Pharm: Fungal Infections Flashcards
What is the MOA of amphotericin B?
Binds to the sterol component of cell membrane –> alteraction in cell permeability –> death
Also binds cholesterol component of mammalian cell –> cytotoxicity (very nephrotoxic)
What is the standard tx for invasive fungal infections?
Amphotericin B
Reserved for those with severe, life-threatening infections or those who cannot tolerate other meds due to toxicities
What are the indications for amphotericin B?
Cryptococcus neoformans
Blastomyces dermatitidis
What are the contraindications of amphotericin B?
Hypersensitivity
Renal impairment
Make sure you monitor serum electrolytes
What are the AEs of amphotericin B?
Nephrotoxicity biggest
Lots of others too
What is the big warning for amphotericin B?
Inadvertent overdose –> fatal cardiac or cardiopulmonary arrest
Make sure you verify the name and dosage before administration
Observe pt closely during 1st administration
Anaphylaxis reported
N/V, chills, and rigors are common with IV
May require use of phenothiazine such as promethazine
What is the black box warning for amphotericin B?
Should not be used for non-invasive forms of fungal infection
Serious risk of nephrotoxicity (binds to cholesterol in human tissues and disrupts cell membranes)
What are some drug interactions with amphotericin B?
aminoglycoside –> nephrotoxicity
cyclosporine –> nephrotoxicity
anti-neoplastic agents –> nephrotoxicity
Muscle relaxants –> hypokalemia
Digitalis glycosides –> hypokalemia
Flucytosine –> increases toxicity
Pregnancy category B
What are the azole drugs we have to know?
fluconazole
itraconazole
voriconazole
What is the MOA of fluconazole?
interrupts conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes
What are indications for fluconazole?
Candida UTI/peritonitis
Vaginal candidiasis
Thrush
Cryptococcal meningitis
Prophylaxis of candidiasis with BM transplant
What are containdications of fluconazole?
coadministration of terfenadine
coadministration of drugs know to prolong QT interval
coadministration with CYP3A4 metabolized drugs
What are some warnings associated with fluconazole?
hepatic injury (some cases of serious hepatic toxicity)
Potential for fetal harm in pregnant patients –> birth defects
QT prolongation (inhibits recrifier K channel current, may cause torsades especially in pts with hypokalemia and cardiac failure)
How is fluconazole metabolized?
Substrate and inhibitor of CYP450 (CYP3A4)
Lots of drug interactions (CCBs, immunosupressants, chemo drugs, benzodiazapines, anti-depressants, macrolides, SSRIs)
Renal elmination, removed by hemodialysis and peritoneal dialysis
What is the MOA of itraconazole?
Interrupts conversion of lanosterol to ergosterol via binding to CYP450 in fungi and disrupting fungal membranes
What are the indications for itraconazole?
broad spectrum
Aspergillus spp.
dematiaceous molds
Sporothrix schenckii
What are some contraindications for itraconazole?
pregnancy
LV dysfunction
active CHF
use caution in CF patients, CVD, pulmonary dz, and elderly
What are some warnings for itraconazole?
Serious liver disease
Monitory for n/v, loss of appetite, abdominal pain, jaundice, dark urine
What is the black box warning for itraconazole?
inotripic effects –> BBW in pts with heart failure
BBW against use with other CYP3A4 affecting enzymes
What is the MOA of voriconazole?
interrupts conversion of lanosterol to ergosterol via binding to fungal CYP450 –> disruption of fungal membranes
What are indications for voriconazole?
Invasive aspergillosis
deep tissue candida infections
Esophageal candidiasis
scedosporium apiospermum
Fusarium spp.
What are some contraindications of voriconazole?
galactose malabsorption/intolerance
Lapp lactase deficiency
glucose malabsorption
uncorrected electrolyte abonormalities
pregnancy
creatinine clearance <50 mL/min
Use with caution in QT prolongation/hx of torsades
Why shouldn’t you give voriconazole to pts with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption?
It contains lactose
How is vorconazole metabolized?
Greater affinity for CYP2C19
Parenteral administration solubilized in compound secreted by kidneys –> need to change dose for pts with renal impairment
Oral dose doesn’t have to be adjusted
What are some drug interactions associated with voriconazole?
inhibitors of induces of CYP450 enzymes have interactions
What drugs are in the echinocandin class?
caspofungin
micafungin
anidulafungin
When do you use echinocandins?
use IV in systemic candida infections
What is the MOA of echinocandins?
inhibit beta (1,3)-D-glucan synthase
this enzyme forms glucan, a major component of fungal cell wall
Damage to fungal cell wall
What is the indication for micafungin?
candidemia
acute disseminated candidiasis
candida peritonitis/abscess
esophageal candidiasis
Prophylaxis of candida infections in pts undergoing stem cell transplant
What is a major AE or echinocandins?
Red man syndrome
What is the black box warning for micafungin?
Foci of altered hepatocytes & hepatocellular tumor (not by US FDA but warning exists in Europe)
What is the MOA of flucytosine?
pyramidine analogue that interferes with purine and pyramidine metabolism
What drugs can you use flucytosine with?
ketoconaxole
fluconazole
itraconazole
liposoma amphotericin B for cryptococcal meningitis
What is the black box warning for flucytosine?
extreme caution in pts with:
renal impairment
hematologic, hepatic, and renal function impairment
pregnant women
breastfeeding women
bone marrow supression
How is flucytosine eliminated?
96% eliminated in urine as unchanged drug
