Immunology pharm – Non-antibody immunosuppressants

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HY points about each drug followed by a quiz at the end

Cyclosporin

MOA of cyclosporine? –> inhibits cyclophilin (intracellular protein) –> decreases intracellular calcineurin –> decreases IL-2 transcription.

Important toxicities of cyclosporine? –> answer = nephrotoxicity (hyperkalemia), hypertension, hypertrichosis (↑ hair growth), gingival hyperplasia. USMLE wants you to know all of these. This isn’t just some random list of arbitrary yieldness.

  • USMLE vignette will tell you someone is on an immunosuppressant and that the creatinine has increased –> answer = cyclosporine.
  • Cyclosporine, verapamil (non-dihydropyridine CCB), and phenytoin (anti-convulsant that blocks Na channels) all are HY for causing gingival hyperplasia.
  • Random context: On my peds rotation years ago, I sat in on a consult with a family where the kid was on cyclosporine. I remember the pediatrician looked at the gums, checked the blood pressure, and asked the mom if she noticed any changes in hair growth. I was like, “What do you know? The stuff we study actually does sometimes apply to real life.”

Tacrolimus

MOA of tacrolimus? –> answer = inhibits FK506 –> decreases intracellular calcineurin –> decreases IL-2 transcription.

Important side-effects of tacrolimus? –> answer = type II diabetes, nephrotoxicity (hyperkalemia).

  • USMLE likes dysglycemia for tacrolimus.
  • Random context: met two people in real life who were on tacrolimus. Both had type II diabetes because of it.

Sirolimus

MOA of sirolimus? –> answer = blocks mTOR –> does not decrease intracellular calcineurin –> decreases responsiveness to IL-2.

Important side-effects of sirolimus? –> answer = dyslipidemia; does not cause nephrotoxicity.

Summary table

MEHLMANMEDICAL MOA ↓ Calcineurin? Effect on IL-2? Nephrotoxic?
Cyclosporine Inhibits cyclophilin Yes ↓ Transcription Yes
Tacrolimus Inhibits FK-506 Yes ↓ Transcription Yes
Sirolimus Inhibits mTOR No ↓ Responsiveness No

1. MOA of cyclosporine?

2. Important toxicities of cyclosporine? (4)

3. Name three drugs associated with gingival hyperplasia.

4. MOA of tacrolimus?

5. Important side-effects of tacrolimus? (2)

6. MOA of sirolimus?

7. Important side-effects of sirolimus?

8. a) Name two important calcineurin inhibitors.

b) Which drug notably does not inhibit calcineurin?

9. Cyclosporine, tacrolimus, sirolimus: which drug is the odd one out, and give three reasons why.

10. Which drug inhibits mTOR?

11. Which drug inhibits FK-506?

12. Which drug inhibits cyclophilin?

13. Which immunosuppressant inhibits responsiveness to IL-2?

14. Which two immunosuppressants decrease transcription of IL-2?

15. Which immunosuppressant causes type II diabetes?

16. Which immunosuppressant notably causes hypertension?

17. Which immunosuppressant notably causes dyslipidemia?

18. Cyclosporine, tacrolimus, sirolimus: which two cause nephrotoxicity and hyperkalemia?