Buy PDFs here:
Hello in this video we’re going to talk about the pharmacology of calcineurin inhibitors calcineurin inhibitors such as tacrolimus and cyclosporine are immunosuppressants they are used mainly to prevent organ transplant rejection in combination with mycophenolate and steroids it can also be used for severe atopic dermatitis they’re not really used as much for
Rheumatological conditions any more possibly can be used for lupus nephritis calcineurin inhibitors essentially inhibit the synthesis of interleukin 2 normally antigen presenting cells such as macrophages picks up an antigen a new one either foreign or a self antigen processes it and then presents it on an mhc class 2 molecule on towards t cells now these t-cells
Will become activated and they require interleukin 2 key autocrine t-cell activator activation of t-cells will stimulate the adaptive immune response consisting of cytotoxic t cells t helper cells and then they will also activate plasma cells the antibody producing cells calcineurin inhibitors inhibit calcineurin a key protein required to allow transcription of
Interleukin 2 the key autocrine t cell activator the mechanism of action is a bit more complicated let’s take a closer look at how naive t-cells become activated so an antigen is presented to t-cell receptors which will initiate a cascade of intracellular events this begins with activation of phospholipase c first of all i play c hydrolyzes phosphatidyl inositol
For five bisphosphate also known as pip2 to generate the secondary messengers inositol one for five triphosphate ip3 and diacylglycerol d ag i p3 increases intracellular calcium levels calcium binds to calmodulin later binding to calcineurin a calcium calmodulin dependent phosphatase calcineurin when it’s bound to all the stuff d phosphor eliza’s nuclear factor
Of activated t-cells nfat which when de phosphorylated targets the interleukin-2 gene to make interleukin 2 cytokines interleukin-2 is released by the t-cells which in turn acts as an autocrine molecule binding on to interleukin 2 receptors on the surface of the t-cells interleukin-2 will activate this t-cell and eventually it will initiate the activation of the
Adaptive immune system cyclosporine is a calcineurin inhibitor which works by binding to the intra cellular receptor cycle of fillin 1 producing a complex known as cyclosporine cyclo fillin this complex subsequently inhibits calcineurin which in turn stops the dephosphorylation as well as the activation of the nuclear factor of activated t-cells tacrolimus is the
Other calcineurin inhibitor which binds to a intracellular protein called nk v p12 it then continues to form a complex consisting of tacrolimus fk b p 12 calcium calmodulin and then later calcineurin which will inhibit the phosphatase activity of calcineurin and when the phosphatase activity is inhibited the nfat doesn’t get d phosphorylated calcineurin inhibitors
Have a number of side-effects hyperuricemia increasing the risk of gout nephrotoxicity hypertension and hyperlipidemia as well as hyperglycemia the side effects are more common in certain types of calcineurin inhibitors for example hyperglycemia is more common with tacrolimus hypertension hyperlipidemia and hyperuricemia is more common for patients using cyclosporine
I hope you enjoyed this video on calcineurin inhibitors and their mechanism of action thank you for watching you
Transcribed from video
Calcineurin Inhibitors (Tacrolimus and Cyclosporine) IL2 – Mechanism of action, adverse effects By Armando Hasudungan
