Immunosuppression in Organ Transplantation

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Chapter: Essential pharmacology : Immunosuppressant Drugs, Gene Therapy

Use of immunosuppressants is essential for successful organ transplantation. In general 3 types of regimens are used depending upon the stage of transplantation.


IMMUNOSUPPRESSION IN ORGAN TRANSPLANTATION

 

Use of immunosuppressants is essential for successful organ transplantation. In general 3 types of regimens are used depending upon the stage of transplantation.

 

Induction Regimen: This is given in the perioperative period: starting just before the transplant to about 2–12 weeks after it. Accelerated rejection develops in the first week, while acute rejections are most likely from 2–12 weeks. The most common regimens include triple therapy cyclosporine + prednisolone + azathioprine (with or without muromonab CD3/ATG), but 2 drug and single drug regimens are also used. Many experts do not give cyclosporine preoperatively, and try to dealy its induction as far as possible to avoid nephrotoxicity, particularly in renal transplantation. If no rejection develops, the doses are gradually reduced after 2 weeks and this phase merges imperceptably with maintenance phase.

 

Maintenance Regimen: This is given for prolonged periods, may be lifelong. Triple drug regimen is favoured because each component is needed in lower doses—reduces toxicity and cost. Cyclosporine is the most costly and its nephrotoxicity is often the limiting factor. Long-term steroid therapy has its own problems. The component which produces toxicity in a given patient is curtailed or dropped. Two drug and one drug regimens are also used, but are associated with more episodes of acute rejection. After 1 year, cyclosporine is generally dropped, but its continuation is associated with fewer acute rejections. In case of intolerance to the first line drugs cyclosporine, azathioprine and prednisolone, the second line drugs like cyclophosphamide, MMF, chlorambucil are substituted.

 

Anti-Rejection Regimen: This is given to suppress an episode of acute rejection. Steroid pulse therapy (methylprednisolone 0.5–1 g i.v. daily for 3–5 days) is effective in majority of cases. In case of no response, muromonab CD3/ATG is given as rescue therapy or the antibodies are combined with steroids. Tacrolimus, MMF have also been used in rescue therapy of steroid resistant rejection. If the maintenance regimen had not included cyclosporine, its addition can treat acute rejection, but can be damaging to the transplanted kidney.

 

Adverse Effects The two general untoward effects of immunosuppressant therapy are:

 

·      Increased risk of bacterial, fungal, viral (especially CMV) as well as opportunistic infections.

 

·      Development of lymphomas and related malignancies after a long latency.

 

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