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Antifungals > Boards 2018 > Flashcards

Boards 2018 Flashcards

1
Q

What is the main side effect noted with Amphotericin B?

A

Nephrotoxicity. This drug has a low therapeutic index. There is direct tubular damage. Recommend monitoring for renal function - K+ loss, renal tubular acidosis. It’s best to use this in a lipid formulation as it may reduce toxicity.

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2
Q

This drug binds to Ergosterol in cell membrane creating a pore. The K+ and other small molecules leak from the fungal cells. There is some binding to mammalian cells

A

What is Amphotericin B?

This is given via IV. There is infrequent resistance.

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3
Q

What are two polyene macrolide antibiotics that have anti fungal actions?

A

Amphotericin B and Nystatin

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4
Q

This antibiotic has some anti fungal properties however it does not include ringworm treatment. This is limited to topical administration

A

Nystatin

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5
Q

What antifungals are fungistatic?

A

Azoles, Griseofulvin

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6
Q

What is the mechanism of action of all azoles

A

All azaleas block the fungal CYP450 pathway responsible for synthesis of ergosterol, increase membrane permeability, and interference with action of membrane associated enzymes. They inhibit Candidia yeast into hyphae.

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7
Q

What part of the ergosterol pathway do the azoles affect?

A

They block the cytochrome P450 pathway which happens just around the Lanosterol point in the pathway.

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8
Q

What potential side effects are seen with ketoconazole?

A

Gastrointestinal, hepatotoxicity, cataractes, pruritus, alopecia, teratogenic, mutagenic

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9
Q

What kind of environment is favourable for ketoconazole administration?

A

Requires an acidic environment, therefor decreased food is better.

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10
Q

Ketoconazole can be used to treat HAC - why?

A

Ketoconazole can inhibit synthesis of androgens and adrenal steroids. Fluconazole has minimal effects on adrenal steroidgenesis

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11
Q

How longs does Ketoconazole take to reach it’s steady state?

A

10-14 days

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12
Q

What antifungals penetrate the CNS?

A

Ketoconazole (enter CSF), Fluconazole (low protein binding, enters CSF. It is also seen in the nails, skin, saliva, and vagina)

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13
Q

How is Ketoconazole metabolized?

A

Liver

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14
Q

How is Fluconazole metabolized?

A

Liver and excreted in the bile and urine.

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15
Q

What has the longer half life? Ketoconazole or Itraconaozle?

A

Itraconazole (28-30 hrs).

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16
Q

Is fluconazole bioavailability affected by food intake?

A

No it’s not affected.

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17
Q

What azole is in the imidazole group and how many N’s are in the azole ring?

A

Ketoconazole. 2N’s in the azole ring

18
Q

What azole is in the triazole group and how many N’s are in the azole ring?

A

Itraconazole, Posaconazole. 3N’s in the azole ring

19
Q

What azole is in the bistriazole group ?

A

Fluconazole, Voriconazole (synthetic derivative of fluconazole)

20
Q

What is a broad-spectrum triazole?

A

Posaconazole.

21
Q

What species should we use caution when using Posaconazole?

A

Cats. This broad spectrum Triazole is eliminated by glucoronidation and biliary excretion.

22
Q

What adverse effects are noted with Posaconazole?

A

Dogs - hepatotoxicity, hypokalemia, thrombocytopenia, anemia, cardiac abnormalities. Cats - erythema, pruritus of face and pinna, retinotoxicity, neurologically, cardiac abnormalities.

23
Q

What is the mechanism of action of Voriconazole?

A

It inhibits sterol and CYP450 synthesis as well as inhibiting 24-metylene dehydrolanosterol demthylation. Is efficacious with dimorphic and filamentous fungi.

24
Q

What kind of drugs are Terbinafine or Lamisil? What is the mechanism of action.

A

Allylamines. Squalene Epoxidase Inhibitors. It decreases the synthesis of ergosterol. Toxic amounts of squalene results in the death of fungal cells.

25
Q

True or False - Terbinafine is affected by Cytochrome P450 enzyme.

A

False - it is note.

26
Q

Terbinafine has high protein binding - is it Fungicidal or Fungistatic?

A

Fungicidal.

27
Q

Terbinafine has effect on dermatophytes and Candida how long will it live in the hair for?

A

Terbinafine can live in the hair for 5 weeks after 2 weeks of treatments

28
Q

What side effects are noted with Terbinafine and cats?

A

vomiting, facial pruritus, macular to papular dermal hypersensitivity.

29
Q

Is Griseofulvin fungistatic or fungicidal?

A

Fungistatic.

30
Q

This drug inhibits Na synthesis and cell metaphase by interfering with function of the single microtubules.

A

Grisofulvin. It also may antagonize chitin synthesis.

31
Q

What side effects are seen with Griseofulvin?

A

GI, hepatotoxicity, teratogenic, myelotoxicity (idiosyncratic)

32
Q

What anti fungal has good action against sporothrix? And why wouldn’t we use this in cats?

A

Iodides (Na/K) iodides. Causes iodize in cats - muscle twitching, vomiting, anorexia, cardiomyopathy and scaling.

33
Q

What is the mechanism of action of Iodides

A

Facilitate phagocytic killing of fungal cells, anti-inflammatory, iodides enhance the halide-peroxidase killing system.

34
Q

5-Flucytosine - what is this converted to? What is the anti fungal MOA?

A

This is a synthetic drug. Usually used in combination with Amphotericin B. Inhibits DNA synthesis. It is converted to 5-fluoruracil. Fluroinated pyrimidine is taken up into the cell by cytosine permeate and deaminated by cytosine deaminase.

35
Q

Lufenuron is an insect growth regulator and mainly an insect development inhibitor but how is this also an anti fungal?

A

Inhibits chitin synthesis - fleas and dermatophytes.

36
Q

What is the mechanism of action of Caspofungin?

A

Cyclic hexapeptides interferes with cell wall biosynthesis. Inhibition of 1,3-beta-D gluten synthesis. It is not affected by CYP450. Has effect on mold and yeast. IV administration

37
Q

Is Nystatin fungistatic or fungicidal?

A

Both! It binds sterol in the cell membrane

38
Q

Enliconazole - can this be given PO?

A

No. This is not absorbed PO. This is fungicidal. Used for dermatophytes and Aspergillus.

39
Q

What is the mechanism of action of Lime Sulfur?

A

Conversion to penthathionic acid and H2S.

40
Q

List the order of specificity to fungal cytochrome P450 enzymes for the azoles.

A

Flu>itra>keto

Antifungals (1 decks)

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