Antifungals Flashcards
List the azole antifungals (synthetic triazole)
Fluconazole = BS
Itraconazole = BS
Ketoconazole = BS
miconazole
posaconazole
voriconazole
Which azoles inhibit cyp?
Fluconazole = narrow spectrum
Itraconazole = broad spectrum
What is the MOA of azoles? (mention kind of action)
Prevent the conversion of lanosterol into ergosterol (similar to cholesterol responsible for fungal cell wall) through inhibition of fungal cyp450 (3A4) enz 14-alpha-demethylase
Broad-spectrum fungistatic action
What are some ADRs of azoles?
Rash, headache, dizziness, elevated liver enz (in oral forms)
Constipation = itraconazole
Thrombocytopenia (voriconazole)
What are some C/I to azoles?
Allergy to azoles –> inc exposure –> sensitisation of immune system
Summarise the drug interactions seen with azoles
Inhibits CYP3A4
- inc lvls of midazolam, lovastatin, warfarin, ritonavir, CCB, cyclosporin, digoxin
Azole lvls altered by drugs that inhibit/induce CYP3A4
List the relevant polyene antifungals
Amphotericin
Nystatin (not systemic due to lack of absorption –> IV)
What is the MOA of polyene antifungals? (mention kind of action)
Bind ergosterols –> inc mem permeability –> inc leakage of cell contents
Fungicidal
List the ADRs of amphotericin
Chills, fever
Diarrhoea
N/V
Nephrotoxicity = be careful w/ use alongside other nephrotoxic drugs (vancomycin, aminoglycoside
Hypokalaemia
Summarise the drug interactions associated with amphotericin
cyclosporine, antineoplastic = Inc renal tox
Thiazides and corticosteroids = inc hypokalaemia
List the relevant echinocandin antifungals
Caspofungin
Anidulafungin
What is the MOA of echinocandin antifungals? (mention kind of action)
Inhibit synthesis of fungal cell wall component beta-1,3-D-glucan
Fungicidal, broad-spectrum
What are some ADRs of echinocandins?
Headache, fever, phlebitis
Abnormal LFT
What is the MOA of flucytosine (5-FC)?
Converted by cytosine deaminase to fluorouracil in fungal cells –> phosphorylation of fluorouracil –> inhibit fungal DNA synth + incorporation into fungal RNA –> inhibit protein synth
What are some ADRs of flucytosine?
Common
- anaemia, leucopenia, thrombocytopenia, diarrhoea, nausea, vomiting, elevated liver enz
Rare/infreq
- hepatic necrosis, agranulocytosis, GI haemorrhage, allergic reaction, toxic epidermal necrolysis, cardiac tox
What is terbinafine and what is its MOA?
Allylamine drug
MOA = inhibits squalene oxygenase –> inhibits formation of squalene epoxide during fungal membrane ergosterol synth
Fungicidal, narrow spectrum
What are some ADRs of terbinafine?
Common = N/V, diarrhoea, abdominal pain, transient elevation of liver enzymes, arthralgia
Infreq = reversible taste dist
Rare = hepatitis, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, psoriaform lesions, worsening psoriasis
What is the MOA of Griseofulvin?
Deposits in keratin precursor cells of skin, hair, nails —> disrupt microtubules –> blocks mitosis of dermatophytes
Fungistatic antibiotic, not active against candida
What are some ADRs of Griseofulvin?
Common = the usual stuff
Infreq = photosensitivity, urticaria, taste dist, blurred vision
Rare = toxic epidermal necrolysis, precipitation/exacerbation of lupus, menstrual irregularities, leucopenia, hypersensitivity
