Antifungal Drugs (Amphotericin B (AmB))

Question 1

Properties of Amphotericin B

Answer 1

• a natural antifungal produced by the bacteria
  Streptomyces nodosus
• concentration-dependent fungicidal
• it is the DoC for life- threatening mycoses; as WHO has listed AmB in its List of Essential Medicine

Question 2

RoA of Amphotericin B

Answer 2

• IV
• due to its nephrotoxicity, it should be co-formulated with a liposome-forming agent like Sodium deoxycholate. These liposomes are expensive to prepare and only reserved for renal failure patients
• no dose adjustment is required for hepatic failure
• Half-life is 15 days

Question 3

Spectrum of Amphotericin B

Answer 3

Broad:
→ Mycoses
→ Leishmaniases

Question 4

MoA of Amphotericin B

Answer 4

Theory #1: with ergosterol in cell membrane of fungi by the weak hydrophobic Van der Walls bond, this will form pores which allow monovalent ions, especially K+ to leak from the cell; resulting in cell death
Theory #2: Amphotericin B will act as an oxidative agent, creating ROS that kills the fungal cells

Question 5

Resistance of Amphotericin B

Answer 5

Theory #1: fungi will decrease ergosterol content in the cell membrane
Theory #2: fungi will release antioxidants to inhibit AmB

Question 6

A.D.M.E of of Amphotericin B

Answer 6

D: it is highly albumin-bound and can penetrate the:
→ BBB into CSF
→ Peritoneal fluid
→ Vitreous fluid
→ Synovial fluid
M: metabolized in kidneys
E: some unchanged AmB is found in urine & some is excreted in bile

Question 7

Adverse Effects of Amphotericin B

Answer 7

• Fever, chills, anaphylaxis
  → occurs due to innate immune reactions after 1-3
  hours of IV administration
• Renal impairment
  → AmB disturbs nephron filtration, leading to K+ loss - indicated by ↓ClCr & ↓KFT (Kidney Function Test)
• Hypotension
  → shock-like drop in BP due to hypokalemia
  → prevented by administering K supplements
• Decreased erythropoietin secretion
  → this causes anemia and ↓O2
• Thrombophlebitis
  → the formation of clots in the site of IV

Question 8

Supportive Measures of Amphotericin B

Answer 8

1) Avoid nephrotoxic drugs with AmB
2) Administer the following agents:
A. Normal saline → minimize nephrotoxicity
B. Potassium supplements → avoid hypokalemia and hypotension
C. Antipyretics → decrease immune reactions
D. Heparin → avoid thrombophlebitis