Sketchy Pharm: Amphotericin, Flucytosine

Question 1

Recall that fungal membranes are composed of _______________ instead of cholesterol.

Answer 1

ergosterol

Question 2

How does amphotericin work?

Answer 2

It binds ergosterol and forms pores in the fungal cell membrane.

(Think of the holes in the amphibian tank that are letting the water out.)

Question 3

How can fungi develop resistance to amphotericin?

Answer 3

They can down-regulate ergosterol in the membrane. Without ergosterol, amphotericin is not able to penetrate the cell membrane.

Question 4

How is amphotericin administered?

Answer 4

Intravenously (like the ivy on the frog’s cage)

Question 5

Typically, amphotericin is only used for _______________.

Answer 5

systemic, life-threatening infections (represented by the anatomical body system model next to the frog’s cage)

Question 6

How have drug developers packaged amphotericin so that it’s less toxic?

Answer 6

They make liposomal fat formulations that slow the delivery of the drug into the system and limit binding to human cholesterol.

(Think of the large frog chin representing a swollen liposome.)

Question 7

What are the infusion-related toxicities?

Answer 7

• Hypotension (teacher fainting)
• Headache (teacher grabbing his head)
• Fever (frog sweating next to bunsen burner)

Note: the teacher is doing this in response to the frog suddenly jumping on him, which represents the infusion reaction.

Question 8

For CNS infections, amphotericin is administered ___________________.

Answer 8

intrathecally (like the frog’s tongue directly on the model’s brain)

Question 9

________________ can occur at the injection site.

Answer 9

Thrombophlebitis (like the blue veins swollen on the frogs)

Question 10

Intrathecal administration can cause ____________.

Answer 10

seizures (like the shaking seizure lines around the model)

Question 11

_________________ occurs in almost all patients receiving amphotericin.

Answer 11

Irreversible renal damage (often type 1 acidosis)

Think of the chemist holding the yellow fluid in the tube shaped like a 1.

Question 12

What electrolyte abnormalities are seen in amphotericin renal toxicity?

Answer 12

Hypokalemia from the renal tubular acidosis (think of the chemist slipping on the banana peel) and hypomagnesemia (like the magnets falling into the sink

Question 13

To counteract the renal effects of amphotericin, ____________ is often administered during or before amphotericin.

Answer 13

saline (like the emergency saline shower)

Question 14

How does amphotericin cause anemia?

Answer 14

From kidney damage leading to decreased EPO production (like the broken kidney-shaped jar that’s spilling blood)

Question 15

Amphotericin is often used with ______________ to treat Cryptococcal meningitis.

Answer 15

flucytosine (like the flute player across the hall)

Question 16

How does flucytosine work?

Answer 16

It gets converted to 5-fluorouracil in the cell. 5FU then inhibits fungal DNA and RNA synthesis.

(Think of the sheet music with F and C getting turned over so it looks like F and U. Next, the frog has smeared the helical chalk design just above the sheet music)

Question 17

Flucytosine and amphotericin are used to treat ________________.

Answer 17

Cryptococcal meningitis (like the crypt design on the chalkboard)

Question 18

_______________ has the same mechanism of action as amphotericin.

Answer 18

Nystatin

Think of the sign saying “Be NYce to lab animals” with the frog emblem.

Question 19

Nystatin is often used for ________________.

Answer 19

vaginal candidiasis and oropharyngeal candidiasis (like the Canadian flag above the girl getting hit in the crouch with the snowball and the water fountain – which represents the oral nystatin rinse done to treat oral candidiasis)