Anti-fungal agents

Question 1

What organisms are the most common cause of infection of the hair, nails and skin?

Answer 1

Dermatophytes. - colonise keratinised areas.

Question 2

Why does it take a long time for dermatophytes to respond to drugs?

Answer 2

As they have a slow metabolism

Question 3

What do dermatophytes use as virulence factors?

Answer 3

Keratinase, elastase and other proteinases.

Question 4

How do you treat dermatophytes?

Answer 4

• Over the counter topical creams, powders, tablets.
• Only oral when topical hasnt worked.
• Active ingredients: Terbinafine, Itraconazole, ketoconazole, miconazole.

Question 5

List 3 systemic fungal infections and their causative agents?

Answer 5

Fungal meningitis: Cryptococcus neoformans
Aspergillus of the lungs: Aspergillus Fumigatus
Pneuocystis pneumonia: pneumocystic Jiroveci

Question 6

Why is treatment of systemic fungal infections difficult?

Answer 6

Need to reach fungus at high dose without being systematically toxic.

Question 7

How are systemic fungal infections normally transmitted?

Answer 7

Via airways.

Question 8

What is Crytococcus Neoformans?

Answer 8

Encapsulated yeast - fluffy capsule makes it airborne.

Question 9

what do you get cryptococcus neoformans from?

Answer 9

Environment e.g. pigeon droppings.

Question 10

How do you treat cryptococcus neoformans infection?

Answer 10

2 weeks of IV amphotercin B for meningitis.

Fluconazole or flucytosine (but this drug cant get in the CNS).

Question 11

What 3 conditions can Aspergillus Fumigatus give rise to?

Answer 11

1. Allergic bronchopulmonary aspergiliosus
2. Invasive pulmonary aspergilliosus.
3. Aspergilloma

Question 12

What is allerigic bronchopulmonary asperilliosus?

Answer 12

An allergic reaction to fungal infection.

Question 13

How do you treat allergic bronchopulmonary aspergilliosus?

Answer 13

Prednisone.

Question 14

What patients are prone to allergic bronchopulmonary aspergilliosus?

Answer 14

Associated with CF and asthma.

Question 15

What patients are prone to invasive pulmonary aspergilliosus?

Answer 15

Immunocompromised.

Question 16

How do you treat invasive pulmonary aspergilliosus.

Answer 16

Voriconazole or amphotercin B

Question 17

What is invasive pulmonary aspergilliosus?

Answer 17

fungal infection that becomes systemic and spreads throughout the body.

Question 18

What is aspergillioma?

Answer 18

A fungal ball that develops in an area of past lung disease or scarring. It is normally encapsulated so is pretty harmless.

Question 19

What patients are prone to aspergillioma?

Answer 19

Those who have had TB or a lung abcess.

Question 20

What treatment is given for aspergilliomas?

Answer 20

None - surgery if bleeding occurs.

Question 21

How do you treat pneumocystis jiroveci?

Answer 21

Treatment and prophylaxis for the immunocompromised

- Trimethoprim and sulfamethoxazole.

Question 22

What structuer do all axole antifungals have?

Answer 22

An azole ring.

Question 23

How do azole’s act?

Answer 23

Inhibit 14-mthylsterol alpha demethylase which produces ergosterol.
Ergosterol is essential in the fungal plasma membrane.

Question 24

What is the function of sterols e.g. cholesterol, ergosterol?

Answer 24

Insert into the lipid bilayer of the plasma membrane. They are needed for fluididty and help control what passes through the membrane.

Question 25

What drug inhibits the enzyme squalene 2,3 epoxidase which is involved in sterole biosynthesis?

Answer 25

Terbinafine.

Question 26

How does Amphotericin B work?

Answer 26

Exploits the presence of ergosterone.
Has a hydrophobic side which interacts with ergosterol and a charged hydrophilic side which creates a pore in the membrane to allow water and ions to flow freely into the fungus.
- Unregulated membrane passage means the fungus dies.

Question 27

How is amphotericin B given?

Answer 27

IV and it is not soluable.

Question 28

How is amphotericin B infused? why?

Answer 28

In a liposome to which it is incorporated (not encapsulated in) to give improved delivery and reduced toxicity.