Antifungal Drugs Med class- Quiz 2 Flashcards
Antifungals Overview
-Infections from fungus are called mycoses
-Fungal cell membrane contains ergosterol rather than cholesterol
-Incidence of candidemia has been on the rise—this is thought to be related to the increased number of patients with chronic immunosuppression
-2 types: Yeast, molds (intermediary category that has combo of both)
Newest bad actor—Candida auris
- This yeast is hard to
identify and difficult to treat
-Candida has 20 different species
-Candidiasis is treated with polyenes, azoles, nucleoside analogs,
echinocandins and allylamines
-MDR-C. auris is related to preventative use of antifungal drugs
-In order to identify this strain of yeast—one of two methods of testing —matrix assisted laser desorption/ ionization time of flight [MALDI-TOF] or Bruker MALDI Biotyper [preferred—100% accurate]
-90% of C. auris is resistant to Fluconazole, 30% is resistant to Amphotericin B
-In neonates 2 months and younger, the DOC is Amphotericin B
-For adults and children older than 2 months, echinocandins are the DOC
Amphotericin B
-The “Big Momma”
-Despite toxic potential remains DOC for severe mycoses
-MOA: disrupts membrane function, allows K to leak out of the cell causing cell death
-Effective against wide spectrum of fungi
-Extensively bound to plasma and distributed throughout the body
-Has low therapeutic index
-ADE’s: fever, chills, renal impairment, hypotension, thrombophlebitis
Antimetabolite Antifungals
-Flucytosine [5FC]
-MOA: it is converted to a series of
compounds that disrupt nucleic acid and protein synthesis
-Used with other antifungals
-Well absorbed after oral dose
-Distributes throughout body water and penetrates well into CSF
-ADE’s: Reversible neutropenia, Thrombocytopenia, Dose related bone marrow depression, hepatic
dysfunction and elevated LFTs, Nausea, Vomiting, Diarrhea, Severe enterocolitis
Azole Antifungals
-Fluconazole [Diflucan]—PROTOTYPE drug
-Azoles are made up of 2 different classes of drugs— the Imidazoles and the Triazoles
-They have similar MOA and spectra, but the pharmacokinetics and therapeutic uses vary a lot
-Imidazoles are used topical for
cutaneous infections while the Triazoles are given systemically for treatment
-MOA: Disrupt fungal cell membrane structure, inhibiting fungal cell growth
-Resistance to Azoles is become huge problem
-They all inhibit hepatic CYP34A
-CI: Tetaratogenic in pregnancy
Ex: Itraconazole, Posaconazole,
Voriconazole, Isavuconazole
Fluconazole
-PROTOTYPE Drug for Triazoles
-Is the least active of all triazoles
-Used to prevent invasive fungal infections in BMT patients
-DOC for Cryptococcus neoformans after induction therapy with Amphotericin B and Flucytosine
-Used for treatment of Candidemia and Coccidioidomycosis
-Effective against most forms of mucocutaneous Candidiasis
-Absorbed well after oral dose
-Doses must be reduced in those
with renal disease
-ADEs—n/v, headache and rashes
Itraconazole
-Triazole with broad antifungal
spectrum compared to Fluconazole
-DOC in Blastomycosis, Sporotrichosis, Paracoccidioidomycosis, Histoplasmosis
-Available as capsules, tablets and solution
-Extensively metabolized by the liver
-ADEs—nausea, vomiting, rash, low K+, HTN, edema, headache; liver toxicity
-NOTE* It is a negative inotropic effect—avoid in those with ventricular dysfunction or HF
Posacanazole
-Broad spectrum antifungal
similar to Itraconazole
-Used for treating and prevention of invasive Candida and Aspergillus in the immunocompromised
-Low bioavailability and should be given with food
-Only one NOT metabolized by CYP450
-Inhibitor of CYP34A (lot of interactions)
Voriconazole
-Broad spectrum antifungal available orally and IV
-DOC for invasive Aspergillus
-High oral bioavailability and penetrates into tissues well
-Extensively metabolized by CYP 450
-Inhibitors and inducers of these isoenzymes can affect levels of
Vfend—causing toxicity or clinical failure
-High trough levels are associated with visual &auditory hallucinations and an increased risk of liver damage
-Contraindicated with Rifampin, Rifabutin, Carbamazepine and St.
John’s wort
Isavuconazole
-Broad spectrum antifungal which is supplied as the prodrug
Isavuconazonium in oral and IV forms
-Approved for invasive Aspergillus and invasive mucormycosis
-Co-administration with other potent CYP 450 3A4 inhibitors and inducers is contraindication
-ADEs—nausea, vomiting, diarrhea,
hypokalemia
Who are the new kids on the block for antifungals?
-Echinocandins
Echinocandins
-MOA: interfere with the synthesis of the fungal cell wall, leading to lysis and cell death
-All of these agents are given IV once daily
-Potent against Aspergillus and most Candida (don’t work on much else)
-ADEs—fever, rash, nausea, phlebitis
-Must be given by slow IV infusion to prevent a histamine induced flushing seen with rapid infusion
-Ex: Capsofungin, Micafungin,
Anidulafungin
Capsofungin
-Echinocandin
-1 st line for those with invasive Candida
-Co-administration with CYP 450 enzyme inducers [Rifampin] mandates an increase in dose
-Should not be given with Cyclosporine—due to elevation of LFTs
Micafungin and Anidulafungin
-Echinocandin
-1st line options for invasive Candidiasis
-Do not have any associated drug interactions
-Micafungin is ONLY drug in this category where you don’t need a loading dose
-Micafungin is also indicated for
prevention of invasive Candida
infections in those undergoing stem cell transplants
Cutaneous mycotic infections
-Mold-like fungi that cause cutaneous
infections are called dermatophytes or tinea
- 3 fungi cause the majority of these
infections—Trichophyton, Microsporum, Epidermophyton
