Anti-fungal agents Flashcards
What organisms are the most common cause of infection of the hair, nails and skin?
Dermatophytes. - colonise keratinised areas.
Why does it take a long time for dermatophytes to respond to drugs?
As they have a slow metabolism
What do dermatophytes use as virulence factors?
Keratinase, elastase and other proteinases.
How do you treat dermatophytes?
- Over the counter topical creams, powders, tablets.
- Only oral when topical hasnt worked.
- Active ingredients: Terbinafine, Itraconazole, ketoconazole, miconazole.
List 3 systemic fungal infections and their causative agents?
Fungal meningitis: Cryptococcus neoformans
Aspergillus of the lungs: Aspergillus Fumigatus
Pneuocystis pneumonia: pneumocystic Jiroveci
Why is treatment of systemic fungal infections difficult?
Need to reach fungus at high dose without being systematically toxic.
How are systemic fungal infections normally transmitted?
Via airways.
What is Crytococcus Neoformans?
Encapsulated yeast - fluffy capsule makes it airborne.
what do you get cryptococcus neoformans from?
Environment e.g. pigeon droppings.
How do you treat cryptococcus neoformans infection?
2 weeks of IV amphotercin B for meningitis.
Fluconazole or flucytosine (but this drug cant get in the CNS).
What 3 conditions can Aspergillus Fumigatus give rise to?
- Allergic bronchopulmonary aspergiliosus
- Invasive pulmonary aspergilliosus.
- Aspergilloma
What is allerigic bronchopulmonary asperilliosus?
An allergic reaction to fungal infection.
How do you treat allergic bronchopulmonary aspergilliosus?
Prednisone.
What patients are prone to allergic bronchopulmonary aspergilliosus?
Associated with CF and asthma.
What patients are prone to invasive pulmonary aspergilliosus?
Immunocompromised.
How do you treat invasive pulmonary aspergilliosus.
Voriconazole or amphotercin B
What is invasive pulmonary aspergilliosus?
fungal infection that becomes systemic and spreads throughout the body.
What is aspergillioma?
A fungal ball that develops in an area of past lung disease or scarring. It is normally encapsulated so is pretty harmless.
What patients are prone to aspergillioma?
Those who have had TB or a lung abcess.
What treatment is given for aspergilliomas?
None - surgery if bleeding occurs.
How do you treat pneumocystis jiroveci?
Treatment and prophylaxis for the immunocompromised
- Trimethoprim and sulfamethoxazole.
What structuer do all axole antifungals have?
An azole ring.
How do azole’s act?
Inhibit 14-mthylsterol alpha demethylase which produces ergosterol.
Ergosterol is essential in the fungal plasma membrane.
What is the function of sterols e.g. cholesterol, ergosterol?
Insert into the lipid bilayer of the plasma membrane. They are needed for fluididty and help control what passes through the membrane.
What drug inhibits the enzyme squalene 2,3 epoxidase which is involved in sterole biosynthesis?
Terbinafine.
How does Amphotericin B work?
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.
How is amphotericin B given?
IV and it is not soluable.
How is amphotericin B infused? why?
In a liposome to which it is incorporated (not encapsulated in) to give improved delivery and reduced toxicity.
