3c Immunosuppressants and treatment of autoimmune diseases

What drug type is Cyclosporine and Tacrolimus?

Inhibitors of Calcineurin. Prevents graft (implant) rejection and treats acute autoimmune diseases. Can be given PO or IV.

What is Calcineurin?

A key molecule in the pathway that activates the T cell through CD3 complex.

In what other form is Tacrolimus available in?

An ointment for atopic dermatitis

What are the side effects of Cyclosporine & Tacrolimus?

Kidney damage (Neprotoxic), liver damage (Hepatoxic), gum swelling, hyperkalemia, diabetes, tremors.

What are the severe side effects of Cyclosporine & Tacrolimus?

Life‑threatening infections (mainly viral), lymphoma (T-cells are responsible to Kill cancer cells but here they are being inhibited).

What is the treatment of autoimmune diseases?

Local or systemic suppression of the immune system and inflammatory factors.

What is the mechanism of action of Azathioprine & 6-MP (Mercaptopurine)?

Azathioprine gets decomposed to 6-MP. They are metabolized into Thionosinic acid.

What does Thioinosinic Acid do?

It’s an analogue of nucleosides. Inhibits purine synthesis. Blocks DNA/RNA production. Prevents cell proliferation, especially lymphocytes.

What disease are Azathioprine & 6-MP (Mercaptopurine) used to treat?

Lupus, Crohn’s disease, Ulcerative colitis, leukemias

What are side effects of Azathioprine & 6-MP (Mercaptopurine)?

Bone marrow suppression, infections, nausea, vomiting

Mycophenolate - Mechanism

Inhibits inosine monophosphate dehydrogenase (IMPDH) → blocks de novo purine synthesis → inhibits lymphocyte & granulocyte proliferation

Mycophenolate - Uses

Organ transplantation (prevent rejection), autoimmune diseases

What is the mechanism of action of Adalimumab (Humira)?

Monoclonal antibody against TNF-α receptor → blocks inflammation

What is Adalimumab (Humira) clinically used for?

Rheumatoid arthritis, various arthritis, Crohn’s disease

What are side effects of Adalimumab (Humira)?

Infections, bone marrow suppression, rash, nausea, vomiting, headaches

What is the mechanism of action of Abatacept (Urancia)?

Protein that competes for CD28 binding on T cells → inhibits T cell activation

What is the clinical use of Abatacept (Urancia)?

Mainly rheumatoid arthritis

What are side effects of Abatacept (Urancia)?

Risk of infections, headache

What happened to treatment of Autoimmune Diseases with Corticosteroids?

Was used widely in the past; now it is reduced due to significant side effects

What is the strategy for Treatment of Autoimmune diseases through corticosteroids?

Combine drugs with different mechanisms when possible. Avoid deep immunosuppression

What is the most dangerous side effects of Corticosteroids?

Bone marrow suppression and severe infections