25A20: Exam Report

Fluconazole, amphotericin and caspofungin are anti-fungal drugs.

  1. For each drug listed above, outline the following:
    1. the class (15% of marks).
    2. the mechanism of action (45% of marks).
    3. TWO microbes against which they are active (30% of marks).
      (marks in each section are equally distributed between the 3 drugs listed)
  2. List TWO serious side effects seen with ANY anti-fungal drug, include the agent most associated with each effect listed in your answer (10% of marks).

65% of candidates passed this question.

The question breakdown allowed for a simple but structured approach to this question.

For common fungi like candida, full binomial names were required e.g. “candida albicans, candida glabrata”.

The mechanisms of actions were well outlined, and expected details included the target for the drug (e.g. enzyme or sterol), the effect on the cell membrane or wall, and whether it was fungicidal or fungistatic.

A broad range of serious side effects were accepted for part b however specificity was required with respect to which drug is most likely linked to each.

T2ii / 25B20: Fluconazole, amphotericin and caspofungin are anti-fungal drugs

a) For each drug listed above, outline the following:

Fluconazole

Amphotericin

Caspofungin

Class

Fluconazole

Azole

Amphotericin

Polyene

Caspofungin

Echinocandin

MoA

Fluconazole

Inhibits ergosterol synthesis → impairing cell membrane formation

Amphotericin

Binds ergosterol in fungal cell membrane, forming pores → loss of intracellular ions → cell death

Caspofungin

Inhibit beta-glucan synthesis → blocking fungal cell wall synthesis → osmotic instability & lysis

Microbes Yeast

Fluconazole

C Albicans

Cryptococcus

Amphotericin

C Albicans

C Glabrata

Cryptococcus

Caspofungin

C Albicans

C Glabrata

Microbes Moulds

Fluconazole

Amphotericin

Aspergillus

Caspofungin

Aspergillus

a) List TWO serious side effects seen with ANY anti-fungal drug, include the agent most associated with each effect listed in your answer

Adverse Effect

Anti-Fungal Associated

Nephrotoxicity

Amphotericin

Hypokalaemia

Amphotericin

RTA

Amphotericin

Bone marrow suppression

Flucytosine

Hepatotoxicity

Fluconazole, Voriconazole

Prolonged QTc

Voriconazole

LFT derangement

Voriconazole > Fluconazole

Class Polyene
(Nystatin, Amphotericin B)		 Azole
(Fluconazole)
Mechanism of Action Damage ergosterol in fungal cell membranes Inhibit ergosterol synthesis (via CYP450)
Yeast Effective Variable
• Candida albicans Yes Yes
• Candida glabrata Yes No
• Cryptococcus Yes Yes
Moulds Effective Not Effective
• Aspergillus, Zygomyces Yes No
• Scaedosporium, Lomentospora Yes No
Metabolism & Elimination
  • Minimal metabolism
  • Renal and fecal elimination of unchanged drug
  • 20% metabolized by CYP450
  • 80% renal excretion unchanged
Adverse Effects
  • Nephrotoxicity
  • Hypokalemia/renal tubular acidosis
  • Bone marrow suppression - anaemia
  • Hepatotoxicity
  • Prolonged QTc interval

Author: Krsisoula Zahariou