Calcineurin inhibitors
Blocking calcineurin so T cells cannot switch on interleukin-2.
Also called CNIs.
Class card
- Drugs
- Ciclosporin and Tacrolimus
- Used for
- Preventing rejection of kidney, liver and heart transplants
- Severe plaque psoriasis (ciclosporin)
- Severe rheumatoid arthritis (ciclosporin)
- Atopic dermatitis (tacrolimus ointment)
- Known for
- Kidney damage (nephrotoxicity), acute or chronic
- Tremor and other nerve toxicity
- Name stems
- -rolimus
3 cards: the class, and each drug in it.
Mechanism of action
How do calcineurin inhibitors work?
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.
The drugs
Calcineurin inhibitors with a card
Uses
What are calcineurin inhibitors used for?
- Preventing rejection of kidney, liver and heart transplants
- Severe plaque psoriasis (ciclosporin)
- Severe rheumatoid arthritis (ciclosporin)
- Atopic dermatitis (tacrolimus ointment)
Side effects
Side effects of calcineurin inhibitors
- Kidney damage (nephrotoxicity), acute or chronicKnown forSerious
- Tremor and other nerve toxicityKnown for
- High blood pressure
- High potassium (hyperkalemia)Serious
- High blood sugar and new diabetes after transplantSerious
- Low magnesium (hypomagnesemia)
- Serious infectionsSerious
- Lymphoma and other cancersSerious
- Skin cancerSerious
- Gum overgrowth, with ciclosporin
What the class has in common. Each drug's card has its own, and Known for marks what an exam expects you to know.
Watch for
Cautions
- Narrow therapeutic range: trough blood levels are measured and doses adjusted.
- Both are CYP3A4 substrates: azoles, macrolides, diltiazem and grapefruit raise levels; rifampicin and St John's wort lower them.
- Kidney function, potassium and blood pressure are checked; potassium-sparing diuretics and other nephrotoxic drugs need care.
- Live vaccines are avoided, and sun exposure is limited because of the skin cancer risk.
Remember them
A way to remember them
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
Name stems
-rolimus means macrolide immunosuppressant
Tacrolimus binds FKBP-12 and blocks calcineurin; sirolimus and everolimus also bind FKBP-12 but block mTOR. Ciclosporin, the other calcineurin inhibitor, lacks the stem.
- Every drug name stem
Don't mix them up
Classes easily confused with these
Sources
Checked against
Written for biofideX in plain words, after checking these references:
- Tacrolimus capsules: label (DailyMed)
- Cyclosporine capsules (modified): label (DailyMed)
- Tacrolimus ointment: label (DailyMed)
- Calcineurin Inhibitor (NCI Thesaurus)
- Peptidyl-Prolyl Cis-Trans Isomerase A (NCI Thesaurus)
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
Practice calcineurin inhibitors with the other classes in this group: what each drug is, how it works, what it treats and what it's known for.
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