32 Antifungal drugs

Question 1

32.01 ANTIFUNGAL ANTIBIOTICS

Amphotericin, nystatin - actions and MOA

Answer 1

kill fungi by binding to the ergosterol in the fungal cell membrane (missing in mammalian cells) and increasing membrane permeability

Question 2

32.01 ANTIFUNGAL ANTIBIOTICS

Amphotericin, nystatin - abs/distrib/elim

Answer 2

not absorbed in the GIT
given by IV infusion in a lipid formulation
can cross the blood-brain barrier in meningitis
given topically by lozenge for oral fungal infections
nystatin given orally

Question 3

32.01 ANTIFUNGAL ANTIBIOTICS

Amphotericin, nystatin - clinical use

Answer 3

candidiasis, cryptococcal meningitis, histoplasmosis, aspergillosis, blastomycosis, coccidiomycosis, mucormycosis
nystatin: GIT candidiasis

Question 4

32.01 ANTIFUNGAL ANTIBIOTICS

Amphotericin, nystatin - adverse effects

Answer 4

amphotericin: when given IV - renal toxicity, CVS toxicity, GIT disturbances, neurological disturbances, anaphylactoid reactions, infusion reactions (fever, headache, chills), myalgia, arthralgia
nystatin: nausea, vomiting, diarrhoea

Question 5

32.02 SYNTHETIC ANTIFUNGAL DRUGS - AZOLES

Fluconazole, itraconazole, voriconazole - actions

Answer 5

fungistatic by inhibiting the synthesis of ergosterol - a crucial component of fungal cell membranes (missing in mammalian cells)

Question 6

32.02 SYNTHETIC ANTIFUNGAL DRUGS - AZOLES

Fluconazole, itraconazole, voriconazole - MOA

Answer 6

inhibits 14α-demethylase - a P450-dependent enzyme important in the conversion of lanosterol to ergosterol

Question 7

32.02 SYNTHETIC ANTIFUNGAL DRUGS - AZOLES

Fluconazole, itraconazole, voriconazole - abs/distrib/elim

Answer 7

given orally or IV
widely distributed, passing into CSF, ocular fluids, vaginal tissue, nails, saliva, skin
half-life of fluconazole ~25h

Question 8

32.02 SYNTHETIC ANTIFUNGAL DRUGS - AZOLES

Fluconazole, itraconazole, voriconazole - clinical use

Answer 8

fluconazole: candidiasis - local (dermal, mucosal) and invasive, tinea corporis, tinea cruris and tinea pedis, cryptococcal meningitis, histoplasmosis, blastomycosis, coccidiomycosis
itraconazole: fungal skin infections
voriconazole: life-threatening fungal infections

Question 9

32.02 SYNTHETIC ANTIFUNGAL DRUGS - AZOLES

Fluconazole, itraconazole, voriconazole - adverse effects

Answer 9

GIT disturbances
headache, rash
liver toxicity
hypersensitivity reactions

Question 10

32.03 OTHER ANTIFUNGAL DRUGS

Griseofulvin

Answer 10

narrow-spectrum antifungal agent
interferes with mitosis by binding to fungal microtubules
used to treat dermatophyte infection of the skin or nails when local administration is ineffective
largely been superseded by other drugs

Question 11

32.03 OTHER ANTIFUNGAL DRUGS

Caspofungin

Answer 11

fungicidal by weakening fungal cell wall
given by IV infusion
given for candidiasis and aspergillosis

Question 12

32.03 OTHER ANTIFUNGAL DRUGS

Flucytosine

Answer 12

synthetic, orally active antifungal agent that is effective against a limited range of systemic fungal infections
given orally or by IV infusion
half-life 3-5h

Question 13

32.03 OTHER ANTIFUNGAL DRUGS

Terbinafine

Answer 13

broad-spectrum antifungal
inhibits synthesis of ergosterol
used in fungal infections of the nails and skin (tinea corporis, tinea cruris and tinea pedis, aka ‘ringworm’)
similar drug: naftifine (not in United Kingdom)

Question 14

32.03 OTHER ANTIFUNGAL DRUGS

Amorolfine

Answer 14

interferes with fungal sterol synthesis
available as nail lacquer for onychomycoses