Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Infectious Disease > Duncan Antifungals > Flashcards

Duncan Antifungals Flashcards

1
Q

Polyene Drugs

A

Amphotericin B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Amphotericin B Structural Features

A

Structure similar to membrane phospholipid w/ 7 conjugated double bonds

  1. Hydrophilic “rod”
  2. Hydrophobic “rod”
  3. Polar, negative charged portion (COOH)
  4. Polar, positive charged sugar
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Amphotericin B Formulations

A

Deoxycholate
Lipid Formulations - Abelcet, Ambisome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Amphotericin B Lipid Formulations

A

Decreases nephrotoxicity and allows for higher dosing
Abelcet = ring-like structure
Ambisome = lipsome formulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Amphotericin B MOA

A

Membrane targeting agent (like associates with like) - similar MOA to polymyxin

Initially interacts with LPS, is recruited to fungal membrane, and then is able to interact with lipid bilayer

Hydrophilic, ionic head associates with hydrophilic heads of phopholipids

Hydrophobic rod can insert into nonpolar interior of membrane

Unfavorable insertion of hydrophilic rod into nonpolar interior

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What interaction provides major binding energy for Amphotericin B?

A

Binding interaction between ergosterol and hydrophobic rod of Amphotericin B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Details of MOA of Amphotericin B

A

Forms pores in membrane

However, modified Amphotericin B that cannot form pores in the membrane still has full antifungal activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What part of the Amphotericin B molecule plays an important role in stabilizing the pore?

A

C35 OH

Removing C35 OH abolishes pore formation and only slightly reduces activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Removing _____ abolishes activity of Amphotericin B

A

mycosamine (AmdeB)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Structural modifications made to Amphotericin B molecule to reduce nephrotoxicity

A

Adding urea-based side chains reduce nephrotoxicity and maintain antifungal activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why doesn’t Amphotericin B affect bacteria?

A

Bacterial membranes don’t contain sterols, such as ergosterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Ways to minimize nephrotoxicity of Amphotericin B

A

Administer with CCB, such as diltiazem

Salt loading

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Flucytosine

A

Prodrug - metabolized into 5-fluorouracil (anti-cancer agent)

Should NOT be used as monotherapy - resistance develops quickly

Frequently used in combination with Amphotericin B for synergy - pore formation from Amphotericin B enhances penetration of flucytosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Flucytosine MOA

A

Metabolic antagonist - inhibition of DNA and RNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Enzyme that converts flucytosine → 5-FU

A

Cytosine deaminase (high activity in fungi, low activity in humans)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Imidazole Structure

A

2 nitrogens in 5 atom ring

More toxic than triazoles

Mostly used topically due to systemic toxicities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Imidazole Drugs

A

Miconazole

Clotrimazole

Econazole

Ketoconazole (newer, less toxic imidazole)

18
Q

Triazole Structure

A

3 nitrogens in 5 aton ring

Less toxic than imidazoles

Can be used systemically

19
Q

Triazole Drugs

A

Fluconazole

Itraconazole

Voriconazole

Posaconazole

Isavuconazole

20
Q

Isavuconazole

A

Significantly higher aqueous solubility than other triazoles because of prodrug (isavuconium) form side chain (aminocarboxyl portion) - isavuconium side chain is rapidly removed in plasma by plasma esterases

Cyclodextrin-free solution

21
Q

Azoles MOA

A

Metabolic antagonists

Block biosynthesis of ergosterol

Primarily fungistatic

22
Q

Imidazole MOA

A

Directly interacts with cell membrane → contributes to its toxicity

23
Q

Triazole MOA

A

Inhibit lanosterol demethylase (CYP450) → instead of making ergosterol, pathway makes 14alpha-methyl ergosterol, which packs more loosely in membranes → leaky and unstable membranes

24
Q

Azoles DDIs

A

CYP3A4 - Ketoconazole and Itraconazole

CYP2C9 (Warfarin) - Fluconazole

Systemic imidazoles interact with H2RAs, PPIs, and. antacids

25
Q

Efinaconazole

A

First approved azole for topical treatment of onychomycosis

Has improved activity due to reduced keratin binding (nail-binding), which allows greater penetration to sites of fungi

26
Q

Allylamines Drugs

A

Terbinafine (PO)

Naftiline (topical)

27
Q

Allylamine and Thiocarbamate MOA

A

Block epoxidase step in ergosterol synthesis

28
Q

Griseofulvin MOA

A

Affects microtubules → affects cell division

Can bind to keratin in skin and nails

29
Q

Pentamidine Structure

A

Central sting of 5 CH2s sandwiched between two para-modified phenols

Each phenol has identical amino side chain

30
Q

Pentamidine MOA/Use

A

Alters nucleic acid function

Used for PCP pneumonia as an alternative to Bactrim

31
Q

Polyoxins and Nikkomycins Structure

A

Pyrimidine linked to a peptide

Structural analogue of UDP-N-Acetyl-Glucosamine

32
Q

Polyoxins and Nikkomycins MOA

A

Target cell wall biosynthesis by blocking biosynthesis of chitin

33
Q

Papulacandins and Echinocandins/Pneumocandins MOA

A

Noncompetitive inhibitor of glucan synthase

Work synergistically with Amphotericin B, polyoxins, and nikkomycins

Fungicidal

34
Q

Echinocandin/Pneumocandin Structure

A

Lipopeptide

Cyclic hexapeptide nucleus

35
Q

Glucan Synthase

A

Enzyme made up of multiple subunits: FKS1, FKS2, and Rho1

36
Q

What do echinocandins/pneumocandins bind to?

A

FKS1

37
Q

Echinocandin/Pneumocandin Sensitivity and Resistance

A

Fungi are uniquely sensitive due to the unique use of glucan ploysaccharide in cell wall

Fungi with little to no glucan in cell wall are resistant

Mutations in FKS1 gene cause resistance

38
Q

Limitations of Echinocandins/Pneumocandins

A

Limited oral absorption - IV only

Increasing resistance

39
Q

Ibrexafungerp

A

Newest glucan synthase inhibitor - FDA approved in June 2021 for candidiasis

40
Q

Ibrexafungerp Structure

A

Triterpenoid core

41
Q

Ibrexafungerp Advantages

A

Oral bioavailability

Activity/stability in serum environment

42
Q

Ibrexafungerp MOA

A

Binds to and inhibits FKS1p at a similar site to echinocandins/pneumocandins → fungal cell wall loses structural integrity → fragile cell wall subject to lysis (osmotic pressure)

Sufficiently different from echinocandins/pneumocandins to not be affects by mutations leading to echinocandin/pneumocandin resistance

Infectious Disease (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions