Sketchy Pharm: Azathioprine, 6-Mercaptopurine, Mycophenolate Mofetil

Question 1

How is purine synthesis distinct from pyrimidine synthesis?

Answer 1

Purine starts with the ribose, while pyrimidine starts with the nitrogenous base.

This is why purine synthesis starts with the enzyme phosphoRIBOSYL pyrophosphate (PRPP) amidotransferase.

(Think of the guys starting to carve near the five-pointed block with the two P-shaped hammers.)

Question 2

Purine synthesis begins with ____________.

Answer 2

IMP (like the imp standing watch over the two golden purine derivative statues)

Question 3

Azathioprine is converted to __________ inside cells.

Answer 3

6-mercaptopurine

Think of Ezmerelda –azomerelda –being CAPTured.

Question 4

What enzyme converts 6MP to its active metabolite?

Answer 4

HGPRT (like the HiGh PRiesT prodding CAPTured Ezmerelda)

Question 5

6MP and azathioprine ultimately inhibit _______________.

Answer 5

IMP synthesis (like the CAPTured woman kicking over the IMP)

Question 6

Like the pyrimidine synthesis inhibitors, azathioprine is ___________-specific.

Answer 6

S phase

This makes sense because it disrupts DNA synthesis.

(Think of the Stairs that are broken.)

Question 7

6MP and azathioprine are mainly used to treat what diseases?

Answer 7

• Hematologic malignancies (represented by the cracked stained glass window with the archers and knights)
• Rheumatoid arthritis (like the red, inflammed lanterns lining the street)
• IBD (like the haustra-shaped lanterns to the left of the image)

Question 8

What are the side effects of 6MP and azathioprine?

Answer 8

• Myelosuppression (like the nun sprinkling seed from her bone pan)
• Immunosuppression (like the canes held by the statues)
• Pancreatitis (like the nun polishing the statue with the pancreas sponge)
• Hepatotoxicity (liver stain on nun’s shirt)

Question 9

6MP and azathioprine should be dosed carefully in those taking ________________.

Answer 9

allopurinol, because xanthine oxidase degrades 6MP and azathioprine and inhibiting it with allopurinol can raise the serum levels of these drugs

Question 10

How does mycophenolate mofetil work?

Answer 10

It inhibits IMP dehydrogenase and thus prevents it from converting IMP to GMP (like Quasi-Mofetil kicking over the GruMP statue)

Question 11

The most common side effect of mycophenolate mofetil is __________________.

Answer 11

GI upset (like the hunchback about to vomit) and immunosupression