5/05 PHARM Antifungals

Question 1

difference btwn yeast, mold, and dimorphic fungi in terms of cellularity?

Answer 1

Yeast = Unicellular
Mold = Multicellular 
Dimorphic = Yeast at BT, Mold at RT

Question 2

examples of Dimorphic fungi?

Answer 2

Histoplasma, Blastomyces, Coccidioides (indigenous to specific areas and pt populations - ex: HIV)

Question 3

How can you tell on a plate if it is growing yeast or mold?

Answer 3

yeast: Pasty colonies (resembles bacteria)
mold: Surface texture: Cottony/ woolly/ velvety/ granular…

Question 4

Are cell membranes present in mammals? fungi?

Answer 4

cell wall: present only in fungi

cell membrane: present in both, but comprised of different compositions

Question 5

What is the basic composition and function of the cell wall? is it antigenic or non-antigenic?

Answer 5

polysaccharide, proteins, and glycoproteins

fxn: shape, rigidity, strength and protection from osmotic shock

ANTIGENIC

Question 6

What is the basic composition and function of the cell membrane? is it antigenic or non-antigenic?

Answer 6

phospholipids, sterols

fxn: Protects cytoplasm, Rregulates intake/secretion of solutes, facilitates capsule and cell wall synthesis

didn’t say whether it’s antigenc or not, but personally, I don’t think it’s antigenic??

Question 7

How does the cell membrane composition differ btwn fungi and mammals?

Answer 7

Present – contains ergosterol

Present – contains cholesterol

Question 8

knowing the compositional differences btwn the cell wall and cell membrane, what drugs can you use to target each one?

Answer 8

cell wall: Enchinocandins – glycan synthesis inhibitor

cell membrane: Azoles or polyenes to inhibit cell membrane synthesis

Question 9

• Terbinafine MoA? Indications? Side effect?

Answer 9

MoA: blocks squalene epoxidase to prevent lansterol synthesis (for cell membrane)

Indication: Onychomycosis

GI upset, HA, hepatotoxicity, taste disturbance

Question 10

name some ergosterol synthesis inhibitors

Answer 10

fluconazole
itraconazole
voriconazole
posconazole*

Question 11

mechanism of “azoles”?

Answer 11

inhibits ergosterol synthesis by inhibiting the cytochrome p450 enzyme (14-a-demethylase) that converts lanosterol -> ergosterol (for cell membrane)

Question 12

of all the azoles that we learned, which one has the poorest GI absorption/CNS penetration?

Answer 12

itraconazole

Question 13

of all the azoles that we learned, which one has the least drug interactions?

Answer 13

fluconazole

Question 14

indications for fluconazole?

Answer 14

suppression of

• cryptococcal neoforman meningitis in AIDs**
• candida albicans infections in all drug of choice

Question 15

indication for itraconazole?

Answer 15

histoplasma **
blastomyces
coccidioides

Question 16

indication for voriconazole?

Answer 16

aspergillus**

prophylaxis during neutropenia and gvhd

Question 17

indication for posconazole?

Answer 17

mainly zygomycosis (mucormycosis)**
but also great activity against: 
-	candida albicans**
-	cryptococcus**
-	aspergillus**
-	fusarium**

Question 18

general side effects of azoles?

Answer 18

• testosterone synthesis inhibitor
• liver dysfunction/hepatitis (inhibits cytochrome p450)
• increase drug conc. of drugs metabolized by cyp450

Question 19

which azole is commonly associated with gynecomastia?

Answer 19

ketoconazole** and itraconazole (likely due displacement of steroid hormones from serum binding proteins, resulting in a net increasein free E)

Question 20

which azole has a greater likelihood of hepatitis? What ADR also associated with this particular drug?

Answer 20

voriconazole; also associated with visual disturbances

Question 21

name 2 drugs that commonly form membrane pores in fungi. What class of drugs do they fall under?

Answer 21

amphotericin b (deoxycolate or lipid formulations)
nystatin

both fall under the polyene class

Question 22

MoA for amphotericin B?

Answer 22

binds ergosterol (unique to fungi); forms membrane pores that allows leakage of electrolytes and proteins from the cell

“amphoTEARicin tears holes in the fungal membrane”

Question 23

What must you administer with amphotericin B and why?

Answer 23

must give K supplements and Mg supplements because of electrolyte losses that occur as a result of altered renal tubule permeability

Question 24

Why is the liposomal formulation preferred over the deoxycolate formulation of amphotericin B?

Answer 24

liposomal formulation decrease toxicity/adrs, but requires higher doses to achieve the same therapeutic effect

Question 25

Indications for amphotericin B?

Answer 25

``` serious systemic mycoses - cryptococcus - blastomyces - coccidiodes - histoplasma - candida - mucormycosis fungal meningitis (intrathecal) ```

Question 26

ADRs of amphotericin B? What is cool about these particular symptoms?

Answer 26

``` ampho“terrible”: fever, chills/rigors “shake & bake” hypotension nephrotoxicity** anemia (due to decr. EPO) iv phlebitis ``` most of these symptoms can be prevented with prophylactic treatments (ie aspirin, diphenhydramine, hydrocortisone, slow infusion)

Question 27

MoA for nystatin?

Answer 27

same mxn as amphotericin b - tears holes in the membrane

Question 28

how is nystatin administered?

Answer 28

topic administration - too toxic for systemic use!

Question 29

nystatin indications?

Answer 29

“swish and swallow” oral candidiasis diaper rash vaginal candidiasis

Question 30

antifungals that inhibits cell wall synthesis? What class do they fall under?

Answer 30

caspofungin micafungin* anidulafungin* all fall under the echinocandins class

Question 31

MoA for caspofungin?

Answer 31

inhibit cell wall synthesis by inhibiting synthesis of ß1,3-d-glucan

Question 32

Indications for caspofungin?

Answer 32

- invasive aspergillosis (3rd line rx) | - candida resistant to azoles or azole-allergic patients

Question 33

ADR for caspofungin?

Answer 33

``` gi upset flushing (due to histamine release) fever, rash, n/v phlebitis, hepatits ```

Question 34

nucleic acid synthesis inhibitors used as a anti-fungal therapy?

Answer 34

5-flucytosine*

Question 35

MoA of 5-flucytosine?

Answer 35

inhibit DNA/RNA biosynthesis via conversion to 5-FU by cytosine deaminase

Question 36

5-flucytosine is often used in combination with..?

Answer 36

amphotericin b

Question 37

Indications of 5-flucytosine?

Answer 37

systemic fungal infections (cryptococcus meningitis)

Question 38

ADR of 5-flucytosine

Answer 38

bone marrow suppression

Question 39

p450 inhibitors?

Answer 39

``` "SICKFACES.COM Group" sodium valproate isoniazid cimetidine ketoconazole fluconazole alcohol (binge) chloramphenicol erythromycin sulfonamides ciprofloxacin omeprazole metronidazole grapefruit juice ```

Question 40

p450 inducers?

Answer 40

``` CRAP GPS induce me to madness carbemazepines rifampicin alcohol (chronic) phenytoin griseofulvin phenobarbitone sulphonylureas ```