B/30. Immunopharmacology II. (Inhibitors of cytokine gene expression, 5-ASA derivatives)

Question 1

Drugs need to know in this topic

Answer 1

cyclosporin A, tacrolimus, sirolimus, tofacitinib, sulfasalazine

Question 2

Cyclosporine A

Answer 2

Calcineurin inhibitors

Binds to cyclophilin → inhibits calcineurin → altered activation of Tcell
transcription factors → IL-2, IL-3, IFN-γ ↓

1. Oral, parenteral
2. Hepatic P450 metabolism
3. Bone-marrow transplantation (1st-line agent)
4. Solid-organ transplantation
5. Autoimmune diseases (RA, psoriasis, uveitis)
6. Nephrotoxicity
7. Hepatotoxicity
8. Hypertension
9. Gingival hypertrophy

Question 3

Tacrolimus

Answer 3

Calcineurin inhibitors

Binds to FK-binding protein → inhibits calcineurin → altered activation of Tcell
transcription factors → IL-2, IL-3, IFN-γ ↓

Oral, parenteral

1. Solid-organ transplantation
2. Autoimmune diseases
3. Atopic dermatitis (topical formulation)
4. Nephrotoxicity

Question 4

Sirolimus

Answer 4

mTOR inhibitors

Binds to FK-binding protein → inhibit the kinase activity of mTOR

1. Oral, parenteral
2. Hepatic P450 metabolism
3. Neuroendocrine tumors, breast, and renal
4. Solid-organ transplantation
5. Sirolimus-eluting stents are used to prevent
   restenosis after coronary angioplasty
6. Myelosuppression
7. Hepatotoxicity
8. Pneumonitis

Question 5

Tofacitinib

Answer 5

Inhibitor of JAK-1 and JAK-3

1. Oral
2. Hepatic P450 metabolism
3. Autoimmune disease
   (RA, IBD, ankylosing spondylitis)
4. Monotherapy or in combination with methotrexate
5. Infections
6. Hyperlipidemia
7. Elevated liver enzymes

Question 6

Sulfasalazine

Answer 6

Prodrug, converted by colon bacteria into 5-ASA

1. PPAR-γ agonist (NFκB, TLR’s ↓)
2. Cytokine expression ↓
3. COX and LOX inhibition
4. Antioxidant role

Oral, topical

1. Autoimmune diseases
2. IBD (UC >> CD)
3. Sulfasalazine - nausea, vomiting, headache, rash
4. Other agents are generally well-tolerated