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Infectous Disease > Dr. James Antifungal > Flashcards

Dr. James Antifungal Flashcards

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

A

C. krusei, and C. glabrata

21
Q

Itraconazole (Sporanox®)

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?

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?

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?

A

Itraconazole Tolsura

25
Q

Voriconazole (Vfend®)

A

-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
Q

Where is Posaconazole (Noxafil®) used?

A

-Immunocompromised prophylaxis (AML/MDS)
-Potential use for zygomycosis

27
Q

Posaconazole(Noxafil®)

A

-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
Q

Isavuconazonium (Cresemba®)

A

-covers Aspergillus/mucormycosis
-broad coverage
-few drug interactions and fewer side effects
-requires load

29
Q

Echinocandins

A

-Caspofungin (Cancidas®)
-Micafungin (Mycamine®)
-Anidulafungin (Eraxis®)
-Rezafungin (Phase III

29
Q

Echinocandins

A

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
Q

Difference between Echinocandins

A

-Caspofungin requires load, hepatic adjustment needed, and few drug interactions (Rifampin, cyclosporine, tacrolimus)

-Anidulafungin requires load

-all IV

31
Q

Echinocandins

A

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
Q

Polyenes

A

-Nystatin (swish and swallow)
-Amphotericin B (works systemically)
-MOA: inserts into the membrane and creates pores

33
Q

What is the purpose of the 3 lipid-associated formulations of Amphotericin B?

A

-Lipid complex (Abelcet®) - common
-Liposomal (AmBisome®) - common
-Cholesteryl Sulfate Complex (Amphotec®)

to reduce toxicity

34
Q

When is the conventional formulation of Amphotericin used?

A

-Symptomatic candiduria
-Extemporaneous compounds
BUT
-multiple adverse events
-Saline dosing to reduce nephrotoxicity

35
Q

Where are Lipid Associated Amphotericin used?

A

-Life-threatening fungal infections
-Category D: avoid in pregnants

36
Q

Advantages of Life-threatening fungal infections

A

-Can give higher doses
-Reduced nephrotoxicity
-Limited use in urine

Disadvantage: Expensive

37
Q

Adverse effects of Amphotericin

A

-Flu-like symptoms: chills, fever,
headache, malaise
-Hypotension
-Electrolyte imbalances (must be replaced)
-Arrhythmias
-LFTs go up
-and more

38
Q

Pharmacist role in Amphotericin

A

weight-based dosing
-not compatible with saline alone, saline -> dextrose -> Amphotericine -> Dextrose -> saline
-monitor: K, Mg, Ca, HCO3, CBC

39
Q

Flucytosine (5-FC)

A

5-FC gets converted into 5-FU -> phosphorylation and incorporated into Thymidylate synthase -> Inhibition of DNA synthesis

  1. Substition for Uracil -> Inhibition of protein synthesis
40
Q

How is Flucytosine used?

A

-Given in combination with Amphotericin for Candida and Cryptococcus

-sometimes monotherapy for UTIs, bc it gets in the urine so well - Candi

41
Q

Important to know - Flucytosine

A

Weight-based dosing
-Renal adjustment

Side effects:
-Diarrhea, abdominal cramping -> dose is too high
-skin diseases

42
Q

MOA Ibrexafungerp

A

-inhibits glucan synthase, an enzyme involved in the
formation of 1,3-β-D-glucan

43
Q

Terbinafine

A

-Oral and topical Allylamine
-Onychomycosis of the toenail or fingernail
-inhibits squalene epoxidase (biosynthesis ergosterol)

44
Q

Side effects: Terbinafine

A

-Skin reactions, SJS/TENS
-liver toxicity - not for pt with liver disease

45
Q

Broad overview:

A

-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
Q

Natamycin

A

-Antifungal eyedrop

47
Q

Topical Antifungals

A

-Imidazoles
-Triazoles
-Allylamines
-Ciclopirox
-Tolnaftate - similare to Terbinafaine

Infectous Disease (29 decks)

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