ID: Antimicrobials #4 - Antifungals Year 2

Question 1

interacts selectively with ergosterol containing

membranes

Answer 1

Amphotericin B

Question 2

fungi produce less ergosterol or have thicker

membranes, so that pores don’t form as easily.

Answer 2

Resistance to Amphotericin B

Question 3

Pharmacokinetics of Amphotericin B

Answer 3

Not well absorbed Oral 
Extensive distribution (very hydrophobic)
Excretion Biliary, and renally with long half life (>15 days)

Question 4

Amphotericin B

Adverse reactions.

Answer 4

Nephrotoxicity with systemic administration

Anemia (75% incidence)

Question 5

Resistance via efflux pumps (mdr); target mutation

Answer 5

Azoles: Imidazole and triazoles

Question 6

Azoles: Imidazole and triazoles MOA

Answer 6

Inhibit ergosterol biosynthesis (lanosterol 14-α demethylase; Erg11) by OXIDATION of a methyl group

Fungistatic/cidal depending on the concentration and bug

Moderately broad spectrum; some activity vs Aspergillus

Question 7

Ketoconazole and Itraconazole kinetics

Answer 7

Absorption. Good orally; antacids hinder absp

Distributed to keratinocytes and vaginal secretions

Hepatic metabolism/ excretion.

Question 8

A broader spectrum triazole

with fewer adverse effects

Answer 8

Itraconazole

Question 9

Ketoconazole S/E

Answer 9

• Inhibits P450
• reversible endocrine abnormalities
• gynecomastia
• GI disturbances
• teratogenic
• rare – hepatitis

Question 10

Completely orally available and distributed well, even to CSF

Answer 10

Fluconazole

Question 11

4th most common nosocomial infection

Answer 11

Candidiasis (yeast)

Question 12

Disseminated infection, especially meningoencephalitis.

Meningitis may lead to permanent neurologic damage.

Answer 12

Cryptococcosis (yeast)

Question 13

“San Joachin Valley fever”

Meningitis - permanent neurologic damage.
Mortality is high in AIDS and lung disease patients

Answer 13

Coccidiomycosis

Question 14

~40 million people have been infected.

Of newly infected people ~10% will have symptoms

Answer 14

Histoplasmosis

Question 15

Permanent lung damage with chronic disease.

Mortality rate is about 5%.

Answer 15

Blastomycosis

Question 16

Drug of choice for Cryptococcal meningitis (AIDS)

Drug of choice for Coccidioidal meningitis

Answer 16

Fluconazole

Question 17

Fluconazole S/E

Answer 17

-GI upset- worsens at high dose
-Rarely hepatic failure
- teratogenic
-inhibits metabolism of rifampin, theophylline,
warfarin, etc.

Question 18

Chitin

Answer 18

Give fungal wall structure

Question 19

Glycosylated proteins on fungal surface

Answer 19

Mannoproteins

Question 20

High toxicity

Nephrotoxicity

Answer 20

Amphotericin B

Nystatin (topical)

Question 21

Drug interactions, rash, fever,

GI- NV

Answer 21

Caspofungin
Micfungin
Anidulafungin

Question 22

GI upset (n/v/d)
 rashes,
enterocolitis
Rev hepatic
disfunction. 
*Bone marrow depression

Answer 22

Flucytosine

RNA and DNA synthesis
fungicidal

Question 23

Headache (10%)
GI upset, rashes
Candida superinfection

Answer 23

Griseofulvin

Microtubules-inhibition of
mitosis fungicidal/static

Question 24

Minor GI upset rash, headache.
Taste disturbances.
Drug interactions.
Contraindicated in pregnancy

Answer 24

Terbinafine

Inhibits squalene oxidase in
ergosterol biosynthesis.

Question 25

RNA and DNA synthesis

fungicidal

Answer 25

Flucytosine

Question 26

Microtubules-inhibition of

mitosis fungicidal/static

Answer 26

Griseofulvin

Question 27

Inhibits squalene oxidase in

ergosterol biosynthesis.

Answer 27

Terbinafine

Question 28

Ergosterol synthesis
inhibition-P450
fungicidal

Answer 28

Azoles
Ketoconazole
Itraconazole
Fluconazole
Voriconazole
Posaconazole

Question 29

Fungal membrane
disruption
fungicidal

Answer 29

Amphotericin B

Nystatin (topical)

Question 30

Invasive aspergillosis – salvage
therapy
Candidiasis
Empirical therapy

Answer 30

Caspofungin
Micfungin
Anidulafungin

*teacher seems to care what works on aspergillus

Question 31

severe fungal infections
blastomycosis, histoplasmosis,
aspergillosis, coccidioidomycosis
in immunocompromised host

Answer 31

Amphotericin B

Nystatin (topical)

Question 32

Dermatophytes: hair skin nails

Systemic/topica

Answer 32

Griseofulvin

Terbinafine

Question 33

Amphotericin B
Nystatin (topical)

SE

Answer 33

High toxicity

Nephrotoxicity

Question 34

Azoles
Ketoconazole
Itraconazole
Fluconazole
Voriconazole
Posaconazole

SE

Answer 34

GI upset (n/v/diarrhea)
 itching
K: Gynecomastia
 inhib of steroid
biosynth. 
P450 interactions. 
Hepatitis-rare
Avoid in pregnancy
P450 drug interactions

Question 35

Caspofungin
Micfungin
Anidulafungin

SE

Answer 35

Drug interactions, rash, fever,

GI- NV

Question 36

Flucytosine

SE

Answer 36

GI upset (n/v/d)
rashes,
enterocolitis
 Rev hepatic dysfunction.
 Bone marrow depression

Question 37

Griseofulvin

SE

Answer 37

Headache (10%)
GI upset
rashes
Candida superinfection

Question 38

Terbinafine

SE

Answer 38

Minor GI upset rash
HA
Taste disturbances.
Drug interactions.
Contraindicated in pregnancy

Question 39

Fluconazole
Voriconazole
Posaconazole

Special Bugs

Answer 39

F: Crypt. and Coccid meningitis
V: Invasive aspergillosis
P: Asp. and Cand. prophylaxis

Question 40

Azoles Bugs

Answer 40

Dermaphytes, yeasts, dimorphic fungi-coccidioides, blastomyces, histoplasm

Question 41

The side effects of azole anti fungals comes from

Answer 41

CYP 450

Question 42

Used in combination for severe infections with amphotericin B
 Orally available and distributes well (to CSF)

Answer 42

Flucytosine

Question 43

Only drug you can use in prego

Answer 43

Ampho B

SCARY!