tacrolimus and Hypotension

The prevalence of psychiatric disorders in dialyzed patients is estimated around 5-20% of the cases. This explains the high use of antidepressant drugs in these patients. We present the case of a 68-year-old woman with a history of renal failure, with chronic hemodialysis and a depressive syndrome in treatment with Mirtazapine. In November 2008, the patient received a renal graft. An immunosuppressant treatment was started with Basiliximab, Tacrolimus, Mycophenolate Mofetil, and corticosteroids. The patient did not present renal immediate renal function. Four days after the transplant, the treatment with Mirtazapine was re-applied, with an asymptomatic hypotension after 2 hours, and without surgical complications. Tacrolimus blood levels were higher than 15 ng/ml. In our opinion, hypotension was a consequence of the interaction Mirtazapine-Tacrolimus in a patient without immediate renal function. This situation has not been described in the literature before, and hypotension could have had negative consequences in the evolution of the graft.

Topics: Aged; Antidepressive Agents, Tricyclic; Blood Pressure; Depressive Disorder; Drug Interactions; Female; Humans; Hypotension; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Mianserin; Mirtazapine; Tacrolimus

Endothelin-1 (ET-1), a novel vasoconstrictor, possibly plays a role in the mediation of ischemia/reperfusion (I/R) injury. Tacrolimus (FK506) and cyclosporin A (CsA) were reported to maintain tissue microcirculation of the liver subjected to I/R. This study investigated the effects of these immunosuppressants on intestinal I/R in terms of intestinal tissue microcirculation associated with ET-1.. Male S-D rats were pretreated twice with FK506 (0.2 mg/kg), CsA (10 mg/kg) or only saline solution (0.5 mL). The tissue microcirculation in the control was reduced after I/R (29% +/- 10%) accompanied by hypotension, increased tissue ET-1 expression (25.0% +/- 6.4% to 67.9% +/- 5.0% 60 minutes after reperfusion), and increased ET-1 level in the portal blood (3.4 +/- 0.9 to 23.6 +/- 6.1 pg/mL). FK506 suppressed ET-1 expression (27.3% +/- 5.2%, 4.1 +/- 2.2 pg/mL), maintained microcirculation (96% +/- 16%), and blood pressure, reduced histologic damage, and improved survival. CsA had a similar but weaker effect compared with FK506. An additional experiment was performed with BQ485Na (BQ), an ETA receptor antagonist, to evaluate the genuine role of ET-1. BQ showed almost the same effects as FK506.. FK506 and CsA, particularly the former, maintain microcirculation and protect the tissue from I/R injury by suppressing the production and release of ET-1.

Topics: Animals; Azepines; Blood Pressure; Cyclosporine; Endothelin Receptor Antagonists; Endothelin-1; Hypotension; Immunosuppressive Agents; Intestine, Small; Ischemia; Male; Microcirculation; Oligopeptides; Portal System; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptors, Endothelin; Reperfusion Injury; Survival Rate; Tacrolimus; Time Factors