Calcineurin inhibitors

Cyclosporine:
cyclic polypeptide, obtained from fungus
Highly selective immunosuppressant which markedly increased the success of organ transplantation
Selectively inhibit T lymphocyte proliferation, IL-2 & other cytokine production without affecting suppressor T cells
Tacrolimus
Sirolimus
Mechanism
Cyclosporine enter target cells, bind to cyclophilin
The complex then bind & inactivate calcineurin
Calcineurin is membrane associated serine/ threonine phosphatase enzyme, present in T lymphocytes
Calcineurin help in transcription of cytokine genes, leading to production of IL-2, GM-CSF, TNF alpha & interferons
Selectively suppress CMI, humoral immunity remains intact
Recipient is able to deal with bacterial infection
No toxicity of bone marrow & RES
Adverse effects
Nephrotoxicity
Hypertension
Precipitate diabetes
Impair Liver functions
Hyperkalemia
Gum hyperplasia
Opportunistic infections
Hirsutism
Anorexia, lethargy
Tremor
seizures
Therapeutic uses
Kidney, liver, heart, and other organ transplantation (First line drug) along with other immunosuppressant
Second line drug in autoimmune disorders, when not controlled by primary drugs
Severe rheumatoid arthritis
Psoriasis
Behcet’s acute ocular syndrome
Endogenous uveitis,
Atopic dermatitis,
Inflammatory bowel disease
Nephrotic syndrome, when standard therapies have failed