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Clinical Pathology - > CP4 - Introduction to Antifungal agents > Flashcards

CP4 - Introduction to Antifungal agents Flashcards

1
Q

what are the 3 classes of pathogenic fungi?

A
  1. filamentous fungi
  2. moulds/yeasts
  3. dimorphic - can exist in both forms depending on the conditions that they are exposed to
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2
Q

which type of fungi can cause disease?

A

microfungi

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3
Q

name some targets of antifungals

A
  1. DNA synthesis
  2. mitosis
  3. cell membrane
  4. protein synthesis
  5. cell wall
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4
Q

what is the main component of the cell membrane in humans and fungi?

A

humans - cholesterol

fungi - ergosterol

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5
Q

what is the main component of a fungal cell wall?

A

B-1,3-glucan

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6
Q

what is the function of ergosterol in fungal PM?

A
  1. regulates membrane permeability

2. important for the normal growth and function of the fungal cell wall

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7
Q

which 2 stages of ergosterol synthesis are attacked by drugs?

A

squalene –> lanosterole via squalene epoxidase

lanosterol –> ergosterol via lanosterol 14alpha demethylase

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8
Q

what are beta-1,3-glucans?

A
  1. large polymers of UDP-glucose
  2. form a large component of the fungus and its cell wall
  3. synthesised by B-1,3-glucan synthase
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9
Q

what are the classes of antifungals?

A
  1. polyenes
  2. Allylamines
  3. azaleas
  4. echinocandins
  5. others
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10
Q

name some examples of polyenes

A

amphotericin B

Nystatin

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11
Q

what is the mode of action of polyenes?

A
  1. associated with ergosterol
  2. form pore-like aggregations in the PM
  3. membrane loses its integrity and K+ leaks out of the cell, causing it to die
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12
Q

what is the spectrum of activity of amphotericin B?

A

most fungi of medical importance

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13
Q

what is the clinical use of amphotericin B?

A

Aspergillus candida
Cryptococcus
used for serious or systemic infections
parenteral administration

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14
Q

what are the adverse effects of polyenes?

A
  1. allergic reactions
  2. nephrotoxicity, due to a potential spillover effect on human membranes, usually to a lesser extent and reversible, but not used in patients with existing nephrotoxicity
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15
Q

what is the clinical use of nystatin?

A

only used for superficial infections, because it is not absorbed orally and is too toxic for systemic use.
oral.vaginal candidiasis
no systemic side effects

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16
Q

name an example of Allylamines

A

terbinafine

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17
Q

what is the mode of action of allylamines?

A

they stop ergosterol synthesis by inhibiting squalene epoxidase, therefore PM cannot form properly.

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18
Q

what is the spectrum of activity go allylamines?

A

broad spectrum in vitro

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19
Q

what is the clinical use of allylamines?

A 
dermatophyte infections (superficial/topical use)
1. athlete's foot
2. tinea corporis
3. cruris
systemic
1. scalp ringworm
2. onychomycosis
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20
Q

what are the adverse effects of allylamines?

A

liver toxicity, jaundice, hepatits, but this is rarely fatal

21
Q

what are azoles?

A

synthetic compounds containing a 5 membered azalea ring

22
Q

what are the 2 types of azoles?

A
  1. imidazole - 2 N atoms

2. triazoles - 3 N atoms

23
Q

gives examples of imidazoles and triazoles

A
  1. imidazoles- clotrimazole, ketoconazole

2. triazoles - fluconazole, itraconzole, voriconazole

24
Q

what is the mode of action of azoles?

A

inhibit ergosterol synthesis, leading to a build-up of monomers. fungus loses its viability because the PM cannot function

25
Q

what is the spectrum of activity azoles?

A

together, azaleas cover all fungi. fluconazole is the only azole that is ineffective against aspergillus

26
Q

what is the clinical use of imidazoles?

A

superficial infections -clotrimazole for candidiasis

27
Q

what are the adverse effects of imidazoles?

A

toxic, rarely used systemically, they can cause life threatening hepatitis

28
Q

what is the clinical use of triazoles?

A

systemic infections - aspergillosis, candidiasis (fluconazole), serous fungal infections

29
Q

what are the adverse effects of triazoles?

A

less toxic, therefore systemic use is more common. can cause mild liver enzyme abnormalities

30
Q

name some examples of echinocandins

A

anidulafungin
caspofungin
micafungin

31
Q

what is the mode of action of echinocandins

A

inhibit B-1,3-glucan synthase, which is the main structural component of the cell wall. leads to a severely abnormal cell wall

32
Q

what is the spectrum of actions of echinocandins?

A

aspergillus and candida, misses certain moulds and cryptococcus

33
Q

what is the clinical use of echinocandins?

A

systemic infections, only available as IV

34
Q

what are the adverse effects of echinocandins?

A 
minimal. skin rash
nausea
vomiting
headache
this is due to a lack of B-1,3-glucan analogue in humans
35
Q

what is 5-flurocytosine (5-FC)

A

a synthetic analogue of cytosine, a pyrimidine nucleoside

36
Q

what is the mode of action of 5-fluorocytosine?

A

inhibits RNA/protein synthesis and DNA synthesis. it is selectively toxic because entry into the cell required fungal cytosine permease

37
Q

what is the spectrum of activity of 5-fluorocytosine?

A

yeasts only, candida and cryptococcus

38
Q

what is the clinical use of 5-fluorocytosine?

A

cryptococcal meningitis, in combination with Amphotericin B (only indication)

39
Q

what is an adverse effect of 5-fluorocytosine?

A

can penetrate into human cells, but to a smaller extent. could cause bone marrow suppression

40
Q

what is the mode of action of griseofulvin?

A

inhibits fungal mitosis

41
Q

what is the spectrum of activity of griseofulvin?

A

dermatophytes

42
Q

what is the clinical use of griseofulvin?

A

infections in children requiring systemic treatment, eg. scale infections

43
Q

what are the adverse effects of griseofulvin?

A

minimal

44
Q

what is a general adverse effect of azoles?

A

hepatotoxicity

45
Q

what are the drug interactions of azoles?

A

inhibit cytochrome p450 enzyme, as a result,the concentration of all drugs metabolised by this enzyme increases

46
Q

which fungi are fluconazole, itra/voriconazole and posa/isavuconazole effective against?

A
  1. yeasts only
  2. yeasts and aspergillus
  3. yeasts, aspergillus and mucoraceous moulds
47
Q

why is therapeutic monitoring of drugs necessary?

A
  1. to minimise toxicity

2. to maximise efficacy

48
Q

which antifungals require TDM?

A
  1. intraconazole
  2. 5-flurocytosine
  3. voriconazole

Clinical Pathology - (15 decks)

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