Anti-Fungal Drugs (Habal) Flashcards Preview

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

Flashcards in Anti-Fungal Drugs (Habal) Deck (61):
1

What fungi cause superficial infections?

Dermatophytes
Malassezia furfur

2

What fungi cause subcutaneous infections?

Sporothrix schenckii
Basidiobolus ranierum

3

What fungi cause primary systemic infections?

Histoplasma capsulatum
Blastomyces dermatitidis
Coccidiodes immitis
Paracoccidiodes brasiliensis

4

What fungi cause primary opportunistic infections?

Candida albicans
Cryptococcus neoformans
Aspergillus fumigatus
Mucor/Rhizopus
Pneumocystis jirovecii

5

What are possible targets of anti-fungal drugs?

Cell wall
Cell membrane
Nucleus
Vacuoles
Cytoplasm
Mitochondria

6

What is the fungal cell wall made up of?

Chitin, glucan, mannan

7

What is the fungal cell membrane made up of?

Phospholipids & sterols (ergosterol)

8

What are the 3 classes of antifungal drugs?

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

9

An optimal antifungal will have?

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

10

Anti-fungal antibiotics include what drugs?

Polyenes - Amphotericine B, Nystatin
Griseofluvn

11

Anti-fungal antimetabolites include?

Flucytosine

12

Anti-fungal azoles include?

Imidazoles - Ketoconazole, Miconazole
Triazoles - Itraconazole, Fluconazole

13

Anti-fungal allylamines include?

Terbinafine

14

What do allylamines such as Terbinafine interfere with?

Squalene epoxidase

15

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

Cytochrome P450 14-alpha demethylase

16

What do polyenes such as Amphotericine B and Nystatin do?

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

17

What resistance might you see against polyenes?

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

18

Are polyenes stable or unstable when taken orally?

Unstable

19

At what concentration are polyenes fungasidal?

High

20

What produces Amphotericin B?

Streptomyces nodosus

21

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

Amphotericin B

22

How is Amphotericin B administered? Why?

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.

23

What causes tubular nephrotoxicity due to administration of Amphotericin B?

Leakage of Na+, K+, Ca+

24

Which anti-fungal drug is the big gun?

Amphotericin B

25

What produces Nystatin?

Streptomyces noursei

26

How is Nystatin administered?

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

27

What is Nystatin routinely used to treat?

Oral thrush (swish and spit).

28

Why is Nystatin so toxic?

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

29

What is a bad side effect of Azoles?

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

30

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

Gynocomastia

31

How can azoles be administered?

Topically, orally, IM, IV

32

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

Most infections, from superficial to systemic

33

What is the mechanism of action for Azoles?

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

34

What are some drugs that Azoles can potentiate?

Diazepam, Cyclosporin, Phynetoin, Warfarin, Isoniazide

35

What are the 2 types of Azoles?

Imidazoles, Triazololes

36

What are the Imidazoles?

Ketoconazole, Miconazole

37

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?

Ketoconazole

38

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

Miconazole

39

What are the triazololes?

Clotrimazole, Fluconazole, Itraconazole, Voriconazole

40

Which Triazolole is administered topically or via vaginal suppositories?

Clotrimazole

41

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

Fluconazole

42

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

Itraconazole

43

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

Voriconazole

44

What should you avoid taking while on Azoles?

Antacids

45

Why is fluconazole used for Cryptococcal meningitis?

Highest CSF penetration rate & highest bioavailability

46

What is the mechanism of allylamines?

Inhibit squalene epoxidase, thus decreasing ergosterol synthesis

47

How are allylamines administered?

Orally or as a topical cream

48

What are allylamines mainly used to treat?

Superficial fungal infections

49

Are there any side effects of allylamines?

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

What 2 drugs are used in conjunction against Cryptococcal meningitis?

Flucytosine & Amp-B

51

How does Flucytosine work?

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

52

What is Flucytosine dose dependent for?

Bone marrow suppression (decreased white blood cells, platelets)

53

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

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

54

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

Echinocandins

55

How is Echinocandins administered?

IV (low oral bioavailability)

56

What is the mechanism for Grieofulvin?

It binds fungal tubulin, interfering with microtubule function.

57

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

Grieofulvin

58

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

Grieofulvin

59

What are the side effects of Grieofulvin?

Teratogenic, increased CYP450 metabolism

60

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

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

61

What are the benefits of combination therapy?

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