Pharm: Pulmonary Antifungals

Question 1

What are a handful of common (endemic) fungal infections of the lungs?

Answer 1

1. Histoplasmosis
2. Coccidiodomysosis (Valley Fever)
3. Blastomycosis
4. Cryptococcosis
5. Penicilliosis
6. Paracoccidiomycosis

Question 2

Coccidiodiomycosis (Valley Fever) Demographic?

Answer 2

Central Valley of CA and Arizona

Question 3

Cryptococcosis Demographic?

Answer 3

NW USA

Question 4

Penicilliosis Demographic?

Answer 4

Asia

Question 5

Paracoccidiomycosis Demographic?

Answer 5

Central & South America

Question 6

What are several opportunistic fungal infections that cause pulmonary pneumonia in the immunocompromised?

Answer 6

1. Candidiasis
2. Aspergillosis
3. Sporotrichosis

Question 7

What are the 4 categories of antifungal meds used for fungal pneumonia?

Answer 7

1. Polyene Antifungals
2. Antimetabolites
3. Azoles
4. Echinocandins

Question 8

What med is a Polyene Antifungal?

Answer 8

Amphotericin B & Nystatin

Question 9

What med is an Antimetabolite?

Answer 9

Flucytosine (cytosine analog)

Question 10

What meds are Azoles?

Answer 10

Fluconazole & Itraconazole

Question 11

What meds are Echinocandins?

Answer 11

Micafungin & Caspofungin

**cyclic peptides; end in “-fungins”

Question 12

What is the MOA of Flucytosine?

Answer 12

Inhibition of fungal DNA & RNA synthesis by being converted into fluorouridine phosphates.

Question 13

What is the MOA of Fluconazole & Itraconazole?

Answer 13

Inhibition of P450 enzyme -> inhibiting ergosterol synthesis/formation within the fungal cell membrane.

Question 14

What is the MOA of Amphotericin B & Nystatin?

Answer 14

Binds to ergosterol within the fungal cell membrane -> Forming channels or pores in the membrane -> increasing membrane permeability

Question 15

What is the MOA of Micafungin & Caspofungin?

Answer 15

Inhibition of B-glycan synthase, uniquely a part of fungal cell membrane/wall.

**Fungicidal; referred as fungal penicillins

Question 16

Is ergosterol found within fungal, mammalian or both cell membranes?

Answer 16

ONLY Fungal

Question 17

Do polyene antifungals have a broad or limited spectrum of action? Why?

Answer 17

Broad spectrum of action because they have an incomplete selectivity for fungal cell membranes.

Question 18

What are polyene antifungals “poor” absorption, distribution and soluble actions?

Answer 18

1. Poor oral absorption
2. Poor CNS distribution
3. Poor water solubility -> difficult IV administration

Question 19

What form of administration is preferred for polyene antifungals?

Answer 19

Liposomal Form

Question 20

What are the adverse effects of Amphotericin B?

Answer 20

Infusion-Related -

1. Fever, chills, muscle spasms, headaches
   * **reduced by adding administration of antihistamines, corticosteroids, & antipyretics

Chronic Toxicity -

2. Renal damage (can be irreversible)
3. Renal tubular acidosis
4. Hepatic Injury (reversible)

Question 21

Amphotericin B is administered by? Nystatin?

Answer 21

Amphotericin B = systemic & topical

Nystatin = topical ONLY

Question 22

Are human cells able to convert Flucytosine into DNA and RNA molecules?

Answer 22

NO!

Question 23

Flucytosine is administered by? And, has a broad or limited spectrum of action?

Answer 23

Oral administration, and a Limited spectrum of action

Question 24

What are the adverse effects of Flucytosine and how are they caused?

Answer 24

Anemia, Leukopenia & Thrombocytopenia resulting from the conversion of 5-fluorouracil by GI flora.

Question 25

Are Fluconazole & Itraconazole have a broad or limited spectrum of action? What is that action?

Answer 25

Broad spectrum of action -> Fungistatic (inhibits the growth of fungus)

Question 26

Do Azoles penetrate the CNS?

Answer 26

Yes!

Question 27

What are the adverse effects of Azoles?

Answer 27

1. Drug interactions (common) | 2. GI upset

Question 28

What is the route of administration for Echinocandins?

Answer 28

IV ONLY

Question 29

What are the adverse effects of Micafungin & Caspofungin?

Answer 29

1. Elevation of aminotransaminases 2. Drug interactions 3. Histamine release

Question 30

Severe Histoplasmosis or Blastomycosis tx? Moderately severe tx?

Answer 30

``` Severe = Amphotericin B + Glucocorticoid Moderate = Itraconazole ```

Question 31

Coccidiomycosis tx?

Answer 31

a. Amphotericin B + Glucocorticoid, followed by Itraconazole OR b. prolonged Itraconazole

Question 32

Severe Cryptococcus tx? Moderately severe tx?

Answer 32

``` Severe = Amphotericin B + Corticosteroid, followed by Fluconazole or Flucytosine Moderate = Fluconazole ```

Question 33

Pulmonary Candidiasis tx?

Answer 33

a. Amphotericin B + Glucocorticoid b. Fluconazole c. Caspofungin

Question 34

Aspergillosis tx?

Answer 34

a. Voriconazole b. Micafungin c. Amphotericin B + Glucocorticoid

Question 35

Sporotrichosis tx?

Answer 35

a. Itrazconazole | b. Amphotericin B + Glucocorticoid

Question 36

Penicilliosis tx?

Answer 36

a. Amphotericin B + Glucocorticoid, then Itraconazole | b. Itraconazole ONLY (milder forms)

Question 37

Paracoccidioidomycosis tx?

Answer 37

Itraconazole

Question 38

What is the preferred tx in a severe symptomatic pulmonary infection or immunocompromised patient?

Answer 38

Fungicidal IV Amphotericin B + Glucocorticoid **The patient can be switched to the appropriate oral azole antifungal w/subsequent improvement.

Question 39

What may mild pulmonary fungal infections be treated with?

Answer 39

Fungistatic Oral Azoles = Fluconazole or Itraconazole

Question 40

What are the 2 tx options used in long-term fungal pulmonary infection therapy?

Answer 40

4-6 wks of Amphotericin B &/or 3-12 mths of oral Azoles (Fluconazole or Itraconazole)