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- Helldén, Anders, et al.
(författare)
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Adverse drug reactions and impaired renal function in elderly patients admitted to the emergency department : a retrospective study
- 2009
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Ingår i: Drugs & Aging. - : Wolters Kluwer. - 1170-229X .- 1179-1969. ; 26:7, s. 595-606
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adverse drug reactions (ADRs) are common in elderly patients. There are various reasons for this, including age- and disease-related alterations in pharmacokinetics and pharmacodynamics as well as the common practice of polypharmacy. The decline in renal function in elderly patients may also predispose them to pharmacological ADRs (type A, augmented). Patients receiving home healthcare may be at even higher risk.OBJECTIVES: To study ADRs as a cause of acute hospital admissions in a defined cohort of elderly patients (aged >or=65 years) registered to receive home healthcare services, with special reference to impaired renal function as a possible risk factor.METHODS: This was a retrospective study of 154 elderly patients aged >or=65 years admitted to the emergency department of a university hospital in Stockholm, Sweden, in October-November 2002. Estimated creatinine clearance (eCL(CR)) was calculated from the Cockcroft-Gault formula, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation. ADRs were defined according to WHO criteria. All medications administered to patients at admission and at discharge were collated. These and other data were collected from computerized hospital records.RESULTS: ADRs were judged to contribute to or be the primary cause of hospitalization in 22 patients, i.e. 14% of 154 patients registered to receive home healthcare. Eleven of the 22 patients were women. All but one ADR were type A. Excessive doses or drugs unsuitable in renal insufficiency were present in seven patients in the ADR group compared with only four patients in the group without ADRs (p = 0.0001). Patients with ADRs did not differ significantly from those without ADRs in relation to age, plasma creatinine, eCL(CR), weight or number of drugs prescribed at admission. However, women with ADRs were significantly older than women without ADRs (mean +/- SD age 88.8 +/- 5.7 years vs 82.5 +/- 8.0 years, respectively; p = 0.014) and had significantly lower mean +/- SD eCL(CR) values (25.5 +/- 10.8 and 37.1 +/- 17.1 mL/min, respectively; p = 0.035). Median MDRD eGFR was significantly higher than median eCL(CR) (59 [range 6-172] mL/min/1.73 m2 vs 38 [range 5-117] mL/min, respectively; p = 0.0001).CONCLUSIONS: In elderly patients registered to receive home healthcare, 14% of hospital admissions were primarily caused by ADRs. One-third of these ADRs were related to impaired renal function, generally in very old women. These ADRs may be avoided by close monitoring of renal function and adjustments to pharmacotherapy (drug selection and dose), particularly in very elderly women.
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- Helldén, Anders, et al.
(författare)
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Death delusion. : Cotard's syndrome as an adverse drug reaction to (val-)aciclovir
- 2007
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Ingår i: BMJ (Clinical research ed.). - 1468-5833. ; 335:7633
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Tidskriftsartikel (refereegranskat)abstract
- We report two cases of Cotard’s syndrome that occurred as an adverse drug reaction to aciclovir and its prodrug valaciclovir. In the 1880s Jules Cotard first described his eponymous syndrome, a rare psychiatric condition with strong delusions of being dead. Aciclovir or valaciclovir may cause neuropsychiatric side effects such as confusion, somnolence, and hallucinations, mainly in patients with impaired renal function. To our knowledge, Cotard’s syndrome has never been reported as a suspected adverse drug reaction but associated with severe somatic stress as well as general and localised cerebral pathologies. Our findings add adverse response to an antiviral drug as another cause and provide clues to the syndrome’s possible neuropsychiatric origin. Clinicians should be aware of the association between body scheme disturbances and (val)aciclovir. Affected patients with Cotard’s syndrome and renal failure should preferably be sent to the dialysis unit, not to the department of psychiatry.
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- Helldén, Anders, et al.
(författare)
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Fluconazole-induced intoxication with phenytoin in a patient with ultra-high activity of CYP2C9
- 2010
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 66:8, s. 791-5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The cytochrome P450 enzyme CYP2C9 metabolizes several important drugs, such as warfarin and oral antidiabetic drugs. The enzyme is polymorphic, and all known alleles, for example, CYP2C9*2 and*3, give decreased activity. Ultra-high activity of the enzyme has not yet been reported.METHODS: We present a patient with Behçet's disease who required treatment with high doses of phenytoin. When fluconazole, a potent inhibitor of CYP2C9, was added to the treatment regimen, the patient developed ataxia, tremor, fatigue, slurred speech and somnolence, indicating phenytoin intoxication. On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed.RESULTS: The patient was shown to have a higher activity of CYP2C9 than any of the 190 healthy Swedish Caucasians used as controls.CONCLUSIONS: Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions.
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- Odar-Cederlöf, Ingegerd, et al.
(författare)
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Neuropeptide-Y and atrial natriuretic peptide as prognostic markers in patients on hemodialysis
- 2003
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Ingår i: ASAIO journal (1992). - Philadelphia, PA, United States : Lippincott Williams & Wilkins. - 1058-2916 .- 1538-943X. ; 49:1, s. 74-80
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a study of the influence of the vasoactive peptides atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) on survival of patients on hemodialysis and their association and relative importance with cardiac and clinical variables. Thirty-three hemodialysis patients were characterized by age, sex, diagnosis, blood pressure, serum (S)-albumin, serum (S)-urea, hemoglobin, dialysis dose, weight gain, duration of dialysis, cardiac hypertrophy, volume, failure, and ischemia and plasma levels of ANP and NPY. The outcomes were analyzed for early deaths (<1 year) and for all deaths. The association of the variables to early deaths and all deaths, respectively, was studied in Cox proportional hazard analyses. The variables were also studied in three hierarchical steps: clinical variables only, clinical and cardiac variables, and all variables. For all deaths, the independent variables were plasma NPY (pmol/L) (hazard ratio [HR] = 1.035, p = 0.004), heart volume (ml/m2) (HR = 1.009, p = 0.001), and S-albumin (g/L) (HR = 0.750, p = 0.034). For early deaths, the independent variables were predialysis ANP (pmol/L) (HR = 1.008, p = 0.034) and NPY (pmol/L) (HR = 1.031, p = 0.026). In the hierarchical study, excluding the vasoactive peptides, heart volume, heart failure and S-albumin were independently associated with all deaths, and mean arterial blood pressure was associated with early death. When also excluding the cardiac parameters, S-albumin was associated with all deaths and mean arterial blood pressure with early death. In conclusion, plasma levels of the vasoactive peptides ANP and NPY are the most important group in a hierarchy of variables that predict imminent death in hemodialysis patients, and NPY is associated with late death. ANP and NPY apparently sum up the detrimental influence of many factors in hemodialysis patients.
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- Törner, Anna, et al.
(författare)
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Renal function in community-dwelling frail elderly : comparison between measured and predicted glomerular filtration rate in the elderly and proposal for a new cystatin C-based prediction equation
- 2008
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Ingår i: Aging Clinical and Experimental Research. - Milano : Editrice Kurtis. - 1594-0667 .- 1720-8319. ; 20:3, s. 216-225
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: There is a great need to evaluate renal function regularly in elderly people. This study aimed at analyzing renal function in stable, community-dwelling elderly people of 75 years and over, to compare measured and predicted glomerular filtration rates (GFR) and to develop an accurate prediction equation for this age group. METHODS: Forty-five ambulatory elderly people in stable health in ordinary living were randomly selected into four age-classes, aged 75-95. Demographic data, personal activities of daily living, continuous drug prescriptions, body composition, blood pressure and blood chemistry were analysed. GFR was measured as Iohexol clearance based on three time-points 3, 4 and 7 hours after Iohexol injection. RESULTS: Mean GFR was well preserved in all four age-classes. The GFR range was 18-83 mL/min and declined with age. The Cockcroft-Gault prediction equation systematically underestimated measured GFR. A new 'GFRA' prediction equation is presented, based on the inverse of serum cystatin C and independent of gender, body surface area, body weight, lean body mass or serum creatinine. The proposed equation underestimated measured GFR with a mean of only 0.1 mL/min, had better precision compared with the Cockcroft-Gault equation, and was evaluated by the method of cross-validation. CONCLUSIONS: GFR exhibits extensive heterogeneity in frail, community-dwelling elderly people. The proposed GFRA was clearly more precise than the Cockcroft-Gault prediction equation in the study group. However, it needs to be validated in a larger population of elderly subjects, including more individuals in stable health with substantially reduced renal function in whom GFR is measured by a reference method with adequate sampling time.
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- Uhlin, Fredrik, et al.
(författare)
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Vasoactive Peptide Levels after Change of Dialysis Mode.
- 2015
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Ingår i: Nephron Extra. - : S. Karger AG. - 1664-5529. ; 5:3, s. 68-78
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Plasma concentrations of the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) are increased in end-stage renal disease. Improvement in hemodynamic stability has been reported when switching from hemodialysis (HD) to on-line hemodiafiltration (ol-HDF). The aim of this study was to investigate plasma concentrations of NT-proBNP, BNP and neuropeptide Y (NPY) during a 1-year follow-up, after a change from high-flux HD to postdilution ol-HDF. Additional variables were also studied, e.g. pulse wave velocity and ordinary clinical parameters.METHOD: We conducted a prospective, single-center study including 35 patients who were switched from HD to HDF. Plasma concentrations of NT-proBNP, BNP and NPY before and after dialysis were measured at baseline (i.e. HD) and at 1, 2, 4, 6 and 12 months on HDF.RESULTS: All three peptide levels decreased significantly during HD and HDF when comparing concentrations before and after dialysis. Mean absolute value (before/after) and relative decrease (%) before versus after dialysis was 13.697/9.497 ng/l (31%) for NT-proBNP, 62/40 ng/ml (35%) for BNP and 664/364 pg/l (45%) for NPY. No significant differences were observed when comparing predialysis values over time. However, postdialysis NT-proBNP concentration showed a significant decrease of 48% over time after the switch to HDF.CONCLUSION: The postdialysis plasma levels of NT-proBNP, BNP and NPY decreased significantly during both dialysis modes when compared to before dialysis. The postdialysis lowering of NT-proBNP increased further over time after the switch to ol-HDF; the predialysis levels were unchanged, suggesting no effect on its production in the ventricles of the heart.
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