100 QUESTIONS IN CARDIOLOGY

61 What drugs do post-transplant patients require,

and what are their side effects? How should I

follow up such patients?

Brendan Madden

Following successful cardiac, cardiopulmonary or pulmonary

transplantation, patients require life-long immunosuppressive

therapy. Routine immunosuppression consists of cyclosporin-A

and azathioprine, occasionally supplemented by cortico-

steroids. Episodes of acute allograft rejection are treated with

intravenous methylprednisolone therapy or occasionally anti-

thymocyte globulin or OKT3. Other drugs used include

tacrolimus, mycophenolate mofetil and cyclophosphamide.

Early evidence suggests that mycophenolate mofetil (an

antimetabolite drug) may be a useful alternative to azathioprine

as maintenance postoperative immunosuppression. OKT3 is a

monoclonal antibody raised in mice, which is directed against

the lymphocyte CD3 complex. Although it is sometimes used

for induction following transplantation it is now more

frequently employed in the management of severe episodes of

acute cardiac rejection.

Common complications following transplantation include

allograft rejection and infection. It is of paramount importance to

immunosuppress the patient to minimise the risk of allograft

rejection, without over-immunosuppressing and thereby

increasing susceptibility to opportunistic infection. For this

reason, cyclosporin-A blood levels are regularly monitored post-

operatively. Side effects include renal failure, hypertension,

hyperkalaemia, hirsutism, gum hypertrophy and increased

susceptibility to opportunistic infection and to lympho-

proliferative disorders. Tacrolimus acts in a similar way to

cyclosporin-A although it may be a more potent immunosup-

pressive agent. Although its side effect profile is similar, diabetes

mellitus can be a complication. Azathioprine is an antimetabolite

whose major side effects include bone marrow suppression and

hepatic cholestasis. Occasionally pancreatitis can occur. Some

patients who are intolerant of azathioprine are prescribed

mycophenolate mofetil (which is less likely to cause bone

marrow suppression) or cyclophosphamide. At the present time

the precise role of tacrolimus and mycophenolate in post-cardiac