SF - anti-mycotics Flashcards
What are the broad categories of fungal disease?
Dermatophytes - skin infection
Internal - aspergillosis
What are the 4 main classes of anti-fungal drugs?
Azoles
Echinocandins
Allyamines
Polyenes
What component is found in cell membranes of fungal cells that is targeted by polyenes? What is it’s effect?
Ergosterol.
It impairs cell membrane function.
What is the spectrum of activity of polyenes?
Wide
What is the route of administration of polyenes and why?
IV. This is because of poor water solubility and poor GI absorption.
What are the side effects of polyenes?
Nephrotoxicity.
GI disturbances.
Type I hypersensitivity
What reaction do allyamines inhibit? What enzyme is involved?
Squalene -> lanosterol
Squalene epoxidase
What is the effect of accumulation of squalene?
Toxicity
What are allyamines used to treat?
Dermatophytosis
Subcutaneous fungal infections
Systemic fungal infections
Aspergillosis
What reaction do azoles inhibit? Which enzyme?
Lanosterol -> ergosterol
Lanosterol 14a-demethylase
What effect do azoles have on the cell?
Build up of precursors
Disrupts membrane bound enzyme activity.
Increases cell permeability which leads to cell death
How are azoles administered?
Orally, topically or IV
What are the 3 factors that cause anti-fungal resistance to azoles?
Mutation in the lanosterol 14a-demethylase gene.
Increased expression of lanosterol 14a-demethylase.
Expression of azole efflux pump.
What enzyme is affected by echinocandins?
1,3 B-glucan synthase
What are the cellular changes due to the effect of echinocandins?
Decreased synthesis of glucans. These are required to maintain the structural integrity of the cell wall.
So the cell loses the structural integrity and lyses.
