Antifungal Drugs

Question 1

What fungi are superficial?

Answer 1

Dermatophytes

Malassezia furfur

Question 2

What fungi are subcutaneous?

Answer 2

Sporothrix schenckii

Basidiobolus ranierum

Question 3

What fungi are primary systemic?

Answer 3

Histoplamsa capsulatum
Blastomyces dermatitidis
Coccidioides immits
Paracoccidiodes brasiliensis

Question 4

What fungi are primary opportunistic?

Answer 4

Candida albicans
Cryptococcus neoformans 
Aspergillus fumigatus
Mucor/Rhizopus 
Pneumocystis jirovecii

Question 5

What are the possible structures in a fungus that a drug could target?

Answer 5

Cell membrane (ergosterol) 
Cell wall (chitin, glucan, mannan)
Nucleus
Vacuole
Cytoplasm
Mitochondria

Question 6

What antifungal inhibit cell wall (glucan) synth?

Answer 6

Echinocandins

Question 7

What antifungals inhibit cell membrane (ergosterol) synth?

Answer 7

Polyene

Azoles

Question 8

What antifungals RNA/DNA synth by the pyrimidine sythesis?

Answer 8

Flucytosine

Question 9

What are the characteristics of the optimal antifungal?

Answer 9

Wide spectrum of activity
Favorable bioactivity
Adequate in vivo efficacy
High therapeutic index 
Low cost

Question 10

What are the polyenes?

Answer 10

Amphotericin B and Nystatin

Question 11

What is the action of polyenes against fungi?

Answer 11

Binds to ergosterol to form a pore making the membrane leaky

Question 12

Describe the structure of a polyene.

Answer 12

A large lactone ring with conjugated double bond with a lipophillic side and a hydrophillic side

Question 13

What is amphotericin B produced by?

Answer 13

Streptomyces nodosus

Question 14

In the cell membrane, what does amphotericin cause to happen?

Answer 14

Causes a leakage of NA+, K+ and Ca+2

Question 15

Is amphotericin B a broad spectrum fungicidal?

Answer 15

Yes

Question 16

How would you administer amphotericin B to a pt?

Answer 16

Intravenous ONLY

Question 17

Why doesn’t amphotericin B work well in oral form?

Answer 17

It’s highly unstable in the GI and wants to be bound to serum proteins so it works better in the blood
Lipsomal amp-B exists for oral but its expensive

Question 18

What adverse effects could amp-B have?

Answer 18

Binds to host cell of cholesterol causing the affinity to lessen and becoming toxic
The injection might hurt
Could cause acute chills, fever and vomiting
Could chronically cause nephrotoxicity

Question 19

What is nystatin produced by?

Answer 19

Streptomyces noursei

Question 20

Which polyenes are used for a local infection and which is used for severe fungal infections?

Answer 20

Nyastin for local

Amp-b for severe

Question 21

How should nystatin be administered?

Answer 21

Topical cream or as a mouth wash (oral thrush)

Question 22

How is an azole composed?

Answer 22

5-membered azole ring with at least one non-carbon atom

Classified by the number of nitrogen

Question 23

Are azoles broad spectrum antifungals?

Answer 23

Yes

Question 24

What is the mechanism for azoles?

Answer 24

Inhibits ergosterol synthesis by inhibition of CYP450

Question 25

What could happen if an azole interacts with a human CYP450?

Answer 25

Drug detox could be impaired | Steroid hormone biosynth in adrenal gland could be impaired

Question 26

What would you call an azole with two nitrogens? And what are some examples?

Answer 26

Imidazole | Ketoconazole and Miconazole

Question 27

What would an azole be called if it had 3 nitrogens? And what are some examples?

Answer 27

Triazole | Itraconazole, Fluconazole, Clotrimazole and Voriconazole

Question 28

What azole is effective against candida?

Answer 28

Voriconazole

Question 29

What are the properties of Ketoconazole (KCZ)?

Answer 29

Broad spectrum PO administration Mostly replaced by fluconazole

Question 30

What are the side effects of Ketoconazole?

Answer 30

Gynocomastia and hepatic failure

Question 31

What are the properties of Miconazole?

Answer 31

Topical and vaginal suppositories | Dermatophytes

Question 32

What are the properties of Clotrimazole?

Answer 32

Topical and vaginal suppositories

Question 33

What are the properties of Fluconazole (FCZ)?

Answer 33

Oral, esophageal and vaginal candidas Generally used post initial treatment with amp-b Used for cryptococcal meningitis Oral and IV

Question 34

What are the properties of Itraconazole (ICZ)?

Answer 34

Broad spectrum inclusing tinea unguium Indicated for systemic fungal infections Also for oral and esophageal candidiasis

Question 35

What are the properties of Voriconazole (VCZ)?

Answer 35

Oral and IV High bioavailability Indicated for invasive aspergillosis

Question 36

Azole have very excellent _____ penetration.

Answer 36

CSF

Question 37

What is the action of allylamine?

Answer 37

Inhibit squalene expoidase to dec erogsterol synthesis

Question 38

What type of fungal infections do allylamines work against?

Answer 38

Superficial

Question 39

How are allylamines administered?

Answer 39

Oral and topical

Question 40

How do flucytosines work?

Answer 40

Blocks DNA and RNA synth

Question 41

How are flucyosines adminstered and where do they penetrate the best?

Answer 41

Oral, CSF

Question 42

What are flucyosines used against?

Answer 42

Candida and Cryptococcus neoformans

Question 43

What is the mechanism of actions for flucyosines?

Answer 43

Cyostine specific permases Converted to 5Fdump to distrucpt DNA Converted to 5FUMP to disrupt RNA

Question 44

What are echinocandins (caspofungin) produced from?

Answer 44

Glarea lozoyensis

Question 45

How do you administer echinocandins?

Answer 45

IV

Question 46

What is the mechanism of action for echinocandin?

Answer 46

Inhibits 1,3-B-glucan synthase | Cell wall synth inhibitor

Question 47

What are echinocandins used for?

Answer 47

Invasive amp-B resistant aspergillosis Esophageal candidiasis Pneumocystis pneumonia

Question 48

What is grieofulvin isolated from?

Answer 48

Pencillium griseofulvum

Question 49

How does grieofulvin work?

Answer 49

Binds to fungal tubulin which interferes with microtubular function

Question 50

What is grieofulvin highly effective against?

Answer 50

Athlete's foot and other taenia infections

Question 51

What are the side effects of grieofulvin?

Answer 51

Teratogenic and inc CYP450 metabolism