Issues with immunosuppressive drugs Flashcards

1
Q

What is the MOA of tacrolimus?

A

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

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2
Q

Which metabolic condition can be caused by immunosuppressive agents?

A

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.

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3
Q

What are the two main calcineurin inhibitors drugs and what are their main side effects?

A

Tacrolimus and ciclosporin

Renal fibrosis, ­BP, post-transplant diabetes, cosmetic

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4
Q

What are the two main side effects of mycophenolate mofetil?

A

oral ulceration and bone marrow suppression

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5
Q

5 drugs are prescribed when patients are started on immunosuppressive therapy. What are they and what ae they prescribed to protect against?

A
  1. Ranitidine = ¯ risk of peptic ulceration from high dose steroids
  2. Nystatin = ¯ risk of oral candida
  3. Co-trimoxazole = ¯ risk of PCP
  4. 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
  5. If indicated (high risk groups) Isoniazid = to prevent TB. Pyroxidine is prescribed alongside this to prevent vitamin depletion
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6
Q

Which cancers are more common in immunosuppressed patients?

A

There is a x25 ­risk of cancer with immunosuppression, particularly skin and Post-Transplant lymphoproliferative disorder (PTLD).

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7
Q

What drugs should be avoided in patients on immunosuppressive therapy?

A

• Avoid clarithromycin / azole antifungals / trimethoprim

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8
Q

Should immunosuppression be stopped early or late in a sick patient?

A

As late as possible

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