[Interaction of opioid analgesics at the level of biotransformation]. / Interaktionen der Opioidanalgetika auf Ebene der Biotransformation.

Opioids are an important component of the drug treatment of patients with acute and chronic pain. They differ in effectiveness, side effect profile and the risk of interactions. In this article the pharmacokinetic mechanisms of drug-drug interactions at the level of biotransformation are described and the clinical consequences which can arise are discussed. The relation of the active components to the two isoenzymes CYP2D6 and CYP3A4 is of major importance for assessing the potential drug-drug interactions of opioid analgesics at the level of the cytochrome P450 enzyme.

[Chronic chest pain]. / Chronischer Brustschmerz.

BACKGROUND: Chest pain is a symptom commonly reported by persons in the general population and represents a differential diagnostic challenge. MATERIAL AND METHODS: The paper is based on a narrative review with a selective search of the literature in Medline for reviews and guidelines on the prevalence and treatment of non-malignant diseases with chronic chest pain in gastroenterology, gynecology and cardiology. RESULTS: The prevalence and current treatment recommendations for the different forms of gastroesophageal reflux disease (GERD), erosive and non-erosive types and irritable esophagus, non-cardiac chest pain, refractory angina in coronary heart disease and postmastectomy nand poststernotomy syndromes are presented. In cases of failure of the established therapy of a single medical discipline, an interdisciplinary assessment including psychosocial issues is recommended. Evidence-based guidelines are available for the management of GERD and of refractory angina. Treatment of postmastectomy and poststernotomy syndromes is based on case reports and expert opinion. CONCLUSION: There is a need for controlled studies on the symptomatic treatment of pain in irritable esophagus, non-cardiac chest pain, postmastectomy and poststernotomy syndromes.

[Improving medication safety]. / Verbesserung der Arzneimitteltherapiesicherheit.

Drug treatment is beneficial in most patients but can also cause adverse events and death. Since preventable adverse drug events are a relevant cause of morbidity and mortality, strategies for improving medication safety are warranted. Studies demonstrate that system failure is the most relevant cause of preventable adverse drug events, with prescribing errors being the most relevant. Lack of information either about the patient, the functioning of a patient's organs and concurrent medications, or about the prescribed drug, its correct dosing, contraindications and drug interactions often lead to preventable adverse drug events. International studies show that medication errors result in more people dying than from traffic accidents. Therefore, in addition to the safety of the drug, it is necessary that the safety of the process of drug treatment must be taken care of. This is called medicine safety. In order to improve medicine safety, it is necessary to consider the organization of the medication process, instead of looking for an individual to blame. The goal of the "Action Plan for Medication Safety in Germany" ("Aktionsplan Arzneimitteltherapiesicherheit für Deutschland") from the Federal Ministry of Health is to optimize patient safety in drug treatment by the joint efforts of physicians, pharmacists, patients, and politicians.

Impairment of health-related quality of life in functional dyspepsia and chronic liver disease: the influence of depression and anxiety.

BACKGROUND: Health-related quality of life (HRQOL) is a marker of disease severity. Data on the relative impairment of HRQOL in chronic liver disease (CLD) and functional gastrointestinal disorders are lacking and no studies have assessed the link between impairment of HRQOL and psychosocial factors yet. AIM: To assess predictors for, and the impairment of, HRQOL in CLD and FD. METHODS: In 181 functional dyspepsia (FD) patients, 204 CLD patients and 337 healthy blood donors, HRQOL was assessed with the Short Form-36 (mental and physical component), and anxiety and depression utilizing the Hospital Anxiety and Depression Scale. RESULTS: Compared with HC, HRQOL is significantly lower in FD and CLD (P-value for all <0.001). The mental but not physical component of HRQOL was significantly more impaired in FD compared with CLD (P < 0.05). After adjusting for confounders, impairment of mental (P < 0.001) and physical (P = 0.005) component of HRQOL was associated with the severity of CLD and FD. In FD, the multivariate analysis revealed depression and severity of symptoms as the most important predictors of HRQOL (R2 = 21.9 and 7.1). In CLD, the mental component of HRQOL was associated with depression and anxiety (R(2) = 9.9 and 9.7). CONCLUSIONS: In tertiary care, HRQOL is more severely impaired in FD compared with CLD. Co-morbid psychiatric conditions significantly contribute to the impairment of HRQOL.

[Frequency, relevance, causes of and strategies for prevention of medication errors]. / Häufigkeit, Relevanz, Ursachen und Strategien zur Vermeidung von Medikationsfehlern.

Drug therapy has led to major advances in medicine. The beneficial effects of drug therapy are coupled with the inevitable risk of adverse drug reactions especially in elderly patients. Many adverse drug reactions are preventable. The electronic health card that will be introduced in Germany starting in 2006 is designed to support electronic decision support to prevent medication errors. Studies have demonstrated that CPOES can reduce medication errors by 80%. The necessary steps to improve medication safety in Germany are outlined and discussed.

[Is an evidence-based therapy of inpatients with type 2 diabetes possible from studies used for formulating therapy guidelines?]. / Ist eine evidenzbasierte Therapie von stationären Typ-2-Diabetikern mit den zur Leitlinienerstellung verwendeten Studien möglich?

BACKGROUND AND OBJECTIVE: Evidence-based guidelines are based on controlled trials and expert knowledge. Controlled trials often exclude elderly patients and those with diseases of several organs. It was the aim of this study to assess to what extent evidence-based guidelines of the German Diabetes Society (DDG) for antihyperglycaemic treatment were applicable to hospitalized patients with type 2 diabetes. PATIENTS AND METHODS: The exclusion criteria of the clinical trials listed in the guidelines of the DDG (Diabetes und Stoffwechsel 12/2003; supplement 2, 29-31) were analysed. The study cohort consisted of all patients on drug treatment of type 2 diabetes who had been hospitalized during August and September 2003 in the two medical units of the Saarbrucken University Hospital. Current data on diabetes-associated and diabetes-dependent diseases were recorded. RESULTS: 91 of 125 literature citations (72%) contained clinical studies of evidence class I-III. 33.3% od studies had explicitly excluded patients with renal disease, 31.1% with liver disease, 10.9% with an age >75 years, 15.2% with coronary heart disease and 12.3% with heart failure. These exclusion criteria were used regardless of the drugs used. In 153 of 982 patients (15.5%) had drug-treated type 2 diabetes mellitus, median age was 73 years. In 138 of 153 patients (90.1%) medical and and social data could be obtained. 18.1% of these patients would have been excluded because their creatinine was >1.5 mg/dl, 45.5% because they were older then 75 years, 50.7% because they had coronary heart disease, and 15.9% because of heart failure (some patients met more than one of these items). CONCLUSION: Treatment of hospitalized patients with type 2 diabetes with cardiac, hepatic and/or renal disease or older than 75 years was not possible if medical management was based on clinical studies with an evidence level I-III.

[Chronic abdominal pain--internistic-psychosomatic aspects]. / Bauchschmerz aus internistisch-psychosomatischer Sicht. Gestresster Magen--gereizter Darm?

Abdominal pain is considered to be chronic when it persists for at least three months or when a patient experiences such pain for a total of three months during the course of a year. Pathophysiologically, nociceptive/neuropathic functional pain syndrome, mental disorders with the cardinal symptom of chronic pain, and mixed forms can be distinguished. In 50% of the patients, the cause of chronic abdominal pain is a functional gastrointestinal disorder e.g. functional dyspepsia irritable bowel syndrome. On the basis of a structured pain history, a physical examination and a basic "technical" diagnostic program (laboratory investigations, abdominal ultrasonography, Esophagogastroduodenoscopy, colonoscopy), correct assignment to one of the above-mentioned can be achieved in most of the cases.

Validation of the inflammatory bowel disease questionnaire IBDQ-D, German version, for patients with ileal pouch anal anastomosis for ulcerative colitis.

BACKGROUND AND AIMS: The inflammatory bowel disease questionnaire (IBDQ) is the standard instrument for assessment of health-related quality of life (HRQOL) in patients with inflammatory bowel diseases. It has not been validated for patients with ileal pouch anal anastomosis (IPAA) and ulcerative colitis (UC). METHODS: To determine acceptance (percentage of completed items), reliability (Cronbach's alpha of the IBDQ-D subscales) and convergent validity (correlations of the IBDQ subscales with the questionnaires used for validation) 61 patients with UC (age 52.7 +/- 13.9 years; 47 % female, 53 % male) and IPAA completed the German (Competence Network IBD) version of the Inflammatory Bowel Disease Questionnaire (IBDQ-D), the Short Form Health Survey (SF-36) the Hospital Anxiety and Depression Scale German Version (HADS-D) and the Giessener Symptom List (GBB 24). Face validity was assessed by a physicians' and patients' panel. All 37 patients underwent endoscopy making it possible to differentiate between patients with and without pouchitis (discriminant validity). RESULTS: With 97.7 % completed items the acceptance was high. Cronbach's alpha value for the subscales ranged from 0.71 to 0.93. Missing items covering extraintestinal manifestations of IBD were criticized by patients. The correlation coefficients with comparable subscales of other instruments ranged between 0.41 and 0.76. Patients with clinical pouchitis scored significantly lower in all subscales than patients without pouchitis (p < 0.001). CONCLUSION: The IBDQ-D has good acceptance, reliability, convergent and discriminant validity, but limited face and construct validity in patients with IPAA and UC.

[Validation of a German Version of the Fatigue Impact Scale FIS-D]. / Validierung der deutschen Version der Fatigue Impact Scale FIS-D.

OBJECTIVE: The Fatigue Impact Scale, FIS, is an internationally used instrument for the assessment of the impact of fatigue on Health-Related Quality of Life, HRQOL, also in patients with chronic liver diseases. In the German-speaking countries a validated instrument for measuring the impact of fatigue on patients with chronic liver diseases has not been available so far. METHODS: The German linguistic adaptation of the FIS using a forward-backward procedure was administered to 204 patients (age 52,7 +/- 13,9 years; 47 % female, 53 % male, 45 % no cirrhosis, 22 % Child's A, 15 % Child's B and 17 % Child's C cirrhosis; 53 % with chronic viral hepatitis, 32 % with alcoholic and 15 % with other liver diseases) of a secondary care hospital. The following internationally accepted instruments were used for validation: The Short Form Health Survey, SF 36, the Hospital Anxiety and Depression Scale German Version, HADS-D, and the Giessener Symptom Scale, GBB 24. Fifty patients in clinically stable situation filled out the FIS-D within 3 - 8 days. RESULTS: The acceptance of the FIS-D was high with 98 % answered items. The internal consistency of the three subscales was excellent (0.94 - 0.96), the test-retest reliability of the three subscales was good (0.72 - 0.83). The correlation coefficients with the validation instruments ranged between 0.49 and 0.80 (all p < 0 001). No differences in the FIS-D subscale scores were found in patients with and without cirrhosis and between the different Child-Pugh stages of liver cirrhosis. Patients treated with tranquilizer or antidepressants scored higher in the FIS-D than patients without this treatment (p < 0.05). CONCLUSION: The FIS-D is well accepted by patients in clinical routine care and has been shown to have good acceptance and reliability in the assessment of fatigue in chronic liver patients.

[Psychophysiology of visceral pain syndromes]. / Psychosomatik viszeraler Schmerzsyndrome.

Psychosomatics of visceral pain syndromes. From a psychosomatic point of view visceral pain syndromes can be classified into nociceptive (somatic and visceral) pain syndromes without and with maladaptive pain coping resp.psychic comorbidity, functional pain syndromes (typical symptom clusters without biochemical or structural abnormalities in clinical routine diagnostics) and psychic disorders with pain as main symptom. With regard to the etiology and the course of chronic inflammatory bowel diseases (IBD) as representatives of somatic pain syndromes and of irritable bowel syndrome/chronic pelvic pain as representatives of functional pain syndromes empirically validated psychosocial aspects are summarized: Personality traits, illness behavior, daily hassles, life events and psychic comorbidity and effects of psychotherapy. Psychosocial factors are decisive in the etiology and the course of functional pain syndromes as determinants of their severity (psychosomatic disease in a narrow sense). Psychosocial factors are not decisive for the etiology, but for the course of IBD (psychosomatic disease in a broader sense). Within general pain therapy of visceral pain syndromes a biopsychosocial approach should be applied right from the beginning (psychosomatic basic care). Within special pain therapy of visceral pain syndromes a qualified psychiatric - psychotherapeutic diagnostics and co-therapy should be mandatory.

[Tobacco associated gastrointestinal disorders: smoking cessation therapy - a task for gastroenterologists]. / Tabakassoziierte gastrointestinale Erkrankungen: Raucherentwöhnung - eine Aufgabe für Gastroenterologen.

Tobacco smoking is an independent risk factor in the etiology of Crohn's disease, functional dyspepsia, GERD, chronic pancreatitis and gastrointestinal carcinomas (oesophagus, stomach, colon, pancreas and liver). The current knowledge of the effects of tobacco smoking on the gastrointestinal tract is summarised. Non-smoking should be recommended to everybody as primary prevention against cardiopulmonary and gastrointestinal diseases. Despite lacking of clinical studies tobacco abstinence should be recommended as a secondary preventive therapy of Crohn's disease, functional dyspepsia, GERD and chronic pancreatitis because of epidemiological studies and pathophysiological considerations. All gastroenterologists should help patients with the above mentioned diseases to stop smoking. Evidence based methods of smoking cessation and methods suited to routine clinical care are presented. Pharmacological (nicotine replacement therapy) and psychological therapies (cognitive behavioural group therapies) should be adapted to the prior experiences of the patient, his stage of motivation to stop smoking and his co-morbidity. In refractory ulcerative colitis controlled tobacco smoking can be recommended to ex-smokers.

[Colitis ulcerosa and opioid addiction]. / Opioidsucht bei Colitis ulcerosa.

The occurrence of an opioid addiction within an opioid treatment of pain or diarrhoea in inflammatory bowel disease is rarely reported. We report on a 36-year-old male with a 14 years lasting left sided chronic ulcerative colitis who developed after the initiation of a therapy with tincture of opium because of abdominal pain and diarrhoea an opioid addiction with the consumption of opium and later buprenorphin. Additionally to the diagnostics and therapy of the ulcerative colitis a detoxication was carried out. The diarrhoea slightly increased during the buprenorphin withdrawal. Diarrhoea refractory to other treatment should be treated by loperamid because of its lacking effects on the central nervous system. In chronic abdominal or musculoskeletal pain in inflammatory bowel disease opioids can be used if no surgical or other medical pain relief is possible. A consequent control of the therapeutic and side effects of the opioid therapy is necessary, especially of an abuse of opioid medication. The published case reports of a therapeutic induction of opioid addiction demonstrate that psychiatric comorbidity is an essential or even necessary risk factor. A checklist with seven criteria of opioid addiction during opioid therapy is presented.

[Smoking cessation. A physician's responsibility]. / Raucherentwöhnung. Eine ärztliche Aufgabe.

Giving up smoking is a cost-effective measure in the secondary prevention of chronic arterial disease and chronic obstructive pulmonary disease. The involvement of the physician in the primary prevention of smoking and kicking the habit in the case of tobacco-related disease, must receive greater emphasis than has so far been the case in Germany. Weaning smokers suffering from tobacco-related disease from their habit is a task for the physician, and may take the form either of a single minimal intervention, or successive consultations that can be integrated in every medical activity. The concept of stepwise smoking dishabituation is supported by evidence-based consensus recommendations on the part of relevant national and international medical societies and public institutions.

[Chronic intestinal pseudo-obstruction. Clinical symptomatology and course]. / Die chronische intestinale Pseudoobstruktion. Untersuchung zur klinischen Symptomatik und Verlauf.

BACKGROUND AND OBJECTIVE: Chronic intestinal pseudoobstruction (CIP) is a motility disorder clinically characterized by recurrent symptoms of small intestinal or large bowel obstruction without organic stenosis. The aim of the present study was to assess the clinical presentation and course of the disease. PATIENTS AND METHODS: During a four year period all available data including the symptoms as assessed by the bowel disease questionnaire (BDQ) of all patients with newly established diagnosis of CIP were analyzed including duration of symptoms and previous surgical interventions due to the abdominal symptoms. RESULTS: Data of nine patients (five females, four males, age 20 - 64 years) with newly diagnosed CIP were available for analysis. Median age at initial onset of symptoms were 24 years. The final diagnosis of CIP was established after a median of 7 years (range 1 - 20). Initially, the majority of patients suffered from uncharacteristic symptoms such as abdominal fullness and abdominal pain. All patients had undergone repeated abdominal surgical interventions for suspected mechanical bowel obstruction. On average, the first surgical intervention was performed 5 years after the onset of symptoms and there was a median number of 10 treatments as in-patients. Suspected acute bowel obstruction occurred between 1 and 14 times and laparotomies were performed in 50 % of these events. CONCLUSION: The diagnosis of CIP is usually preceded by several years with uncharacteristic abdominal symptoms. During this time, most patients undergo multiple surgical interventions. Thus, in patients with repeated suspected acute bowel obstruction without definite proof of mechanical obstruction, CIP has to be taken into consideration as differential diagnosis. In this context, small bowel manometry is an important diagnostic tool.

[Measuring quality of life in gastroenterology--concepts, instruments and problems]. / Lebensqualitätsmessung in der Gastroenterologie--Konzepte, Instrumente und Probleme.

Health-related quality of life (HRQOL) is becoming an increasingly more important primary or secondary end point of clinical studies. Patients and their self help organizations demand a greater regard to their subjective experience of their disease and its treatment. Cost-effectiveness analyses measuring quality-adjusted life years are becoming more and more decisive in health politics. Therefore it is important for gastroenterologists to know the concepts and methods of HRQOL-measurement. The present article discusses the definitions of (health-related) quality of life and reviews generic- and disease-specific quality of life instruments in gastroenterology including quality criteria. Rules for the adaptation of Anglo-American questionnaires into German-speaking countries are pointed out. Finally the limitations of the concepts of HRQUOL and its measurement are discussed.

Antisecretory mechanisms of peptide YY in rat distal colon.

Peptide YY (PYY) is a potent regulator of intestinal secretion. These studies investigated the role of Y1 and Y2 receptor subtypes in mediating the antisecretory effects of PYY on mucosa-submucosa preparations of rat distal colon. Addition of vasoactive intestinal peptide (VIP) to these tissues resulted in a 140 +/- 18% increase in basal short-circuit current (Isc) and the induction of Cl- secretion. VIP-stimulated increases in Isc were abolished by the addition of each of PYY, (Pro34)-PYY, a Y1 receptor-selective agonist, and PYY-(3-36), an endogenous Y2 receptor-selective ligand. However, when tissue neural transmission was blocked with tetrodotoxin, neither PYY nor its receptor subtype-selective analogs were able to inhibit VIP-stimulated increases in Isc. These results suggest that in the rat distal colon, the antisecretory actions of PYY are mediated through a combination of Y1 and Y2 receptor subtypes or through a novel receptor subtype that is unable to discriminate between (Pro34)-PYY and PYY-(3-36).

Altered postprandial motility in chronic pancreatitis: role of malabsorption.

BACKGROUND & AIMS: Intraileal nutrients modulate gastrointestinal motility, but effects of maldigestion on postprandial motility are unknown. The aim of this study was to compare motor responses with ileal nutrient exposure in health and pancreatic insufficiency after a meal or intraluminal perfusion. METHODS: After oroileal multilumen intubation for duodeno-jejuno-ileal sampling, marker perfusion, and motility recording, 14 normal subjects and 12 patients with severe pancreatic insufficiency received a labeled liquid meal twice, either with placebo or pancreatin. Effects of intraileal nutrient perfusion on fed motility induced by duodenal amino acid perfusion were also investigated. RESULTS: Compared with normals, untreated patients had greater cumulative ileal nutrient delivery (69 +/- 21 vs. 487 +/- 232 kJ), shorter fed pattern (196 +/- 22 vs. 131 +/- 14 minutes), greater 90% gastric emptying (163 +/- 12 vs. 128 +/- 10 minutes), and faster small intestinal transit (86 +/- 9 vs. 44 +/- 6 minutes). Pancreatin reversed these changes. Ileal nutrient perfusion converted fed into interdigestive-like motility in normals (7 of 8) and patients (4 of 5). CONCLUSIONS: In subjects with pancreatic insufficiency, a low-energy liquid meal induces shorter fed motor pattern associated with accelerated gastric emptying and intestinal transit compared with healthy subjects. Because changes responded to enzyme treatment and could be reproduced by ileal nutrient perfusion, ileal delivery of malabsorbed chyme may be involved as a mechanism.

Neuropeptide Y 3-36 is an endogenous ligand selective for Y2 receptors.

Neuropeptide Y (NPY 1-36) binds to Y1 and Y2 receptors with similar affinity. No endogenous molecular form of NPY with selectivity for Y1 or Y2 receptors has been described so far. We report the presence of an endogenous fragment of NPY in porcine brain, NPY 3-36, which lacks the amino-terminal dipeptide Tyr-Pro of NPY 1-36. NPY 3-36 accounts for 35% of NPY-like immunoreactivity in porcine brain. We have compared binding of NPY 3-36 and NPY 1-36 in model systems of Y1-like (SK-N-MC cells) and Y2-like receptors (CHP234 cells). NPY 3-36 and NPY 1-36 had similarly high affinity for Y2-like receptors on CHP234 cells, but NPY 3-36 had a 1000-fold lower affinity than NPY 1-36 for Y1-like receptors on SK-N-MC cells. Thus amino-terminal cleavage of NPY 1-36 generating NPY 3-36 converts an unselective Y1/Y2 receptor ligand into a highly Y2 selective ligand. This may be a means of fine tuning NPY biological actions.

Inhibition of canine exocrine pancreatic secretion by peptide YY is mediated by PYY-preferring Y2 receptors.

It is still unclear, which receptor subtype, Y1 and/or Y2, mediates the inhibitory action of PYY on exocrine pancreatic secretion. The present study was undertaken to characterize functionally the Y receptor subtype that mediates the inhibition of exocrine pancreatic secretion by peptide YY (PYY). In eight conscious dogs with chronic gastric and pancreatic fistulas, we compared the action of intravenous infusion of 200 and 400 pmol/kg/h of the Y receptor agonists PYY 1-36, PYY 3-36, PYY 13-36, Pro34PYY 1-36, and NPY 1-36 on the pancreatic secretory response to secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). PYY 13-36, Pro34PYY 1-36, and NPY 1-36 were also studied by giving a fivefold dose (1,000 and 2,000 pmol/kg/h). PYY 1-36 and the Y2 receptor agonist PYY 3-36 significantly inhibited pancreatic secretory responses to secretin and cerulein, whereas inhibition by NPY 1-36 and the Y2 receptor agonist PYY 13-36 was attainable only at doses of 1,000 and 2,000 pmol/kg/h. The Y1 receptor agonist Pro34PYY 1-36 was without effect on pancreatic secretion. We conclude that in dogs the inhibition of exocrine pancreatic secretion by PYY is mediated via Y2 receptors of a PYY-preferring subtype.