Lecture #4 - Anti Fungals

Question 1

Amphoterecin B

Indications

Answer 1

Broad Spectrum- All life-threatening mycotic infections

Candida, Cryptococcus Histoplasma, Blastomyces, Coccidioides,
Aspergilus, Fusarium, Mucor
     Not C. lusitaniae
     Not Pseudallerischeri boydii
 TOC Mucormycosis

Question 2

Amphoterecin B

MOA

Adverse

Answer 2

Binds to ergosterol in fungal plasma
membrane and forms pores causing
increased membrane permeability
and loss of cytoplasmic K+

Infusion Related (ampho-terrible)

• fever, chills, spasm, vomiting
• Cumulative = Nephrotoxicity /Hepatoxocity/ Anemia

Avoid using other nephrotoxic agents like AG’s & Cyclosporine

Question 3

Name that drug:

Only Antifungal drug approved
for use in pregnancy

Used for initial induction therapy
followed by consolidation therapy
with less toxic Azole

Answer 3

Amphoterecin B

Question 4

Flucytosine

Indications
MOA

Answer 4

Narrow spectrum
Cryptococcus neoformans
-especially cryptococcal meningitis
Candida sp
Agents of chromblastomycosis

Taken up via cytosine permease and
converted by fungal-specific cytosine
deaminase to 5-FU analogs that inhibit
thymidylate synthase and RNA synthesis

Question 5

Flucytosine

Adverse

CSF penetration?

Answer 5

GI (frequent) nausea/vomiting/diarrhea
BM toxicity- more common in those
with blood disorder
Tetratogenic

 Good CSF penetration
 Used in combination with Amph B
 Frequent resistance
 Dosage adjustment in Renal failure
 Not to be used in pregnancy

Question 6

Echinocanins

name the 3

Answer 6

Caspofungin
Micafungin
Anidulafungin

Question 7

Echinocanins

Indications

MOA

Answer 7

Candida
inc C. glabrata/C. kruseii
Treatment of invasive Candida
Treatment of Invasive Aspergillus

No activity for Cryptococcus or
Dimorphic fungi

MOA:
 Acts on fungal cell wall
 Inhibits alpha(1-3) D glucan synthase 
  complex
   - Impairs membrane structure
     - Increases osmotic instability

Question 8

Echinocanins

Adverse

Misc (CSF?)

Answer 8

adverse:
Well tolerated
Histamine-like effect with
Rapid infusion

Misc:
Poor CSF penetration
Not to be used in pregnancy

Question 9

Griseofulvin

Clinical

MOA

Answer 9

Treatment of mycotic
infections of Skin, nail and hair
due to dermatophytes

MOA: Fungistatic
 Binds fungal microtubules and 
inhibits mitotic spindle
 Accumulates in newly differentiated
Keratin producing cells preventing 
fungal growth

Question 10

Griseofulvin

Adverse

Misc

Answer 10

Many adverse effects

• Headache, lethargy, vertigo, blurred vision
• Urticuria, photosensitivity, rash
• Hepatotoxicity
• Leukopenia, neutropenia, monocytosis
• Fetal abnormalities

Very insoluble
Strong CYP450 inducer
- many drug interactions
Not to be used during pregnancy

Question 11

Terbinafine

Indications

MOA

Answer 11

Treatment of onchomycosis
and superficial skin infections
Candida Albicans
Dermatophytes

Treatment of tinea captis,
tinea carpis, tinea cruis & tinea pedis

MOA:
Inhibits fungal squalene epoxidase
resulting in formation of toxic products
and inhibition of ergosterol synthesis

Question 12

Terbinafine

Adverse

Misc

Answer 12

adverse:
 Well tolerated
 Adverse effects rare
      Hepatotoxicity
      neutropenia
      Stevens Johnson 

Misc:
Long half life (> 200 hrs)
Not recommended in
hepatic/renal insufficiency

Question 13

TOC for cryptococcal meningitis

Answer 13

Fluconazole

Question 14

Name that drug:
Hypertension/Hypokalemia/
Peripheral edema

Contraindicated in
Ventricular Dysfunction/CHF

Answer 14

Itraconazole

Question 15

Drug:

TOC: Dermatophytes
TOC: Onchomycosis

Answer 15

Itraconazole

(NOT FOR
Cryptococcal meningitis)

Question 16

Adverse effect:

Photosensitivity/
Rash/Periostitis/
Visual changes/
Hallucination/
Seizures

Answer 16

Voriconazole

Question 17

TOC:
Invasive
Apsergillus/Fusarium

DRUG?

Answer 17

Voriconazole

Question 18

Treatment of invasive
Fungal infections
Candida/Aspergillus

Answer 18

Posaconazole

Question 19

Salvage therapy

for mucormycosis?

Answer 19

Posaconazole

Question 20

Which azoles penetrate CSF?

Answer 20

Fluconazole

Voriconazole

Question 21

Which azole needs renal dose adjustment

Answer 21

Fluconazole

Question 22

Which azole treats the following:

Dermatophytes

Candida sp

Cryptococcus

Coccidioides
Histoplasma
Blastomyces

Answer 22

Ketoconazole

• many drug interactions

Question 23

MOA of all azaleas

Answer 23

Inhibition of 14alpha-sterol demethylase involved in synthesis of ergosterol

(fungal membrane)

Question 24

Azole Drug for the following:

Dermatophytes

Candida sp
C. Glabrata (+/-);C.krusei (-)

Cryptococcus

Coccidioides
Histoplasma (+/-)
Blastomyces (+/-)

Answer 24

Fluconazole

Question 25

Azole for the following:

Dermatophytes

Candida sp
C. glabrata (+/-)/C.krusei (+/-)

Cryptococcus

Coccidioides
Histoplasma
Blastomyces

Pseudoallerischeri
Boydii/Scedosporium (+/-)

Aspergillus
(+)

Answer 25

Itraconazole

Question 26

Azole for the following:

Dermatophytes

Candida sp
Inc C. glabrata/C.krusei

Cryptococcus

Coccidioides
Histoplasma
Blastomyces

Pseudoallerischeri
Boydii/Scedosporium

Aspergillus
(+++)

Fusarium

Answer 26

Voraconazole

Question 27

State the order of azoles from narrow to broad spectrum (5)

Answer 27

1. Ketoconazole
2. Fluconazole
3. Itraconazole
4. Voriconazole
5. Posaconazole (treats mucor!)

Question 28

Azole for the following:

Dermatophytes

Candida sp
Inc C. glabrata/C.kruseii

Cryptococcus

Coccidioides
Histoplasma
Blastomyces

Pseudoallerischeri
Boydii/Scedosporium

Aspergillus
(+++)

Fusarium!

MUCOR!!! (KEY)

Answer 28

Posaconazole

Question 29

______ can be used to treat Coccidioidmycosis

and is DOC for Disseminated disease/meningitis

Answer 29

Fluconazole

Question 30

Which drug is NOT recommended for candiasis due to poor CNS penetration

Answer 30

NOT AN ECHINOCANDIN- poor CNS penetration

Question 31

Note: Topical antifungals are ineffective for what 2 things?

Answer 31

1. Tinea captitis

2. Onchomycosis

Question 32

Nystatin is not active against ____

Answer 32

Dermatophytes

Tinea pedis
Tinea corporis
Tinea cruris

Question 33

Which drug is

1. broadest of anti fungals
2. Most adverse effects

Which 2 fungi is it not active against tho?

Answer 33

Amphoterecin B

(active for all except C. lusitaniae & Pseudallescheria boydii )

Used as an initial induction therapy (typically 4 weeks) to reduce
fungal burden, then replaced by newer, less toxic AZOLE drugs for
consolidation therapy and prevention of relapse

Question 34

Amphoterecin is the DOC for what?

Answer 34

Treatment of choice for Zygomycosis/mucormycosis

Question 35

only antifungal agent that is approved for use in

pregnant/breastfeeding women: ____

Answer 35

Amphoterecin B

B is for babies

Question 36

Azores are Major inhibitors and substrates of _____

Answer 36

CYP450

• require skeptic enzyme monitoring

Question 37

What two drugs should never be given to a patient taking statins due to increased rhabdo?

Answer 37

Itraconazole and Voriconazole should NEVER be given to a patient
taking STATINs due to increased risk of developing fatal Rhabdomyolysis

Question 38

Griseofulvin only has activity against what?

Static or cidal?

Answer 38

DERMATOPHYTES

• microsporum, epidermophyton, trichophyton

fungistatic :
-binds to fungal microtubules, preventing the
formation of the mitotic spindle and inhibiting fungal mitosis

Treatment needs to be continued until affected tissue is completely replaced
by by new tissue

Question 39

Terbinafine:

MOA

ACTIVITY

Answer 39

MOA: Inhibition of fungal SQUALENE EPOXIDASE

• increase squalene (toxic)
• impaired fungal membrane fx.

Specifically deposits in the skin, nails, hair and fat

Activity:

1. dermatophytes
2. candida albicans

Question 40

DRUG that is:

1. Too toxic for IV
2. Not active for dermatophytes

Answer 40

Nystatin

Question 41

Which drugs should be adjusted for renal insufficiency? (2)

Which drug is not advised for renal/hepatic insufficiency?

Answer 41

1. FLucytosine
2. Fluconazole
   (voriconazole does NOT need to be adjusted)
3. Terbanifine