28 - 188 - ANTIFUNGALS

Question 1

systemic antifungals are indicated in what?

Answer 1

onychomycosis and tinea capitis

Question 2

the main target of both systemic and topical antifungals

Answer 2

Ergosterol - which is the fundamental mycotic cell membrane sterol

Question 3

what are the 3 main antifungal categories targeting ergosterol?

Answer 3

(1) allylamines and benzylamines,
(2) azoles (imidazole and triazoles), and
(3) polyenes.

Question 4

examples of allylamines

Answer 4

Terbinafine

Naftifine

Question 5

What is the first line of treatment of dermatophytosis?

Answer 5

Terbinafine

Question 6

MOA of Terbinafine

Answer 6

inhibits squalene epoxidase enzyme leading to accumulation of squalene (fungicidal) and deficiency of ergosterol (fungistatic)

Question 7

the only FDA approved drugs for the treatment of tinea capitis in children

Answer 7

Terbinafine and griseofulvin

terbinafine is **less effective **than griseofulvin in eradicating ectothrix tinea capitis in the pediatric population, particularly, that caused by Microsporum canis and Trichophyton tonsurans, because of its high tendency to accumulate in sebum

Question 8

mechanism of action of azoles

Answer 8

inhibition of lanosterol demethylase enzyme (14α-demethylase), a fungal cytochrome P450 (CYP)–dependent enzyme that catalyzes the conversion step of lanosterol into ergosterol, thereby blocking the biosynthesis of ergosterol.

Question 9

considered the best choice in treatment of Candida and nondermatophyte onychomycosis

Answer 9

Itraconazole

Question 10

the only FDA-approved treatment for pediatric onychomycosis,

Answer 10

Griseofulvin

Question 11

mainstay treatment of tinea capitis and onychomycosis

Answer 11

Systemic antifungals

Question 12

Overall, this structure is the main target of both systemic and topical antifungals

Answer 12

ergosterol

the fundamental mycotic cell membrane sterol

Question 13

3 main antifungal categories targeting ergosterol

Answer 13

(1) allylamines and benzylamines,
(2) azoles (imidazole and triazoles), and
(3) polyenes

• allylamines, benzylamines, and azoles block the biosynthesis of ergosterol,
• polyenes bind the molecule with high affinity, creating cell membrane pores

Question 14

this class of antifungal exhibit superior activity against yeasts compared to allylamines

Answer 14

azoles

but less activity against dermatophytes

Question 15

examples of ALLYLAMINES

Answer 15

terbinafine and naftifine

Question 16

are allylamines fungistatic or fungicidal against Candida and dermatophytes?

Answer 16

Candida species (fungistatic),
dermatophytes (fungicidal)

Question 17

They act through the suppression of ergosterol synthesis by** inhibiting the action of squalene epoxidase enzyme, **the enzyme that catalyzes the conversion of squalene precursors into ergosterol.

Answer 17

ALLYLAMINES

terbinafine and naftifine

Question 18

what is responsible for the fungistatic and fungicidal effects of allylamines?

Answer 18

The resultant deficiency of ergosterol is responsible for the fungistatic effect, while the buildup of squalene accounts for fungicidal activity

Question 19

In addition to its antifungal activity, this allylamine has antibacterial activity (gram-positive and gram-negative) as well as antiinflammatory properties secondary to its ability to suppress the synthesis of leukotrienes and prostaglandins

Answer 19

naftifine

Question 20

first line treatment of dermatophytosis

Answer 20

terbinafine

Question 21

how do you give oral terbinafine for tinea unguium?

Answer 21

Question 22

how long should you give terbinafine in tinea unguium of the fingernails?

Answer 22

6 weeks

Question 23

how long should you give terbinafine in tinea unguium of the toenails?

Answer 23

9 - 12 weeks

Question 24

how do you give oral fluconazole in onychomycosis?

Answer 24

150-300 mg/wk
Fingernail for 6-9 mo
Toenail for 9-15 mo

Question 25

how long do you give oral fluconazole in onychomycosis of the fingernails?

Answer 25

6 - 9 months

Question 26

how long do you give oral fluconazole in onychomycosis of the toenails?

Answer 26

9 - 15 months

Question 27

how do you give oral itraconazole in onychomycosis?

Answer 27

Continuous: **200 mg/d ** Fingernail for 6 wk Toenail for 12 wk Pulse:** 400 mg/d for 1 wk/mo ** Fingernail 2 pulses Toenail 3 pulses

Question 28

unique side effect of terbinafine

Answer 28

altered taste

Question 29

most common terbinafine adverse effects

Answer 29

Minimal GI tract upset (eg, abdominal pain, nausea, vomiting, diarrhea), appetite changes, and weight gain

Question 30

the only available antifungal derivative of benzylamine

Answer 30

Butenafine

Question 31

subclassifications of azoles

Answer 31

1. imidazoles 2. triazoles

Question 32

Examples of Imidazoles

Answer 32

ketoconazole, butoconazole, clotrimazole, econazole, luliconazole, miconazole, and sertaconazole,

Question 33

examples of triazoles

Answer 33

fluconazole, itraconazole, efinaconazole, and isavuconazole

Question 34

azoles inhibit what enzyme?

Answer 34

lanosterol demethylase enzyme (14α-demethylase)

Question 35

The only category D antifungal

Answer 35

amorolfine

Question 36

the prescription of oral preparations of this antifungal has now been markedly restricted by the FDA and other health organizations due to drug interaction and serious side effects on the liver and adrenal glands.

Answer 36

Ketoconazole

Question 37

how do you use ketoconazole shampoo in pityriasis versicolor and scalp seborrheic dermatitis

Answer 37

* PV: once daily (left for 5-10 minutes) for 1 to 4 weeks and once weekly for prophylaxis * Scalp seborrheic dermatitis: twice a week for 4 weeks

Question 38

difference of imidazoles and triazoles

Answer 38

Imidazoles have 2-ring nitrogen atoms, whereas triazoles contain 3 and are less prone to metabolic degradation.

Question 39

Fluconazole is efficacious against all Candida except?

Answer 39

C. krusei

Question 40

considered the best choice in treatment of Candida and nondermatophyte onychomycosis

Answer 40

Itraconazole

Question 41

Elderly patients on itraconazole often experience a triad of?

Answer 41

edema, hypertension, and hyperkalemia

Question 42

topical **polyene** derived from Streptomyces spp

Answer 42

Nystatin

Question 43

* has both **fungistatic and fungicidal **activity. * It acts through binding to the mycotic ergosterol, for which its affinity is higher than that of the cholesterol found in mammalian cells. * This binding will result in **creation of pores in the cell membrane **with subsequent leakage of essential fungal intracellular components, resulting in cell death

Answer 43

Nystatin

Question 44

* exhibits broad-spectrum fungicidal and fungistatic, antibacterial, and antiinflammatory activities. * It acts through the i**nhibition of the transmembrane uptake of RNA, DNA, and protein precursors.**

Answer 44

Ciclopirox

Question 45

* novel **oxaborole** antifungal drug that encloses a fluorine atom, decreasing the pH of the boronic center, which inhibits fungal peptide synthesis * acts through **inhibiting a new target, aminoacyl transfer RNA synthetase (AARS)**, for which its affinity is a thousand times that of the mammalian cell and thereby selectively inhibits the mycotic protein synthesis

Answer 45

Tavaborole

Question 46

binds **tubulin**- and m**icrotubule-associated proteins (MAPs**) along the polymerized microtubules, suppressing the formation of the mitotic spindle at the G2/M phase of the cell cycle

Answer 46

Griseofulvin

Question 47

remains the **first line of treatment for tinea capitis caused by Microsporum species** owing to its higher efficacy compared to terbinafine, and similar efficiency yet lower cost compared to itraconazole and fluconazole

Answer 47

Griseofulvin

Question 48

the only FDA-approved treatment for pediatric onychomycosis, though its efficacy is limited to dermatophytes only

Answer 48

Griseofulvin