Infection: Antifungals, mechanism of action + adverse effects Flashcards

1
Q

What is the mechansim of action of the azoles?

A

Inhibit 14alpha-demethylase which produces ergosterol.

Side effects of azoles: p450 inhibition and liver toxicity

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2
Q

What are the adverse effects of the azoles?

A

P450 inhibition and liver toxicity

Azoles inhibit 14alpha-demethylase which is needed to produce ergosterol.

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3
Q

How does amphotericin B work?

A

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

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4
Q

What are the side effects of Amphotericin B?

A

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.

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5
Q

How does terbinafine function?

A

inhibits squalene epoxidase

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6
Q

How does griseofulvin function?

A

Interacts with microtubules to disrupt mitotic spindle.

Side effects: induces the p450 system, teratogenic.

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7
Q

What are the adverse effects of griseofulvin?

A

Induction of the p450 system, teratogenicity.

Works by interacting with microtubules to disrupt the mitiotic spindle.

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8
Q

How does flucytosine work?

A

Flucytosine is converted by cytosine deaminase to 5-fluorouracil, which inhibits TS and disrupts fungal protein synthesis.

Side effects: Vomiting.

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9
Q

What are the side effects of fluctyosine?

A

Vomiting.

Flucytosine is converted by cytosdine deaminase to 5-fluorouracil, which inhibits TS and thus disrupts fungal protein synthesis.

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10
Q

How does caspofungin function?

A

Inhibits the synthesis of beta-glucan, a major fungal cell wall component.

Side effect of flushing.

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11
Q

What are the adverse effects of caspofungin?

A

Flushing

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12
Q

How does nystatin work?

A

Binds with ergosterol forming a transmembrane channel that leads to monovalent ion leakage. Like amphotericin B.

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13
Q

What antifungals interfere with the p450 system?

A
Azoles = inhibit (also liver toxiciy)
Griseofulvin = induces (also teratogenic)
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14
Q

What antifungals inhibit 14alpha-demethylase which produces ergosterol?

A

Azoles

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15
Q

What antifungal functions by inhibiting squalene epoxidase?

A

Terbinafine.

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16
Q

Which antifungals work via binding with ergosterol forming a transmembrane channel that leads to monovalent ion leakage?

A

Nystatin and Amphotericin B.

17
Q

What antifungal is most typically associated with hypokalaemia and hypomagnaseamia?

A

Amphotericin B plus flu-like symptoms and nephrotoxicty.

18
Q

What antifungal is teratogenic?

A

Griseofulvin (also p450 enzyme inducer)

19
Q

Which antifungal has flushing as the most characteristic side effect?

A

Caspofungin which functons by inhibiting the synthesis of beta-glucan, a major fungal cell wall component.

20
Q

Which antifungal has vomiting as a predominant side effect?

A

Flucytosine.

21
Q

Which of the following antifungal is most effective in the treatment of invasive aspergillosis?

Ketoconazole
Fluconazole
Flucytosine
Voriconazole

A

Voriconazole belongs to the triazole class of antifungal drugs.

It is effective, alongside amphotericin B, in the treatment of invasive aspergillosis.

22
Q

Which class of antifungal drugs work by inhibiting squalene epoxidase?

Echinocandins
Allylamines
Polyenes

A

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.

23
Q

Which antifungal drug is associated with “shake and bake” adverse effects?

Griseofulvin
Caspofungin
Amphotericin B
Micafungin

A

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.

24
Q

Nystatin belongs to which class of drugs?

Allylamines
Polyenes
Echinocandins
Thiocarbamate

A

Polyenes

25
Q

Which of the following classes works by inhibiting lanosterol 14alpha-demethylase?

Imidazoles
Polyenes
Echinocandins
Thiocarbamate 
Triazoles
A

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.

26
Q

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
A

Flucytosine is a pyrimidine analogue. It is converted into 5-FU by the fungal enzyme cytosine deaminase.

Flucytosine is mostly active against yeast infections.

27
Q

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
A

Griseofulvin

28
Q

Which antifungal drug, at high doses, has an antiandrogen effect?

Clotrimazole
Caspofungin 
Ketoconazole
Itraconazole
Nystatin
Flucytosine
Griseofulvin
A

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.

29
Q

Which antifungal class works by targeting glucans?

Azoles
Polyenes
Echinocandins

A

Echinocandis - caspofungin, micafungin, work by targeting glucans, specifically by inhibiting the enzyme 1,3-Beta-glucase synthase.

This disrupts the fungal cell wall.