Pharm - Amphotericin B

Question 1

Mechanism of action of amphotericin B

Answer 1

• Binds ergosterol in the fungal cell membrane, forms pores in the membrane that allow leakage of cellular components with eventual cell death (fungicidal).
• This affinity may also account for its toxic effects against select mammalian cells.

Question 2

Identify the three formulations of amphotericin B

Answer 2

• Amphotericin B deoxycholate (conventional)
• Amphotericin B lipid complex (Abelcet)
• Liposomal amphotericin B (AmBisome)

Question 3

Daily dose of the amphotericin B deoxycholate

Answer 3

o Usual dose for most invasive mycoses is 0.5 to 1.5 mg/kg per day ( > 1mg/kg usu reserved for severe infections)
o Daily doses of 1.5 mg/kg per day should not be exceeded.

Question 4

Daily dose of the amphotericin B lipid complex (Abelcet) and AmBisome

Answer 4

o Doses of lipid formulations is usually in the 3 to 6 mg/kg/day range
o Administer IV

Question 5

Identify the symptoms of infusion related reaction

Answer 5

• nausea, vomiting, chills, and rigors, are common with IV amphotericin B deoxycholate admin
• usually occurring either during infusion (w/i 15 min to 3 hrh following initiation) or immediately following admin of the dose

Question 6

What is the need to pretreat with medications to reduce occurrence of infusion related reactions

Answer 6

• Pretreatment with acetaminophen, hydrocortisone and diphenhydramine may reduce incidence
• Treatment of amphotericin B–related nausea and vomiting: promethazine, prochlorperazine or ondansetron.

Question 7

Identify the ways to prevent phlebitis due to amphotericin B

Answer 7

• Infusion of the drug using a central line
• Use of alternating infusion sites
• Avoidance of final amphotericin B infusion concentrations exceeding 0.1 mg/mL
• Avoidance of infusion times of less than four hours

Question 8

Identify the monitoring parameters of a patient on amphotericin B

Answer 8

• Monitor for infusion-related reactions
• Measurements of renal function should be performed daily during initiation of therapy (up to two weeks) and at least weekly thereafter, if stable.
• Assess serum electrolytes (particularly potassium and magnesium) at baseline and at least twice weekly throughout therapy—more often for patients experiencing hypokalemia and hypomagnesemia
• CBC should be measured weekly throughout therapy—anemia and leukopenia can occur

Question 9

Identify the pathogenesis of amphotericin B nephrotoxicity

Answer 9

• Renal vasoconstriction of afferent arteriole
• Distal tubular injury is present
• Amphotericin B toxicity may be mediated by deoxycholate, a detergent used as a solubilizing agent for amphotericin B

Question 10

Identify the electrolyte changes with amphotericin B nephrotoxicity

Answer 10

• Urinary potassium wasting and hypokalemia, urinary magnesium wasting and hypomagnesemia, metabolic acidosis due to type 1 (or distal) renal tubular acidosis, and polyuria due to nephrogenic diabetes insipidus.

Question 11

Identify the risk factors for development of amphotericin B nephrotoxicity
-nephrotoxins

Answer 11

Concurrent therapy with other nephrotoxins, such as an aminoglycoside, cyclosporine, or foscarnet, increases the risk of acute kidney injury.

Question 12

Identify the risk factors for development of amphotericin B nephrotoxicity
-CKD

Answer 12

Chronic kidney disease at baseline and the severity of the underlying illness also increase the risk.

Question 13

Identify the risk factors for development of amphotericin B nephrotoxicity
-dose dependent

Answer 13

The likelihood of renal disease is also dose dependent, with the risk of renal dysfunction being low at doses of less than 0.5 mg/kg per day and a cumulative dose of less than 600 mg.

Question 14

Preventing or reducing the occurrence of nephrotoxicity

Answer 14

• salt loading

- lipid based formulations