Arzneimitteltherapie im Alter aus der Sicht des klinischen Pharmakologen

Zusammenfassung Ältere Patienten können aufgrund häufiger Multimorbidität den behandelnden Arzt zu einer Polypharmakotherapie (Polypragmasie) mit kaum vorhersagbaren Interaktionen veranlassen. Arzneimittelinduzierte Symptome sind oft für Krankenhauseinweisungen in der Geriatrie verantwortlich. Dies kann zu einer Ausweitung der Medikation führen. Geriatrische Patienten weisen häufig eine veränderte Pharmakokinetik auf. Im Rahmen einer individualisierten Arzneimitteltherapie sollten nicht nur Lebensalter, Leber- und Nierenfunktionen sondern auch individuelle Variabilitäten der hepatischen Metabolisierung und intestinalen Resorption auf der Basis genetischer Polymorphismen berücksichtigt werden. Prinzipiell ist es wichtig, gerade bei geriatrischen Patienten eine bestehende oder neue Arzneimitteltherapie hinsichtlich des Risiko-Nutzen-Verhältnisses zu prüfen und ggf. bestimmte Medikationen um- oder gar ganz abzusetzen.     

Pharmakotherapie im Alter aus internistisch-pneumologischer Sicht

Pharmacotherapy of the elderly requires a complex view on pharmacology in an ageing population. Aging leads to changes in metabolism which influence pharmacodynamics and pharmacokinetics. Age is often accompanied by multimorbidity which in turn requires the intake of several lines of pharmaceutical treatment. Altered metabolism in combination with polypharmacy is likely to result in an increased number of drug interactions and undesired or adverse events. A critical consideration of every additional drug with respect to age-induced metabolic changes is a prerequisite for a less hazardous and adjusted mode of therapy. Elderly people are underrepresented in clinical trials and guidelines so this might be an appropriate approach to improve therapy in the sense of more evidence-based. From a pneumological point of view it is necessary to learn more about age-associated pneumophysiological changes, illnesses und risk factors and to critically question the therapy in the context of multimorbidity and polypharmacy of elderly patients.     

Synkope aus der Sicht des Neurologen

Syncope is a pathogenetically diverse syndrome that often requires an interdisciplinary investigation. In addition to cardiovascular reasons of syncope neurological diseases and differential diagnoses have to be considered. In particular, neurodegenerative disorders, such as Parkinson’s disease or polyneuropathy may cause orthostatic intolerance and syncope due to a malfunction of autonomic reflexes. Furthermore, important differential diagnoses of syncope, such as epilepsy, drop attacks or circulatory disorders in the territory of the basilar artery are attributed to the neurological field.     

Rolle der Vitamin-K-Antagonisten aus Sicht des Hepatologen

Vitamin K antagonists are often used as oral anticoagulants for primary and secondary prevention of thromboembolic events. Vitamin K antagonists induce an anticoagulant effect by interfering with the vitamin K metabolism in the liver. Well-known complications are bleeding events and skin necrosis. Recent data indicate increasing numbers of cases with hepatic complications due to vitamin K antagonists ranging from mild hepatopathy to acute liver failure with high mortality. Hepatotoxicity is usually developed after a few months of latency, which is associated with unspecific symptoms, jaundice, elevated transaminase levels as well as cholestatic enzymes. Hepatotoxicity due to vitamin K antagonists is seldom; however, it should be considered in cases of elevated liver enzymes. In this case coumarin therapy should be discontinued. Caution is needed when changing to another coumarin derivative because cross-reactivity has been described.     

EHEC 2011 – aus der Sicht des Klinikers

In early summer 2011 northern Germany was overrun by the greatest Entero-Haemorrhagic Escherichia coli (EHEC) O104:H4 outbreak so far. In contrast to earlier reported EHEC outbreaks young adults were affected mainly, and complications were frequent with 72% of 61 hospitalized patients in our cohort. In consequence of the genetic and clinical characteristics we concur with Brzuszkiewicz et al. to describe this syndrome as EAHEC syndrome (??Entero-Aggregative-Haemorrhagic Escherichia coli??). Because of the variability of the clinical courses, intensified monitoring at close intervals is necessary; we suggest the ??Altona EAHEC Monitoring Standard??. From the clinical point of view we could not observe an unfavorable influence of antibiotics.     

Kolorektale Lebermetastasen aus der Sicht des Internisten und des Chirurgen

Liver metastases are common in colorectal cancer. However, despite the presence of hematogenic metastasis a cure can still be possible. A broad spectrum of surgical or ablative procedures and systemic treatment options are available for this. In many cases a combination of various therapy modalities, either simultaneously or sequentially, is the most sensible approach. In each individual case the strategies must be discussed by an interdisciplinary tumor board. It is essential that an experienced hepatic surgeon is included in order not to miss the opportunity of a resection with curative outcome. The terms ?resectability” and ?non-resectability” depend greatly on the experience and the armamentarium of the surgeon. Neoadjuvant and adjuvant strategies can be useful in many cases and are currently under evaluation in studies. For conversion therapy it makes sense to perform a resection as soon as ?resectability” has been achieved.     

Akutes Leberversagen aus der Sicht des Internisten und des Chirurgen

Acute liver failure is defined as the sudden loss of liver function without preexisting liver disease. In addition to virus hepatitis infections, drug toxicity is the cause of acute liver failure. In the industrial nations drug toxicity is the main cause. In Germany there is also an etiological change from acute viral hepatitis to drug-induced liver failure. The prognosis for acute liver failure is still poor. Decisive for the course is the clinical diagnosis of the findings of the treating physician. Due to improved diagnostic and intensive care treatment it is nowadays possible to recognize and stabilize affected patients in order to prepare them for transplantation. Orthotopic transplantation is currently the only treatment option which has been shown to improve the survival and prognosis in these patients.     

Das cholangiozellul?re Karzinom aus der Sicht des Internisten und des Chirurgen

Cholangiocellular carcinomas (CCC) are rare tumors with an incidence of 2–4/100,000 per year. They are a heterogeneous group of neoplasias that includes the perihilar or Klatskin tumors (at 60%, the most common of the CCC), the intrahepatic (peripheral) CCC, extrahepatic bile duct cancer, gallbladder cancer, and cancer of the ampulla of Vater. At the time of diagnosis, only 30% of patients are eligible for surgery, which offers the only chance for cure. Due to high recurrence rates, liver transplantation is restricted to select patients with small but nonresectable tumors. Patients with advanced nonresectable carcinoma have a dismal prognosis, with an overall survival of only 6–8 months. In inoperable patients, prevention or treatment of cholestasis is the main objective. This can be achieved endoscopically, percutaneously, or by surgical biliodigestive anastomosis. Palliative chemotherapy results in tumor stabilization rates of up to 60%. The most frequently used agents are fluoropyrimidines and gemcitabine in combination with a platin derivative. When different treatment modalities are combined, significant survival can be achieved in some patients.     

Mechanismen des Alterns aus biogerontologischer Sicht

Ohne Zusammenfassung     

Diagnostik der Beckenbodeninsuffizienz aus chirurgischer Sicht

Evaluation and exploration of the pelvic floor insufficiency should be integrated in a complete proctologic examination. The case history concentrating upon feacal incontinence and defaecation disorders is of primary importance. A rectocele, an enterocele, a sphincter insufficiency or a prolapse become evident and are diagnosed during clinical examination. Technical explorations are mainly by defaecography (rectocele, enterocele, intussusception) and endosonography (sphineter mapping). Endosonography is mandatory in planning sphincter reconstructive procedures.     

Proktitis aus Sicht der Proktologie*

Proctitis may cause anal bleeding, anal mucus secretion, diarrhea, urge incontinence, pain at defecation, etc. At digital rectal examination a thickened mucosal lining may be palpated and blood is found on the examination glove. At endoscopy erosive or ulcerative lesions are found that bleed easily on contact. Also polyp-like or even tumor-like lesions, telangiectasias and atypical fistulas can be seen. The symptoms and the findings on examination are quite often unspecific; a detailed history of the patient is most important in the work-up for the differential diagnosis. Serological and microbiological examinations should be done as well as biopsies (except for radiation proctitis). Proctitis may occur after applying external agents that cause chemical, thermal as well as pharmaceutical reactions in the rectum. Proctitis may occur after fecal diversion. Ischemic proctitis causes severe pain and fecal incontinence and may occur postoperatively, after shock/anaphylaxis, etc. The solitary rectal ulcer (syndrome) has a more or less mechanical etiology and shows clearly defined pathohistological lesions. It often occurs in women with outlet obstruction and/or rectal, mucosal or hemorrhoidal prolapse. Except for rectal prolapse, treatment of the solitary rectal ulcer is not always simple or successful. The same applies to radiation proctitis that may occur after radiotherapy. Radiated anorectal tissue regenerates slowly or not at all. Therefore invasive procedures should not be performed because of the high risk for the development of ulceration or fistula. Treatment of radiation proctitis is not always simple and it does not have a high level of evidence. In most cases therapy should be performed individually, according to the severity of complaints.     

Sicherheit der Rheumatherapie im Alter

Mainly due to the general demographic changes and decreasing mortality in rheumatic diseases based on therapeutic progress, the proportion of older patients treated by rheumatologists is growing. Drug treatment in the elderly, however, harbors certain risks including age-specific pharmacokinetic features and high rates of multimorbidity and polypharmacy resulting in a risk of drug interactions and adherence problems. Nevertheless, older patients suffering from rheumatic diseases ought to be treated with the same intensity and same targets as the younger counterparts. Bearing all these facts in mind it is a balancing act for rheumatologists to find an optimal treatment for the individual elderly patient. Fear of risks should not lead to hesitant use of drugs leaving these patients alone with treatment deficits, as some studies have suggested.     

Pharmakotherapie der Harninkontinenz im Alter

The prevalence and the incidence of Urinary Incontinence is growing. Women suffer predominantly from stress and mixed urinary incontinence and men from urge incontinence. In elderly people, the pathophysiological and the physiological change in the lower urinary tract system must be considered as well as an underlying multimorbidity. Stress urinary incontinence is among others caused by an insufficient urethral closure mechanism and urge incontinence is followed by unhibited detrusor contractions. Medical treatment is beside other important conservative options only one part of the treatment strategy in incontinence. Duloxetine, a serotonine-norepinephrine reuptake inhibitore can increase activity of the external urethral sphincter and is able to reduce incontinence episodes in up to 64?%. Antagonists of muscarinic receptors can reduce urgency, frequency and urge incontinence as well as increase bladder capacity significantly. In Germany, darifenacin, fesoterodin, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride are available to treat urge incontinence. The efficacy of these agents are almost comparable in the elderly with the exception of oxybutynin IR. However, tolerability is different and not well studied in the elderly population with the exception of fesoterodin. Side effects, especially dry mouth, dizziness and constipation often limit their use. None of the agents show ideal efficacy or tolerability in all patients. Last summer therefore a β₃-agonist mirabegron was also introduced in Germany but was withdrawn.     

Genetik des Asthma – aus klinischer Sicht

Zweck dieses Beitrages ist es, die Aufmerksamkeit des Lesers auf Entwicklungen zu lenken, die in den letzten Jahren unser Verst?ndnis über klinische Ph?nomene und den Verlauf von allergischen Erkrankungen durch neue wissenschaftliche Ergebnisse erweitert und neu gepr?gt haben. Dagegen kann es nicht Ziel dieses Beitrags sein, eine ersch?pfende übersicht über das Thema der genetischen Ursachen von Allergien zu geben. Dieses ist alleine aus Platzgründen nicht m?glich und würde auch den Fokus der Zeitschrift der “Internist” weit überschreiten. Der interessierte Leser sei deswegen auf neuere übersichtsarbeiten hierzu verwiesen [5, 6, 12, 13, 14, 17, 18, 21].