Calcineurin inhibitors and mTOR inhibitors
How tacrolimus and ciclosporin block IL-2 transcription and sirolimus and everolimus block the IL-2 signal, why CYP3A4 and P-glycoprotein interactions dominate their dosing, and how afferent arteriolar vasoconstriction explains CNI nephrotoxicity, hyperkalaemia and hypertension.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Calcineurin inhibitors (CNIs): tacrolimus and ciclosporin stop IL-2 transcription in T cells. Tacrolimus is the backbone of most Australian kidney, liver and heart transplant regimens.
- mTOR inhibitors: sirolimus and everolimus block the response to IL-2, halting T-cell proliferation in G1.
- All four have narrow therapeutic indices, are CYP3A4 and P-glycoprotein substrates, and need whole-blood trough monitoring.
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Sources
- KDIGO clinical practice guideline for the care of kidney transplant recipientsAmerican Journal of Transplantation (KDIGO Transplant Work Group, 2009;9 Suppl 3:S1-155), 2009
- Australian Medicines Handbook: tacrolimus, ciclosporin, sirolimus and everolimus monographsAU/NZAustralian Medicines Handbook Pty Ltd, online, accessed November 2026
- Therapeutic Goods Administration: product information for tacrolimus (immediate- and prolonged-release), ciclosporin, sirolimus and everolimusAU/NZTherapeutic Goods Administration, online, accessed November 2026
- Calcineurin inhibitor nephrotoxicityClinical Journal of the American Society of Nephrology (Naesens, Kuypers and Sarwal, 2009;4:481-508), 2009
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosingClinical Pharmacology and Therapeutics (Birdwell et al., 2015;98:19-24), 2015
- Last updated
- 14 November 2026
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