NR-566: Week 1 Questions with Verified Answers (Correct
Update)
Question 1: What is the mechbinds anism of action for amphotericin B?
Answer: to ergosterol on the fungal cell membrane to increase the permeability, which leads to leakage
of intracellular cations (esp. K+), reducing viability
Question 2: Is amphotericin B active against bacteria?
Answer: No - for amphotericinB to be ettective, the cytoplasmic membrane must contain sterols for the
cell to be susceptible and bacterial membranes lack sterols
Question 3: Why is amphotericinB toxic to human cells?
Answer: It binds to cholesterol on the cell membrane. There is some selectivity, though, because the
drug binds more strongly to ergosterol than it does cholesterol. Thus, fungi are ettected more.
Question 4: How is amphotericinB administered?
Answer: IV - poor absorption from the GI tract
Question 5: How is amphotericinB distributed?
Answer: Undergoes extensive binding to sterol-containing membranes of tissues. Levels are about of
serum in tissues like aqueous humor and peritoneal, pleural, & joint fluids.
Question 6: How is amphotericinB metabolized and excreted?
Answer: It is unclear if it is metabolized or ultimately removed from the body. Renal excretion of
unchanged amphotericin is minimal. Complete elimination takes a long time; the drug has been detected
in tissues more than 1 year after cessation.
Question 7: How does amphotericinB affect the kidneys?
Answer: Causes renal impairment in practically all patients - extent of kidney damage is r/t total dose
administered over the full course of treatment. In most cases, renal function normalizes after treatment
stops. If the total dose exceeds 4g, residual impairment is likely.
Question 8: How can nephrotoxicity r/t amphotericinB administration be reduced?
Answer: 1. Infusing 1L of NS on the days the drug is given 2. Staying well hydrated 3. Avoiding other
nephrotoxic drugs - NSAIDs, aminoglycosides, etc. 4. Monitor renal function (BUN & Cr) every 3-4
days. If creatinine content rises >3.5mg/dL, reduce dosage. 5. Monitor I&Os 6. Give lipid-based
formula, if possible, to reduce this SE
Page 1
, Question 9: What are the SEs/ADRs of amphotericinB?
Answer: 1. Infusion reactions - fever, chills, rigors, nausea, HA, hypotension, anaphylaxis *d/t pro
inflammatory cytokines 2. Phlebitis 3. Nephrotoxicity - dose dependent (>4g) 4. Anemia - d/t decreased
erythropoietin s/t renal impairment 5. hypokalemia - r/t renal tubular acidosis s/t reduced GFR & renal
impairment *can l/t arrhythmias 6. hematologic ettects - risk bone marrow suppression l/t normocytic,
normochromic anemia 7. intrathecal injection reactions - N/V, HA, back/leg/abd pain *rare - visual
disturbance, hearing impairment, paresthesia
Question 10: What is the thera- Treatment peutic use of amphotericinB?
Answer: of systemic mycoses: aspergillum, blastomyces, Candida albicans, cryptococcus,
histoplasmosis, & mucor Fungistatic or fungicidal - depends on concentration & susceptibility
Question 11: What is the major Inhibition consideration for drug interactions with itraconazole
and other azole antifungals?
Answer: of CYP450 enzymes l/t significant drug interactions. Itraconazole inhibits CYP3A4 & can l/t
increased levels of many other drugs:
- cisapride, pimozide, dofetilide, quinidine (can l/t fatal dysrhythmias & therefore concurrent use is CI)
- cyclosporine (monitor drug levels)
- digoxin (monitor drug levels)
- sulfonylureas (monitor BG)
- warfarin (monitor PT/INR)
Question 12: What must be considered with itraconzaole administration and pH raising drugs?
acid
Answer: Antacids, H2RAs, and PPIs can greatly reduce absorption, so give at least 1 hour before or 2
hours after itraconazole administration. Because PPIs have a prolonged duration of action, there may be
insuflcient gastric for absorption regardless of when PPI is taken.
Question 13: What is the MOA of itraconazole?
Answer: Inhibits 14-alpha-demethylase enzyme, which converts lanosterol (precursor) into ergosterol.
This inhibits the synthesis of ergosterol for the fungal cell membrane, which leads to increased
membrane permeability and leakage of cellular components.
Question 14: What are the therapeutic uses for azole antifungals?
Answer: Superficial mycoses - dermatophysis ("ring worm"), yeast infections, tines versicolor Systemic
mycoses - 1st line for blastomycosis, histoplasmosis, and sporotrichosis
Question 15: What are the SEs/ADRs r/t PO itraconazole?
Answer: 1. GI upset - N/V, diarrhea 2. Cardiac suppression - negative inotropic action that leads to
transient reduction in EF 3. Hepatic injury - rare
Page 2
Update)
Question 1: What is the mechbinds anism of action for amphotericin B?
Answer: to ergosterol on the fungal cell membrane to increase the permeability, which leads to leakage
of intracellular cations (esp. K+), reducing viability
Question 2: Is amphotericin B active against bacteria?
Answer: No - for amphotericinB to be ettective, the cytoplasmic membrane must contain sterols for the
cell to be susceptible and bacterial membranes lack sterols
Question 3: Why is amphotericinB toxic to human cells?
Answer: It binds to cholesterol on the cell membrane. There is some selectivity, though, because the
drug binds more strongly to ergosterol than it does cholesterol. Thus, fungi are ettected more.
Question 4: How is amphotericinB administered?
Answer: IV - poor absorption from the GI tract
Question 5: How is amphotericinB distributed?
Answer: Undergoes extensive binding to sterol-containing membranes of tissues. Levels are about of
serum in tissues like aqueous humor and peritoneal, pleural, & joint fluids.
Question 6: How is amphotericinB metabolized and excreted?
Answer: It is unclear if it is metabolized or ultimately removed from the body. Renal excretion of
unchanged amphotericin is minimal. Complete elimination takes a long time; the drug has been detected
in tissues more than 1 year after cessation.
Question 7: How does amphotericinB affect the kidneys?
Answer: Causes renal impairment in practically all patients - extent of kidney damage is r/t total dose
administered over the full course of treatment. In most cases, renal function normalizes after treatment
stops. If the total dose exceeds 4g, residual impairment is likely.
Question 8: How can nephrotoxicity r/t amphotericinB administration be reduced?
Answer: 1. Infusing 1L of NS on the days the drug is given 2. Staying well hydrated 3. Avoiding other
nephrotoxic drugs - NSAIDs, aminoglycosides, etc. 4. Monitor renal function (BUN & Cr) every 3-4
days. If creatinine content rises >3.5mg/dL, reduce dosage. 5. Monitor I&Os 6. Give lipid-based
formula, if possible, to reduce this SE
Page 1
, Question 9: What are the SEs/ADRs of amphotericinB?
Answer: 1. Infusion reactions - fever, chills, rigors, nausea, HA, hypotension, anaphylaxis *d/t pro
inflammatory cytokines 2. Phlebitis 3. Nephrotoxicity - dose dependent (>4g) 4. Anemia - d/t decreased
erythropoietin s/t renal impairment 5. hypokalemia - r/t renal tubular acidosis s/t reduced GFR & renal
impairment *can l/t arrhythmias 6. hematologic ettects - risk bone marrow suppression l/t normocytic,
normochromic anemia 7. intrathecal injection reactions - N/V, HA, back/leg/abd pain *rare - visual
disturbance, hearing impairment, paresthesia
Question 10: What is the thera- Treatment peutic use of amphotericinB?
Answer: of systemic mycoses: aspergillum, blastomyces, Candida albicans, cryptococcus,
histoplasmosis, & mucor Fungistatic or fungicidal - depends on concentration & susceptibility
Question 11: What is the major Inhibition consideration for drug interactions with itraconazole
and other azole antifungals?
Answer: of CYP450 enzymes l/t significant drug interactions. Itraconazole inhibits CYP3A4 & can l/t
increased levels of many other drugs:
- cisapride, pimozide, dofetilide, quinidine (can l/t fatal dysrhythmias & therefore concurrent use is CI)
- cyclosporine (monitor drug levels)
- digoxin (monitor drug levels)
- sulfonylureas (monitor BG)
- warfarin (monitor PT/INR)
Question 12: What must be considered with itraconzaole administration and pH raising drugs?
acid
Answer: Antacids, H2RAs, and PPIs can greatly reduce absorption, so give at least 1 hour before or 2
hours after itraconazole administration. Because PPIs have a prolonged duration of action, there may be
insuflcient gastric for absorption regardless of when PPI is taken.
Question 13: What is the MOA of itraconazole?
Answer: Inhibits 14-alpha-demethylase enzyme, which converts lanosterol (precursor) into ergosterol.
This inhibits the synthesis of ergosterol for the fungal cell membrane, which leads to increased
membrane permeability and leakage of cellular components.
Question 14: What are the therapeutic uses for azole antifungals?
Answer: Superficial mycoses - dermatophysis ("ring worm"), yeast infections, tines versicolor Systemic
mycoses - 1st line for blastomycosis, histoplasmosis, and sporotrichosis
Question 15: What are the SEs/ADRs r/t PO itraconazole?
Answer: 1. GI upset - N/V, diarrhea 2. Cardiac suppression - negative inotropic action that leads to
transient reduction in EF 3. Hepatic injury - rare
Page 2
