Antifunagl Agents

Question 1

Which fungi causes common infections of the skin, nails and hair?

Answer 1

Dermatophytes

Question 2

Where do dermatophytes live?

Answer 2

They don’t colonise live tissues - instead living in keratinised areas such as nails and the outer skin

Question 3

What are the virulence factors of dermatophytes?

Answer 3

Keratinises, elastase and other proteinases - so they can attack and infect the dead areas of the body which they live on

Question 4

Who is more susceptible to get a dermatophytes infection and why?

Answer 4

Anybody - including healthy people

- the fungus lives on dead parts of the body, and so isn’t exposed to the host immune system

Question 5

Why are dermatophytes also known as ringworm or tinea?

Answer 5

Because when the fungus infects the skin, it looks round, like a ringworm infection

Question 6

How are dermatophytes treated?

Answer 6

Mostly over the counter products
- sprays, creams, powders and liquids 
Normally topical administration
Oral mediation
- only needed for severe infection or nail infection, when topical medication hasn't worked 
- only used for adults

Question 7

What are the topical treatments in dermatophyte treatment?

Answer 7

Terbinafine
Itraconazole
Ketoconazole
Miconazole

Question 8

What are the systemic fungal infections?

Answer 8

1) Fungal meningitis - cryptococcosis neoformans
2) Aspergillosis of the lungs - aspergillius fumigatus
3) Pneumocystis pneumonia - pneumocystis jiroveci

Question 9

In which kinds of patients are systemic fungal infections most common in?

Answer 9

Immunocompromised patients

- immunocompetent people should be able to fight of spores that they encounter everyday

Question 10

How is Cryptococcus neoformans contracted?

Answer 10

Contracted from the environment (e.g pigeon droppings)

- encapsulated yeast fungus is very fluffy and can be carried by the air

Question 11

What infections does Cryptococcus neoformans cause?

Answer 11

Crytococcosis of the lungs
Meningitis
These are commonly secondary infections in HIV

Question 12

What is the treatment for Cryptococcus neoformans?

Answer 12

2 weeks of IV Amphotericin B for meningitis
Fluconazole or flucytosine for non-CNS infections
- because it doesn’t need the penetration effect in through the blood brain barrier

Question 13

What are the three main conditions that Aspergillus fumigatus can cause?

Answer 13

Allergic bronchopulmonary aspergillosis
Invasive pulmonary aspergillosis
Aspergilloma

Question 14

Describe allergic bronchopulmonary aspergillosis, and it’s treatment.

Answer 14

Allergic reaction to the fungal infection

• can cause breathing problems, making asthma and cystic fibrosis worse
• treated with an anti-allergy agent (Prednisolone)

Question 15

Describe invasive pulmonary aspergillosis and its treatment.

Answer 15

Colonises the lungs, then becomes systemic and spreads through the body
- common in the immunocompromised and very life threatening
Treatment
- Voriconazole
- Amphotericin B
- or a combination of both - infection needs to be stopped quickly

Question 16

Describe an aspergilloma and it’s treatment.

Answer 16

This is when a fungal ball developing in an areas of the lung that has been previously damaged - causing scar tissue, more susceptible to colonisation
- e.g. TB or a lung abscess
Treatment
- no treatment unless bleeding occurs, then they require surgery
- not as life threatening if it remains small and doesn’t bleed

Question 17

What are the common problems caused by a pneumocystis jiroveci infection?

Answer 17

Pneumonia, causing large scale lung tissue destruction

• cough
• fever
• shortness of breath - rapid breathing

Question 18

What is the treatment for a pneumocystis jiroveci infection?

Answer 18

Trimethoprim-sulfamethoxazole

• pneumocystis is not a typical fungus (mix of fungus and protazoa)
• atypical treatment

Question 19

What is the largest class of antifungal drugs?

Answer 19

Azole antifungals

Question 20

List some of the members of the family of Azole antifungals.

Answer 20

Main drugs 
- Imidazole - two nitrogens 
- Triazole - three nitrogens 
- Thiazole - one nitrogen 
Extra brands
- Miconazole 
- Ketoconazole 
- Clotrimazole 
- Econazole

Question 21

What is the mechanism of action of the Azole antifungal drug group?

Answer 21

They inhibit 14-methylsterol alpha-demethylase (14-MD) which produces ergosterol

• ergosterol is an important part of the fungal plasma cell membrane (none in animal and plant cells)
• yeast/fungi equivalent of cholesterol (slightly bigger)

Question 22

What is the drawback in all Azole inhibiting the same enzyme?

Answer 22

If you are resistant to one azole, then you are resistant to all of them

Question 23

Why are sterols so important in cells?

Answer 23

They insert themselves into the lipid bilayer and are essential for its proper functioning and viscosity

• cholesterol in eukaryotes
• ergosterol in fungi

Question 24

Why is there little resistance to Amphotericin B?

Answer 24

Because it doesn’t act on any enzymes, it acts directly on the ergosterol molecule (not cholesterol, as this doesn’t have the extra double bond)

Question 25

What is the mechanism of action of Amphotericin B?

Answer 25

Amphophilic molecule - one side hydrophobic and one side hydrophilic

• hydrophobic side (many hydroxyl groups) binds to the hydrophobic side of the ergosterol molecule, inhibiting it
• hydrophilic side wont bind to the plasma membrane, so it forms pores, letting in sodium and calcium, and upsetting the membrane potential of the fungal cell

Question 26

What is ambisome, and why is it better than IV amphotericin B?

Answer 26

Liposome formulation of amphotericin B

• the Amphotericin B is part of lipid droplets, so it isn’t free in the blood
• this makes the administration less toxic and more diffuse in the blood
• still IV administration officials