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Infectious Disease II (P3 Spring) > Exam #4: Antifungal Agents- Part 2 (Moniri) > Flashcards

Exam #4: Antifungal Agents- Part 2 (Moniri) Flashcards

1
Q

______ is an inhibitor of the enzyme SQUALENE EPOXIDASE

A

lamisil (terbenafine)

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2
Q

What happens when you inhibit squalene epoxidase?

A
  • NO formation of squalene epoxide, so NO formation of ERGOSTEROL in the end
  • BUILD UP of squalene precursor
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3
Q

T/F The cell wall of fungi purpose is to provide rigidity and structural support

A

FALSE: only really for the attachment of the glycoproteins

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4
Q

T/F SQUALENE is toxic to fungal cells

A

TRUE

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5
Q

inhibition of ________ is the target of -AZOLE antifungals

A

CYP 450 14-alpha demethylase

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6
Q

What happens when you inhibit CYP 450 14-alpha demethylase?

A
  • NO formation of ergosterol

- Build up of precursor lanosterol (much more fluid vs. ergosterol)

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7
Q

What happens when there is no ERGOSTEROL in the fungi cell wall?

A

the cell wall is susceptible to leaking–> lead to bursting

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8
Q

Describe the structure Amphoteracin B

A
  • POLYENE (double bonds)
  • has HYDROPHILIC (top) and LIPOPHILIC (bottom) regions
  • Amphoteric: acidic AND basic groups
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9
Q

T/F Conjugation is directly related to antifungal activity and human toxicity

A

TRUE

7 C=C is optimal
If you remove double bond–> LOSE antifungal activity AND cause MORE toxicity

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10
Q

POLYENE MEMBRANE DISRUPTER:

Where does AMPHOTEROCIN B bind? What does this cause to happen?

A

directly to the ergosterol (lipophilic region

hydrophilic regions come together and form a PORE–> leading to leaking of K and H20

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11
Q

POLYENE MEMBRANE DISRUPTER:

How can toxicity (LIVER and KIDNEY) occur from Amphoterocin B?

A

can SEQUESTER CHOLESTEROL from human membranes

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12
Q

POLYENE MEMBRANE DISRUPTER:

Amphoteracin B has an _____ spectrum of activity. What does it cover?

A

excellent

yeast
mold
thermally dimorphic fungi

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13
Q

POLYENE MEMBRANE DISRUPTER:

Describe the structure of Nystain

A

-sim to Ampho except ONE less double bond= less antifungal activity–> more TOXIC (highly toxic if systemically administer)

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14
Q

POLYENE MEMBRANE DISRUPTER:

Nystatin is ONLY effective against

A

candida sp (Candidiasis)

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15
Q

POLYENE MEMBRANE DISRUPTER:

Why can Nystatin used for oral thrush be swish AND swallowed?

A

because its too large to cross into systemic circulation

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16
Q

POLYENE MEMBRANE DISRUPTER:

If _________ is in magic mouth rinse NEED to expectorant b/c it will make you sleepy

A

diphenhydramine

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17
Q

All -AZOLES contain either: (2)

A

imidazole OR triazone

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18
Q

CYP 450 14 alpha demethylase is _____ dependent. What attaches to this part of the enzyme?

A

heme

the imidiazole OR triazone

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19
Q

When the imidiazole OR triazone binds to the heme in CYP 450 14-alpha demethylase this causes what to happen?

A
  • the active site is sterically blocked by the AZOLE so lanesterol CAN NOT bind
  • the heme is “tied up” which the enzyme is dependent on
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20
Q

T/F Mammals DO NOT express CYP 450 14 alpha demethylase found in fungal cells

A

FALSE: THEY DO and its used for cholesterol biosynthesis

21
Q

Why don’t -AZOLES inhibit mammalian CYP 450 14 alpha demethylase and lead to the accumulation of 14-sterols in mammal cells?

A

b/c the affinity of the drugs for the fungal enzyme is MUCH better than the human enzyme

22
Q

AZOLES also have good affinity for other human CYP enzymes such as_______. They are EXTENSIVELY and RAPIDLY DEGRADED BY 1st pass metabolism

A

CYP 3A4

23
Q

-AZOLES have a drug interaction with _____ and _____ due to the competition for CYP 3A4

A
  • statin

- BZ

24
Q

AZOLES:

_______ is a metabolized ALOT by CYP 450. Describe an example

A

ketoconazole

ketoconazole + triazolam (sedative)= 22x increase in AUC—> patient is still drowsy !!

25
Q

-AZOLES can be used as pharmacologic booster for ______

A

cyclosporine

26
Q

What is the primary MOA of AZOLE resistance?

A

mutation in the gene encoding for CYP 450 14 alpha methylase

27
Q

AZOLE Resistance

You can select for mutations by changing the dose. Would this mutation inhibit lanosterol?

A

NO

28
Q

__________ is IMIDAZOLE based
-covers Candida sp., Tinea, Thermally Dimorphic Agents, and __________.

Poor efficacy in (2)

A

Ketoconazole

Pityrosporum ovale (dandruff)

immunosuppressed pts; meningitis

29
Q

Itraconazole effects CYP 450 metabolism to a less degree than Ketoconazole b/c

A

the imidazole is replaced by A TRIAZOLE

30
Q

What are the DOC for Itraconazole in pts w/ NON-MENINGEAL infections

A

Oral Capsules

31
Q

Itraconazole capsules COVER: _______

Solution COVER:_______

A

capsules (require normal stomach acidity): TDM, aspergillus, tinea

solution:candidiasis

32
Q

Gastric Acid suppression will ______ the plasma concentration of itraconazole CAPSULES

A

decrease

33
Q

Posaconazole is similar to Itraconazole except…. (3)

A
  • stomach acidity does not matter
  • covers Aspergillus and CA in IMMUNOCOMPROMISED
  • effective for mucormycosis
34
Q

What is the main difference between Fluconazole vs. other -azoles? (3)

A
  • rapid and almost complete absorption from GI
  • readily crosses the BBB
  • metabolized by CYP 450 2C9 and 2C19
35
Q

Fluconazole is a major cause of _______ resistance

A

CANDIDA
(C. parapsilosis and C.glabrata)

3-day monistat is better than oral fluconazole in the long run

36
Q

Fluconazole does NOT have coverage against?

A

Aspergillus sp

37
Q

Difference between Voriconazole?

A

has activity against Aspergillosis

covers esophageal candidiasis, can cross BBB, same metabolism

38
Q

Isacuonazonium sulfate (Cresemba); parent is a prodrug of _______. What is this drug approved for?

A

isavuconazole

invasive aspergillosis and murcormycosis

39
Q

Topical AZOLEs are NOT approved for systemic use. But they have excellent coverage against?

A

tinea

cutaneous candida (i.e. vagina)

40
Q

T/F A Troche (tablet that is sucked on) is absorbed systemically

A

FALSE: this drug is a topical GI agent

covers mouth, pharynx, esophagus

41
Q

The squalene Epoxidase inhibitors (i.e. Terbinafine) are used ONLY for? WHich is the only one available for ORAL USE

A

tinea

terbinafine

42
Q

How is uracil converted to thymine with (cancer anti-metabolite). Why can’t this occur with 5-FluroUracil?

A

via thymidylate synthetase

because there is a fluro group and it can’t be removed

43
Q

T/F thymine is critical to DNA synthesis

A

TRUE

cell undergoes apoptosis when its not there

44
Q

When is Flucytosine useful?

A

when “things” become resistant

45
Q

What enzyme converts Flucytosine to 5-FU?

A

fungal cytosine-deaminase

46
Q

What occurs to 5-FU? (2)

A
  • ribosylation (add ribose sugar)

- triphosphorylation (add phosphate)–> leads it being stuck in DNA chain

47
Q

MOA of Griseofulvin

A

inhibition of fungal spindles

48
Q

_______ ABSOLUTELY decreases the effectiveness of OCs

A

Griseofulvin

49
Q

What is the MOA of Echinocandins?

A

inhibitors or fungal cell wall synthesis by inhibiting BETA-GLUCANS SYNTHASE

Infectious Disease II (P3 Spring) (13 decks)

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