Ciclosporin
A calcineurin inhibitor from a fungus, used to prevent transplant rejection and to treat severe psoriasis and rheumatoid arthritis.
Also called cyclosporine (US name) or CsA (abbreviation).
Drug card
- How it works
- Blocking calcineurin so T cells cannot switch on interleukin-2
- Used for
- Preventing rejection of kidney, liver and heart transplants
- Severe plaque psoriasis
- Severe rheumatoid arthritis not helped by methotrexate
- Dry eye from ocular inflammation (eye drops)
- Known for
- Kidney damage (nephrotoxicity)
- Gum overgrowth (gingival hyperplasia)
- Excess hair growth (hirsutism)
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does ciclosporin work?
Ciclosporin, a cyclic peptide, binds cyclophilin in T cells, and the complex inhibits calcineurin, so NFAT stays out of the nucleus and interleukin-2 is not made. Helper T cells in the G0 and G1 phases are its main target, and unlike antiproliferative drugs it does not suppress the bone marrow.
Like other calcineurin inhibitors: Inside T cells ciclosporin binds cyclophilin and tacrolimus binds FKBP-12, and each drug-protein complex blocks calcineurin, the calcium- and calmodulin-dependent phosphatase that activates the transcription factor NFAT. NFAT then cannot enter the nucleus, so the T cell does not make interleukin-2 and other cytokines and is not activated, which prevents graft rejection.
Uses
What is ciclosporin used for?
- Preventing rejection of kidney, liver and heart transplants
- Severe plaque psoriasis
- Severe rheumatoid arthritis not helped by methotrexate
- Dry eye from ocular inflammation (eye drops)
Side effects
Side effects of ciclosporin
- Kidney damage (nephrotoxicity)Known forSerious
- Gum overgrowth (gingival hyperplasia)Known for
- Excess hair growth (hirsutism)Known for
- High blood pressure
- Tremor
- High potassium (hyperkalemia)Serious
- High uric acid (hyperuricemia)
- Liver damageSerious
- Seizures and brain swelling (PRES)Serious
- JC virus brain infection (PML)Serious
- Lymphoma and other cancersSerious
- Skin cancerSerious
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- Blood levels are monitored, and its oral formulations are not interchangeable without close supervision.
- Azoles, macrolides, diltiazem, verapamil and grapefruit raise its levels; rifampicin, carbamazepine and St John's wort lower them.
- Potassium-sparing diuretics are avoided, and NSAIDs and other nephrotoxic drugs need care; creatinine and blood pressure are checked.
- It raises levels of statins and colchicine, which can then damage muscle.
Good to know: Hirsutism and gum overgrowth are typical of ciclosporin; in trials, tacrolimus caused more new-onset diabetes and tremor than ciclosporin did.
Remember it
A way to remember it
No calcineurin, no NFAT, no interleukin-2
Calcineurin removes a phosphate from NFAT so it can enter the nucleus and switch on the interleukin-2 gene; with calcineurin blocked, T cells never get the interleukin-2 signal to activate and multiply.
Written for biofideX
Its class
Calcineurin inhibitors
Other calcineurin inhibitors with a card:
Easily mixed up with antiproliferative immunosuppressants and glucocorticoids.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
- Cyclosporine capsules (modified): label (DailyMed)
- Cyclosporine (NCI Thesaurus)
- Peptidyl-Prolyl Cis-Trans Isomerase A (NCI Thesaurus)
- Calcineurin Inhibitor (NCI Thesaurus)
- Cyclosporine ophthalmic emulsion: label (DailyMed)
- Tacrolimus capsules: label (DailyMed)
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Targeted therapy and the immune system
Ciclosporin is one of 13 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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