Antifungal drugs

Question 1

Name the main types of antifungal drugs and examples.

Answer 1

1) Polyenes:
eg. **Amphotericin B, Nystatin

2) Azoles:
a) Imidazole
• Clotrimazole
• Miconazole
• Ketocanazole:

b) Triazoles-
• **Fluconazole: does cross BBB, with oral and IV
• itraconazole
• voriconazole
• posoconazole
[*Fluconazole < itraconazole < voriconazole = posoconazole]

3) Echinocandins
• Caspofungin

4) Other antifungal drugs:
• Terbinafine: prevent lanosterol synthesis
• **Flucytosine: inhibit fungal cell proliferation [Flucytosine with amphitericin]
• Griseofluvin

Question 2

Examples of Polyenes as antifungal drugs. and state its mechanisms

Answer 2

1) Amphotericin B: interact with ergosterol in fungal membrane form cation pores for K+ efflux and disrupt membrane permeability
2) Nystatin

Question 3

Polyenes are used to treat which types of medical conditions?

Answer 3

1) Crytococcal meningitis:
- IV amphotericin + flucytosine
- Switch to fluconazole 400mg daily for 8 weeks- when spinal fluid is –ve
- fluconazole 200mg daily to prevent relapse in AIDS patients

2) Oral candidiasis: nystatin (for mouth care)

Question 4

Examples of Imidazoles as antifungal drugs,
and state its mechanisms,
and what does this type of drug treat

Answer 4

> > Examples of Imidazole:
• Clotrimazole
• Miconazole
• Ketocanazole

> > Mechanism: Inhibitors of ergisterol synthesis by inhibiting a fungal P450 enzyme (14-alpha-demethylase, an enzyme that converts lanosterol to ergosterol)

> > Treatment:

• Vulvovaginal candidiasis (thrush), and
• Dermatophyses (ringworm and athletes foot)

Question 5

Examples of Triazoles as antifungal drugs and state its mechanisms.

Answer 5

Triazoles-
• **Fluconazole: does cross BBB, with oral and IV
• itraconazole
• voriconazole
• posoconazole
[*Fluconazole < itraconazole < voriconazole = posoconazole]

> > Mechanism: Inhibitors of ergisterol synthesis by inhibiting a fungal P450 enzyme (14-alpha-demethylase, an enzyme that converts lanosterol to ergosterol)

Question 6

Examples of Echinocandins as antifungal drugs and state its mechanisms.

Answer 6

Example: Caspofungin

Mechanism: inhibit the synthesis of beta-1,2 glucan ( a critical component of fungal cell walls)

Treatment: backup drug given for disseminated Candida infections or invasive aspergillosis

Question 7

Flucytosine as antifungal drugs and state its mechanisms, and what does this type of drug treat.

Answer 7

> Mechanism:
activated by fungal cytosine deaminase to 5-FU (5- fluorouracil)

> Combine use with amphotericin B in severe candidal and cryptococcal infections- enters CSF

Note: toxic to bone marrow

Question 8

Name antibiotics and drugs that cause drug interactions with Cytochrome (CYP enzyme).

Answer 8

1. Erythromycin:
   - Inhibits CYP enzymes: increases levels of drugs metabolised by liver
2. Histamine (H2) antagonist:
   i. e. Ranitidine and Cimetidine: inhibits P450
3. Proton pump inhibitors:
   i. e. Omeprazole (completely metabolised by the CYP450 system in liver.), Rabeprazole (completely metabolised by the CYP450 system in liver.)
4. Grapefruit juice:
   - inhibit CYP3A4 drug metabolic enzymes
5. Pharmacokinetic inhibitor:
   i. e. Ritonavir-
   i) Inhibits major drug metabolising enzymes - CYP3A4 & CYP2D6
   ii) Induces CYP1A2