Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclosporine is a new immunosuppressive drug that acts early in the exposure of a host to allogeneic stimulation. It is a peptide of fungal origin. It has selective action on T cells, leaving the other cells of the immune system intact. It acts by preventing the function of the early activation signals of T cells, such as the acquisition of receptors for Il 2 and Il 1. It is lipophilic, moderately well absorbed by the gut, and metabolized by the liver. Factors affecting absorption or hepatic metabolism alter the amount of cyclosporine available in the circulation. Circulating levels can be measured by radioimmunoassay or HPLC. Doses should be tailored to trough levels taken approximately 12 hours after an oral or intravenous dose or to individual pharmacokinetic curves. The drug is nephrotoxic, hepatotoxic, and neurotoxic. In addition, cyclosporine has been associated with hypertension, hemolytic-uremic syndrome, increased incidence of intravascular thrombotic events, hypertrichosis, gum hyperplasia, pericardial effusion, and lymphoproliferative disorders. Despite these complications, cyclosporine usage seems to have improved short-term cardiac allograft survival and to have reduced the complications associated with side effects of steroids. As a result, cyclosporine has spawned a resurgence of interest in cardiac transplantation, which will be of great benefit in prolonging the lives of patients with end-stage cardiac disease.
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PMID:Cyclosporine in cardiac transplantation. 389 34

The clinical course of 29 liver graft recipients in the Cambridge/King's College Hospital series who have received cyclosporin A (CyA) for up to five years (median 40 months) was analysed with particular reference to the immunosuppressive effectiveness and adverse effects of the drug. Eight patients had been maintained on prednisolone and azathioprine for two to six years before treatment was changed to cyclosporin A and the remainder were started on cyclosporin A after operation. Results in both groups over a one to five year study period are similar, and showed that cyclosporin A was effective in maintaining adequate immunosuppression, allowing complete withdrawal of prednisolone in 16 patients. Episodes of rejection were observed in only three patients and in two of these it was of the chronic 'vanishing bile duct' variety. Some evidence of nephrotoxicity (serum creatinine greater than 150 mumol/l) occurred in 72 per cent (21 of 29 patients) but it was necessary to discontinue treatment in only two. Hypertension, occasionally of sudden onset, was found in nine patients and led to the withdrawal of the drug in two. Additional hypotensive drug treatment was required in five. In one other patient cyclosporin A was discontinued on account of severe headaches. Cyclosporin A was withdrawn in two further patients. Withdrawal led to considerable risk of acute rejection and increased doses of corticosteroids as well as substitution of azathioprine were required at that time.
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PMID:Long-term use of cyclosporin in liver grafting. 391 95

Cyclosporine, a cyclic endecapeptide of fungal origin, has been used for nine years in clinical transplantation to suppress allograft rejection. Nephrotoxicity represents the most frequent and severe complication associated with its use and may ultimately define the limits of its utility as a drug for long term immunosuppression. However, this nephrotoxicity cannot be truly assessed in kidney transplant recipients for obvious reasons. It has recently been reported in heart transplant recipients. In addition, cyclosporine therapy is responsible for a persistent elevation of blood pressure requiring intensive and combined anti-hypertensive regimens. This hypertension develops within the first weeks post-transplantation in 60% to 90% of heart allograft recipients. This study analyzes the renal function and blood pressure of patients operated on in our department where cyclosporine was introduced in 1981.
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PMID:Renal function and blood pressure in heart transplant recipients treated with cyclosporine. 391 15

Cyclosporine nephrotoxicity after heart transplantation can lead to acute renal failure requiring haemodialysis. In four long-term heart-transplant survivors, cyclosporine nephropathy was characterised by extensive fibrosis, with uraemia, hypertension and/or anaemia. In contrast, the long-term survivor of heart-lung transplantation who had received her graft for accelerated respiratory failure, did not develop chronic renal disease. Thus, chronically reduced renal perfusion before heart transplantation may play a critical role in the development of chronic cyclosporine nephropathy.
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PMID:Cyclosporine nephropathy after heart and heart-lung transplantation. 392 60

The benefit:detriment ratio of Cyclosporine (CsA) in renal transplantation was examined by analysis of the data accumulated within the Canadian Transplant Study Group (CTSG). Transplantation was performed according to commonly defined protocols, and 496 patients were analysed following cadaveric or live-related transplantation. One-year patient and graft survival were 96% and 86%, respectively, following living-related HLA nonidentical transplantation, 92% and 75% following primary cadaveric transplantation, and 97% and 58% following cadaveric retransplantation. A clear beneficial effect of blood transfusion was observed following primary cadaveric renal transplantation (P = 0.04), with a trend towards improved graft survival in donor/recipient pairs matched at the B or Dr locus (89% v 73%, P = NS). Prolonged machine preservation (greater than 24 hours) of the kidney or long (greater than than 45 minutes) surgical anastomosis time, and an elevated serum CsA level adversely influenced allograft function. Graft function in patients receiving CsA stabilized by approximately 6 months posttransplant, and subsequently remained constant as determined by both serum creatinine and calculation of creatinine clearance. Hypertension was more common (P = 0.003) in patients receiving CsA, and vascular complications were more frequent although this difference was not statistically significant. Infectious complications were comparable between the two groups. Two lymphomas were confirmed in patients receiving CsA. The mean cost of CsA throughout the first 12 months posttransplant based on a 60 kg patient weight was $4,490, and reduced by $3,397 each subsequent year of maintenance treatment.
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PMID:Examination of parameters influencing the benefit:detriment ratio of cyclosporine in renal transplantation. The Canadian Transplant Study Group. 392 63

Since 1981 the authors have performed 14 orthotopic heart transplantations and one heart-lung transplantation, using cyclosporine and prednisone as immunosuppressants. Eight of the recipients had terminal congestive cardiomyopathy and six had ischemic cardiac dysfunction. The combined heart-lung transplantation was performed on a patient with a congenital ventricular septal defect with Eisenmenger's syndrome. Twelve of the patients were alive and well at follow-up 9 to 34 months (mean 17.4 months) after transplantation. One patient died of acute rejection and one of acute pancreatitis and secondary peritonitis. The third death, due to acute right ventricular failure, occurred immediately after transplantation. Rejection was diagnosed histologically on seven other occasions in four patients and was treated successfully. Infection was not a major problem. Cyclosporine -induced reversible nephrotoxicity was evident in 12 patients, 2 of whom required dialysis. Other side effects of cyclosporine seen in these patients included hypertension, gastrointestinal upset, headaches and hirsutism. This experience suggests that cyclosporine is a potent immunosuppressive agent that has greatly reduced the hazards of rejection and infection. However, the frequency of nephrotoxicity is high; careful monitoring of cyclosporine blood levels and renal function is essential.
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PMID:Cyclosporine in cardiac transplantation. 623 93

Cyclosporin A(CyA) is a valuable post graft immunosuppressive agent in allogeneic bone marrow transplantation. The use of CyA is associated with a reduction in severity of graft versus host disease and improved marrow engraftment. A major side effect of CyA is nephrotoxicity. In 33 patients studied during the first 4 weeks of therapy there is a close correlation between trough (12 h) serum cyclosporin A concentrations and plasma creatinine (r = 0.93, P less than 0.001) and urea (r = 0.88, P less than 0.001). Trough CyA serum concentrations of greater than 500 ng/ml are potentially nephrotoxic. Other risk factors for early nephrotoxicity in cyclosporin therapy are the concurrent use of aminoglycoside antibiotics (P = 0.01) and hyperbilirubinaemia (P = 0.01). Early nephrotoxicity can be prevented by maintaining trough CyA levels in the range 100-400 ng/ml. During prolonged CyA therapy, cumulative renal impairment can occur and nephrotoxic episodes associated with microangiopathic peripheral blood changes and hypertension are seen in a minority of patients.
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PMID:Nephrotoxicity in bone marrow transplant recipients treated with cyclosporin A. 634 56

Twenty-six patients with ocular inflammatory disorders of presumed autoimmune origin were treated with oral cyclosporine. Cyclosporine is a potent T cell regulatory agent that has been utilized extensively in organ transplantation. In general, the patients in this study did not have chronic debilitating illnesses that are observed in organ transplant recipients, did not receive corticosteroids in addition to cyclosporine, and did not undergo any surgical procedure during their treatment. This study describes the observed adverse reactions in this group of patients not undergoing transplantation. The reported side effects of cyclosporine in organ transplant recipients have included nephrotoxicity, hepatotoxicity, infections, lymphoma, hirsutism, gingivitis, and central nervous system toxicity. Side effects were observed that were similar to those in previous reports, but the severity of the nephrotoxicity and hepatotoxicity appeared to be less. Nephrotoxicity occurred in eight patients and hepatotoxicity occurred in one patient. No lymphomas were seen. Hypertension and anemia each were observed in six patients. In addition, previously unreported effects of hyperuricemia, elevated sedimentation rate, and hidradenitis were observed. However, the overall severity of the side effects did not seriously affect the usage of cyclosporine in the patients in this study. Cyclosporine may be useful in the treatment of other autoimmune diseases.
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PMID:Side effects of systemic cyclosporine in patients not undergoing transplantation. 648 41

Oral cyclosporin A was used as prophylaxis against graft-versus-host disease in (a) 31 patients with acute leukaemia or aplastic anaemia given transplants of HLA-matched bone marrow and (b) five patients with inborn errors of metabolism given transplants of haplotype-identical (parental) bone marrow. Twenty-six patients survived longer than two months after the operation. Despite the cyclosporin A, 31 patients (86%) suffered an acute form of graft-versus-host disease and 22 (61%) a chronic form. Nevertheless, the disease was usually treatable with immunosuppressive agents and caused the death of only one patient. Cyclosporin A caused renal toxicity in all cases; occasionally this was associated with a "capillary leak" syndrome, fatal in two patients. In children hypertension, fits, and fluid retention were common side effects. Blood concentrations of cyclosporin A correlated with blood urea values and blood pressure but did not predict the occurrence of graft-versus-host disease. Four different dose schedules were used to find the optimum way to administer this drug. Oral cyclosporin A is extremely effective at reducing the severity of graft-versus-host disease, but prevention of the disease is limited by toxicity of the drug and variable absorption. Better results might be achieved with parenteral administration or by using the drug in combination with other methods.
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PMID:Cyclosporin A as prophylaxis against graft-versus-host disease in 36 patients. 680 91

Cyclosporine, a potent immunosuppressant, is associated with the development of hypertension and nephrotoxicity. We have previously shown that endothelin release from the arteries is increased in rats with cyclosporine-induced hypertension. We conducted the present study to determine whether the specific endothelin type A (ETA) receptor antagonist FR 139317 prevents cyclosporine-induced hypertension and whether cyclosporine increases ETA receptor mRNA in blood vessels. Cyclosporine (25 mg/kg per day) given for 4 weeks increased blood pressure from 98 +/- 12 to 156 +/- 14 mm Hg; this increase was blunted by coadministration of 10 mg/kg per day FR 139317 (ie, blood pressure was 138 +/- 14 mm Hg) in Wistar-Kyoto rats. Cyclosporine induced greater vasoconstrictor responses to norepinephrine and angiotensin II in isolated mesenteric arteries. FR 139317 normalized the vasoconstrictor responses to angiotensin II and norepinephrine. Cyclosporine (25 mg/kg per day) given for 4 weeks increased ETA receptor mRNA expression in the rat aorta and mesenteric artery (170% and 176%, respectively). Little change was observed in ETB receptor mRNA. These results indicate that cyclosporine may increase blood pressure by increasing not only endothelin production but also ETA receptor in the vasculature. The specific ETA receptor antagonist FR 139317 may prevent the hypertension induced by cyclosporine.
Hypertension 1995 Dec
PMID:Effects of an endothelin receptor antagonist in rats with cyclosporine-induced hypertension. 749 Jan 51


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