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Infectous Disease > Dr. James Antifungal > Flashcards

Dr. James Antifungal Flashcards

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1
Q

What to be careful of when administering Antifungals?

A

-Electrolytes
-Renal function (Azole)

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2
Q

Types of Fungi

A

Non-invasive: mushrooms, rusts, smuts, puffballs, truffles, morels

Invasive (threats to humans): Yeast (unicellular), Molds, Dimorphics

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3
Q

How is a fungal cell different from a mammalian cell?

A

-Bacteria is prokaryotic (before nucleus - no nucleus)

-Fungal are eukaryotes, the difference to mammalian cells is the cell wall (mammalian cells have a cell membrane)
-> Newer drugs target the cell wall, rather than cell membrane to reduce toxicity

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4
Q

What are the most common fungi to cause infections?

A

Candida
-> Candida albicans (species)

for Molds: Aspergillus
-> A. fumigatus

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5
Q

How is the outer cell compartment of fungi structured?

A

-Cell wall: ß-(1,6)-glucan and ß-(1.3)-glucan

-Cell membrane: phospholipid bilayer -> Ergosterol embedded in the cell membrane

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6
Q

How is Ergosterol produced?

A

From Squalene

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7
Q

What is one MOA of Triazoles?

A

Triazoles
-Inhibition of 14-alpha-methylation of lanosterol -> reducing production of ergosterol

Resistance through efflux pumps and altered demethylase

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8
Q

Why is toxicity associated with Ketoconazole?

A

Interfere with Cholesterol pathway
-not seen in newer Azoles

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9
Q

How are newer Azoles different from the older ones?

A

They have less hormonal inhibition and a broader spectrum

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10
Q

Does Fluconazole need renal adjustment?

A

Yes

IV, PO available

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11
Q

Adverse effects of Fluconazole

A

Monitor LFT
-Prolonged QT
-rash
-SJS

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12
Q

What is a Contraindication of Itraconazole?

A

It is a negative inotrope
-> contraindicative in pt with heart failure

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13
Q

Adverse effects of Voriconazole

A

-Visual toxicity !!!
-Flourid, Bone, and Neurotoxicity
-rash
-hepatic
-QT prolongation

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14
Q

Why is Voriconazole dangerous in pt with renal impairment?

A

The IV form is compounded in Cyclodextrin,
Cyclodextrin is eliminated through the kidney, it accumulates in pt with renal impairment (CrCl less than 50)

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15
Q

Posaconazole

A

first to treat Myco category of fungal
-Adverse effects: hepatic, QT prolongation

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16
Q

Isavuconazonium

A

Prodrug, which increased it solubility

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17
Q

Which drug interactions are important to check when Azoles are administered?

A

CYP Interactions

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18
Q

Which diseases are treated with Fluconazole (Diflucan®)

A

-Candida species (except for C. krusei, and C. glabrata)
-Cryptococcus (starting with Amphotericin and flucytosine -> Fluconazole is used as a step down or when the fungi is in the brain)

-good penetration to CNS and urinary tract

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19
Q

Is IV to PO switch for Flucanozole possible?

A

Yes

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20
Q

Which organisms are not covered by Fluconazole?
Treatment gap

Study These Flashcards
A

C. krusei, and C. glabrata

21
Q

Itraconazole (Sporanox®)

Study These Flashcards
A

-Broader spectrum than Flucanozole (includes molds and dimorphic fungi)
-IV to PO possible
-AVOID in heart failure patients !!! bc it is a negative inotrope

22
Q

How is the capsule formulation of Itraconazole different from the suspension?

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A

-Capsule: erratic absorption, has to be given with food/cola (to stimulate acid production of the stomach)
proton pump inhibitor raises the pH and decreases the absorption of Itraconazole -> switch to suspension

-Suspension: contains Cyclodextrin enhancing the absorption -> has to be given on an empty stomach - doesn’t matter if pt is on PPI

23
Q

How is Itraconazole Tolsura different from Sporanox?

Study These Flashcards
A

-Tolsura uses the SUBA Technology
-utilizes a solid dispersion of drug, improves the dissolution of poorly soluble drugs - compared to their normal crystalline form

-not interchangeable with Sporanox in terms of dosing

24
Q

What Antifungal drug can be used in a patient who is on an acid-suppressive drug and additionally can’t use a suspension?

Study These Flashcards
A

Itraconazole Tolsura

25
Voriconazole (Vfend®)
-Spectrum similar to itraconazole -DOC for Aspergillus (before it Amphotericin Amphoterrible) -weight-based dosing -drug interaction with cyclosporine and tacrolimus -changing from IV to PO is possible, but has to be discussed with the ID -requires renal and hepatic adjustment -> IV vehicles can accumulate!!!! EXAM -for UTI: little efficacy
26
Where is Posaconazole (Noxafil®) used?
-Immunocompromised prophylaxis (AML/MDS) -Potential use for zygomycosis
27
Posaconazole(Noxafil®)
-Suspension must given with a meal -dosing depends on if for treatment or prophylaxis -DR is more convenient, and more often used -It is not interchangeable!!!
28
Isavuconazonium (Cresemba®)
-covers Aspergillus/mucormycosis -broad coverage -few drug interactions and fewer side effects -requires load
29
Echinocandins
-Caspofungin (Cancidas®) -Micafungin (Mycamine®) -Anidulafungin (Eraxis®) -Rezafungin (Phase III
29
Echinocandins
Inhibit 1,3-beta-glucan -Covers most yeasts as well as some molds; Candida and Aspergillus (not the best for Aspergillus) -Concentration dependant killing -IV only -Minimal drug interactions -Minimal adverse effects
30
Difference between Echinocandins
-Caspofungin requires load, hepatic adjustment needed, and few drug interactions (Rifampin, cyclosporine, tacrolimus) -Anidulafungin requires load -all IV
31
Echinocandins
empiricall over Fluconazole -severe candidiasis -recent azole exposure -pt with neutropenic (despite broad-spectrum antibiotics pt can not tolerate other agents Micafungin has 3 different doses
32
Polyenes
-Nystatin (swish and swallow) -Amphotericin B (works systemically) -MOA: inserts into the membrane and creates pores
33
What is the purpose of the 3 lipid-associated formulations of Amphotericin B?
-Lipid complex (Abelcet®) - common -Liposomal (AmBisome®) - common -Cholesteryl Sulfate Complex (Amphotec®) to reduce toxicity
34
When is the conventional formulation of Amphotericin used?
-Symptomatic candiduria -Extemporaneous compounds BUT -multiple adverse events -Saline dosing to reduce nephrotoxicity
35
Where are Lipid Associated Amphotericin used?
-Life-threatening fungal infections -Category D: avoid in pregnants
36
Advantages of Life-threatening fungal infections
-Can give higher doses -Reduced nephrotoxicity -Limited use in urine Disadvantage: Expensive
37
Adverse effects of Amphotericin
-Flu-like symptoms: chills, fever, headache, malaise -Hypotension -Electrolyte imbalances (must be replaced) -Arrhythmias -LFTs go up -and more
38
Pharmacist role in Amphotericin
weight-based dosing -not compatible with saline alone, saline -> dextrose -> Amphotericine -> Dextrose -> saline -monitor: K, Mg, Ca, HCO3, CBC
39
Flucytosine (5-FC)
5-FC gets converted into 5-FU -> phosphorylation and incorporated into Thymidylate synthase -> Inhibition of DNA synthesis 2. Substition for Uracil -> Inhibition of protein synthesis
40
How is Flucytosine used?
-Given in combination with Amphotericin for Candida and Cryptococcus -sometimes monotherapy for UTIs, bc it gets in the urine so well - Candi
41
Important to know - Flucytosine
Weight-based dosing -Renal adjustment Side effects: -Diarrhea, abdominal cramping -> dose is too high -skin diseases
42
MOA Ibrexafungerp
-inhibits glucan synthase, an enzyme involved in the formation of 1,3-β-D-glucan
43
Terbinafine
-Oral and topical Allylamine -Onychomycosis of the toenail or fingernail -inhibits squalene epoxidase (biosynthesis ergosterol)
44
Side effects: Terbinafine
-Skin reactions, SJS/TENS -liver toxicity - not for pt with liver disease
45
Broad overview:
-DNA synthesis/protein inhibition: Flucytosine -Squalene epoxidase inhibition: Terbinafine -Inhibit Ergosterol formation: Azoles -Insertion and pore-formation into the cell membrane: Amphotericin B, nystatin -disrupting the cell wall: Ibrexifungerp, Echinocandins
46
Natamycin
-Antifungal eyedrop
47
Topical Antifungals
-Imidazoles -Triazoles -Allylamines -Ciclopirox -Tolnaftate - similare to Terbinafaine

Infectous Disease (29 decks)

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