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