(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