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Biomedical subjects

K Mörike

Publications and source records attributed to K Mörike.

At least 19 recordsLinked to original sources
PubMed2006

Multiple drug prescribing by general practitioners in a German region: Implications for drug interactions and patient safety.

OBJECTIVE: An increased number of drugs used by patients enhances the risk of potentially hazardous drug interactions. So far, no representative data are available about how common this problem is in German general practices. METHODS: We performed a retrospective analysis using a prescription database for a German region. The 50 general practitioners (out of 1,457) who wrote the most prescriptions during January to March 2003 were included. Data on 4,153 patients who were prescribed at least 10 drugs were analyzed for 92 predefined Drug Combinations Prone to Interact (DCPI) to a clinically relevant extent and possible contraindications. RESULTS: From 92 DCPIs, 71 occurred in the analyzed population between 1 and 275 times. The total number of DCPI cases was 1,295, which included 10% (n = 129) of contraindicated combinations. Among 4,153 analyzed patients, 822 patients (19.8%) were affected by at least 1 DCPI. In 268 patients (6.5%), multiple DCPIs occurred. The most frequently found drug pairs were digitalis/diuretics, digitalis/calcium channel blockers, and theophylline/quinolones. Among contraindicated combinations, tricyclic antidepressants, St. John's wort and antiarrhythmic drugs were most frequently involved. In about 1/3 of patients treated for chronic heart failure, pharmacotherapy appeared not to be guideline-adherent. CONCLUSION: Drug interactions, especially in polypharmacotherapy, represent a potential hazard which must be taken into account by the prescribing physician. Our study is the first to use a prescription database for the evaluation of drug prescriptions within a German region.

Databases, Factual↗
PubMed2005

Effect of acute hyperhomocysteinemia on methylation potential of erythrocytes and on DNA methylation of lymphocytes in healthy male volunteers.

Homocysteine is a precursor of S-adenosylmethionine (AdoMet) and a metabolite of S-adenosylhomocysteine (AdoHcy). The ratio of AdoMet to AdoHcy, defined as the methylation potential (MP), indicates the flow of methyl groups within the cells. Chronic elevations of total homocysteine (tHcy) in plasma correlate with increased AdoHcy concentrations, decreased MP, and impaired DNA methylation. However, the influence of acute hyperhomocysteinemia on MP is unknown. We induced acute hyperhomocysteinemia in 14 healthy volunteers by oral administration of l-homocysteine (65.1 micromol/kg body wt) in an open, randomized, placebo-controlled two-period crossover study. The kinetics of tHcy in blood and urine, MP in blood, and global DNA methylation in lymphocytes were studied systematically during 48 h. Plasma tHcy concentrations reached a peak at 34 +/- 11 min after an oral load with l-homocysteine and decreased with a half-life of 257 +/- 41 min (means +/- SD). Only 2.3% of the homocysteine dose were recovered in urine. AdoHcy concentrations and MP in whole blood and erythrocytes were not affected by the oral homocysteine load. Furthermore, global DNA methylation in lymphocytes did not change under these conditions. We found no difference between the genotypes of 5,10-methylenetetrahydrofolate reductase in response to the homocysteine load. However, AdoMet content in erythrocytes was significantly higher in the C677T carriers (CT; n = 7) compared with the CC genotype (n = 7). Although chronic elevation of tHcy has been shown to affect MP and DNA methylation, acute elevation of plasma tHcy above 20 micromol/l for 8 h is not sufficient to change MP and to induce DNA hypomethylation in lymphocytes.

Adult↗
PubMed2005

Valproic acid-associated sialadenosis of the parotid and submandibular glands: diagnostic and therapeutic aspects.

Sialadenosis has been defined as a non-inflammatory, parenchymatous salivary gland disease causing recurrent, bilateral swelling of the salivary glands. As an adverse drug reaction of valproic acid, sialadenosis is very rare. To our knowledge, it has been reported only once in the world literature to date. We present herein the case of a patient with valproic acid-associated sialadenosis of both the parotid and submandibular glands. This appears to be the first published case of a patient who received surgical treatment. On light and electron microscopy of all the affected salivary glands, granular sialadenosis with predominantly moderate electron-dense secretory cytoplasmatic granules was observed. No relevant degenerative alterations were seen. There was no histological evidence of peripheral neuropathy of the nerve supply, leading to disordered activity of acinar cells by loss of neurosecretory granules. Lateral parotidectomy, performed under neuromonitoring control for safety reasons, is the treatment of choice for chronic recurrent parotitis that does not respond to conservative therapy, particularly if the cosmetic deformity is unacceptable to the patient. If the submandibular glands are involved, partial removal is recommended.

Adult↗
PubMed2004

[The German guideline clearing-project on bronchial asthma - part 2: recommendations and key topics for a national guideline on bronchial asthma].

BACKGROUND: In order to promote the quality of asthma management in Germany, a national asthma guidelines clearing project was initiated in 2000 by the German Guidelines Clearinghouse (Sponsors: German Medical Association (GMA), National Association of the Statutory Health Insurance Physicians (NASHIP), German Hospital Federation, Federal Association of the Statutory Sickness Funds. This Part shows the key topics which should be dealt with in a German guideline on bronchial asthma. SUMMARY POINTS: For quality promotion of bronchial asthma management in Germany, the development of a national evidence-based guideline, using the internationally accepted quality criteria for clinical practice guidelines, was recommended by an expert group of the German Guideline Clearinghouse. The experts identified and peer-reviewed 16 out of 54 guidelines, which might be useful as benchmarks and examples for a German asthma guideline. From the peer review results, the expert group identified 18 key topics for a national asthma guideline.

Asthma↗
PubMed2004

[The Guideline Clearing Project COPD. Recommendations for a National Guideline].

In order to promote the care of patients with COPD in Germany a national guideline clearing project was initiated jointly by autonomous corporate bodies of the German health care system. Following a systematic search of literature data bases between 1992 and 2002, 20 guidelines were identified that met the inclusion criteria and were evaluated with the German Checklist for Methodological Guideline Appraisal. Following this, a multidisciplinary expert group appointed by the German Guideline Clearinghouse (Leitlinien-Clearingstelle im Arztlichen Zentrum fur Qualitat in der Medizin, AZQ) reviewed the suitability of these guidelines for the use in the German health care system. Referring to methodological aspects, criteria were best met by the guideline of the Veteran's Health Administration/Department of Defense (US), followed by the one of the Deutsche Atemwegsliga and the Deutsche Gesellschaft fur Pneumologie. Aiming at the production respectivly a revision of a German national guideline for COPD the expert group agreed on recommendations organized in 19 chapters. Among others these strengthened the role of a precise definition of COPD based primarily on the pathogenesis, of a subtle description of all diagnostic and therapeutic tools and of a detailed description of quality assurance and quality management. The feasability of recommendations were demonstrated by examples chosen from the evaluated guidelines. Additionally the presented findings may be used as steering tools in the German Health care system.

Delivery of Health Care↗
PubMed2003

[Phytotherapeutic medicines. A possible source of drug interactions].

Herbal drugs are popular. Coming from nature, many people are still reluctant to link them with the risk of adverse effects. Many of these products do not require a prescription. Thus, their use and any potential risks may easily escape the physician's attention. Interactions, causing either adverse effects or treatment failures, with synthetic drugs have attracted increasing interest and recent case reports (e.g. about patients suffering from transplant rejection upon using of St John's wort with subsequently insufficient cyclosporine levels) have triggered some systematic research. As of yet, however, a substantial part of knowledge is based on case reports only. In this situation, the assessment of potential risks arising from herb drug interactions is difficult. More research is needed. This review is a brief account of interactions involving garlic, ginkgo, ginseng, echinacea, and St John's wort.

Drug Interactions↗
PubMed2003

[Medicinal drugs and automobile driving ability].

When prescribing drugs, the physician is responsible to warn his patient about potential impairment of driving capability. To do this, he needs to be aware of the duration and profile of actions, notably sedative and other effects affecting vigilance, cognitive and psychomotor functions. It is advisable to keep written records about such information. Impairment of driving capability may be more pronounced when ethanol is used during the action of drugs affecting central nervous function. The majority of published studies, particularly from epidemiological work with drivers, indicate an increased risk of accidents associated with the therapeutic use of benzodiazepines or cyclic antidepressants. Epidemiological data for other drugs available so far do not allow definite conclusions. Among antihistamines for drivers, loratadine or fexofenadine are probably preferable to ceritizine or older antihistamines. Patients with diabetes who drive should be informed about the risks and self-management of hypoglycaemia.

Accidents, Traffic↗
PubMed2003

Do alterations of endogenous angiotensin II levels regulate erythropoietin production in humans?

AIMS: Recent evidence suggests a potential role of angiotensin II in the physiological regulation of erythropoietin (Epo) production. While the administration of exogenous angiotensin II (AII) has been used so far to study its effects, the role of endogenous AII has remained unclear. METHODS: To alter endogenous AII in humans experimentally we used furosemide bolus injection as a short-term (study 1) and dietary salt as a long-term modulator (study 2). In an open crossover design, 12 healthy male volunteers received furosemide (F) 0.5 mg kg(-1) intravenously or placebo (P) in random order (study 1). With the same design, 12 volunteers received high-salt (HS), normal-salt (NS) and low-salt (LS) diet (study 2). Plasma renin activity (PRA) was analysed along with AII. Inulin and paraaminohippurate (PAH) clearances were used to indicate glomerular filtration rate (GFR) and renal plasma flow (RPF), respectively. RESULTS: While F stimulated AII and PRA and decreased GFR and RPF significantly, no concomitant alteration of Epo was observed [AUCEpo: placebo 5709 +/- 243 (% of baseline x h), furosemide: 5833 +/- 255 (% of baseline x h); 95% confidence interval (CI) -608.4, 856.0; P = 0.73]. F decreased GFR (from 103.6 +/- 4.0 to 90.6 +/- 4.8 ml min(-1) 1(-1) 73 m-2; 95% CI 1.1, 24.9; P < 0.05), but not RPF (study 1). Correspondingly, LS stimulated and HS decreased AII and PRA significantly. HS increased GFR and RPF. Again, Epo concentrations were not affected (AUCEpo: normal sodium 44 +/- 6.7 mIU x day ml(-1), low sodium 39 +/- 2.4 mIU x day ml(-1), high sodium 48.5 +/- 6.1 mIU x day ml(-1); normal salt/low salt 95% CI -11.9, 21.9, P = 0.54; normal salt/high salt 95% CI -14.4, 23.3, P = 0.63; study 2). CONCLUSIONS: We conclude that, at least in the physiological setting in healthy volunteers, increased concentrations of endogenous AII may not be a major factor of Epo regulation.

Adult↗
PubMed2003

[The German guideline clearing-project on bronchial asthma-part 1: Methodology and results of formal appraisal].

BACKGROUND: In order to promote quality of asthma management in Germany, a national asthma guidelines clearing project was initiated in 2000 by the German Guidelines Clearinghouse (Sponsors: German Medical Association (GMA), National Association of the Statutory Health Insurance Physicians (NASHIP), German Hospital Federation, Federal Association of the Statutory Sickness Funds. Part 1 of this article shows the methodology and the results of the appraisal, part 2 (to be published) shows the key topics which should be dealt with in a german guideline on bronchial asthma. OBJECTIVES: To identify and compare evidence-based, high-quality German- and English language asthma guidelines as benchmarks for ongoing guideline development and implementation programmes. To disseminate information about asthma guidelines developed in accordance with current methodological know-how. To identify and consent key topics for a national evidence-based guideline for Germany. METHODS: Search procedure, formal appraisal: Systematic search using literature databases (XMED, incl. Medline and Embase) and English-/German-language guideline databases (via www. leitlinien.de), published between January 1990 and March 2000. Abstract screening of the search results according to the inclusion criteria (n = 54 of a total of 502 hits). Methodological guideline evaluation of 16 guidelines using the German checklist for methodological guideline appraisal. Appraisal of guidelines' contents: Peer review of guidelines with the following inclusion criteria: Bronchial Asthma-general, German and English language, based in references published later than 1994, new guideline or actual update. Peer review was performed by a multidisciplinary focus group of EBM experts (clinical and ambulatory settings). No expert was involved in guideline production during the review period. RESULTS: Methodological appraisal: 16 out of guidelines were in accordance with the formal minimal standard with a wide range within the following domains: "description of the development process", "declaration of authors' independence", "explicit link between recommendations and the supporting evidence", "management options", "tools for implementation". The focus group recommended for future national asthma guidelines to rely on the following procedures: (1) to formulate the recommendations using standardized, clearly described consensus methods basing on evidence retrieved and selected in a systematic way (2) to prove links between recommendations and supporting evidence (3) to develop guideline versions for health care professionals as well as for consumer/patients (4) to develop guideline-based education tools (5) to ensure periodical updates of the asthma guideline (6) to consider the methodological recommendations and to give reasons for deviations from the methodological recommendations. APPRAISAL OF GUIDELINES CONTENT: None of the guidelines identified comprised information about all of the following key topics considered to be relevant for a German national guideline by the focus group: (1) intended guideline users/goals, (2) definition (3) cause of disease, (4) form of disease, (5) severity, (6) diagnosis, (7) therapeutic goals, (8) prevention, (9) pharmacotherapy, (10) non-pharmacotherapy, (11) therapy control and compliance, (12) emergency treatment, (13) rehabilitation, (14) comorbidity, (15) special aspects, (16) coordination of care, (17) quality assurance/quality management, (18) implementation. SUMMARY POINTS: For quality promotion of bronchial asthma management in Germany, the development of a national evidence-based guideline, using the internationally accepted quality criteria for clinical practice guidelines, was recommended by an expert group of the German Guideline Clearinghouse. The experts identified and peer-reviewed 16 out of 54 guidelines, which might be useful as benchmarks and examples for a German asthma guideline. From the peer review results, the expert group identified 18 key topics for a national asthma guideline.

Asthma↗
PubMed2002

["Off-label" prescribing of drugs in the ambulatory care of children and adolescents].

BACKGROUND AND OBJECTIVE: Hospitalised children receive up to 90 % of their drug prescriptions without ("unlicensed use") or outside ("off-label use") the terms of their product license. As no data are available for pediatric outpatients in Germany, we determined "off-label" use in a representative cohort of children and adolescents. PATIENTS AND METHODS: We analyzed 1.74 million prescriptions, written from January 1 st through March 31 st, 1999, to 455 661 children and adolescents aged 0 to 16 years by 6886 specialists in pediatric, general or internal medicine. All prescriptions were covered by the public health insurance, Allgemeine Ortskrankenkasse, (AOK) Baden-Wuerttemberg. License status of 1 592 006 identifiable prescriptions comprising more than 10 000 differently branded drugs was determined in 5 age groups and in different groups of the Anatomical Therapeutical Chemical Classification (ATC). As reference documents for licensing status we used the "Fachinformation" (summary of product characteristics), the "Rote" and "Gelbe" Liste, respectively. RESULTS: 13.2 %, i. e. 210 528 of the 1.59 million prescriptions, were "off-label". 75 % of these "off-label" prescriptions were due to a lack of information on pediatric use in the summary of product characteristics. The highest "off-label" fractions were found in drugs topically used in eyes and ears (78.6 %), dermatological (57.9 %), cardiovascular drugs (55.2 %), drugs für musculoskeletal (45.2 %) and urogenital disorders (48.5 %) and antidepressants (36.6 %). CONCLUSION: "Off-label" prescribing in outpatient children is less frequent than in pediatric inpatients. Considering the high absolute number of prescriptions however, 13.2 % cannot be neglected. Doctors prescribing drugs for children and adolescents should be aware of their actual licensing status because of its medical and legal consequences.

Adolescent↗
PubMed2002

[Celecoxib].

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Influence of CYP2D6 genotype and medication on the sparteine metabolic ratio of psychiatric patients.

OBJECTIVE: To investigate the influence of CYP2D6 genotype and medication on the reliability of phenotyping in a naturalistic setting of psychiatric inpatients. METHODS: The phenotype of 160 psychiatric inpatients was estimated by taking the urinary metabolic ratio (MR) of the concentrations of sparteine to 2- and 5-dehydrosparteine. Genotyping identified CYP2D6*1, *3, *4, *5 and *6 alleles as well as duplication of the CYP2D6 gene. All subjects underwent detailed drug history including drug dose and therapeutic drug monitoring to control compliance and abuse of other psychotropic drugs. These data were compared with those of 195 unmedicated healthy Germans. RESULTS: The cumulative distribution of the MR in patients showed a significant shift to higher MR when compared with that of healthy subjects (P < or = 0.001). Patients medicated either with selective serotonin reuptake inhibitors (SSRIs, P < or = 0.001), antipsychotic drugs (P= 0.002) or other drugs known to be substrates or inhibitors of CYP2D6 (P < or = 0.001) showed a significantly higher mean MR than unmedicated patients. However, there was no significant effect of tricyclic antidepressants on the MR. Healthy subjects with CYP2D6 deficiency were separated by a MR of greater than 20 from those who expressed functional CYP2D6. Seven patients carrying at least one functional CYP2D6 allele revealed a MR of greater than 20, indicating the occurrence of phenocopying. CONCLUSION: The results of phenotyping may be falsified by drugs known to be substrates or inhibitors of CYP2D6; thus, this method is not sufficiently reliable. However, since we observed the phenomenon of phenocopying only in patients treated with a SSRI such as fluoxetine, fluvoxamine or paroxetine, we conclude that sparteine phenotyping of medicated patients detects CYP2D6 deficiency correctly, provided that patients treated with these SSRIs are excluded.

Adult↗
PubMed2001

Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers.

AIMS: To establish the bioavailability of tropisetron (5 mg) administered orally as capsule compared with 2 mg given intravenously. METHODS: Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropisetron (2 mg) separated by a wash-out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated. RESULTS: The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml(-1), t(max) 2.6 h, t(1/2) 5.7 h and AUC(0,infinity) 32.9 ng ml(-1) h. After intravenous administration initial plasma concentration was 15.1 ng ml(-1), t(1/2) 5.6 h, AUC(0,infinity) 20.7 ng ml(-1) h, V 678 l and CL 1800 ml min(-1). An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27-0.99) of oral tropisetron. CONCLUSIONS: Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.

Administration, Oral↗
PubMed2001

Disposition and pharmacologic effects of R/S-verapamil in patients with chronic atrial fibrillation: an investigation comparing single and multiple dosing.

BACKGROUND: Racemic (R /S)- verapamil is widely used in the management of chronic atrial fibrillation. The negative dromotropic effect is mainly mediated by the S -enantiomer, which is preferentially metabolized. Previous studies report an accumulation of R /S- verapamil during long-term oral treatment of patients with chronic atrial fibrillation. However, the specific disposition of S -verapamil and the pharmacologic effects were not assessed. Therefore uncertainties about the need for dose adjustments remain. METHODS: Using stable isotope technology and a stereospecific assay, we compared the pharmacokinetics and pharmacodynamics of intravenous (10 mg of d(7)-R /S -verapamil) and oral (240 mg of slow release (SR) d(0)-R /S -verapamil) R -verapamil and S -verapamil after the first dose (day 1) and after 3 weeks (day 21) of continuous oral therapy in 8 patients with long-term atrial fibrillation. On both study days, serum samples were obtained for the analysis of d(7)- and d(0)-R -verapamil and S -verapamil. Heart rate (HR) was monitored with electrocardiography (with each blood sample) and Holter electrocardiography (before the study, on day 1, and on day 21). RESULTS: Compared with day 1, clearance of oral R -verapamil and S -verapamil was significantly reduced on day 21 (1007 +/- 380 versus 651 +/- 253 mL/min [-35%] and 5481 +/- 2731 versus 2855 +/- 1097 mL/min [-48%], respectively; P <.05), whereas only a moderate decrease was observed for intravenous R -verapamil and S -verapamil (-23% and -14%, respectively, not significant). Mean HR (89 +/- 11 bpm before verapamil) was effectively reduced, with the same effects on day 1 (68 +/- 8 bpm) and day 21 (68 +/- 8 bpm). Compared with day 1, the HR reduction per ng/mL of S -verapamil (calculated by the area under the curve [from 0-24 hours] ratio of HR reduction and S -verapamil concentration) was significantly lower on day 21 (0.7 +/- 0.4 versus 1.2 +/- 0.7 [bpm]. [ng/mL](-1), for day 21 versus day 1; P <.01). CONCLUSIONS: In patients with chronic atrial fibrillation, clearance of oral, but not intravenous, S -verapamil and R -verapamil is significantly reduced with multiple doses compared with a single dose, thereby indicating predominant impairment of prehepatic rather than hepatic metabolism as the underlying mechanism. However, this kinetic change is clinically compensated by a decrease in the responsiveness to S -verapamil observed with regular dosing. The data suggest that despite accumulation of the drug individual verapamil doses can be maintained during long-term oral rate control therapy.

Administration, Oral↗
PubMed2000

Pharmacokinetics and pharmacodynamics of R- and S-gallopamil during multiple dosing.

AIMS: Using a stable isotope technique we investigated the pharmacokinetics and pharmacodynamics of gallopamil after administration of 50 mg pseudoracemic gallopamil every 12 h for 7 doses (72 h). METHODS: Six male healthy volunteers were studied. After the seventh dose the pharmacokinetics and pharmacodynamics were assessed. Serum levels of gallopamil were measured by gas chromatography/mass spectrometry. Effects of gallopamil were measured by ECG recording. RESULTS: The apparent oral clearances (R: 4.8 l min-1 (95% CI: 2.9-6.8); S: 5.5 l min-1 (95% CI: 2.5-8.5)) and half-lives (R: 6.2 h; S: 7.2 h) of R- and S-gallopamil were similar (P >0.05). The serum protein binding (fu R: 0.035 (95% CI: 0.026-0. 045); S: 0.051 (95% CI: 0.033-0.069)) and the renal elimination (% of dose R: 0.49%; S: 0.71%) were enantioselective. Gallopamil had a potent effect on the PR interval (% prolongation 35.7% (95% CI: 14. 0-57.3)). No changes in other electrocardiographic or cardiovascular parameters were observed. CONCLUSIONS: The pharmacokinetics and bioavailability of the racemic drug gallopamil are not stereoselective at steady-state and are therefore not substantially altered compared with the single dose administration of gallopamil.

Area Under Curve↗