Antifungal Drugs

Question 1

Azoles Drugs

Answer 1

Systemic: Fluconazole, Ketoconazole, Itraconazole, Voriconazole, Posaconazole, Isuvaconazole

Topical: Clotrimazole, Miconazole, Luliconazole

Question 2

Function of Azoles Drugs?

Answer 2

Act on 14-a-demethylase which inhibits formation of ergosterol (static action) –> increases cell permeability and leakage

Generally treat candida fungi infections

Question 3

What is Itraconazole generally used?

Answer 3

Dimorphic fungi

Question 4

Voriconazole is the DOC for?

Answer 4

Aspergillus infection

Given PO or IV

Question 5

Posaconazole & Isuvaconazole

Answer 5

• Broad spectrum activity to treat lots of yeasts and molds (oral moulds)
• Commonly used in immunocompromised patients- cancer pts, bone marrow transplant pts
• Do not cover Sporothrix

Question 6

What is AmphoB the antiviral drug of choice for? Why is it used as second or third line treatment with other fungi?

Answer 6

Drug of choice for Crytococcal infections especially in immunocompromised patients (ex. cryptococcal meningitis in HIV patient)

AmphoB has high toxicity so we want to only use it if other drugs fail

Question 7

Main use of echinocandins?

Answer 7

Severe candida infections

Question 8

Class wide adverse effects of azoles?

Answer 8

QT prolongation (except with Isuvaconazole which usually shortens QT)

Drug-drug interactions: CYP450 3A4 substrates and inhibitors

• should always check D-D interactions because they’re inhibitors (make substrate levels go up) and can create toxicity

Hepatotoxicity (worst offender= Ketoconazole, do liver function tests)

Question 9

Adverse effects of Voriconazole?

Answer 9

Hepatotoxic

Nephrotoxic with IV form via Cyclodextran

Vision changes –> seeing blue color, shaded colors, 3D vision

Question 10

Fluconazole fun facts

Answer 10

Used for: oral thrush, vaginal yeast infections

Has high oral BA: IV to PO is 1:1 dosing

Question 11

Posaconazole fun facts

Answer 11

Very broad spectrum activity

Oral solution is very pH dependent (needs an acidic environment for absorption, take with food)

*PO < delayed release < IV

Question 12

Isuvaconazole is the exception for what in the azoles class?

Answer 12

Azoles have an adverse effect of prolonging QT, but Isuvaconazole actually shortens QT

Given as a prodrug**

Question 13

What is AmphoB used for?

Answer 13

Drug of choice for Cryptococcal infections (with flucytosine)

Salvage therapy for Candida and moulds

Lipid formulations available in US to decrease nephrotoxicity (but are way more $$$)

Question 14

Adverse effects of AmphoB?

Answer 14

Nicknamed “AmphoTerrible” because toxicities can be so significant

Nephrotoxicity (salt compound: give saline bolus to flush out the kidneys, lipid form: make sure patient is hydrated)

Electrolyte wasting- patients will pee them out (monitor and replace when necessary)

Infusion related reactions

Question 15

What should echinocandins be used for?

Answer 15

Cidal agents- first line therapy for Candidemia (severe candida infections)

Not any SUPER intense adverse effects but Caspofungin could have a slightly higher rate of them (pyrexia, blood dyscrasias), limited D-D interactions

Question 16

What are some Echinocandin pearls?

Answer 16

Available IV only

No renal adjustment needed because they are mostly excreted in fecal matter or other non-renal ways

Highly protein bound –> could need increased dose in morbidly obese patients

“Eagle effect”- increasing dose can actually give opposite effect on killing activity so be careful

Question 17

What does Flucytosine do and how does it do it?

Answer 17

Flucytosine blocks protein synthesis by incorporating into RNA (after it is converted to 5-FU)

Used in COMBO (not used as monotherapy) with AmphoB against Cryptococcal disease

Question 18

What does Nystatin do and how?

Answer 18

Nystatin is part of the Polyenes group that acts directly on ergosterol to kill fungi (cidal)

Oral suspension for oral thrush, topical for Tinea or Candida infections (not systemically distributed through the body)

Question 19

In what forms do dimorphic fungi exist?

Answer 19

Yeast inside the body and mould outside the body (yeast in the heat, mould in the cold)

Question 20

How does Tinea infection usually present?

Answer 20

Topical infections (on the skin)

Examples: tinea versicolor, athlete’s foot, ring worm

Question 21

Examples of Candida infection?

Answer 21

Most common types of infection (Candida albicans being the most common culprit)

Examples: oral thrush (most common), vaginal yeast

Question 22

What kind of patients are mould infections usually found in? Most common ones?

Answer 22

Immunocompromised patients (ex. bone marrow transplant patients)

Common ones to be aware of: Aspergillus (drug of choice= Voriconazole), Zygomycetes (Rhizopus, Candidobolus, Basidiobolus), Fusarium (type of Mycetoma)

Question 23

What are the systemic drugs in the Azoles group?

(there are 6)

Answer 23

Fluconazole

Ketoconazole

Itraconazole

Voriconazole

Posaconazole

Isuvaconazole

Question 24

What are the topical drugs in the Azoles group?

(there are 3)

Answer 24

Clotrimazole

Miconazole

Luliconazole

Question 25

Which drugs make up the Polyenes class?

Answer 25

Ampho B

Nystatin

Question 26

MOA of AmphoB and Nystatin?

Answer 26

Work directly on ergosterol (fungal cell wall) to cause apoptosis

Question 27

ADE of Flucytosine?

Answer 27

Primarily blood dyscrasias

Question 28

Which echinocandin may have a slightly higher rate of ADEs?

Answer 28

Caspofungin