Tasty Morsels of Critical Care 004 | Transplant drugs

14 Nov

Welcome back to the tasty morsels of critical care podcast.

All of these posts are simplifications of much more complex topics but when it comes to the immunosuppressants used in solid organ transplant I’m wading out of my depth even more than I usually do. This summary is basically enough to get by but perhaps not enough to say anything sensible about.

All of them are of course immunosuppressant but depending on the type of solid organ transplant may need more or less suppressing. Acute rejection in kidney transplant is a big deal but at least we have a backup organ with dialysis. Acute rejection in a liver might be easier managed but we have no backup option for support if the graft is rejected. All that to say that it’s complicated and there are reasons that transplant physicians are one of the few groups allowed to prescribe in our generally closed ICUs.

There is a concept of “induction” chemo where the immune system is flattened at the time of antigen presentation basically telling the immune system “nothing to see here, move along…” while sneaking a new organ into place. This allows the delayed introduction of the supertoxic maintenance agents. Basiliximab is the one I’ve seen used as an antibody to the IL-2 receptor which I presume does something complicated to the immune system that I would understand even less than most things.

The main drugs used in the long term fall into 2 groups

  • calcineurin inhibtors such as ciclosporin and tacrolimus
  • antimetabolites such as azathioprine or mycophenelate

So here’s one sentence on each

  • Ciclosporin
    • found in a soil sample produced by a fungus (which is a common and somewhat inexplicable theme in transplant drugs)
    • p450 metabolism (which is medical code for ask a pharmacist before starting a new med) with no renal excretion
    • extensive side effects most importantly is nephrotoxicity
    • TMA and PRES are also important ICU conditions on the list of bad things
  • Tacrolimus
    • less dependant on bile for gut absorption
    • also p450
    • also nephrotoxic
  • Azathioprine
    • inhibits leucocyte function by interrupting purine synthesis
    • dose dependant myelosuppression
    • xanthine oxidase metabolism and renal excretion
  • Mycophenelate
    • again blocks purine synthesis
    • 100% bioavailability and renal excretion
    • mainly GI side effects
    • marrow suppression
    • increasingly replacing azathioprine apparently

Steroids of course also have a big role by inhibiting T cell proliferation, T cell immunity and cytokines and suppress antibody formation. Usually used in high doses as part of induction and then tapered. Current idea is to try to minimise long term steroids using immunosuppressants above as lifelong steroids is a fate only matched by not having a transplant at all. 

For completeness it’s worth knowing there a variety of unpronounceable biologic agents, either monoclonal or polyclonal antibodies with the main target as IL-2. IL-2 needed for proliferation of cytotoxic T cells which are key cells we’re trying to keep in a drunken stupor in the corner so they don’t notice the honking great new solid organ we just sneaked in. Basiliximab as mentioned above is an example of these drugs

References:

Oh Chapter 103

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