Anti-fungal agents

Question 1

What are the risk factors for invasive fungal infections?

Answer 1

Haematological malignancies
Cancer - chemotherapy
Organ or bone marrow transplant
AIDS/HIV
Broad spectrum antibiotics
Indwelling catheters
Respiratory diseases

Question 2

Define aspergilloma

Answer 2

Growth of fungal ball in pre-existing cavity - patient with previous TB

Question 3

Define aspergillus

Answer 3

Filamentous mould
Saprophytic - lives off organic matter (plant matter)
Inhale these spores everyday - only affects those particular risk factor groups

Question 4

Define aspergillosis

Answer 4

Mainly through inflation of spores
Typically of lung origin

Question 5

Define ABPA

Answer 5

Allergic reaction to the fungi

Question 6

Define pulmonary candidiasis

Answer 6

Fungi in the lung

Question 7

Define candida auris

Answer 7

Highly resistant to antifungals
Several outbreaks worldwide
Thermotolerant - can grow up to 42 degrees

Question 8

Define pan-resistant

Answer 8

Resistant to all drugs that are currently available

Question 9

How are invasive fungal infections diagnosed?

Answer 9

Blood cultures
sputum cultures
Urine samples
microscopy
X-ray/CT
Biopsy samples
Medical history, risk factors, symptoms

Question 10

Explain other methods of diagnosis

Answer 10

Serology based - detection of antigens
(1,3)-beta-D-glucan (BDG)
Galactomannan - only for aspergillus
Nucleic acids - PCR

Question 11

Define the targets for antifungals

Answer 11

They inhibit the protein beta-glucan synthase - involved in the synthesis of the cell wall of fungi
Other drugs work on the membrane in particular the lipid ergosterol

Question 12

Name the common azoles

Answer 12

Triazoles:
Fluconazole
Itraconazole
Posaconazole
Voriconazole

Imidazoles (topical)

Question 13

Define the MOA of triazoles

Answer 13

Decreased ergosterol production through inhibition of fungal cytochrome p450 enzymes
Most are fungistatic - stop the growth rather than kill it

Question 14

What are the side effects of triazoles

Answer 14

Liver toxicity - due to the interaction of other p450 enzymes
QT prolongation - can lead to arrhythmias

Question 15

What do azoles commonly interact with?

Answer 15

Drugs that are also metabolised by Cytochrome p450 enzymes

Question 16

What has lead to azole resistance?

Answer 16

Pre-exposure to azoles - including antifungals in agriculture
Cross-resistance
different mutations can lead to reduced affinity
Some fungi produce more of the enzyme - becomes more of a competition
Pumping out the drug quickly - never achieve high enough concentrations

Question 17

What is the mode of action of amphotericin?

Answer 17

Interacts with cholesterol, creating pores in the membrane
Amphotericin B binds to ergosterol - results in formation of pores and the contents leak out - water can go in and the cells wold die

Question 18

Does amphotericin have broad spectrum activity?

Answer 18

Active against most fungi

Question 19

When is amphotericin used?

Answer 19

For severe systemic infections only

Question 20

What are the side effects of amphotericin?

Answer 20

Toxicity

Question 21

How can toxicity be reduced in amphotericin?

Answer 21

With lipid formulations
- Ambisome - liposomal
- Abelcet - lipid complex

Question 22

What does amphotericin B cause?

Answer 22

Renal toxicity

Question 23

Define MOA of echinoacardins

Answer 23

Inhibit 1,3, beta-glucan synthase

Question 24

What the advantages of echinocandins?

Answer 24

low toxicity
minimal drug interactions

Question 25

What is caspofungin used to treat?

Answer 25

Invasive aspergillosis and candidiasis

Question 26

What is anidulafungin used to treat?

Answer 26

Invasive candidiasis

Question 27

What is micafungin used to treat?

Answer 27

Invasive candidiasis