What are the calcineurin inhibitors?

Calcineurin inhibitors are immunosuppressants used to manage autoimmune conditions including but not limited to lupus nephritis, idiopathic inflammatory myositis, interstitial lung disease, atopic dermatitis, and many more. In addition, they are used as mainstays for immunosuppression in solid organ transplants.

Which drug is a calcineurin?

Generic and brand names of calcineurin inhibitors include: Astagraf XL. Cequa. Cyclosporine.

What calcineurin means?

Calcineurin is a serine-threonine specific Ca(2+)-calmodulin-activated protein phosphatase that is conserved from yeast to humans.

What are advantages of calcineurin inhibitors?

Advantages of topical calcineurin inhibitors over topical corticosteroids include the lack of development of tachyphylaxis, telangiectasias, and thinning and atrophy of the skin.

What are the side effects of calcineurin inhibitors?

The most commonly reported side effect of topical calcineurin inhibitors is local skin irritation (burning, pruritus, and erythema) at the application site. However, this is usually transient and decreases over time (usually within one month). Other adverse effects may include: Allergic contact dermatitis.

Are calcineurin inhibitors safe?

In clinical experience, topical calcineurin inhibitors have been shown to be a safe and effective alternative to topical corticosteroids in almost 7 million patients (>5 million on pimecrolimus; >1.7 million on tacrolimus).

What are calcineurin creams?

Topical calcineurin inhibitors (TCIs) work by altering the immune system and have been developed for treating atopic eczema. There are two types available: tacrolimus ointment (Protopic) for moderate to severe eczema and pimecrolimus cream (Elidel) for mild to moderate eczema. ‘Topical’ means applied to the skin.

What causes calcineurin?

This could be attributed to technical factors, such as the lack of antibodies capable of detecting the low levels of NFAT expression. Alternatively, calcineurin is a physiologically relevant phosphatase for Elk-1,629 NF-κB, and myocyte enhancer factor-2 (MEF2) and may induce hypertrophy independent of NFAT.

Where is calcineurin found?

It is a ubiquitous enzyme, but is highly expressed in forebrain neurons, including striatal MSNs where it is very highly enriched (Goto et al., 1987). Calcineurin is comprised of two subunits, calcineurin A and B (Fig. 29.1D).

What is calcineurin inhibitors mechanism of action?

MECHANISM OF ACTION Calcineurin inhibitors exert their immunosuppressive effects by reducing interleukin-2 (IL-2) production and IL-2 receptor expression, leading to a reduction in T-cell activation. Tacrolimus inhibits T-lymphocyte activation by binding to FKBP-12, an intracellular protein.

How do calcineurin inhibitors cause hypertension?

In this study, stimulation of the β2-adrenergic receptor led to decreased transcription of the gene encoding WNK4 by increasing histone acetylation. In turn, suppression of WNK4 activated NCC, thereby causing salt-sensitive hypertension.

How does a calcineurin inhibitor work?

A calcineurin inhibitor stops calcineurin working, by binding to proteins in the cells called immunophilins. The results are: Reduced release of the cytokine interleukin-2 from the T cells. Reduced T-cell proliferation.