admittomedicine

calcineurin inhibitors

1 min read

transplant backbone

The cornerstone of solid organ and stem cell transplant immunosuppression. Narrow therapeutic index drugs requiring strict therapeutic drug monitoring (TDM).

  • Mechanism: Inhibit calcineurin prevent NFAT dephosphorylation block IL-2 production inhibit T-cell activation.

agents

  1. Tacrolimus (FK506): More potent, preferred in most transplants.
  2. Cyclosporine: Older, causes more gingival hyperplasia/hirsutism.

toxicities

  • Nephrotoxicity:
    • Acute: Afferent arteriolar vasoconstriction (reversible).
    • Chronic: Interstitial fibrosis (irreversible).
  • Neurotoxicity: Tremor (common), Seizures, PRES (Posterior Reversible Encephalopathy Syndrome).
  • Metabolic: Hyperkalaemia, Hyperglycaemia (NODAT - New Onset Diabetes After Transplant), Hypertension.
  • TMA: Can trigger Thrombotic Microangiopathy.

drug interactions (cyp3a4)

Massive list. ALWAYS CHECK.

  • Inhibitors (Raise Levels/Toxicity): Azoles, Diltiazem, Macrolides, Grapefruit Juice.
  • Inducers (Lower Levels/Rejection): Rifampin, Phenytoin, Carbamazepine, St. John’s Wort.

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