Objective To investigate the pharmacy practice of clinical pharmacists' attendance in the treatment of adverse reactions caused by drug interactions. Methods Analysis was conducted on the causes and treatment of hypertension in one pedinatric patient with aplastic anemia induced by combined use of cyclosporine and voriconazole. Results Cyclosporine A could lead to prolonged hypertension.Cyclosporine A dosage should be adjusted;antihypertensive drugs should be used in necessity.When choosing antihypertensive drugs,drug interaction with cyclosporine A should be considered. Conclusion Clinical pharmacists could manage adverse drug reactions by analyzing drug interactions,and offer suggestions for ADR patients.
Key words:
Cyclosporin A
;
Voriconazole
;
Interactions
;
drug
;
Hypertension
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We sought to evaluate the effect of intravenous administration of the nitric oxide--donor substance nitroglycerin (NTG) on metabolic coronary-flow regulation in patients with coronary artery disease (CAD). In 12 patients with stable CAD, we measured coronary sinus blood flow and myocardial oxygen supply and consumption (MVO2) at sinus rhythm and during atrial pacing (30 beats/min above sinus rate), both at control and during infusion of NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min. To study metabolic coronary vasodilation, changes in myocardial oxygen supply were related to pacing-induced changes in MVO2, by using standard regression analysis. The myocardial oxygen supply/consumption ratio (i.e., the slope of the regression line at control, characterizing physiological metabolic coronary flow regulation) was compared with the ratios obtained during infusion of NTG. Compared with control measurements, NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min, attenuated pacing-induced increases in MVO2 by 29 and 60%, respectively, whereas coronary blood flow during pacing remained unchanged. At control, normal metabolic coronary-flow regulation resulted in a myocardial oxygen supply/demand ratio of 1.39 (95% CI, 1.29-1.49). This ratio did not change during NTG, 1 microg/kg/min: 1.44 (95% CI, 1.33-1.56). However, during NTG, 2 microg/kg/min, this ratio significantly increased to 1.84 (95% CI, 1.63-2.05; p<0.01). Intravenous administration of high-dose NTG, a donor of exogenous NO, blunts pacing-induced increases in MVO2 and may increase metabolic coronary vasodilation in patients with CAD.
ROMARO AJ,LE PP,NILSSON LG,et al.Effect of voriconazole on the pharmacokinetics of cyclosporine in renal transplant patients[J].Clin Pharm Therap,2002,71(4):226-234.
Objective: Voriconazole is a broad-spectrum triazole antifungal agent under investigation for opportunistic infections that often target immunosuppressed patients. This study investigated the effect of voriconazole on the pharmacokinetics of cyclosporine (INN, ciclosporin). Methods: This was a randomized, double-blind, placebo-controlled, crossover study in kidney transplant recipients with stable renal function who were receiving cyclosporine (150-375 mg/d). During the first study period (7.5 days), subjects in group A received concomitant voriconazole (200 mg every 12 hours); group B received a matched placebo. After a washout period (4 days), subjects were crossed over to the other treatment regimen. Results: In the 7 subjects who completed both regimens, concomitant administration with voriconazole resulted in a 1.7-fold increase in mean cyclosporine area under the plasma concentration-time curve within a dosage interval (AUC
FRIBERG LE,PATANJALIR,KARLSSON MO,et al.Integrated population pharmacokinetic analysis of voriconazole in children,adolescents,and adults[J].Antim Ag Chem,2012,56(6):3032-3042.
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NEELYM,TKOVACSR.Voriconazole pharmacokinetics and pharmacodynamics in children[J].Clin Infect Dis,2010,50(1):27-36.
BACKGROUND: Voriconazole pharmacokinetic and pharmacodynamic data are lacking in children. METHODS: Records at the Childrens Hospital Los Angeles were reviewed for children with > or =1 serum voriconazole concentration measured from 1 May 2006 through 1 June 2007. Information on demographic characteristics, dosing histories, serum concentrations, toxicity and survival, and outcomes was obtained. RESULTS: A total of 207 voriconazole measurements were obtained from 46 patients (age, 0.8-20.5 years). A 2-compartment Michaelis-Menten pharmacokinetic model fit the data best but explained only 80% of the observed variability. The crude mortality rate was 28%, and each trough serum voriconazole concentration 1000 ng/mL in most patients, but with a wide range of possible concentrations. CONCLUSIONS: We found a pharmacodynamic association between a voriconazole trough >1000 ng/mL and survival and marked pharmacokinetic variability, particularly after enteral dosing, justifying the measurement of serum concentrations.
PONGTANAKULB,DAS PK,CHARPENTIERK,et al.Outcome of children with aplastic anemia treated with immunosuppressive therapy[J].Pediatric Blood Cancer,2008,50(1):52-57.
Abstract Background Immunosuppressive therapy (IST) is the alternative treatment in children with aplastic anemia (AA) who do not have an HLA-matched sibling. The aim of this study is to evaluate the outcome of children with AA treated with IST. Methods We retrospectively reviewed the hospital records of children with AA from 1984 to 2004, treated at our institution with antithymocyte globulin (ATG), cyclosporine (CS), and short course of prednisone. Result Forty-two patients were treated with IST (24 boys, 18 girls); of whom 26% received G-CSF. The median age at diagnosis was 8.5 years. Sixty-nine, 19, and 12% were diagnosed with severe, very severe, and moderate AA, respectively. Twenty-one percent had hepatitis-associated AA. Median follow-up time was 53.3 months. Sixty-two percent had complete response; 19% had partial response. Two patients relapsed and received a second course of ATG; both had a partial response. The actuarial 5 years survival rate was 67.5%. Two patients developed myelodysplastic syndrome (MDS); both received long-term G-CSF and had partial response after two courses of IST. Fifteen percent of survivors had significant hypertension which persisted after CS was discontinued. Conclusions This study shows promising response in children with AA treated with IST; however, the outcome was inferior to our institutional results with hematopoietic stem cell transplantation from a sibling donor. Hypertension and MDS are late complications. Longer follow-up, larger cohorts, and prospective studies are warranted to evaluate late complications and risk factors. Pediatr Blood Cancer 2008;50:52-57. 2007 Wiley-Liss, Inc.
Arterial hypertension is a considerable side effect that accompanies the clinical use of immunosuppressant drugs such as cyclosporine (CSA). In addition to promoting graft rejection, uncontrolled hypertension is a major risk factor for atherosclerosis, left ventricular hypertrophy, heart failure, and premature death. Most, if not all, reports that reviewed the hypertensive effect of CSA and underlying mechanisms focused on the roles of peripheral vasoactive machinaries, perhaps because of the limited capacity of CSA to diffuse to brain tissues and the lack of any appreciable effect for centrally administered CSA on blood pressure (BP) or central sympathetic outflow. This review focuses primarily on evidence that supports a modulatory role for central neural pathways, as go-between afferent and efferent sympathetic circuits, in the elicitation of the hypertensive action of CSA. Other areas covered briefly in the review include (1) an outline of peripheral mechanisms that contribute to the hypertensive action of CSA, and (2) comparisons of the BP effects of CSA and other calcineurin-dependent (tacrolimus) and independent (sirolimus) immunosuppressants. The knowledge of these mechanisms, central and peripheral, may permit the identification of new therapeutic strategies against CSA hypertension.
HOORN EJ,WALSH SB,MCCORMICK JA,et al.Patho-genesis of calcineurin inhibitor-induced hypertension[J].J Nephr,2012,25(3):269-275.
Abstract This article reviews the current understanding of the mechanisms of calcineurin inhibitor-induced hypertension. Already early after the introduction of cyclosporine in the 1980s, vasoconstriction, sympathetic excitation and sodium retention by the kidney had been shown to play a role in this form of hypertension. The vasoconstrictive effects of calcineurin inhibitors are related to interference with the balance of vasoactive substances, including endothelin and nitric oxide. Until recently, the renal site of the sodium-retaining effect of calcineurin inhibitors was unknown. We and others have shown that calcineurin inhibitors increase the activity of the thiazide-sensitive sodium chloride cotransporter through an effect on the kinases WNK and SPAK. Here, we review the pertinent literature on the hypertensinogenic effects of calcineurin inhibitors, including neural, vascular and renal effects, and we propose an integrated model of calcineurin inhibitor-induced hypertension.
ELODIEB,SYLVAING,YCESB,et al.Pharmacokinetic drug-drug interaction of calcium channel blockers with cyclosporine in hematopoietic stem cell transplant children[J].Ann Pharmacoth,2014,48(12):1580-1584.
Abstract Background: Cyclosporine (CsA) is frequently responsible for hypertension in bone marrow transplant children. Calcium channel blockers (CCBs) are considered to be the best treatment for CsA-induced hypertension, but they may alter the exposure and the effect of CsA by inhibiting the CYP3A4 pathway of CsA metabolism or P-gp. However, the inhibitory effect on CYP3A4 may vary among CCBs. Methods: This study aimed to quantify the pharmacokinetic drug-drug interaction between CsA and nicardipine, amlodipine, and lacidipine. In all, 51 children who received CsA and CCB concomitantly were included. Results: Dose-normalized CsA trough blood concentrations significantly increased in patients treated with nicardipine and amlodipine, whereas they remained stable in patients treated with lacidipine. Conclusions: Because lacidipine appears to have no effect on CsA exposure, it may be the best option among CCBs for treating high blood pressure caused by CsA in children.
NAKAYAMAJ,KOGAT,FERUEM.Long-term efficacy and adverse event of nifedipine sustained-release tablets for cyclosporin A-induced hypertension in patients with psoriasis[J].Eur J Dermat Ejd,1998,8(8):563-568.
Thirteen psoriatic patients with hypertension during the course of cyclosporin A therapy were treated for 25 months with a calcium channel blocker, sustained-release nifedipine, to study the clinical antihypertensive effects and adverse events during treatment with both drugs. Seven of the 13 patients had exhibited a subclinical hypertensive state before cyclosporin A therapy. Both systolic and diastolic blood pressures of these 13 patients were decreased significantly after 4 weeks of nifedipine therapy, and blood pressure was maintained within the normal range thereafter for 25 months. The adverse events during combined therapy with cyclosporin A and nifedipine included an increase in blood urea nitrogen levels in 9 of the 13 patients and development of gingival hyperplasia in 2 of the 13 patients. Our findings indicate that sustained-release nifedipine is useful for hypertensive psoriatic patients under long-term treatment with cyclosporin A, but that these patients should be monitored for gingival hyperplasia.
