Anti-Fungal Drugs (Habal)

Question 1

What fungi cause superficial infections?

Answer 1

Dermatophytes

Malassezia furfur

Question 2

What fungi cause subcutaneous infections?

Answer 2

Sporothrix schenckii

Basidiobolus ranierum

Question 3

What fungi cause primary systemic infections?

Answer 3

Histoplasma capsulatum
Blastomyces dermatitidis
Coccidiodes immitis
Paracoccidiodes brasiliensis

Question 4

What fungi cause primary opportunistic infections?

Answer 4

Candida albicans
Cryptococcus neoformans
Aspergillus fumigatus
Mucor/Rhizopus
Pneumocystis jirovecii

Question 5

What are possible targets of anti-fungal drugs?

Answer 5

Cell wall
Cell membrane
Nucleus
Vacuoles
Cytoplasm
Mitochondria

Question 6

What is the fungal cell wall made up of?

Answer 6

Chitin, glucan, mannan

Question 7

What is the fungal cell membrane made up of?

Answer 7

Phospholipids & sterols (ergosterol)

Question 8

What are the 3 classes of antifungal drugs?

Answer 8

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

Question 9

An optimal antifungal will have?

Answer 9

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

Question 10

Anti-fungal antibiotics include what drugs?

Answer 10

Polyenes - Amphotericine B, Nystatin

Griseofluvn

Question 11

Anti-fungal antimetabolites include?

Answer 11

Flucytosine

Question 12

Anti-fungal azoles include?

Answer 12

Imidazoles - Ketoconazole, Miconazole

Triazoles - Itraconazole, Fluconazole

Question 13

Anti-fungal allylamines include?

Answer 13

Terbinafine

Question 14

What do allylamines such as Terbinafine interfere with?

Answer 14

Squalene epoxidase

Question 15

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

Answer 15

Cytochrome P450 14-alpha demethylase

Question 16

What do polyenes such as Amphotericine B and Nystatin do?

Answer 16

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

Question 17

What resistance might you see against polyenes?

Answer 17

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

Question 18

Are polyenes stable or unstable when taken orally?

Answer 18

Unstable

Question 19

At what concentration are polyenes fungasidal?

Answer 19

High

Question 20

What produces Amphotericin B?

Answer 20

Streptomyces nodosus

Question 21

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

Answer 21

Amphotericin B

Question 22

How is Amphotericin B administered? Why?

Answer 22

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.

Question 23

What causes tubular nephrotoxicity due to administration of Amphotericin B?

Answer 23

Leakage of Na+, K+, Ca+

Question 24

Which anti-fungal drug is the big gun?

Answer 24

Amphotericin B

Question 25

What produces Nystatin?

Answer 25

Streptomyces noursei

Question 26

How is Nystatin administered?

Answer 26

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

Question 27

What is Nystatin routinely used to treat?

Answer 27

Oral thrush (swish and spit).

Question 28

Why is Nystatin so toxic?

Answer 28

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

Question 29

What is a bad side effect of Azoles?

Answer 29

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

Question 30

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

Answer 30

Gynocomastia

Question 31

How can azoles be administered?

Answer 31

Topically, orally, IM, IV

Question 32

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

Answer 32

Most infections, from superficial to systemic

Question 33

What is the mechanism of action for Azoles?

Answer 33

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

Question 34

What are some drugs that Azoles can potentiate?

Answer 34

Diazepam, Cyclosporin, Phynetoin, Warfarin, Isoniazide

Question 35

What are the 2 types of Azoles?

Answer 35

Imidazoles, Triazololes

Question 36

What are the Imidazoles?

Answer 36

Ketoconazole, Miconazole

Question 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?

Answer 37

Ketoconazole

Question 38

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

Answer 38

Miconazole

Question 39

What are the triazololes?

Answer 39

Clotrimazole, Fluconazole, Itraconazole, Voriconazole

Question 40

Which Triazolole is administered topically or via vaginal suppositories?

Answer 40

Clotrimazole

Question 41

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

Answer 41

Fluconazole

Question 42

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

Answer 42

Itraconazole

Question 43

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

Answer 43

Voriconazole

Question 44

What should you avoid taking while on Azoles?

Answer 44

Antacids

Question 45

Why is fluconazole used for Cryptococcal meningitis?

Answer 45

Highest CSF penetration rate & highest bioavailability

Question 46

What is the mechanism of allylamines?

Answer 46

Inhibit squalene epoxidase, thus decreasing ergosterol synthesis

Question 47

How are allylamines administered?

Answer 47

Orally or as a topical cream

Question 48

What are allylamines mainly used to treat?

Answer 48

Superficial fungal infections

Question 49

Are there any side effects of allylamines?

Answer 49

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.

Question 50

What 2 drugs are used in conjunction against Cryptococcal meningitis?

Answer 50

Flucytosine & Amp-B

Question 51

How does Flucytosine work?

Answer 51

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

Question 52

What is Flucytosine dose dependent for?

Answer 52

Bone marrow suppression (decreased white blood cells, platelets)

Question 53

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

Answer 53

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

Question 54

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

Answer 54

Echinocandins

Question 55

How is Echinocandins administered?

Answer 55

IV (low oral bioavailability)

Question 56

What is the mechanism for Grieofulvin?

Answer 56

It binds fungal tubulin, interfering with microtubule function.

Question 57

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

Answer 57

Grieofulvin

Question 58

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

Answer 58

Grieofulvin

Question 59

What are the side effects of Grieofulvin?

Answer 59

Teratogenic, increased CYP450 metabolism

Question 60

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

Answer 60

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

Question 61

What are the benefits of combination therapy?

Answer 61

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