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Infect & Immune 2 AW, DJT & ISB > ISB L1 Antifungal Agents Introduction > Flashcards

ISB L1 Antifungal Agents Introduction Flashcards

0
Q

Where do fungi grow?

A

Dark and damp

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1
Q

Are fungi oportunistic of obligate?

A

Most are oportunistic

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2
Q

Your drug metabolism is influenced by….

A

The organisms you share your body with, you have more catering than mammalian cells.

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3
Q

Who is more susceptible to fungal infections

A

Immunocompromised patients - HIV/AIDs

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4
Q

When is taking. One thousand bottles of Yakut useful

A

Only when you’re ill

E.g. Postoperative is useful to recovering pt

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5
Q

5 patient groups at risk of fungal infection

A 
HIV
Transplant patients
Those undergoing chemotherapy
Pt treated wi powerful antibiotics
Those with in dwelling catheters
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6
Q

Two categories of superficial fungal infections

A

True Dermatophytes

Candida

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7
Q

Dermatophytes obtain nutrients from….

A

Keratinised material (hair, skin,nails)

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8
Q

Name three Dermatophytes

A

Trichophyton spp
Epidermophyton spp
Microsporum spp

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9
Q

Dermatophyte spores give rise to ….

A

Tineas

e.g. Athletes foot and ring worm

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10
Q

What organism is responsible for thrust

A

C. Albacans

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11
Q

Superficial candida infection can lead on to…

A

Systemic infection

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12
Q

Best antifungals of the last 20 years are …

A

Azoles

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13
Q

Compare clotrimazole and tioconazole treatment for vaginal thrush?

A

Clotrimazole is as effective as tioconazole,

But fewer clotrimazole pt experienced local side effects.

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14
Q

How common is vaginal thrush?

A

75% of women have an episode in their lives.

5% have recurrent

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15
Q

Factors associated increased risk of vaginal thrush (6)

A 
Diabetes
Pregnancy
Oral contraceptive use
Immunosuppressive therapy
Use if intravaginal sponges or devices
Repeated courses of antibacterial agents
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16
Q

Do most women experiencing repeated episodes of thrush have risk factors such as diabetes?

A

No

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17
Q

Do we tend to culture fungal infecetions?

A

No, we tend to guess.

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18
Q

Complete the course of antibiotics but for Antifungal agents….

A

We usually have just one dose

Shows our antifungals are much better than our antibiotics

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19
Q

Before treatment for vaginal thrush with tioconazole ointment (single dose regime) diagnosis should be confirmed by (2)

A
  • demonstrating yeast or pseudohyphae with microscopy of discharge
  • culture and ruling out other pathogens
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20
Q

What strength tioconazole ointment is used for thrush self medication?

A

6.5%

Suitable in women who are not pregnant, previously diagnosed

21
Q

How many nitrogens in the ring:
Imidazole
Triazole

A

Imidazole - 2

Triazole - 3

22
Q

What are the drug classes of choice for vaginal candida?

A

Imidazole
Triazole
( intravaginal azole antifungal first line)

23
Q

Can intravaginal nyastin be used for treatment for vaginal thrush?

A

Yes but generally less effective than azoles

24
Q

Why do we chose topical treatment over oral as first line for thrush?

A

Fewer side effects

25
Q

What is complicated thrush defined as?

A

Recurrent or severe infections in women who have an underlying medical condition (pregnancy, immunosuppression)

26
Q

Treatment for severe thrush?

A

7-14 days therapy with intravaginal or oral azoles

27
Q

How is amphotericin Antifungal delivered?

A

As a lysosome as it is hard to dissolve

28
Q

What is the ‘Antifungal of choice’?

A

Voriconazole (superior to amphotericin)

29
Q

Treatment for invasive aspergillosis (heart and lungs) and unresponsive treatments?

A

Caspofungin

30
Q

Is fungal resistance a problem?

A

Not really - there is some but not as much as bacterial

31
Q

Fungus that is resisting?

What sort of resistance?

A

Candida - CaMdr1p is a Major Facilitator Superfamily (MFS) Antifungal efflux transporter protein.

32
Q

CaMdr1p has the capacity to…

A

Extrude drug substrates

33
Q

CaMdr1p has ….. TM regions.

CaMdr1p is a putative anti0orter with an ‘………….’ in TM5 called….,

A

12
Antiporter motif
Motif C

34
Q

CaMdr1p drug extrusion is dependent on…. (3)

A

pH
Energy inhibitors
Displayed substrate specificity

35
Q

How do we know that motif c is specifically highlighted in transport

A

Shown by Ala scan by site directed mutagenesis

36
Q

CaMdr1p mutation is highly conserved ….

A

In all functionally related subgroups of bacteria and plants

37
Q

Is CaMdr1p symetrical?

A

No - putative helical wheel projection shows clustering of residues on one side

38
Q

Ala scan of CaMdr1p showed …. Key residues.

How does Ala scan work?

A

4 key Gly residues.

Site specific mutations - replace each one with Ala

39
Q

Three principle mechanisms of candida resistance:

A
  1. Failure of drug accumulation
  2. Alterations to azole target protein Erg11p
  3. Up regulation of ERG11 gene
40
Q

How does the candida achieve failure of drug accumulation?

3 e.g.

A

Mediated by extrusion pump proteins
e.g. Cdr1p and Cdr2p (belonging to the ATP binding cassette)
and
CaMdr1p (belonging to the MFS)

41
Q

What is a particularly neat way candida get resistant?

A

Up regulation of the ERG11 gene - so there is just physically more copies of ERG11 gene

(ERG11 is the azole target protein, so there is just physically more copies so it doesn’t matter that some are bound to the drug - still a healthy fungus)

42
Q

Cdr1p and Cdr2p exhibit properties of ABC transposter, i.e. …..

A

ATP Binding Cassette

  • contains two hydrophobic TM domains (each wi six regions to confer substrate specificity)
  • and two cytoplasm localised nucleotide binding domains
43
Q

What are the substrates of Cdr1p and Cdr2p?

A

They vary enormously.

Includes structurally unrelated compound such as azoles, lipids and steroids

44
Q

What do we know about CaMdr1p?

A

Not a lot - it is a MFS (major facilitator superfamily) multi drug transporters

45
Q

What is the MFS

A 
Major facilitator superfamily – consist of membrane transport proteins (form bacteria to higher level eukaryotes) involved in:
Symport
Antiport
Uniport 
Of various substrates
46
Q

Name a major cluster of the MFS super family

A

Proton motif force (PMF) dependant drug efflux protein.

47
Q

Bacterial MFS and drug transporters are ….

A

Antiporters

48
Q

MFS family proteins share greater similarity between … Than …..

A

Greater similarity between the n terminal half than the c terminal half (the later. Half is responsible for substrate recognition).

49
Q

Additionally MFS drug antiporter proteins posses many others conserved residues.
Motifs A and B are …..
Motif C is ….

A

Motifs A and B are ….. Conserved thought out the MFS

Motif C is …. conserved only in 12 and 14 TMS subfamilies

Infect & Immune 2 AW, DJT & ISB (9 decks)

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