antifungals

Question 1

what’s the mechanism of action of Azoles

Answer 1

inhibition of fungal 14-α-demethylase (CYP450) → inhibition of ergosterol synthesis

Question 2

what’re the adverse effects of Azoles

Answer 2

hepatotoxicity, gynecomastia (ketoconazole), QT prolongation, adrenal insufficiency (ketoconazole), visual impairment (voriconazole), teratogenic

Question 3

which Azole is characteristic for causing ginecomastia upon it’s use? how does it do that?

Answer 3

ketoconazole

ketoconazole decreases the levels of testosterone

Question 4

which Azole causes adrenal insufficiency? what effects does this have on the patient? how does the drug do this?

Answer 4

ketoconazole

it can cause hypotension (because of low aldosterone), hypokalemia and hypoglycemia (because low cortisol) all because of the adrenal insufficiency

it’s caused by the inhibition of 14α-hydroxylase and 17,20-lyase

Question 5

which azole causes visual impairment

Answer 5

voriconazole

Question 6

what are the contraindications for the use of azoles

Answer 6

arrhythmia, PPI use, pregnancy (1st trimester)

azoles need a low gastric ph to be absorbed, so using a PPI will decrease it’s absorption

Question 7

how do Azoles affect the CYPs?

Answer 7

CYP2C9, CYP2C19, CYP3A4 inhibition

Question 8

what are the subdivisions of Azoles

Answer 8

triazoles

imidazoles

Question 9

what’s the administration of triazoles

Answer 9

oral

Question 10

what’s the administration of imidazoles

Answer 10

topical

Question 11

which medications are considered azoles

Answer 11

Fluconazole
Itraconazole
Voriconazole
Posaconazole
Isavuconazole

Question 12

what’s the use of fluconazole

Answer 12

cryptococcal meningitis (maintenance therapy), candidiasis (all forms, including cystitis)

- great bioavailability !! → exception to the PPI rule

Question 13

you need a low stomach ph to absorb azoles correctly, that’s why. you can’t take PPI when using azoles

only one azole is an exception, which one

Answer 13

fluconazole

Question 14

what’s the use of Itraconzole ? does it have any considerations?

Answer 14

sporotrichosis, ABPA, histoplasmosis, blastomycosis, paracoccidioidomycosis, paracoccidioidomycosis, dermatophytosis (follicular involvement), pityriasis versicolor

- it’s a NEGATIVE INOTROPIC → decreases the heart contractility
- poor CNS penetration, bad bioavailability

Question 15

what’s the use of Voriconazole? what’s it’s side effect?

Answer 15

• invasive aspergilosis → FISRT LINE TREATMENT
  
  • causes photosensibility

Question 16

what’s the use of Posaconazole

Answer 16

mucormycosis, invasive aspergilosis (prophylaxis), candidiasis (prophylaxis)

Question 17

what’s the use of Isavuconazole

Answer 17

invasive aspergilosis, mucormycosis

Question 18

which meds are Imidazoles

Answer 18

Ketoconazole

Clotrimazole, Miconidazole

Question 19

what’s the use of Ketoconazole

Answer 19

pityriasis versicolor

it can also be used in cushing syndrome because of it’s effect on the adrenal gland

Question 20

what’s the use of Clotrimitazole, Miconidazole

Answer 20

candidiasis (oropharyngeal, vaginal), dermatophytosis

Question 21

what med is an Allynamines

Answer 21

Terbinafine

Question 22

how do Allynamines work and what’s their use?

Answer 22

• mechanism: inhibition of fungal squalene epoxidase → ⭡squalene → ⭣ergosterol
• use: onychomycosis and other dermatophytosis

Question 23

what are the adverse effects of Allynamines

Answer 23

hepatotoxicity, GI discomfort, taste disturbances

Question 24

what’s the via of administration of Echinocandins

Answer 24

IV

Question 25

which meds are Echinocandins

Answer 25

Caspofungin, Micafungin, Anidulafungin

Question 26

which Enchinocandin is quimicaly degraded in the blood

Answer 26

Anidulafungin

Question 27

what's the mechanism and use of Enchinocandins

Answer 27

- mechanism: inhibition of β-1,3-D-glucan synthesis → ⭣cell wall synthesis - use: **invasive candidiasis**, invasive aspergillosis

Question 28

adverse effects of Enchinocandins

Answer 28

hepatotoxicity, flushing, GI discomfort

Question 29

what meds are Polyenes

Answer 29

Amphotericin B, Nystatin

Question 30

what's the mechanism of action of polyenes

Answer 30

mechanism: binds ergosterol in membrane → formes pores in membranes

Question 31

what's the use of amphotericin B

Answer 31

systemic effect → *cryptococcal meningitis (induction therapy)*, invasive aspergillosis, invasive dimorphic mycosis, invasive candidiasis, mucormycosis Amphotericin B is a dose dependen drug = you need to use high doses = bad nephrotoxicity → IV hydration can help

Question 32

what's the use of nystatin

Answer 32

local effect → candidiasis (oropharyngeal, intertrigo, vaginal)

Question 33

what are the adverse effects of polyenes

Answer 33

nephrotoxicity, phlebitis, anemia, arrhythmias, teratogenic

Question 34

what med is a Benzofurans and what's it via of administration?

Answer 34

- med: Griseofulvin (oral) → this will accumulate in keratin rich tissues

Question 35

what's the mechanism of action and use of Griseofulvin

Answer 35

- mechanism: binds to β-tubulin → ⭣microtubule function → ⭣fungal mitosis - use: dermatophytosis

Question 36

what're the adverse effects of Griseofulvin

Answer 36

- adverse effects: hepatotoxicity, teratogenic, carcinogenic, disulfiram-like reaction - CYP2C9 and CYP3A4 inducer

Question 37

what's Flucytosine? how does it work?

Answer 37

Antimetabolites converted to 5-fluorouracil via fungal cystosine deaminase → ⭣DNA replication and transcription

Question 38

use and adverse effects of Flucytosine?

Answer 38

- use: cryptococcal meningitis (induction therapy + Amphotericin B) - adverse effects: hepatotoxicity, **nephrotoxicity**, teratogenic, **pancytopenia**, GI discomfort

Question 39

what med is a Pyridone Derivative

Answer 39

Ciclopirox

Question 40

what's the use of Ciclopirox

Answer 40

pityriasus versicolor, dermatophytosus, seborrheic dermatitis

Question 41

adverse effects of Ciclopirox

Answer 41

arrhythmias, facial edema, pruritis

Question 42

what's the use of Selenium sulfide

Answer 42

pityriasis versicolor, seborrheic dermatitis

Question 43

tx for Pneumocystis Pneumonia

Answer 43

trimethoprim-sulfamethoxazole, dapsone, pentamidine

Question 44

tx for mild and severe forms of Pityriasis Versicolor

Answer 44

- mild → topical selenium sulfide, terbinafine, ciclopirox, miconazole, ketoconazole - severe → fluconazole, itraconazole

Question 45

tx for Dermatophytosis with no follicular involvemen

Answer 45

No follicular involvement → terbinafine (topical), clotrimazole, miconazole, ciclopirox

Question 46

tx for Dermatophytosis with Extensive/refractory disease

Answer 46

Extensive/refractory disease → terbinafine (oral), fluconazole, itraconazole, grisefulvin

Question 47

tx for Mucormycosis

Answer 47

emergent surgical debridement + amphotericin B, isavuconazole

Question 48

tx for mild and severe forms of: histoplasmosis, blastomycosis, coccidioidomycosis, paracoccidioides, sporotrichosis

Answer 48

- mild → itraconazole, fluconazole - severe → amphotericin B

Question 49

tx for Invasive aspergillosis

Answer 49

Voriconazole +/- Caspofungin

Question 50

tx for Cryptococcosis

Answer 50

Amphotericin B + Flucytosine (induction) → Fluconazole (maintenance)

Question 51

tx for Candidiasis: - intertriginous → - oropharyngeal → - esophageal → - vulvovaginal → - cystitis → - systemic →

Answer 51

- intertriginous → Nystatin (topical) - oropharyngeal → Clotrimazole, Miconazole, Nystatin (oral) - esophageal → Fluconazole (oral), Itraconazole - vulvovaginal → Clotrimazole, Miconazole, Fluconazole - cystitis → Fluconazole - systemic → Echimocandin (immunosuppressed), Amphotericin B