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CMBM Exam 4 CL > Anti-Fungal Drugs (Habal) > Flashcards

Anti-Fungal Drugs (Habal) Flashcards

1
Q

What fungi cause superficial infections?

A

Dermatophytes

Malassezia furfur

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2
Q

What fungi cause subcutaneous infections?

A

Sporothrix schenckii

Basidiobolus ranierum

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3
Q

What fungi cause primary systemic infections?

A

Histoplasma capsulatum
Blastomyces dermatitidis
Coccidiodes immitis
Paracoccidiodes brasiliensis

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4
Q

What fungi cause primary opportunistic infections?

A 
Candida albicans
Cryptococcus neoformans
Aspergillus fumigatus
Mucor/Rhizopus
Pneumocystis jirovecii
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5
Q

What are possible targets of anti-fungal drugs?

A 
Cell wall
Cell membrane
Nucleus
Vacuoles
Cytoplasm
Mitochondria
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6
Q

What is the fungal cell wall made up of?

A

Chitin, glucan, mannan

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7
Q

What is the fungal cell membrane made up of?

A

Phospholipids & sterols (ergosterol)

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8
Q

What are the 3 classes of antifungal drugs?

A 
Cell wall (glucan) synthesis
Cell membrane (ergosterol) synthesis
DNA/RNA synthesis (pyrimidine analogues)
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9
Q

An optimal antifungal will have?

A 
Wide spectrum of availability
Favorable bioavailablity
Adeqhate in vivo efficacy
High therapeutic index
Low cost
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10
Q

Anti-fungal antibiotics include what drugs?

A

Polyenes - Amphotericine B, Nystatin

Griseofluvn

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11
Q

Anti-fungal antimetabolites include?

A

Flucytosine

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12
Q

Anti-fungal azoles include?

A

Imidazoles - Ketoconazole, Miconazole

Triazoles - Itraconazole, Fluconazole

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13
Q

Anti-fungal allylamines include?

A

Terbinafine

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14
Q

What do allylamines such as Terbinafine interfere with?

A

Squalene epoxidase

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15
Q

What do azoles such as Ketoconazole, Fluconazole, Itraconazole, and Miconazole interfere with?

A

Cytochrome P450 14-alpha demethylase

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16
Q

What do polyenes such as Amphotericine B and Nystatin do?

A

Interact with ergosterol and form holes in cell membrane, affecting the integrity of its structure.

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17
Q

What resistance might you see against polyenes?

A

Low amount of ergosterol. If there’s nothing to interact with, then there can’t be an anti-fungal activity.

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18
Q

Are polyenes stable or unstable when taken orally?

A

Unstable

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19
Q

At what concentration are polyenes fungasidal?

A

High

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20
Q

What produces Amphotericin B?

A

Streptomyces nodosus

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21
Q

What broad spectrum anti-fungal drug is indicated for treatment of severe to life-threatening fungal infections?

A

Amphotericin B

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22
Q

How is Amphotericin B administered? Why?

A

IV only; very toxic, especially to the kidneys. Slow-rate IV infusion in a hospital setting is the best way to overcome/sidestep this toxicity.

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23
Q

What causes tubular nephrotoxicity due to administration of Amphotericin B?

A

Leakage of Na+, K+, Ca+

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24
Q

Which anti-fungal drug is the big gun?

A

Amphotericin B

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25
Q

What produces Nystatin?

A

Streptomyces noursei

26
Q

How is Nystatin administered?

A

Used topically for local infection. Too toxic to be administered systemically.

27
Q

What is Nystatin routinely used to treat?

A

Oral thrush (swish and spit).

28
Q

Why is Nystatin so toxic?

A

Poor bioavailability and absorption; have to take a large amount for it to be effective systemically.

29
Q

What is a bad side effect of Azoles?

A

They impact liver enzymes, leading to potentiation of certain drugs that are metabolized in the liver.

30
Q

What happens to some patients with hepatic issues who can’t break down testosterone?

A

Gynocomastia

31
Q

How can azoles be administered?

A

Topically, orally, IM, IV

32
Q

What types of infections can Azoles treat, in general terms?

A

Most infections, from superficial to systemic

33
Q

What is the mechanism of action for Azoles?

A

Inhibit ergosterol synthesis by inhibition of CYP450 - lanosterol 14-alpha demethylase

34
Q

What are some drugs that Azoles can potentiate?

A

Diazepam, Cyclosporin, Phynetoin, Warfarin, Isoniazide

35
Q

What are the 2 types of Azoles?

A

Imidazoles, Triazololes

36
Q

What are the Imidazoles?

A

Ketoconazole, Miconazole

37
Q

Which Imidazole is broad spectrum, PO administration, and has been mostly replaced by Fluconazole, which does not have the gynecomastia and hepatic side effects generally seen with this drug?

A

Ketoconazole

38
Q

Which Imidazole is used to treat dermatophytes and is administered topically or via vaginal suppositories?

A

Miconazole

39
Q

What are the triazololes?

A

Clotrimazole, Fluconazole, Itraconazole, Voriconazole

40
Q

Which Triazolole is administered topically or via vaginal suppositories?

A

Clotrimazole

41
Q

Which Triazolole is used to treat oral/esophageal/vaginal candidiasis and Cryptococcal meningitis, and is administered orally or via IV?

A

Fluconazole

42
Q

Which Triazolole is a broad spectrum drug that is indicated for systemic fungal infections, as well as oral and esophageal candidiasis?

A

Itraconazole

43
Q

Which Triazolole is administered orally or via IV, has high bioavailability, and is indicated for invasive Aspergillosis?

A

Voriconazole

44
Q

What should you avoid taking while on Azoles?

45
Q

Why is fluconazole used for Cryptococcal meningitis?

A

Highest CSF penetration rate & highest bioavailability

46
Q

What is the mechanism of allylamines?

A

Inhibit squalene epoxidase, thus decreasing ergosterol synthesis

47
Q

How are allylamines administered?

A

Orally or as a topical cream

48
Q

What are allylamines mainly used to treat?

A

Superficial fungal infections

49
Q

Are there any side effects of allylamines?

A

Very few, but they include upset stomach, nausea, vomiting, loss of taste. Usually given as a cream because of bad taste that leads to poor compliance.

50
Q

What 2 drugs are used in conjunction against Cryptococcal meningitis?

A

Flucytosine & Amp-B

51
Q

How does Flucytosine work?

A

It’s deaminates to 5-FU, which then interferes with RNA & DNA synthesis

52
Q

What is Flucytosine dose dependent for?

A

Bone marrow suppression (decreased white blood cells, platelets)

53
Q

What is the mechanism of action for Echinocandins (Caspofungin)?

A

Cell wall synthesis inhibitor that inhibits 1,3-beta-glucan synthase

54
Q

What drug is used for invasive Amp-B resistant Aspergillosis, esophageal candidiasis, and Pneumocystis pneumonia?

A

Echinocandins

55
Q

How is Echinocandins administered?

A

IV (low oral bioavailability)

56
Q

What is the mechanism for Grieofulvin?

A

It binds fungal tubulin, interfering with microtubule function.

57
Q

What anti-fungal is used orally to treat Taenia infections?

A

Grieofulvin

58
Q

Which anti-fungal is highly effective against athlete’s foot?

A

Grieofulvin

59
Q

What are the side effects of Grieofulvin?

A

Teratogenic, increased CYP450 metabolism

60
Q

What considerations must you take into account for anti-fungal medications?

A 
Spectrum
Site of infection
Current and past medical history
Liver and kidney tests
Drug interactions
Cost
61
Q

What are the benefits of combination therapy?

A

Improved clinical and microbiologic outcome
Decreased toxicity
Decreased likelihood of resistance
Broader spectrum in empiric therapy

CMBM Exam 4 CL (17 decks)

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