Antifungal Agents Flashcards

1
Q

Amphotericin B

Administration

A

IV only

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2
Q

Amphotericin B

MOA

A

Binds ergosterol in fungal membrane, forming a pore in the membrane and allowing essential small solutes to efflux.
Fungicidal

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3
Q

Amphotericin B

Spectrum

A

Broadest of all the antifungal agents

Effective against all fungi except Candida lusitaniae and Pseudallescheria boydii

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4
Q

Amphotericin B

Clinical Use

A

Reserved for significant toxicities, life threatening fungal infections (immunosuppres pts, cryptococcal meningitis, invasive Aspergillus)

DOC for Zygomycosis/mucormycosis

Only antifungal agent approved for use in pregnancy or breastfeeding women

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5
Q

Amphotericin B

Adverse Effects

A

Infusion related –> fever, chills, muscle spasm, vomiting, HA, hypotension

Cumulative Tox –>
Nephrotoxicity (vasoconstriction causing low renal perfusion; also causes renal tubule injury)
Hepatotoxicity
Anemia (less EPO)

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6
Q

Flucytosine

Spectrum

A

Very narrow

Very effective against Cryptococcal meningitis

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7
Q

Flucytosine

MOA

A

Enters fungal cell through pores in membrane. Gets converted to 5-fluorouracil intracellularly.

Leads to RNA synthesis inhibition and inhibition of thymidylate synthesis (DNA synthesis inhibition)

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8
Q

Flucytosine

Clinical Use

A

Frequently used with amphotericin B for treatment of Cryptococcal meningitis

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9
Q

Flucytosine

Adverse Effects

A

GI symptoms (nausea, vomiting, diarrhea)

Bone marrow toxicity –> anemia, leukopenia, thrombocytopenia

Teratogen - do NOT use in pregnancy

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10
Q

What is the only antifungal agent that may be administered in pregnant women?

A

Amphotericin B

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11
Q

List the drugs in the Azole class of antifungals. Which is the prototype? What are their general spectrums of activity?

A

Ketoconazole (prototype)

FIVP
Fluconazole (most narrow spectrum)
Itraconazole
Voriconazole
Posaconazole (most broad spectrum)
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12
Q

Azoles

MOA

A

Block 12-alpha-sterol demethylase enzyme involved in ergosterol formation

Less ergosterol synthesis impairs the fungal membrane function and increases permeability
Leads to loss of fungal plasma membrane proteins

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13
Q

What are some common adverse effects of all Azole drugs?

A

GI distress
Hepatotoxicity
Teratogen

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14
Q

What are some common drug-drug interactions of Azoles?

A

They either induce or are substrates of CYP450 enzymes.

NEVER give itraconazole or voriconazole with statins, as they can cause fatal rhabdomyolysis

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15
Q

Ketoconazole

Pharmacokinetics

A
Prototypical azole. 
Poor absorption (requires acidic environment) and poor penetration into CSF and urine
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16
Q

Ketoconazole

Adverse Effects

A

Inhibits CYP450 enzymes in adrenal and gonadal steroid synthesis
Low cortisol and low testosterone

Gynecomastia
Dec. libido
Impoetence

17
Q

Fluconazole

Spectrum and Pharmacokinetics

A

Very narrow spectrum (used for Cryptococcal meningitis)

Great CSF penetration
Good oral bioavailability

18
Q

Fluconazole

Adverse effects

A

Nausea
HA
Skin rash
GI upset

19
Q

Itraconazole

Spectrum and Pharmacokinetics

A

Poor CSF, urine, eye penetration

Strong CYP3A4 inhibitor

20
Q

Itraconazole

Clinical Use

A

Broader spectrum than fluconazole

Used for oral dermatophytes
Candida

21
Q

Itraconazole

Adverse Effects

A

GI distress
Hepatotoxicity
Teratogen

Triad: HTN, Hypokalemia, and Peripheral Edema
-Do NOT use in patients with preexisting ventricular dysfunction or CHF

22
Q

Voriconazole

Spectrum

A

Candida
Endemic fungi
Invasive Aspergillus

23
Q

Voriconazole

Adverse Effects

A

Hepatotoxicity, GI distress, Teratogen

Periostitis (bone pain)
Transient vision changes
Photosensitivity/rash

24
Q

Posaconazole

Spectrum

A

Broadest of the azole family

Only azole effective against Mucormycoses/Zygomycosis

25
Posaconazole | Adverse Effects
Hepatotoxicity GI distress Teratogen
26
List the Echinocandins
Capsofungin Micofungin Anidulafungin
27
Echinocandins | MOA
Inhibit B-1,3-D glucan synthase complex, involved in cell wall formation Leads to osmotic instability and cell death
28
Echinocandins | Adverse Effects
Histamine-like effect (skin itching) | Embryotoxic
29
Echinocandins | Clinical Uses
Good activity against Candida and Aspergillus No activity against Cryptococcus or dimorphic fungi
30
Griseofulvin | Clinical Use
Used only for dermatophyte (tinea...) infections
31
Griseofulvin | MOA
Binds fungal microtubules and prevents the mitotic spindle from forming
32
Griseofulvin | Adverse Effects
Inducer of CYP450 enzymes -- may have many drug interactions ``` HA, lethargy, vertigo Urticaria, photosensitivity Hepatotoxicity Leukopenia, neutropenia Teratogen ```
33
Terbinafine | Clinical Use
Used for dermatophytes and Candida albicans High cure rate
34
Terbinafine | MOA
Inhibition of fungal squalene epoxidase. This prevents the conversion fo fungal squalene to ergosterol, thus causing membrane dysfucntion and squalene buildup in cell, leading to cell death
35
Nystatin | Clinical Use
Similar to amphotericin B, but only used in gels, creams, ointments Used for oral candidiasis (swish and swallow)