Exam 4 - Med Chem: Fungal Flashcards Preview

Therapeutics V Spring 2019 (P3 Spring) > Exam 4 - Med Chem: Fungal > Flashcards

Flashcards in Exam 4 - Med Chem: Fungal Deck (70):
1

Fungi Overview:
Diverse Group of _________
_____ cell wall

eukaryotes
rigid

2

what are the two groups of fungi

yeast and mold...

3

Yeast or Mold?
grow as single cell

yeast

4

Yeast or Mold?
Divide asexually

yeast

5

Yeast or Mold?
Divide by budding/fission

yeast (aka asexually)

6

Yeast or Mold?
Filamentous multicellular aggregates (hyphae)

mold

7

Yeast or Mold?
Grow by elongation at their tips

mold

8

Yeast or Mold?
usually separated into cell like units by crosswalls called septa

mold

9

4 characteristics of pathogenic fungi?

can grow at high temperatures
able to reach target tissues...
able to digest and absorb components of human tissues
able to withstand/evade the immune system

10

3 types of fungal infections?

superficial/cutaneous
subcutaneous
systemic/invasive

11

what are examples of superficial/cutaneous fungal infections?

dermatophytosis (ringworm, jock itch, athletes foot)
onchomycosis (nail fungus)

12

what is a dimorphic fungi?

at room temperature it is hyphae (mold)
in humans or media that is 37 celsius it is yeast

13

Histoplasmosis:
is caused by a _______ fungi
comes from what thing in nature?
Spore or non spore forming?

dimorphic endemic
bat/bird droppings
spore

14

Blastomycosis:
caused by a ______ fungi
comes what thing in nature?

dimorphic endemic
rotting wood/soil

15

Candidiasis:
Yeast or mold?
Part of ______ flora
Can be invasive but typically is localized where??

yeast
normal human flora
mucous membrane

16

Risk Factors for Opportunistic fungal infections?

immunosuppression...
burn wounds/trauma
central venous catheters
broad spec abx
diabetes
renal insufficiency requiring dialysis

17

Candida causes what diseases typically?

Cutaneous candidiasis (diaper rash, athletes foot, jock itch)
Esophagitis
Onchomycosis (nail)
Oropharyngeal (thrush)
Vulvovaginitis

18

what women are at risk for vulvovaginitis?

diabetics
pregnant women
women treated with broad spec abx

19

3 disease states of Aspergillosis

opportunistic infections
allergic states..
Toxicoses

20

What drug is apart of the polyene antifungal class?

Amphotericin B

21

Features of Amphotericin B:
Hydro, Lipo, or Amphi -philic?
_____ ring structure
Fungi - cidal or static?
Good or poor bioavailability?

Amphi!
Macrolide structure
cidal
POOR bioavail (use PO only if GI infection, use IV for systemic!)

22

MOA of Amphotericin B

it binds to ergosterol -- leads to leakage of intracellular contents

23

what is egosterol

the main sterol in fungal cell membranes

24

ADEs of Amphotericin B?

V toxic..
Infusion Related rxn -- reduce rate of infusion if issues: fever, chills, muscle spasms, vomiting, headahces and hypotension

Renal damage!!

25

________ is a polyene drug that is similar to amphotericin B but is too toxic for systemic administration/only used for superficial fungal infections

Nystatin

26

what is a way to reduce nephrotoxicity of amphotericin?

put it in a lipid formulation

27

Egosterol Synthesis Pathway:
________ --> ________ --> Egosterol

Squalene --> Lanosterol --> Egosterol

28

what two drugs/classes inhibit egosterol synthesis?

-Azoles and Terbinafine

29

terbinafine inhibits what enzyme?

squalene epoxidase (inhibits egosterol synthesis)

30

Terbinafine:
Fungi -cidal or -static

cidal
(happens bc too much squalene bulidup!)

31

Terbinafine is best for what disease states?

cutaneous/superficial fungal infections:
dermatophytes and onchomycoses

32

Key structure part of -Azoles

5 membered aromatic ring

33

-Azoles:
Fungi -cidal or -static

static

34

-Azoles:
inhibit ergosterol synthesis by inhibiting what enzyme?

14-alpha demethylase
(aka what makes lanosterol into ergosterol)

35

in general: what is the relationship between Azole antifungals and CYP450 enzymes

they are metabolized by the enzymes and they inhibit them

36

Voriconazole:
metabolized by CYP_______ extensively
(genetic polymorphisms will alter levels)

CYP 2 C 19

37

Ketoconazole:
potent ______ of CYP3A4

inhibitor

38

Ketoconazole:
Will increase levels of _______ and _______

CYP3A4 _______ (ex: _______) will reduce ketoconazole levels

triazolam and cyclosporin levels increase

CYP3A4: inducers; ex rifampin

39

Fluconazole:
poor or good bioavailability?
CSF penetration?

good bioavail
and yes CSF

40

which Azole causes visual disturbances in 30% of patients (flickering lights/zigzag lines) AND is teratogenic in animals

Voriconazole

41

Another antifungal drug class is called the Echinocandins: they are what type of molecule?

lipopeptide/ cyclic hexapeptide with fatty side chains

42

what drugs are antifungal lipopeptides/echinocandins

caspofungin
micafungin
anidulafungin

43

MOA of Echinocandins?

inhibit B(1/3) glucan aka a cell wall component by inhibiting Beta(1/3) glucan synthase

44

Echinocandins:
Fungi -cidal or -static

cidal

45

CYP interactions with Echinocandins?

none!!

46

_______ is an antifungal drug that is a pyrimidine analog/antimetabolite

Flucytosine (5-FC)

47

MOA of Flucytosine?

antimetabolite: inhibits thymidylate synthase / interferes with protein synthesis

48

Flucytosine --> _____ --> ______ (which mimics ______)

5-FC --> 5-FU --> F-FdUMP (mimics dUMP)

49

Flucytosine:
Oral or IV?
CSF?
Metabolism?

oral ONLY
good CSF
renally eliminated (renal impairment = toxicity)

50

Griseofulvin:
From a strain of ______
Fungi - cidal or -static
Oral or IV?

penicillium
static
oral ONLY

51

MOA of Griseofulvin?

disrupts fungal microtubules

52

Tavaborole:
MOA?

inhibits leucyl transfer RNA synthetase (LeuRS) aka stops protein synthesis

53

Tavaborole:
what element is essential for its activity

Boron

54

Antifungal drug resistance:
typically transferred between strains - yes or no?

NO!

55

Antifungal drug resistance:
main acquired resistance seen to polyenes?

reduced egosterol content in membrane

56

Antifungal drug resistance:
main acquired resistance to Flucytosine

cytosine deaminase or UPRT (cytosine permease)

57

Antifungal drug resistance:
Common Azole acquired resistance mechanisms?

target site alteration
Efflux pumps
target enzyme upregulation
Development of bypass pathways

58

Antifungal Toxicities:
what drug(s) cause photopsia

voricaonzole

59

Antifungal Toxicities:
what drug(s) cause renal toxicity

amphotericin B
Cyclodextrins (IV voriconazole)

60

Antifungal Toxicities:
what drug(s) cause bone marrow suppresion

5-FC
Amphotericin B (anemia bc decrease EPO production)

61

Antifungal Toxicities:
what drug(s) cause GI toxicity?

Itraconazole
Posaconazole
5-FC

62

Antifungal Toxicities:
what drug(s) cause QT prolongation

all Azoles

63

Antifungal Toxicities:
what drug(s) case cardiomyopathy

intraconzaole

64

Antifungal Toxicities:
what drug(s) cause infusion reactions

amphotericin B
Echinocandins

65

Antifungal Toxicities:
what drug(s) cause hepatic toxicity

all azoles
Amphotericin B
5-FC
Echinocandins

66

Antifungal Toxicities:
what drug(s) cause CNS issues

Voriconazle

67

Antifungal Toxicities:
what drug(s) can cause a rash

all antifungal rxns

68

Antifungal Toxicities:
what drug(s) can cause photosensitivity/malignancy

voriconazole

69

Antifungals and Pregnancy:
what antifungals are full on contraindicated?

voriconazole
flucytosine
griesofulvin

70

Antifungals and Pregnancy:
what antifungals should be avoided in pregnant women - ESPECIALLY in 1st trimester bc birth defects/miscarriage risk

Fluconazole (except single 150 mg dose not a problem tho)
Itraconazole
Posaconazole
Isavuconazole