Calcineurin Inhibitors

(CNI’s)
CICLOSPORIN
TACROLIMUS
Mechanism
 CNI’s block the production of IL-2
 Interleukin 2 = T cell activation fuel
 IL-2 is one of a group related proteins made by leukocytes (WBC) and other
cells in the body. It is made by a type of T lymphocyte.
 T lymphocytes are part of the immune system and develop from stem cells in
the bone marrow. They help the body from infection and may help fight cancer.
 In order to make IL-2, you need a Transcription Factor which is known as NFAT
(Nuclear Factor of Activated T cells)
 NFAT goes to the nucleus of activated T cells and causes the T cells to make IL-
2 and IL-2 receptor.
 But NFAT can only do this if it is free to travel to the nucleus and rather
deliberately in a resting T cell, NFAT is kept far away from the nucleus
because we don’t want the T cell just spontaneously activating itself for no
reason. So until the T cell is activated by an antigen NFAT is kept far away
from the nucleus and is anchored there by a phosphate molecule. And this
is where Calcineurin comes in.
 Calcineurin is a serine threonine protein phosphatase which basically
means that it’s an enzyme in the business of removing phosphate from
other molecules. So Calcineurin can come along to chop the phosphate of
the NFAT and set the NFAT free. NFAT will then travel to the nucleus and
encourage the T cell to make lots and lots of Interleukin 2 and its receptor
Tacrolimus (FK506)

 Tacrolimus
forms a complex with something known as
FKB12 which in turn blocks Calcineurin

Calcineurin
 Ciclosporinbinds to something known as cyclophilin to
form a complex and this complex blocks Calcineurin
Tacrolimus “Tac”

 One of the main anti-rejection medication for lung transplant

 Generic name for Progral
 Should be taken two times daily 9am and 9pm or consistently 12 hours apart
 We measure the amount of Tacrolimus in the body using blood test
 High Tacrolimus level- more side effects and harmful to your kidney
 Low Tacrolimus level- may start to attack your new organ which results in
rejection
 While in the hospital Tacrolimus lab test is drawn multiple times to make dose
adjustments
 Take medication on time and never miss any dosage
 Always get labs drawn before morning dose of medication
 Available in 5mg(red), 1 mg(white) and 0.5mg(yellow) capsules. Liquid also
available.
 Do not cut or crush the medicine in half. It should be swallowed whole.
 Always use same Generic product to avoid changes in Tacrolimus level.
 Make sure that it looks exactly the same when you refill your prescription.
Tacrolimus
SIDE EFFECTS
 Highly nephrotoxic and most of the side effects stems
from nephrotoxicity
 Kidneys shutting down> urine acid will not be
filtered>gout
 Potassium will not be filtered>arrhythmias
 Na retention>hypervolemia>hypertension
 Cerebral vasoconstriction>intentional tremors
 Insulin malfunctioning>hyperglycemia
Cyclosporine

 Generic name for Gengral and Neoral

 Available as 25mg and 100mg capsules
 Don’t cut or crush. Liquid also available
Cyclosporine
SIDE EFFECTS
 Hair and gums overgrowth (gingival hypertrophy/hyperplasia)
 High blood pressure, high cholesterol, high blood sugars
 You should not take Non-Modified Cyclosporine(Sand-Immune).
Take the Modified
 Should not be taken with other medications such as Phenytoin,
Rifampin, Octreotide, Orlistat, St. John’s Wort, and grapefruit juices.