Anti fungals Flashcards
Molds
Aspergillus spp
Dermatophytes
Mucor
Dimorphic
Blastomyces
Coccididomyces
histoplasms
Yeast
Candida Spp
Crytococcus neoformans
Pneumocystis
Allylamines
MOA: inhibits the enzyme squalene epoxidase needed for ergosterol synthesis
Topical Agents
Terbinafine Amorolfine Naftifine Butenafine Clotrimazole
Nystatin
Polyene
MOA: binds to sterols in cell membranes of both fungal and human ells
Administation -
Oral; pool absorbed from GI tract almost entirely excreted in feces
- too toxic for systemic
Topically - not absorbed from intact skin or mucous membranes
CANDIDA ONLY
Amphotericin B
Amphoteric
Soluble in both basic and acidic environments
insoluble in water
MOA: binds to ergosterol in cell membrane, forms pores, exhibits concentration dependent killing
binds to ergosterol itself
BROAD spectrum
Doesn’t cover
- C. lusitanae
- Fusarium
- Tricosporon
- Scedosporium
Amphotericin B deoxycholate
Poor penetration : CNS, saliva,
ADRs
Glomerular nephrotoxicity- Dose dependent decrease in GFR because of vasoconstrictive effects
Tubular nephroxicity - K, Mg and bicarb wasting
Decreased erythropoietin production
acute reaction - chills fevers tachypnea hypotension
Support management
- Fluids
- Add potassium if hypokalemia
- avoid concurrent nephrotoxic agents
- premed with acetaminophen, diphenhydramine or hydrocortisone
- add heparin to the infusion to manage thrombophlebitis
Amphotericin B colloidal dispersion
acute infusion related reactions
reduced rates of nephrotoxicity compared to amphotericin B deoxycholate
Amphotericin B lipid complex
distributed into tissues more rapidly than amphotericin b deoxycholate
reduced rate of nephrotoxicity and infusion related reactions
- distributed in tissues more rapidly
- delivers to lungs more rapidly than liposomal amp
Liposomal amphotericin
higher Cmax and larger AUC
may achieve higher brain concentration
reduced rate of nephrotoxicity and infusion related reactions
Ketoconazole
Imidazole
MOA: inhibits 14 alpha-demethylase which converts lanosterol to ergosterol and is required in fungal cell membrane synthesis
Inactive against aspergillum
Needs acidic gastric pH for absorption
Poor distribution into CSF and eye
Decrease dose for. severe liver failure
can inhibit sterol synthesis in humans (aldosterone, cortisol, testosterone)
DDI ANTACIDS
Triazoles
MOA: inhibits 14- alpha sterol demethylase which is a microsomal CYP 450
Isavuconazole
MOA: inhibits 14- alpha sterol demethylase which is a microsomal CYP 450
only covers aspergillus
DEPENDENT QTc shortening
Flucontazole
only triazole that doesn’t cover aspergillum
MOA: inhibits 14- alpha sterol demethylase which is a microsomal CYP 450
CrCl >50 give full dose
CrCl <50 give 50%
Posaconazole
MOA: inhibits 14- alpha sterol demethylase which is a microsomal CYP 450
only doesn’t cover scedosporium
Tab does not equal suspension
QTc prolongation
