T2ii: Describe the pharmacology of antifungal agents

Class

Fluconazole

Azole

Amphotericine B

Amphotericine

Dose

Fluconazole

Prophylaxis: 100-400mg od

Tx: 400-800mg od

Amphotericine B

1mg/kg od

Mechanism

Fluconazole

Cidal

Amphotericine B

Cidal

MoA

Fluconazole

Inhibits the fungal cytP450 enzyme that syntheses ergosterol

Inhibits cell memb formation

Leakage -> cell death

Amphotericine B

Binds ergosterol in membranes and forms pores in fungus

Leakage → cell death

Time v Conc

Fluconazole

Concentration

Amphotericine B

Concentration

Spectrum

Fluconazole

Covers

C albicans

Cryptococcus

Doesnt

C gilbrata

C Krusei (Kompletely resistant)

Amphotericine B

Covers

All candida

Cryptococcal meningitis

*2nd line for candida bc echinocandins (caspo) are just as effective and less toxic

Doesnt

Except C lustanae +

anti-protozoan

PK

Fluconazole

A

Rapid, complete 100% OBA

D

CNS 50-90% of absorbed levels.

Wide distribution

Good urine penetration can be used for candida cystitis

M

Hepatic

E

Excreted in kidneys

80% unchanged

Amphotericine B

A

IV

D

PPB 90%, 4L/kg

M

?

E

Only 3% excreted unchanged in urine. 

40% still in urine after 7 days

AE

Fluconazole

Hepatic toxicity – watch LFTs; hepatic failure, hepatitis, abnormal LFTs

GI – nausea, vomiting, diarrhea, abdm pain

CVS – pallor angioedema

CNS – headache, dizziness

Haem: thrombocytopenia, leukopenia

Derm – skin rashes, alopecia

Amphotericine B

Nephrotoxic

Hepatotoxic

GI upset

Blood dyscrasias

Seizures

Monitoring

Fluconazole

LFT

Amphotericine B

Cease in renal failure