Antifungals

Question 1

List the azole antifungals (synthetic triazole)

Answer 1

Fluconazole = BS

Itraconazole = BS

Ketoconazole = BS

miconazole

posaconazole

voriconazole

Question 2

Which azoles inhibit cyp?

Answer 2

Fluconazole = narrow spectrum

Itraconazole = broad spectrum

Question 3

What is the MOA of azoles? (mention kind of action)

Answer 3

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

Question 4

What are some ADRs of azoles?

Answer 4

Rash, headache, dizziness, elevated liver enz (in oral forms)

Constipation = itraconazole

Thrombocytopenia (voriconazole)

Question 5

What are some C/I to azoles?

Answer 5

Allergy to azoles –> inc exposure –> sensitisation of immune system

Question 6

Summarise the drug interactions seen with azoles

Answer 6

Inhibits CYP3A4

- inc lvls of midazolam, lovastatin, warfarin, ritonavir, CCB, cyclosporin, digoxin 

Azole lvls altered by drugs that inhibit/induce CYP3A4

Question 7

List the relevant polyene antifungals

Answer 7

Amphotericin

Nystatin (not systemic due to lack of absorption –> IV)

Question 8

What is the MOA of polyene antifungals? (mention kind of action)

Answer 8

Bind ergosterols –> inc mem permeability –> inc leakage of cell contents

Fungicidal

Question 9

List the ADRs of amphotericin

Answer 9

Chills, fever

Diarrhoea

N/V

Nephrotoxicity = be careful w/ use alongside other nephrotoxic drugs (vancomycin, aminoglycoside

Hypokalaemia

Question 10

Summarise the drug interactions associated with amphotericin

Answer 10

cyclosporine, antineoplastic = Inc renal tox

Thiazides and corticosteroids = inc hypokalaemia

Question 11

List the relevant echinocandin antifungals

Answer 11

Caspofungin

Anidulafungin

Question 12

What is the MOA of echinocandin antifungals? (mention kind of action)

Answer 12

Inhibit synthesis of fungal cell wall component beta-1,3-D-glucan

Fungicidal, broad-spectrum

Question 13

What are some ADRs of echinocandins?

Answer 13

Headache, fever, phlebitis

Abnormal LFT

Question 14

What is the MOA of flucytosine (5-FC)?

Answer 14

Converted by cytosine deaminase to fluorouracil in fungal cells –> phosphorylation of fluorouracil –> inhibit fungal DNA synth + incorporation into fungal RNA –> inhibit protein synth

Question 15

What are some ADRs of flucytosine?

Answer 15

Common
- anaemia, leucopenia, thrombocytopenia, diarrhoea, nausea, vomiting, elevated liver enz

Rare/infreq
- hepatic necrosis, agranulocytosis, GI haemorrhage, allergic reaction, toxic epidermal necrolysis, cardiac tox

Question 16

What is terbinafine and what is its MOA?

Answer 16

Allylamine drug

MOA = inhibits squalene oxygenase –> inhibits formation of squalene epoxide during fungal membrane ergosterol synth

Fungicidal, narrow spectrum

Question 17

What are some ADRs of terbinafine?

Answer 17

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

Question 18

What is the MOA of Griseofulvin?

Answer 18

Deposits in keratin precursor cells of skin, hair, nails —> disrupt microtubules –> blocks mitosis of dermatophytes

Fungistatic antibiotic, not active against candida

Question 19

What are some ADRs of Griseofulvin?

Answer 19

Common = the usual stuff

Infreq = photosensitivity, urticaria, taste dist, blurred vision

Rare = toxic epidermal necrolysis, precipitation/exacerbation of lupus, menstrual irregularities, leucopenia, hypersensitivity