(PM3A) Fungal Infections & Anti-fungal Drugs Flashcards
What does ‘mycoses’ refer to?
Fungi
What are the two types of structure of fungi?
Give examples.
(1) Single cell - yeasts - Candida spp.
(2) Filamentous - Multicellular - mould - Aspergillus spp.
What are the two types of infection that can be contracted from fungi?
(1) Localised - acute
(2) Systemic
What is a major difference in the structure of a fungal cell, in comparison to a human (animal) cell?
Fungal cells have a cell wall
What is the structure of a fungal cell wall, from innermost to outermost level of structure?
(1) Nucleus
(2) Cell membrane: ergosterol & beta1-3 glucan synthase
(3) Cell wall: beta1-6 glucans and beta1-3 glucans
(4) Mannoproteins
What are the main anti-fungal drug categories?
(1) Polyenes
(2) Azoles - imidazoles & triazoles
(3) Allylamines (+ amorolfine)
(4) Echinocandins
(5) Flucytosine
(6) Griseofulvin
(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?
(1) Oral - not toxic
(2) IV - highly toxic
What are two types of polyene?
(1) Amphotericin B
(2) Nystatin
When is oral amphotericin B used?
Oral candida
When is IV amphotericin B used?
Life-threatening systemic infections
e.g. cryptococcal meningitis
What is cryptococcal meningitis?
A life-threatening systemic infection
(1) Describe the spectrum of activity for amphotericin B.
(2) What does this mean?
(1) Broad
(2) Kills most fungi
Describe the bioavailability for oral amphotericin B.
Poor oral bioavailability
What are/ is the administration route(s) for nystatin.
Local/ topical
- Oral suspension for oral infections
- Cream for candida of skin
(1) Describe the spectrum of activity for nystatin.
(2) What does this mean?
(1) Broad
(2) Kills most fungi
Can nystatin be taken orally? Give reasons for your answer.
No - it is topical
(1) Absorbed poorly orally
(2) Nephrotoxic
(3) Neurotoxic
Which polyenes can be taken orally?
Just amphotericin B
Nystatin is nephrotoxic & neurotoxic & not absorbed orally
(1) Why is nystatin not given orally?
(2) How is nystatin administered?
(1) Poor absorption + nephrotoxic + neurotoxic
(2) Topical/ locally
Describe the mechanism of action of polyenes.
Give 2 examples of polyenes.
(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
How many stages are there in the mechanism of action of amphotericin B? What are they?
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
How many stages are there in the mechanism of action of nystatin? What are they?
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
(1) How many types of azole are there?
(2) What are they called?
(1) 2 types
(2) Imidazoles and triazoles
Give 2 types of imidazole.
Name ONE brand for each.
(1) Miconazole - e.g. Daktarin
(2) Clotrimazole - e.g. Canesten
What is/ are the route(s) of administration for imidazoles?
Usually topical
What is a superficial mycoses?
Fungal infection of the upper layers of the skin
Can also include nails
What is another name for superficial mycoses?
Cutaneous mycoses
(1) Describe the spectrum of activity of imidazoles.
(2) What does this mean?
(1) Dermatophytes & candidiasis
(2) Narrow spectrum - have specific clinical indications
What is the ‘oromucosal’ route of administration?
Gel placed directly onto the gums and cheek
Drug is absorbed directly into bloodstream
(1) How many types of triazole are there?
(2) Name them.
(1) 4 types
2
- Fluconazole
- Itraconazole
- Voriconazole
- Posaconazole
What is/ are the administration route(s) of fluconazole? What is the general indication for each?
(1) Capsule - systemic
(2) Liquid - systemic
(3) IV - systemic
What is/ are the administration route(s) of itraconazole? What is the general indication for each?
(1) Capsule - systemic
(2) Liquid - systemic
(3) IV - systemic
What type of anti-fungal drug is miconazole?
Imidazole - azoles
What type of anti-fungal drug is clotrimazole?
Imidazole - azoles
What type of anti-fungal drug is fluconazole?
Triazole - azoles
What type of anti-fungal drug is itraconazole?
Triazole - azoles
What type of anti-fungal drug is voriconazole?
Triazole - azoles
What type of anti-fungal drug is posaconazole?
Triazole - azoles
What generic drug is the brand Daktarin?
Miconazole
What generic drug is the brand Canestan?
Clotrimazole
What generic drug is the brand Sporanox?
Itraconazole
What is/ are the route(s) of administration for triazoles?
Depends on infection site
Can be capsule/ oral suspension/ IV/ tablet
(1) Describe the spectrum of activity for triazoles.
(2) What does this mean?
(1) Broad
(2) Can be used for Candida/ Cryptococcus/ Aspergillus
What fungi can triazoles be used for?
(1) Cryptococcus
(2) Candida
(3) Aspergillus
What type of drug is most appropriate for aspergillus, both generally and specifically?
(1) Generally: Azoles - Triazoles
(2) Specifically - voriconazole/ posaconazole
Describe the mechanism of action for azoles.
(1) Targets Cytochrome P450
(2) Thus interferes with ergosterol (cell membrane) biosynthesis
(3) Disrupts plasma membrane - fungistatic
How can an anti-fungal drug that interferes with the fungi plasma membrane be described?
Fungistatic
What does fungistatic mean?
Used to describe an anti-fungal drug which disrupts the plasma membrane of fungi
What is an allylamine? Give an example (name BOTH generic and brand).
Anti-fungal drug
Terbinafine - Lamisil
What is terbinafine?
An allylamine - anti-fungal
(1) What type of anti-fungal drug is terbinafine?
(2) What is a brand of it?
(1) Allylamine
(2) Lamisil
(1) Describe the spectrum of activity of allylamines.
(2) What does this mean in clinical practice?
(1) Usually dermatophytes
(2) Nail infections & ringworm
Describe the mechanism of action of allylamines.
(1) Inhibits squalene epoxidase
(2) Inhibition of squalene epoxidase prevents production of lanosterol
(3) Prevents ergosterol synthesis
Is an allylamine fungistatic or fungicidal?
Both
What is amorolfine?
A synthetic morpholine
Describe the spectrum of activity of amorolfine.
What does this mean?
Broad
Mainly dermatophytes and yeast
Describe the mechanism of action of amorolfine.
(1) Inhibits 2 enzymes
(2) Inhibition of enzymes means ergosterol biosynthesis is halted
Is amorolfine considered fungicidal or fungistatic?
Usually fungicidal
Give an example of an echinocandin.
Caspofungin
What is an echinocandin?
A type of anti-fungal drug
What is/ are the route(s) of administration for an echinocandin?
IV - once a day
(1) Describe the spectrum of activity of echinocandins.
(2) What does this mean in clinical practice?
(1) Broad
(2) Used for serious systemic infections - Candida/ Aspergillus
For which fungal infection is an echinocandin specifically NOT indicated? Why?
For Cryptococcus
Not for central nervous system
Describe the mechanism of action of echinocandins.
(1) Inhibits 1-3 beta-glucan synthase
(2) Prevents production of 1-3 beta-glucan
Are echinocandins considered to be fungicidal or fungistatic?
Fungicidal
What is/ are the route(s) of administration for flucytosine?
(1) Oral
(2) IV
Where are is flucytosine well absorbed, where other anti-fungal drugs are not?
Cerebrospinal fluid - CSF
(1) Describe the spectrum of activity of flucytosine.
(2) What does this mean in clinical practice? Include indications.
(1) Narrow
2
- Used in combination with other anti-fungal drugs
- For severe Candida/ Cryptococcal systemic infections
Describe the mechanism of action of flucytosine.
(1) Metabolised into fluorouracil (5-FU)
(2) Fluorouracil (5-FU) disrupts RNA/ DNA synthesis
What is 5-FU?
Fluorouracil
What is fluorouracil also known as?
5-FU
What is fluorouracil (5-FU)?
A biologically functional metabolite of flucytosine (anti-fungal drug)
Is flucytosine considered fungicidal or fungistatic?
Fungistatic
What is griseofulvin?
A type of benzofuran
Type of anti-fungal drug
What is/ are the route(s) of administration of griseofulvin?
Oral
Tablets or oral suspension
(1) Describe the spectrum of activity of griseofulvin.
(2) What does this mean in clinical practice?
(1) Narrow/ limited
(2) Used for dermatophytes - e.g. Tinea capitis
Describe the mechanism of action of griseofulvin.
(1) Binds to polymerised microtubules
(2) Inhibits mitosis of fungal cell
(3) Inhibits fungal growth
Is griseofulvin considered to be fungistatic or fungicidal?
Fungistatic
What are the common side effects of griseofulvin?
- Rash
- Urticaria
- Nausea
- Vomiting
- Anorexia
Which anti-fungal drug(s) act on the division of fungal cells?
Griseofulvin
Which anti-fungal drug(s) act on the ergosterol in the cell membrane of the fungal cells?
(1) Polyenes
(2) Allylamines
(3) Azoles
What is flucytocin a type of?
Anti-fungal drugs
Fluoropyrimidine
What is candidiasis?
A fungal infection
Is candidiasis a common/ rare/ very rare etc. infection?
Most common fungal infection in the UK
What types of candidiasis infection are there?
(1) C. albicans
(2) C. tropicalis
(3) C. glabrata
(4) C. pseudotropicalis
What is/ are the potential cause(s) of candidiasis?
(1) Broad-spectrum antibiotics
(2) Immunodeficiency
Are the symptoms of candidiasis normally localised or systematic?
Localised
Where candidiasis infect?
(1) Skin
(2) Mucosae - e.g. vaginal/ oral thrush
(3) Nails - e.g. onchomycosis
What is a candidiasis infection of the nails called?
Onchomycosis
What is onchomycosis?
Candidiasis infection of the nails
What are the common symptoms of candidiasis infections?
- Pain
- Itching
- Creamy curd-like plaques on mucosal surface
- Bleeding upon removal of mucosal surface
What is indicated if a candidiasis if the fungal infection is systemic?
Immunocompromised patient
How is a candidiasis infection diagnosed?
(1) Clinical features - symptoms
(2) Laboratory culture
What is/ are the treatment(s) for candidiasis?
(1) Azoles:
- Imidazoles: clotrimazole - Canesten - topical
- Triazoles: fluconazole - Canesten - oral
(2) Polyenes:
- Nystatin
- Amphotericin B - IV for systemic candidiasis
What types of vulvovaginal candidiasis are there?
(1) Vulvitis
(2) Vaginal/ vulvovaginal
What is vulvitis?
Inflammation of the vulva due to infection
What is the treatment for vulvitis candidiasis?
Topical imidazole creams
- e.g. clotrimazole BD/ TDS
- e.g. ketoconazole OD/ BD
What is the treatment for vaginal candidiasis?
Intravaginal cream/ pessary:
- e.g. clotrimazole
- e.g. miconazole
What is the treatment for vulvovaginal candidiasis?
Intravaginal cream/ pessary
- Can be combined with topical treatment
- e.g. clotrimazole
- e.g. miconazole
What is the treatment for vulvovaginal candidiasis in 12-15 year old girls?
Topical imidazole
Oral + intravaginal options are not used
How is treatment of vulvovaginal candidiasis different in 12-15 year olds, as opposed to adults?
Oral and intravaginal imidazoles are not indicated
When is oral treatment not indicated for vulvovaginal candidiasis?
(1) 12-15 year old patients
(2) Pregnant patients
What is oncomycosis?
Candidiasis infection of the nail
What are the symptoms of oncomycosis (candidiasis infection of the nail)?
- Nail appears abnormal + discoloured
How is oncomycosis (candidiasis infection of the nail) diagnosed?
(1) Clinical features - symptoms
(2) Confirmed with microscopy + cultures
What self-care is recommended for those with oncomycosis (candidiasis infection of the nail)?
(1) Good hygiene
(2) Fitting footwear
(3) Clipping nails
(4) Avoid damp + moisture
(5) Avoid nail trauma
What is the general treatment guidelines for oncomycosis (candidiasis infection of the nail)?
(1) Topical - amorolfine 6 months for nail
* Topical - amorolfine - 9-12 months for toes*
(2) Oral anti-fungal if topical is unsuccessful OR contraindicated
What is the first line treatment for oncomycosis (candidiasis infection of the nail)?
- Itraconazole
- 200mg
- BD
- 1 week duration
What is Candida auris?
A fungal infection
Similar to C. albicans
What causes thrush?
Also known as candidiasis
C. albicans
What does C. albicans cause?
Thrush infection
What is of particular note regarding Candida auris?
It has multi-drug resistance
Only discovered in 2009
What causes invasive candidiasis?
C. auris
Candida auris
What does Candida auris (C. auris) cause in infection?
Invasive candidiasis
e.g. bloodstream infections
What is fungemia?
Fungal infection of the blood
Presence of fungus in the bloodstream
What is dermatophytosis?
Ringworm
What are the 3 species of filamentous fungi?
(1) Epidermophyton
(2) Microsporum
(3) Trichophyton
What is ringworm also known as?
Dermatophyton
What are the symptoms of ringworm (dermatophyton)?
- Red scaly lesions on skin
- Nail discolouration and thickening
- Hair loss and scarring
- Itchy
- Not usually painful
How is ringworm (dermatophytosis) diagnosed?
Culture of:
- Skin scrapings
- Nail clippings
- Hair samples
What is the treatment for head/ scalp ringworm (dermatophytosis)?
Systemic griseofulvin
+ topical imidazole
What is the treatment for skin ringworm (dermatophytosis)?
Topical imidazoles
- clotrimazole
- miconazole
- ketoconazole
What is the treatment for nail ringworm (dermatophytosis)?
Same as candidiasis
- Itraconazole
- 200mg
- BD
- 1 week duration
Oral terbinafine if unsuccessful or contraindicated
What is aspergillosis?
Fungal infection of the lungs
IF SEVERE:
Can affect heart/ brain skin/ if immunocompromised
What is/ are the cause(s) of aspergillosis?
Aspergillus - affects respiratory tract
What are the symptoms for aspergillosis?
(1) Wheezing
(2) Breathlessness - SOB
(3) Fatigue
(4) Cough
(5) Malaise
How is aspergillosis diagnosed?
(1) Sputum culture
(2) Bronchoalveolar lavage - washing of a cavity
(3) Antigen detection
What is the treatment for aspergillosis?
(1) 1st line: voriconazole
(2) Can add bronchodilators + steroids if required
(3) Surgery
(4) Avoid further exposure
What is pityriasis versicolor?
A common fungal skin infection
What is/ are the cause(s) of pityriasis versicolor?
Malassezia
Yeast - normally found on skin
What is Malassezia?
Fungi which causes pityriasis versicolor
Causes a fungal infection of the skin
What are the symptoms of pityriasis versicolor?
- Changes in colour to patches of skin
- Itchy
How is pityriasis versicolor diagnosed?
(1) Skin scraping
(2) Clinical examination
What is the treatment for pityriasis versicolor?
(1) Topical anti-fungal creams for 2-3 weeks
(2) Oral anti-fungals only used in treatment failure
What is histoplasmosis?
A fungal lung infection
What is/ are the cause(s) of histoplasmosis?
Histoplasma capsulatum
How is histoplasmosis transmitted?
Inhalation of H. capsulatum spores
What are the symptoms of histoplasmosis?
(1) Cough
(2) Flu-like symptoms
(3) Chronic infection - resembles TB
How is histoplasmosis diagnosed?
Lab diagnostics:
- Blood antibodies
- Cultures
What is the treatment for histoplasmosis?
(1) Oral itraconazole
(2) IF SEVERE: IV amphotericin B
What is a cryptococcal infection?
Fungal infection
Usually of the lungs
(1) How many types of Cryptococcal infection are there?
(2) What are they and what causes them?
(1) 2 types
2
- Lung infection - Cryptococcus neoformans
- AIDS - Cryptococcal meningitis
(1) Are Cryptococcal infections common?
(2) When are they most common?
(1) No. Uncommon
(2) In immunocompromised patients - low CD4 count
What are the symptoms of a Cryptococcal infection?
- Fever
- Fatigue
- Dry cough
- Headache
- Blurred vision
- Confusion
- Nausea
- Chest pain
- Skin rash
How is a Cryptococcal infection diagnosed?
Clinical tests:
- Blood
- Cerebrospinal fluid
- Sputum
- Urine screening/ culture
What is the treatment for Cryptococcal infections?
(1) Amphotericin B + flucytosine - IV for 2 weeks
(2) Followed by oral fluconazole - 8 weeks
(1) How many mechanisms of anti-fungal resistance are there?
(2) What are they?
(1) 4 types
2
- Altered drug metabolism
- Efflux pumps
- Change in protein target
- Prevention of drug entry
