Infection: Antifungals, mechanism of action + adverse effects Flashcards
What is the mechansim of action of the azoles?
Inhibit 14alpha-demethylase which produces ergosterol.
Side effects of azoles: p450 inhibition and liver toxicity
What are the adverse effects of the azoles?
P450 inhibition and liver toxicity
Azoles inhibit 14alpha-demethylase which is needed to produce ergosterol.
How does amphotericin B work?
Binds with ergosterol forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl-) leakage.
Side effects are nephrotoxicty, flu-like symptoms,
hypokalaemia, hypomagnaseamia
What are the side effects of Amphotericin B?
Side effects are nephrotoxicty, flu-like symptoms,
hypokalaemia, hypomagnaseamia.
Binds with ergosterol forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl-) leakage.
How does terbinafine function?
inhibits squalene epoxidase
How does griseofulvin function?
Interacts with microtubules to disrupt mitotic spindle.
Side effects: induces the p450 system, teratogenic.
What are the adverse effects of griseofulvin?
Induction of the p450 system, teratogenicity.
Works by interacting with microtubules to disrupt the mitiotic spindle.
How does flucytosine work?
Flucytosine is converted by cytosine deaminase to 5-fluorouracil, which inhibits TS and disrupts fungal protein synthesis.
Side effects: Vomiting.
What are the side effects of fluctyosine?
Vomiting.
Flucytosine is converted by cytosdine deaminase to 5-fluorouracil, which inhibits TS and thus disrupts fungal protein synthesis.
How does caspofungin function?
Inhibits the synthesis of beta-glucan, a major fungal cell wall component.
Side effect of flushing.
What are the adverse effects of caspofungin?
Flushing
How does nystatin work?
Binds with ergosterol forming a transmembrane channel that leads to monovalent ion leakage. Like amphotericin B.
What antifungals interfere with the p450 system?
Azoles = inhibit (also liver toxiciy) Griseofulvin = induces (also teratogenic)
What antifungals inhibit 14alpha-demethylase which produces ergosterol?
Azoles
What antifungal functions by inhibiting squalene epoxidase?
Terbinafine.
Which antifungals work via binding with ergosterol forming a transmembrane channel that leads to monovalent ion leakage?
Nystatin and Amphotericin B.
What antifungal is most typically associated with hypokalaemia and hypomagnaseamia?
Amphotericin B plus flu-like symptoms and nephrotoxicty.
What antifungal is teratogenic?
Griseofulvin (also p450 enzyme inducer)
Which antifungal has flushing as the most characteristic side effect?
Caspofungin which functons by inhibiting the synthesis of beta-glucan, a major fungal cell wall component.
Which antifungal has vomiting as a predominant side effect?
Flucytosine.
Which of the following antifungal is most effective in the treatment of invasive aspergillosis?
Ketoconazole
Fluconazole
Flucytosine
Voriconazole
Voriconazole belongs to the triazole class of antifungal drugs.
It is effective, alongside amphotericin B, in the treatment of invasive aspergillosis.
Which class of antifungal drugs work by inhibiting squalene epoxidase?
Echinocandins
Allylamines
Polyenes
Allylamines - which include drugs such as terbinafine, naftifine, and amorolfin - work by inhibiting squalene epoxidase.
Another antifungal drug, called tolnaftate, also inhibits squalene epoxidase - but, structurally, tolnaftate is not an allylamine.
Which antifungal drug is associated with “shake and bake” adverse effects?
Griseofulvin
Caspofungin
Amphotericin B
Micafungin
Amphotericin B is associated with the so-called “shake and bake” adverse effects:
Initial use of amphotericin B is associted with chills and fever (“shake and bake” respectively).
This is an acute reactins which may occur shortly after infusion.
Nystatin belongs to which class of drugs?
Allylamines
Polyenes
Echinocandins
Thiocarbamate
Polyenes
Which of the following classes works by inhibiting lanosterol 14alpha-demethylase?
Imidazoles Polyenes Echinocandins Thiocarbamate Triazoles
Imidazoles and triazoles are family members of the broader azole class - which work by inhibiting lanosterol 14alpha-demethylase.
This compromises the integrity of the fungal cell wall.
Which of the following is a pyrimidine analogue which is converted into 5-FU by the fungal enzyme cytosine deaminase?
Clotrimazole Caspofungin Itraconazole Nystatin Flucytosine Griseofulvin
Flucytosine is a pyrimidine analogue. It is converted into 5-FU by the fungal enzyme cytosine deaminase.
Flucytosine is mostly active against yeast infections.
Which of the following works by binding to microtubules and disrupting the mitotic process?
It is administered orally and has a half-life of ~14 hours.
Clotrimazole Caspofungin Itraconazole Nystatin Flucytosine Griseofulvin
Griseofulvin
Which antifungal drug, at high doses, has an antiandrogen effect?
Clotrimazole Caspofungin Ketoconazole Itraconazole Nystatin Flucytosine Griseofulvin
Ketoconazole, at high doses, inhibits the activity of enzymes involved in the conversion of cholesterol to steroid hormones - such as cortisol and testosterone.
Cushings disease treatment via specialist.
Which antifungal class works by targeting glucans?
Azoles
Polyenes
Echinocandins
Echinocandis - caspofungin, micafungin, work by targeting glucans, specifically by inhibiting the enzyme 1,3-Beta-glucase synthase.
This disrupts the fungal cell wall.
