Antifungals

Question 1

clotrimazole

Answer 1

topical OTC for tinea and candida

Question 2

miconazole

Answer 2

topical OTC for tinea and candida

Question 3

ketoconazole

Answer 3

for systemic infection; relies on gastric acidity for absorption
used for superficial dermatophytes, Cushing’s syndrome (dec cort synth), prostate cancer (dec test synth), hypercalcemia in sarcoidosis (inh form active vit D)

Question 4

ADR ketoconazole

Answer 4

less specific affinity for fungal P450 -> GI, rash, inhibits adrenal steroid synthesis (gynecomastira, dec libido), hepatotoxic potential
potent CYP 3A4 inhibitor

Question 5

MOA azoles

Answer 5

inhibit lanosterol -> ergosterol by inhibiting P450-dependent lanosterol C14-demethylase

Question 6

ADR of azoles

Answer 6

drugs intx, cholesterol synthesis, cell toxicity
pregnancy cat C (vori is D)
liver failure (monitor LFTs)

Question 7

fluconazole

Answer 7

oral and IV for candida prophylaxis and tx
*renal elimination
best tolerated of all azoles
ADR: GI, rash, HA, alopecia (high dose); strong CYP 2C9 and 2C19 inhibitor, 3A4 in high doses

Question 8

itraconazole

Answer 8

greater spectrum than flu, includes Aspergillus
used for onychomycosis
ADR: GI, diarrhea, taste disturbances, elevated LFTs, rare HF with long therapy (neg inotrope)
strong CYP 3A4 and P-glycoprotein inhibitor

Question 9

voriconazole

Answer 9

better against Aspergillus than itra
for invasive candidiasis and aspergillosis, penetrates CNS but not urine
ADR: transient visual disturbances, rash, photosensitivity, hallucinations, prolonged QT
inhibits CYP 2C9, 2C19, 3A4; preg cat D

Question 10

posaconazole

Answer 10

better for mucor than vori
oral suspension taken with high-fat meal or liquid supplement, reserved for mod fungal infxn res to itra
poor penetration to CSF and urine
ADR: like flu, strong CYP 3A4 inhibitor

Question 11

terbinafine MOA

Answer 11

inhibits squalene -> squalene epoxide = toxic, suicidal mechanism

Question 12

uses and ADR terbinafine

Answer 12

onychomycosis (> itra)
ADR: GI complaints, HA, rash; less common: hepatotoxicity, SJS, blood dycrasias, taste disturbances
strong CYP 2D6 inhibitor, preg cat B

Question 13

polyenes MOA

Answer 13

bind ergosterol in cell membrane

Question 14

uses amphotericin B

Answer 14

slow IV infusion for systemic infections and in pregnancy

Question 15

lipid formulation of ampho B

Answer 15

fewer acute reactions but more expensive

Question 16

ADR ampho B

Answer 16

infusion-related (fever, chills, n/v, HA, myalgias - prophy with NSAID, hydrocortisone, diphenhydramine), nephrotoxicity d/t aff arteriole constriction (prophy with saline), hypokalemia d/t renal tubule toxicity

Question 17

nystatin

Answer 17

polyene; topical cream or ointment, sometimes oral suspension for oral thrush
can be used for recurrent gut infections in AIDS patients

Question 18

echinocandin MOA

Answer 18

inhibits B-glucan synthase, disrupting glucan polymers in cell wall

Question 19

caspofungin, micafungin, anidulafungin

Answer 19

echinocandin antifungals

Question 20

uses of echinocandins

Answer 20

DOC for invasive candidiasis (minimal CSF or urine penetration), alternative to azole antifungals for candida and aspergillus infections

Question 21

echinocandin ADRs

Answer 21

fever, phlebitis at IV site, elevated LFTs, minimal drug interactions

Question 22

griseofulvin

Answer 22

for dermatophyte infections
poor tolerance d/t allergic reactions, photosensitivity, GI distress, neurologic effects
take with high-fat meal for best absorption
enzyme inducer

Question 23

flucytosine

Answer 23

anti-cancer drug not used anymore d/t BM toxicity
inhibits DNA/RNA synthesis when converted to 5-FU intracellularly (toxic antimetabolite)
was used for severe systemic infections with ampho B