cryptococcus neoformans and Blastomyces dermatitidis?
(also Aspergillus and Candida)
Amphotericin B
Amphotericin B is indicated in ..?
- Cryptococcus neoformans
- Blastomyces dermatitidis
(also aspergillum and candida)
What type of drug is amphotericin B?
polyene
What can Amphotericin B overdose cause?
fatal cardiac arrest
fatal cardiopulmonary arrest
What adverse reaction has been reported with Amphoceterin B?
Anaphylaxis… closely monitor initial dosing
Amphoceterin B can have nephrotoxic effects with which drugs?
- Aminoglycosides
- Cyclosporine
- Antineoplastic agents (cisplatin, nitrogen mustard compounds)
ACA
Which is more nephrotoxic, amphotericin B deoxycholate or Ambisome?
amphotericin B deoxycholate
Should Amphotericin B be used primarily for treating patients with life threatening fungal infections or non-invasive forms of fungal infections such as oral thrush, esophageal or vaginal candidiasis in patients with normal neutrophil counts?
- used primarily for treating patients with life threatening fungal infections
- NOT for non-invasive forms of fungal infections
What happens if amphoceterin B is mixed with skeletal muscle relaxants and digitalis glycosides?
hypokalemia may be exaggerated
Amphotericin B may increase the toxicity of what drug?
flucytosine
Fluconazole, itraconazole, econazole, terconazole, butoconazole, and tioconazole are what class of drug?
Azole
What drug is active against fluconazole-resistant strains of Candida?
Newer triazoles such as Vorivonazole, posaconazole, ravuconazole
What is Vorivonazole?
Newer triazole Active against fluconazole-resistant strains of Candida
What drug mechanism of action, involves interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes?
Fluconazole - this is MOA of other Azoles too
What azole drug is indicated in the tx of
-Candida UTI/Peritonitis
-Vaginal candidiasis
-Oropharyngeal and esophageal candidiasis (thrush),
- Cryptococcal meningitis
- Prophylaxis of candidiasis with bone marrow transplant
Fluconazole
If someone is taking a drug that is known to prolong the QT interval and is metabolized via the enzyme CYP3A4 such as: pimozide, astemizole, cisapride erythromycin quinidine (PACE Q) What anti fungal should NOT be given?
Fluconazole
What drug is contraindicated for co-administration with fluconazole based on multple dose interaction study?
terfenadine
- patients on multiple doses of 400 mg/day or higher of fluconazole should not take terfenadine at the same time
Your patient is pregnant with a fungal infection, can she take fluconazole?
- FDA says no- can cause serious and specific birth defects
- no adequate controlled trials though
How does Fluconazole cause QT prolongation?
inhibition of Rectifier Potassium Channel current
What can amplify QT prolongation in patients on fluconazole?
- The QT prolongation (torsade de pointes) caused by other medicinal products (such as amiodarone) may be amplified via the inhibition of cytochrome P450 (CYP) 3A4
- Erythromycin +fluconazole can amplify torsades (sudden heart death can occur
- Hypokalemia and cardiac failure patients are at increased risk for life threatening ventricular arrhythmias and torsades
What do azole antifungals inhibit?
Azole antifungals also are both substrates and inhibitors of the cytochrome P450 family CYP3A4
Use of azoles with what drugs can increase serum concentration of those drug?
Concomitant use of azoles increases the concentration of…
- serum concentrations of calcium channel blockers
- immunosuppressants, chemotherapeutic drugs
- benzodiazepines
- tricyclic antidepressants
- macrolides
- SSRIs
leads to potentially serious and lethal drug-drug interactions
What is MOA of itraconazole?
interrupts conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes
How can you increase the absorption of itraconazole?
take it with food and a high acidic beverage. -> acid increases its absorption
What drug has a black box warning for pts with heart failure due to its inotropic effects?
Itraconazole
What metabolizes itraconazole?
cytochrome P450 3A4 isoenzyme system (CYP3A4),
What azole has activity against
- Aspergillus,
- Dematiaceous mold
- Sporothrix Schenckii
Itraconazole
What is the MOA of Voriconazole?
interruption of the demethylation of 14-a-lanosterol in the conversion to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes
A patient has
- non stop N/V
- loss of appetite
- stomach/abdominal pain
- yellowing eyes/skin
- dark urine
What antifungal could they be taking?
Itraconazole can cause fatal liver disease
Patients with Hereditary Galactose Intolerance, Lapp Lactase Deficiency or Glucose- Galactose Malabsorption should not take what drug? Why?
Voriconazole, it contains lactose
What enzyme does oral voriconazole have the greatest affinity for? does it affect kidneys?
CYP2C19
- oral voriconazole is not affected by renal failure
What should you consider with parenteral voriconazole?
the parenteral preparation is solubilized in a compound that is secreted by the kidneys
use dose adaptation in cases of renal impairment
Caspofungin, micagugin, and anidulafugin are what drug class?
Echinocandins
What are Echinocandins used for?
- The drugs in this class include caspofungin, micafungin and anidulafungin
- Approved for IV use in systemic Candida infections
What drug class is semisynthetic, cyclic lipopeptides with an N-linked acyl lipid?
Echinocandins (caspofungin, micafungin and anidulafungin)
What echinocandin is indicated in tx of candidemia, acute disseminated candidiasis, candida peritonitis, and absess?
Micafungin (echinocandin class)
What is used for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant?
Micafungin (echinocandin class)
What drug class can cause red man syndrome from histamine?
Echinocandins
Who has a black box warning against micafungin? why?
European medical agency has BBW for micafugin
- caused foci of altered hepatocyte after tx period > 3 months in rats
What drug is a pyramidine analogue against fungal species that interferes with purine and pyrimidine metabolism?
Flucytosine
What drug has a black box warning for extreme caution in bone marrow depression, hepatic impairment, renal impairment and is contraindicated in pregnancy and breast feeding
Flucytosine
What drug class inhibits glucan synthase for fungal cell wall?
Echinocandins
What drug is used with liposomal amphoceterin B for cryptococcal meningitis tx?
flucytosine
