Antifungal Drugs

Question 1

What are the azoles?

Answer 1

clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole

Question 2

What are the echinocandins?

Answer 2

anidulafungin, caspofungin, micafungin

Question 3

What are the polyene macrolides?

Answer 3

amphotericin B, natamycin, nystatin

Question 4

What are the allylamines?

Answer 4

naftifine, terbinafine, tolnaftate

Question 5

What is the “other” antifungal drug?

Answer 5

flucytosine

Question 6

What is mycoses?

Answer 6

an infectious disease caused by fungi

Question 7

What are the most common locations of fungi infection?

Answer 7

skin, mucous membranes, hair, nails

Question 8

Can there be deep fungal infections?

Answer 8

yes, can spread to blood and organs and be life threatening and difficult to treat

Question 9

T/F Antifungals are only topical

Answer 9

false, they are systemic or topical

Question 10

What are the characteristics of fungi?

Answer 10

eukaryote with rigid cell wall composed of chitin NOT peptidoglycan, cell membrane contains ergosterol, can exist in yeast or mold form

Question 11

T/F fungi are usually resistant to antibiotics and bacteria are usually resistant to antifungals

Answer 11

true

Question 12

Why is the incidence of fungal infections on the rise?

Answer 12

more organ transplants (with chronic immune suppression), chemotherapy, HIV, antibiotic treatment

Question 13

What are azoles good for?

Answer 13

wide clinical use but good for superficial infections like candida and dermatophytes

Question 14

What is the MOA of azoles?

Answer 14

inhibits enzyme responsible for converting lanosterol to ergosterol (disrupts fungal cell membrane structure and function)

Question 15

What is the secondary MOA of azoles?

Answer 15

inhibit human gonadal and adrenal steroid synthesis leading to decreased testosterone and cortisol production

Question 16

What are the adverse effects of azoles?

Answer 16

allergies and minor GI disturbances

Question 17

What are the drug interactions of azoles?

Answer 17

inhibits CYP450 (potentiates toxicities of other drugs), decreased absorption when co-administered with agent decreasing gastric activity

Question 18

What should azoles not be combined with?

Answer 18

amphotericin B because it needs ergosterol in the membrane

Question 19

What shortens the duration of action of ketoconazole?

Answer 19

rifampin because it is an inducer of CYP450

Question 20

What is ketoconzaole?

Answer 20

the first azole used, limited to topical, less selective for fungal enzyme=more side effects

Question 21

What is true of fluconazole?

Answer 21

high oral availability and penetration to CNS

Question 22

What is itraconazole?

Answer 22

drug of choice for histoplasmosis (not exactly fungus), administered orally or parenterally

Question 23

What is the bioavailability of voriconazole?

Answer 23

96% bioavailability, oral or parenteral administration

Question 24

T/F coriconazole is an extensive CYP450 inhibitor?

Answer 24

true, dose reduction may be needed for other meds

Question 25

What are the adverse effects of voriconazole?

Answer 25

30% of patients report visual disturbances (blur, changes in color/brightness, occur immediately then resolve) photosensitivity dermatitis also common

Question 26

What is posaconazole?

Answer 26

new oral/parenteral, broadest spectrum, developed to prevent infections in immunocompromised patients

Question 27

Does posaconazole inhibit or induce CYP450?

Answer 27

inhibits some enzymes

Question 28

Which three azoles are most common topically?

Answer 28

clotrimoazole, miconazole, and ketoconazole (shampoo too)

Question 29

What is the MOA of echinocandins?

Answer 29

interferes with synthesis of B-glucan which disrupts fungal cell wall and causes lysis and cell death

Question 30

What is the absorption of echinocandins?

Answer 30

IV only, poor oral absorption

Question 31

What is caspofungin?

Answer 31

the second line if failure of amphotericin B or azole, requires dose adjustment if given with CYP450 inducer

Question 32

What are the adverse effects of echinocandins?

Answer 32

well tolerated with few side effects, infrequent GI problems, flushing which may be histamine mediated

Question 33

What is amphotericin B?

Answer 33

the only antifungal for years, high toxic potential but still drug of choice for life-threatening systemic mycoses

Question 34

What is the MOA of amphotericin B?

Answer 34

binds to ergosterol in plasma membrane and forms a pore allowing electrolytes and small molecules to escape causing cell death

Question 35

What is resistance of amphotericin B related to?

Answer 35

decreased ergosterol content of fungal membranes

Question 36

What are the pharmacokinetic considerations of amphotericin B?

Answer 36

mainly given by slow IV infusion, extensively bound to plasma proteins, kidney and liver elimination

Question 37

What are the adverse effects of amphotericin B?

Answer 37

low therapeutic index, infusion related toxicity, cumulative toxicity

Question 38

What are the infusion related toxicity aspects of amphotericin B?

Answer 38

fever/chills, muscle spasm, vomiting, headache, hypotension

Question 39

What is the cumulative toxicity aspect of amphotericin B?

Answer 39

renal impairment from decreased glomerular filtration rate (reversible) and anemia

Question 40

What are nystatin and natamycin?

Answer 40

antifungals restricted to topical treatment of candida or corneal infections that resemble amphotericin B

Question 41

What is the MOA of nystatin and natamycin?

Answer 41

binds ergosterol in plasma membrane and forms a pore

Question 42

What is the only commercially available ophthalmic anti-fungal medication?

Answer 42

natamycin

Question 43

What is available for the treatment of thrush?

Answer 43

oral mouthwash of nystatin or natamycin

Question 44

What is flucytosine?

Answer 44

developed as anti-cancer with no real effectivity, now a antifungal

Question 45

What is the MOA of flucytosine?

Answer 45

enters fungal cell and disrupts DNA/protein synthesis, converted intracellularly into 5FU an antimetabolite

Question 46

What is resistance to flucytosine caused by?

Answer 46

decreased levels of enzymes used to convert 5FC to 5FU, rate is lower if given with additional antifungal

Question 47

What is flucytosine often combined with?

Answer 47

amphotericin B, enters pores easily

Question 48

What are the pharmacokinetics of flucytosine?

Answer 48

only available as oral drug, excretion via glomerular filtration, can penetrate CNS

Question 49

What are the adverse effects of flucytosine?

Answer 49

neutropenia, thrombocytopenia, bone marrow depression, GI disturbances

Question 50

What is the MOA of allylamines?

Answer 50

inhibits enzyme (squalene epoxidase) that converts squalene to lanosterol (aka blocks biosynthesis of ergosterol) --squalene builds up and becomes toxic

Question 51

Which allylamine is topical and oral?

Answer 51

terbinafine

Question 52

Which allylamine is topical only?

Answer 52

naftifine

Question 53

What is the drug of choice for treating fungal infections of nails?

Answer 53

terbinafine (effective for skin infection as well)

Question 54

What are the pharmacokinetics of allylamines?

Answer 54

40% bioavailability orally, deposited in skin, nails and fat, urinary excretion

Question 55

What are the adverse effects of allylamines?

Answer 55

orally-- GI disturbance, headache, rash, some visual disturbances topically-- irritation and redness when in contact with mucous membranes