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Clinical Pathology > Core Microbiology - Anti-fungal Agents (5) > Flashcards

Core Microbiology - Anti-fungal Agents (5) Flashcards

1
Q

Fungi classification

A
  1. Moulds/filamentous fungi

2. Yeast

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2
Q

Dimorphic fungi

A

Exist as mould and yeast

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3
Q

Erogsterol

A

In fungal cell membranes, forms clusters within phospholipid bilayer, regulates membrane permeability

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4
Q

Ergosterol biosynthesis

A

Squalene > (Squalene epoxidase) > Lanosterol > (Lanosterol 14a demethylase) > Ergosterol

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5
Q

B-1,3-glucans

A

Large polymers of UDP-glucose, form a fibrous network on inner surface of wall, snythesised by B-1,3-glucan synthase

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6
Q

Antifungal classes

A

Polyenes, Allylamines, Azoles, Echinocandins, others..

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7
Q

Polyenes mode of action

A

Association with ergosterol, forms pore-like molecular aggregates, loss of membrane integrity and leakage of K+, cell death

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8
Q

Examples of Polygenes

A

Amphotericin B and Nystatin

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9
Q

Amphotericin B spectrum of activity

A

Most fungi - Aspergillus, Candida, Cryptococcus (Parenterally)

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10
Q

Amphotericin B adverse effects

A

Allergic reactions, nephrotoxicity (reversible), not completely selective to fungi

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11
Q

Lipid associated Amphotericin B (AmB) different formulations

A

Liposomal AmB (L-AmB), AmB lipid complex (ABLC), AmB colloidal disperson (ABCD)

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12
Q

Lipid associated Amphotericin B (AmB) pros

A

Minimises delivery of AmB to kidney cells (liver, spleen and lymph nodes)

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13
Q

Nystatin

A

Too toxin for systemic use, superficial infections - oral/vaginal candidiasis

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14
Q

Allylamines mode of action

A

Inhibit erogsterol synthesis (Squalene epoxidase)

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15
Q

Allylamines examples

A

Terbinafine

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16
Q

Terbinafine spectrum

A

Broad in vitro

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17
Q

Terbinafine adverse effects

A

Liver toxicity (Jaundice, hepatitis)

18
Q

Allylamines clinical use

A

Dermatophyte infections (superficial)

Topical - athletes foot (tinea pedis), tinea corporis (trunk, legs, arm/skin), tinea cruris (groin)

Systemic - scalp ringworm (tinea capitis), onychomycosis (nail)

19
Q

Azoles

A

5-membered ring

20
Q

Examples

A
  • Imidazoles (2N)

- Triazoles (3N)

21
Q

Azoles mode of action

A

Inhibit ergosterol synthesis (Lanosterol 14a-demethylase)

22
Q

Azoles spectrum

A

Broad - yeasts and filamentous fungi (except Fluconazole/Aspergillus)

23
Q

Imidazoles

A

Toxic, rarely used systemically (ketoconazole)

24
Q

Examples of Imidazoles

A

Clotrimazole (Canesten), Miconazole, Ketoconazole

25
Q

Examples of Triazoles

A

Fluconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole

26
Q

Azoles adverse effects

A

Hepatotoxicity

27
Q

Azoles drug interactions

A

Inhibition of Cytochrome P-450 enzymes - increases concentration of all drugs metabolised by Cy P-450 enzymes

28
Q

Imidazoles clinical use

A

Superficial infections - Candidiasis or dermatophyte infections

29
Q

Triazoles clinical use

A

Systemic - aspergillosis and candidiasis

30
Q

Echinocandins mode of action

A

Inhibition of B-1,3-glucan synthase, construction of severely abnormal cell wall

31
Q

Examples of Echinocandins

A

Andiulafungin, Caspofungin, Micafungin

32
Q

Echinocandins spectrum of activity

A

Aspergillus and Candida (not certain moulds and cryptococcus) - serious as iv

33
Q

Echinocandins adverse effects

A

Skin rash, nausea, vomiting, headache, diarrhoea

34
Q

5-fluorocytosine (5-FC)

A

Synthetic analogue of cytosine (pyrimidine nucleoside), developed as anti-cancer drug

35
Q

5-FC mode of action

A

Entry into cells requires fungal cytosine permeases, converted to 5-fluorouracil and 5-fluorodeoxyuridine monophosphate (inhibit RNA/protein synthesis and DNA synthesis)

36
Q

5-FC spectrum of activity

A

Yeasts only (Candida and Cryptococcus)

37
Q

5-FC adverse effects

A

Bone marrow suppression, selective toxicity is incomplete - 5FU anti-cancer

38
Q

5-FC clinical use

A

Cryptococcal meningitis (combination with AmB)

39
Q

Griseofulvin mode of action

A

Inhibition of fungal mitosis

40
Q

Griseofulvin spectrum of activity

A

Dermatophytes

41
Q

Griseofulvin clinical use

A

Dermatophyte infections in children requiring system treatment (kerion, onychomycosis)

42
Q

Antifungal drugs that require therapeutic drug monitoring

A
  • Itraconazole
  • 5-FC (bone marrow)
  • Voriconazole (liver)

Clinical Pathology (60 decks)

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