Antifungals Flashcards
Give examples of anti fungal classes
Azoles Allylamines Polyenes Mitotic inhibitors DNA/RNA inhibitors
Why are cell walls a good target for anti fungal treatment?
Mammalian cells have no cell wall
Azoles have a broad spectrum of activity. How fast is azalea absorption? Is it protein bound?
Rapid - plasma peak in 2 hrs
Yes - by albumin
Azoles are highly distributed in the body. Where are azole levels highest?
Liver
Adrenal glands
Lungs
Kidney
What are the 2 groups of azoles?
Triazoles - very expensive
Imidazoles
How are azoles metabolised and excreted?
Hepatic metabolism
Excreted mainly in bile, some in urine
What are the side effects of azoles?
GI affects (V+, D+, anorexia, nausea)
Hepatoxicity (inhibits cytochrome P450)
Suppression of hormones
What species are more sensitive to side effects of azoles?
Cats
Allylamines inhibit squalene epoxidase (?). They can be fungicidal or fungistatic. What other enzyme do they inhibit and what is the consequence of this?
Cytochrome P450
Slow metabolism of this and other drugs - potentially hepatotoxic
Give an example of an allylamine and what it is used for
Terinafine
Treat Malassezia otitis externa
Systemic use of allylamines is unauthorised. How are allylamines metabolised and excreted?
Hepatic metabolism
Urinary excretion
What are the side effects of allylamines?
GI problems (give with food)
Hepatoxicity
Pruritis of skin
Amphotericin B (AMB) is a fungistatic or fungicidal drug. It is highly protein bound. Is it widely distributed in the body?
Yes
Poor penetration of CNS, pancreas and bone
What is a common side effect of amphotericin B?
Nephrotoxicity (to a certain degree)
Griseofulvin is a fungistatic drug. How does it work?
Disrupts mitosis
How is griseofulvin absorbed? What does it bind to?
Absorbed irregularly from GI tract - only small fraction remains in body tissues
Hair, skin nails
Which is the only species griseofulvin is authorised in?
Horses
How is griseofulvin metabolised and excreted?
Hepatic metabolism
Excreted in faeces
Why should griseofulvin not be used in pregnant animals? (Also not in lactating or food production)
Teratogenic
What are the side effects of griseofulvin?
Tetratogenic Carcinogenic GI disorders Hepatoxictity Atoxia Anaemia, leucopenia
Why might anti fungal treatment fail?
Many are fungistatic, not fungicidal
Fungal cell wall, membrane and capsules can act as a barrier
Poor penetration to infection site
