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Part 3 – PM3A > (PM3A) Fungal Infections & Anti-fungal Drugs > Flashcards

(PM3A) Fungal Infections & Anti-fungal Drugs Flashcards

1
Q

What does ‘mycoses’ refer to?

A

Fungi

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2
Q

What are the two types of structure of fungi?

Give examples.

A

(1) Single cell - yeasts - Candida spp.

(2) Filamentous - Multicellular - mould - Aspergillus spp.

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3
Q

What are the two types of infection that can be contracted from fungi?

A

(1) Localised - acute

(2) Systemic

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4
Q

What is a major difference in the structure of a fungal cell, in comparison to a human (animal) cell?

A

Fungal cells have a cell wall

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5
Q

What is the structure of a fungal cell wall, from innermost to outermost level of structure?

A

(1) Nucleus
(2) Cell membrane: ergosterol & beta1-3 glucan synthase
(3) Cell wall: beta1-6 glucans and beta1-3 glucans
(4) Mannoproteins

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6
Q

What are the main anti-fungal drug categories?

A

(1) Polyenes
(2) Azoles - imidazoles & triazoles
(3) Allylamines (+ amorolfine)
(4) Echinocandins
(5) Flucytosine
(6) Griseofulvin

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7
Q

(1) Which route of administration is used for amphotericin B? Is this toxic?
(2) Which other route(s) of administration for amphotericin B would be toxic?

A

(1) Oral - not toxic

(2) IV - highly toxic

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8
Q

What are two types of polyene?

A

(1) Amphotericin B

(2) Nystatin

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9
Q

When is oral amphotericin B used?

A

Oral candida

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10
Q

When is IV amphotericin B used?

A

Life-threatening systemic infections

e.g. cryptococcal meningitis

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11
Q

What is cryptococcal meningitis?

A

A life-threatening systemic infection

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12
Q

(1) Describe the spectrum of activity for amphotericin B.

(2) What does this mean?

A

(1) Broad

(2) Kills most fungi

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13
Q

Describe the bioavailability for oral amphotericin B.

A

Poor oral bioavailability

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14
Q

What are/ is the administration route(s) for nystatin.

A

Local/ topical

  • Oral suspension for oral infections
  • Cream for candida of skin
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15
Q

(1) Describe the spectrum of activity for nystatin.

(2) What does this mean?

A

(1) Broad

(2) Kills most fungi

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16
Q

Can nystatin be taken orally? Give reasons for your answer.

A

No - it is topical

(1) Absorbed poorly orally
(2) Nephrotoxic
(3) Neurotoxic

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17
Q

Which polyenes can be taken orally?

A

Just amphotericin B

Nystatin is nephrotoxic & neurotoxic & not absorbed orally

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18
Q

(1) Why is nystatin not given orally?

(2) How is nystatin administered?

A

(1) Poor absorption + nephrotoxic + neurotoxic

(2) Topical/ locally

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19
Q

Describe the mechanism of action of polyenes.

Give 2 examples of polyenes.

A

(1)
- Bind to ergosterol in the cell membrane
- Binding forms pores in the cell membrane
- Pores cause leakage of K+ and Mg2+
- Leakage leads to lysis (cell death)

(2) Nystatin and amphotericin B

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20
Q

How many stages are there in the mechanism of action of amphotericin B? What are they?

A

4 stages

(1) Amphotericin B (polyene) binds to ergosterol in the fungal cell membrane
(2) Binding forms pores in the membrane
(3) Pores in membrane allow for potassium ion and magnesium ion leakage
(4) Leakage of ions leads to cell death - called lysis

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21
Q

How many stages are there in the mechanism of action of nystatin? What are they?

A

4 stages

(1) Amphotericin B (polyene) binds to ergosterol in the fungal cell membrane
(2) Binding forms pores in the membrane
(3) Pores in membrane allow for potassium ion and magnesium ion leakage
(4) Leakage of ions leads to cell death - called lysis

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22
Q

(1) How many types of azole are there?

(2) What are they called?

A

(1) 2 types

(2) Imidazoles and triazoles

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23
Q

Give 2 types of imidazole.

Name ONE brand for each.

A

(1) Miconazole - e.g. Daktarin

(2) Clotrimazole - e.g. Canesten

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24
Q

What is/ are the route(s) of administration for imidazoles?

A

Usually topical

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25
Q

What is a superficial mycoses?

A

Fungal infection of the upper layers of the skin

Can also include nails

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26
Q

What is another name for superficial mycoses?

A

Cutaneous mycoses

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27
Q

(1) Describe the spectrum of activity of imidazoles.

(2) What does this mean?

A

(1) Dermatophytes & candidiasis

(2) Narrow spectrum - have specific clinical indications

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28
Q

What is the ‘oromucosal’ route of administration?

A

Gel placed directly onto the gums and cheek

Drug is absorbed directly into bloodstream

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29
Q

(1) How many types of triazole are there?

(2) Name them.

A

(1) 4 types

2
- Fluconazole
- Itraconazole
- Voriconazole
- Posaconazole

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30
Q

What is/ are the administration route(s) of fluconazole? What is the general indication for each?

A

(1) Capsule - systemic
(2) Liquid - systemic
(3) IV - systemic

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31
Q

What is/ are the administration route(s) of itraconazole? What is the general indication for each?

A

(1) Capsule - systemic
(2) Liquid - systemic
(3) IV - systemic

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32
Q

What type of anti-fungal drug is miconazole?

A

Imidazole - azoles

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33
Q

What type of anti-fungal drug is clotrimazole?

A

Imidazole - azoles

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34
Q

What type of anti-fungal drug is fluconazole?

A

Triazole - azoles

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35
Q

What type of anti-fungal drug is itraconazole?

A

Triazole - azoles

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36
Q

What type of anti-fungal drug is voriconazole?

A

Triazole - azoles

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37
Q

What type of anti-fungal drug is posaconazole?

A

Triazole - azoles

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38
Q

What generic drug is the brand Daktarin?

A

Miconazole

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39
Q

What generic drug is the brand Canestan?

A

Clotrimazole

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40
Q

What generic drug is the brand Sporanox?

A

Itraconazole

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41
Q

What is/ are the route(s) of administration for triazoles?

A

Depends on infection site

Can be capsule/ oral suspension/ IV/ tablet

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42
Q

(1) Describe the spectrum of activity for triazoles.

(2) What does this mean?

A

(1) Broad

(2) Can be used for Candida/ Cryptococcus/ Aspergillus

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43
Q

What fungi can triazoles be used for?

A

(1) Cryptococcus
(2) Candida
(3) Aspergillus

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44
Q

What type of drug is most appropriate for aspergillus, both generally and specifically?

A

(1) Generally: Azoles - Triazoles

(2) Specifically - voriconazole/ posaconazole

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45
Q

Describe the mechanism of action for azoles.

A

(1) Targets Cytochrome P450
(2) Thus interferes with ergosterol (cell membrane) biosynthesis
(3) Disrupts plasma membrane - fungistatic

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46
Q

How can an anti-fungal drug that interferes with the fungi plasma membrane be described?

A

Fungistatic

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47
Q

What does fungistatic mean?

A

Used to describe an anti-fungal drug which disrupts the plasma membrane of fungi

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48
Q

What is an allylamine? Give an example (name BOTH generic and brand).

A

Anti-fungal drug

Terbinafine - Lamisil

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49
Q

What is terbinafine?

A

An allylamine - anti-fungal

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50
Q

(1) What type of anti-fungal drug is terbinafine?

(2) What is a brand of it?

A

(1) Allylamine

(2) Lamisil

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51
Q

(1) Describe the spectrum of activity of allylamines.

(2) What does this mean in clinical practice?

A

(1) Usually dermatophytes

(2) Nail infections & ringworm

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52
Q

Describe the mechanism of action of allylamines.

A

(1) Inhibits squalene epoxidase
(2) Inhibition of squalene epoxidase prevents production of lanosterol
(3) Prevents ergosterol synthesis

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53
Q

Is an allylamine fungistatic or fungicidal?

A

Both

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54
Q

What is amorolfine?

A

A synthetic morpholine

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55
Q

Describe the spectrum of activity of amorolfine.

What does this mean?

A

Broad

Mainly dermatophytes and yeast

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56
Q

Describe the mechanism of action of amorolfine.

A

(1) Inhibits 2 enzymes

(2) Inhibition of enzymes means ergosterol biosynthesis is halted

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57
Q

Is amorolfine considered fungicidal or fungistatic?

A

Usually fungicidal

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58
Q

Give an example of an echinocandin.

A

Caspofungin

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59
Q

What is an echinocandin?

A

A type of anti-fungal drug

60
Q

What is/ are the route(s) of administration for an echinocandin?

A

IV - once a day

61
Q

(1) Describe the spectrum of activity of echinocandins.

(2) What does this mean in clinical practice?

A

(1) Broad

(2) Used for serious systemic infections - Candida/ Aspergillus

62
Q

For which fungal infection is an echinocandin specifically NOT indicated? Why?

A

For Cryptococcus

Not for central nervous system

63
Q

Describe the mechanism of action of echinocandins.

A

(1) Inhibits 1-3 beta-glucan synthase

(2) Prevents production of 1-3 beta-glucan

64
Q

Are echinocandins considered to be fungicidal or fungistatic?

A

Fungicidal

65
Q

What is/ are the route(s) of administration for flucytosine?

A

(1) Oral

(2) IV

66
Q

Where are is flucytosine well absorbed, where other anti-fungal drugs are not?

A

Cerebrospinal fluid - CSF

67
Q

(1) Describe the spectrum of activity of flucytosine.

(2) What does this mean in clinical practice? Include indications.

A

(1) Narrow

2
- Used in combination with other anti-fungal drugs
- For severe Candida/ Cryptococcal systemic infections

68
Q

Describe the mechanism of action of flucytosine.

A

(1) Metabolised into fluorouracil (5-FU)

(2) Fluorouracil (5-FU) disrupts RNA/ DNA synthesis

69
Q

What is 5-FU?

A

Fluorouracil

70
Q

What is fluorouracil also known as?

71
Q

What is fluorouracil (5-FU)?

A

A biologically functional metabolite of flucytosine (anti-fungal drug)

72
Q

Is flucytosine considered fungicidal or fungistatic?

A

Fungistatic

73
Q

What is griseofulvin?

A

A type of benzofuran

Type of anti-fungal drug

74
Q

What is/ are the route(s) of administration of griseofulvin?

A

Oral

Tablets or oral suspension

75
Q

(1) Describe the spectrum of activity of griseofulvin.

(2) What does this mean in clinical practice?

A

(1) Narrow/ limited

(2) Used for dermatophytes - e.g. Tinea capitis

76
Q

Describe the mechanism of action of griseofulvin.

A

(1) Binds to polymerised microtubules
(2) Inhibits mitosis of fungal cell
(3) Inhibits fungal growth

77
Q

Is griseofulvin considered to be fungistatic or fungicidal?

A

Fungistatic

78
Q

What are the common side effects of griseofulvin?

A
  • Rash
  • Urticaria
  • Nausea
  • Vomiting
  • Anorexia
79
Q

Which anti-fungal drug(s) act on the division of fungal cells?

A

Griseofulvin

80
Q

Which anti-fungal drug(s) act on the ergosterol in the cell membrane of the fungal cells?

A

(1) Polyenes
(2) Allylamines
(3) Azoles

81
Q

What is flucytocin a type of?

A

Anti-fungal drugs

Fluoropyrimidine

82
Q

What is candidiasis?

A

A fungal infection

83
Q

Is candidiasis a common/ rare/ very rare etc. infection?

A

Most common fungal infection in the UK

84
Q

What types of candidiasis infection are there?

A

(1) C. albicans
(2) C. tropicalis
(3) C. glabrata
(4) C. pseudotropicalis

85
Q

What is/ are the potential cause(s) of candidiasis?

A

(1) Broad-spectrum antibiotics

(2) Immunodeficiency

86
Q

Are the symptoms of candidiasis normally localised or systematic?

87
Q

Where candidiasis infect?

A

(1) Skin
(2) Mucosae - e.g. vaginal/ oral thrush
(3) Nails - e.g. onchomycosis

88
Q

What is a candidiasis infection of the nails called?

A

Onchomycosis

89
Q

What is onchomycosis?

A

Candidiasis infection of the nails

90
Q

What are the common symptoms of candidiasis infections?

A
  • Pain
  • Itching
  • Creamy curd-like plaques on mucosal surface
  • Bleeding upon removal of mucosal surface
91
Q

What is indicated if a candidiasis if the fungal infection is systemic?

A

Immunocompromised patient

92
Q

How is a candidiasis infection diagnosed?

A

(1) Clinical features - symptoms

(2) Laboratory culture

93
Q

What is/ are the treatment(s) for candidiasis?

A

(1) Azoles:
- Imidazoles: clotrimazole - Canesten - topical
- Triazoles: fluconazole - Canesten - oral
(2) Polyenes:
- Nystatin
- Amphotericin B - IV for systemic candidiasis

94
Q

What types of vulvovaginal candidiasis are there?

A

(1) Vulvitis

(2) Vaginal/ vulvovaginal

95
Q

What is vulvitis?

A

Inflammation of the vulva due to infection

96
Q

What is the treatment for vulvitis candidiasis?

A

Topical imidazole creams

  • e.g. clotrimazole BD/ TDS
  • e.g. ketoconazole OD/ BD
97
Q

What is the treatment for vaginal candidiasis?

A

Intravaginal cream/ pessary:

  • e.g. clotrimazole
  • e.g. miconazole
98
Q

What is the treatment for vulvovaginal candidiasis?

A

Intravaginal cream/ pessary

  • Can be combined with topical treatment
  • e.g. clotrimazole
  • e.g. miconazole
99
Q

What is the treatment for vulvovaginal candidiasis in 12-15 year old girls?

A

Topical imidazole

Oral + intravaginal options are not used

100
Q

How is treatment of vulvovaginal candidiasis different in 12-15 year olds, as opposed to adults?

A

Oral and intravaginal imidazoles are not indicated

101
Q

When is oral treatment not indicated for vulvovaginal candidiasis?

A

(1) 12-15 year old patients

(2) Pregnant patients

102
Q

What is oncomycosis?

A

Candidiasis infection of the nail

103
Q

What are the symptoms of oncomycosis (candidiasis infection of the nail)?

A
  • Nail appears abnormal + discoloured
104
Q

How is oncomycosis (candidiasis infection of the nail) diagnosed?

A

(1) Clinical features - symptoms

(2) Confirmed with microscopy + cultures

105
Q

What self-care is recommended for those with oncomycosis (candidiasis infection of the nail)?

A

(1) Good hygiene
(2) Fitting footwear
(3) Clipping nails
(4) Avoid damp + moisture
(5) Avoid nail trauma

106
Q

What is the general treatment guidelines for oncomycosis (candidiasis infection of the nail)?

A

(1) Topical - amorolfine 6 months for nail
* Topical - amorolfine - 9-12 months for toes*

(2) Oral anti-fungal if topical is unsuccessful OR contraindicated

107
Q

What is the first line treatment for oncomycosis (candidiasis infection of the nail)?

A
  • Itraconazole
  • 200mg
  • BD
  • 1 week duration
108
Q

What is Candida auris?

A

A fungal infection

Similar to C. albicans

109
Q

What causes thrush?

A

Also known as candidiasis

C. albicans

110
Q

What does C. albicans cause?

A

Thrush infection

111
Q

What is of particular note regarding Candida auris?

A

It has multi-drug resistance

Only discovered in 2009

112
Q

What causes invasive candidiasis?

A

C. auris

Candida auris

113
Q

What does Candida auris (C. auris) cause in infection?

A

Invasive candidiasis

e.g. bloodstream infections

114
Q

What is fungemia?

A

Fungal infection of the blood

Presence of fungus in the bloodstream

115
Q

What is dermatophytosis?

116
Q

What are the 3 species of filamentous fungi?

A

(1) Epidermophyton
(2) Microsporum
(3) Trichophyton

117
Q

What is ringworm also known as?

A

Dermatophyton

118
Q

What are the symptoms of ringworm (dermatophyton)?

A
  • Red scaly lesions on skin
  • Nail discolouration and thickening
  • Hair loss and scarring
  • Itchy
  • Not usually painful
119
Q

How is ringworm (dermatophytosis) diagnosed?

A

Culture of:

  • Skin scrapings
  • Nail clippings
  • Hair samples
120
Q

What is the treatment for head/ scalp ringworm (dermatophytosis)?

A

Systemic griseofulvin

+ topical imidazole

121
Q

What is the treatment for skin ringworm (dermatophytosis)?

A

Topical imidazoles

  • clotrimazole
  • miconazole
  • ketoconazole
122
Q

What is the treatment for nail ringworm (dermatophytosis)?

A

Same as candidiasis

  • Itraconazole
  • 200mg
  • BD
  • 1 week duration

Oral terbinafine if unsuccessful or contraindicated

123
Q

What is aspergillosis?

A

Fungal infection of the lungs

IF SEVERE:
Can affect heart/ brain skin/ if immunocompromised

124
Q

What is/ are the cause(s) of aspergillosis?

A

Aspergillus - affects respiratory tract

125
Q

What are the symptoms for aspergillosis?

A

(1) Wheezing
(2) Breathlessness - SOB
(3) Fatigue
(4) Cough
(5) Malaise

126
Q

How is aspergillosis diagnosed?

A

(1) Sputum culture
(2) Bronchoalveolar lavage - washing of a cavity
(3) Antigen detection

127
Q

What is the treatment for aspergillosis?

A

(1) 1st line: voriconazole
(2) Can add bronchodilators + steroids if required
(3) Surgery
(4) Avoid further exposure

128
Q

What is pityriasis versicolor?

A

A common fungal skin infection

129
Q

What is/ are the cause(s) of pityriasis versicolor?

A

Malassezia

Yeast - normally found on skin

130
Q

What is Malassezia?

A

Fungi which causes pityriasis versicolor

Causes a fungal infection of the skin

131
Q

What are the symptoms of pityriasis versicolor?

A
  • Changes in colour to patches of skin

- Itchy

132
Q

How is pityriasis versicolor diagnosed?

A

(1) Skin scraping

(2) Clinical examination

133
Q

What is the treatment for pityriasis versicolor?

A

(1) Topical anti-fungal creams for 2-3 weeks

(2) Oral anti-fungals only used in treatment failure

134
Q

What is histoplasmosis?

A

A fungal lung infection

135
Q

What is/ are the cause(s) of histoplasmosis?

A

Histoplasma capsulatum

136
Q

How is histoplasmosis transmitted?

A

Inhalation of H. capsulatum spores

137
Q

What are the symptoms of histoplasmosis?

A

(1) Cough
(2) Flu-like symptoms
(3) Chronic infection - resembles TB

138
Q

How is histoplasmosis diagnosed?

A

Lab diagnostics:

  • Blood antibodies
  • Cultures
139
Q

What is the treatment for histoplasmosis?

A

(1) Oral itraconazole

(2) IF SEVERE: IV amphotericin B

140
Q

What is a cryptococcal infection?

A

Fungal infection

Usually of the lungs

141
Q

(1) How many types of Cryptococcal infection are there?

(2) What are they and what causes them?

A

(1) 2 types

2
- Lung infection - Cryptococcus neoformans
- AIDS - Cryptococcal meningitis

142
Q

(1) Are Cryptococcal infections common?

(2) When are they most common?

A

(1) No. Uncommon

(2) In immunocompromised patients - low CD4 count

143
Q

What are the symptoms of a Cryptococcal infection?

A
  • Fever
  • Fatigue
  • Dry cough
  • Headache
  • Blurred vision
  • Confusion
  • Nausea
  • Chest pain
  • Skin rash
144
Q

How is a Cryptococcal infection diagnosed?

A

Clinical tests:

  • Blood
  • Cerebrospinal fluid
  • Sputum
  • Urine screening/ culture
145
Q

What is the treatment for Cryptococcal infections?

A

(1) Amphotericin B + flucytosine - IV for 2 weeks

(2) Followed by oral fluconazole - 8 weeks

146
Q

(1) How many mechanisms of anti-fungal resistance are there?

(2) What are they?

A

(1) 4 types

2
- Altered drug metabolism
- Efflux pumps
- Change in protein target
- Prevention of drug entry

Part 3 – PM3A (28 decks)

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