Issues with immunosuppressive drugs Flashcards
What is the MOA of tacrolimus?
Tacrolimus is a macrolide calcineurin inhibitor. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor nuclear factor of activated T-cells (NF-AT), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT
Which metabolic condition can be caused by immunosuppressive agents?
Cyclosporin and tacrolimus cause post-transplant diabetes mellitus by a number of mechanisms, including decreased insulin secretion, increased insulin resistance or a direct toxic effect on the beta cell.
What are the two main calcineurin inhibitors drugs and what are their main side effects?
Tacrolimus and ciclosporin
Renal fibrosis, BP, post-transplant diabetes, cosmetic
What are the two main side effects of mycophenolate mofetil?
oral ulceration and bone marrow suppression
5 drugs are prescribed when patients are started on immunosuppressive therapy. What are they and what ae they prescribed to protect against?
- Ranitidine = ¯ risk of peptic ulceration from high dose steroids
- Nystatin = ¯ risk of oral candida
- Co-trimoxazole = ¯ risk of PCP
- Valganciclovir = to prevent CMV reactivation for 6 months in those with +ve serology. CMV infection is most common 1 – 4 months post-transplant and is treated with IV ganiciclovir and cessation of MMF
- If indicated (high risk groups) Isoniazid = to prevent TB. Pyroxidine is prescribed alongside this to prevent vitamin depletion
Which cancers are more common in immunosuppressed patients?
There is a x25 risk of cancer with immunosuppression, particularly skin and Post-Transplant lymphoproliferative disorder (PTLD).
What drugs should be avoided in patients on immunosuppressive therapy?
• Avoid clarithromycin / azole antifungals / trimethoprim
Should immunosuppression be stopped early or late in a sick patient?
As late as possible