The use of psychostimulants in palliative and supportive treatment of cancer patients

Psychostimulants have been used in psychiatric and medically ill patients. The need to control and counteract the multiple distressing symptoms related to cancer and its treatment has brought this group of medications into palliative and supportive care of cancer patients. Psychostimulants have been studied and used in symptoms like cancer-related fatigue, cognitive dysfunction, depression and sedation. This review discusses the pharmacology of methylphenidate, amphetamine and pemoline and other psychostimulants like caffeine and the novel wake-promoting drug, modafinil. Studies evaluating use of these drugs in cancer patients have been reviewed.Psychostimulants have been used in psychiatric and medically ill patients. The need to control and counteract the multiple distressing symptoms related to cancer and its treatment has brought this group of medications into palliative and supportive care of cancer patients. Psychostimulants have been studied and used in symptoms like cancer-related fatigue, cognitive dysfunction, depression and sedation. This review discusses the pharmacology of methylphenidate, amphetamine and pemoline and other psychostimulants like caffeine and the novel wake-promoting drug, modafinil. Studies evaluating use of these drugs in cancer patients have been reviewed

Clinical implications of morphine metabolism

Od wieków opium jest znanym i powszechnie używanym środkiem przeciwbólowym. Składa się z suszonego mleczka, pochodzącego z niedojrzałych makówek maku lekarskiego — Papaver somniferum. Opium zawiera szereg alkaloidów, z których tylko niektóre — morfina, kodeina, noskapina oraz papaweryna — mają zastosowanie kliniczne. W 1803 roku Serturner wyizolował krystaliczną próbkę głównego alkaloidowego składnika opium — morfiny, która, jak się później okazało, jest w pełni odpowiedzialna za przeciwbólowe działanie nieoczyszczonego opium. Mimo że w minionym wieku pojawiło się kilka nowych syntetycznych opioidów o silnym działaniu, morfina jest nadal podstawowym i najpowszechniejszym opioidowym środkiem przeciwbólowym. Dzięki bardziej liberalnym wskazaniom dotyczącym podawania tych leków, zwłaszcza u pacjentów z nowotworem, a w ostatnich latach także u chorych z przewlekłym bólem o niezłośliwym pochodzeniu, stosuje się je znacznie częściej. Jednak nadal istnieją kraje, w których dostęp do opioidów jest znacznie ograniczony. W związku z dłuższym czasem stosowania oraz większym dawkowaniem zarówno morfiny, jak i innych leków opioidowych u chorych cierpiących na przewlekły ból rozpoczęto ostatnio kilka nowych badań klinicznych, dotyczących ich działania przeciwbólowego oraz skutków ubocznych. Dzięki rozwojowi nauki więcej wiadomo o sposobie działania oraz toksyczności tych leków. Dla naukowców i klinicystów morfina pozostaje nie do końca poznanym lekiem, mimo że stosuje się ją od tak dawna. Celem tej pracy jest ocena metabolizmu oraz przydatności klinicznej morfiny i jej głównych metabolitów.Opium has been known and used as an analgesic since the beginning of times. It consists of the dried milk juice derived from the unripe seed capsules of the opium poppy, Papaver somniferum. Opium contains a number of alkaloids, of which only a few — morphine, codeine, noscapine and papaverine — are of clinical use. In 1803, Serturner isolated a crystalline sample of the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the analgesic activity of crude opium. Although several new synthetic strong opioids have occured in the past century, morphine is still the most widely used opioid and remains the “gold standard” when effects of other opioid analgesics are to be compared. Due to a more liberal approach to opioid analgesics especially in cancer patients, but within the later years also in patients with pain of chronic non-malignant origin, the consumption of opioids is vastly increasing. However, there are still countries where access to opioids are extremely limited. As morphine and other opioid drugs today are used for longer periods and in higher doses in patients suffering from chronic pain a number new clinical observations concerning analgesic action and side effects have occurred recently. Furthermore basic science has increased the knowledge of mode of action and toxicity considerably. Despite having been known for so long, morphine is still a puzzling drug to the scientists and clinicians. The scope of this article is to review morphine metabolism and update the clinical implications of morphine and its major metabolites

Direct stimulation of bone mass by increased GH signalling in osteoblasts of Socs2-/- mice

The suppressor of cytokine signalling (Socs2−/−)-knockout mouse is characterised by an overgrowth phenotype due to enhanced GH signalling. The objective of this study was to define the Socs2−/− bone phenotype and determine whether GH promotes bone mass via IGF1-dependent mechanisms. Despite no elevation in systemic IGF1 levels, increased body weight in 4-week-old Socs2−/− mice following GH treatment was associated with increased cortical bone area (Ct.Ar) (P<0.01). Furthermore, detailed bone analysis of male and female juvenile and adult Socs2−/− mice revealed an altered cortical and trabecular phenotype consistent with the known anabolic effects of GH. Indeed, male Socs2−/− mice had increased Ct.Ar (P<0.05) and thickness associated with increased strength. Despite this, there was no elevation in hepatic Igf1 expression, suggesting that the anabolic bone phenotype was the result of increased local GH action. Mechanistic studies showed that in osteoblasts and bone of Socs2−/− mice, STAT5 phosphorylation was significantly increased in response to GH. Conversely, overexpression of SOCS2 decreased GH-induced STAT5 signalling. Although an increase in Igf1 expression was observed in Socs2−/− osteoblasts following GH, it was not evident in vivo. Igf1 expression levels were not elevated in response to GH in 4-week-old mice and no alterations in expression was observed in bone samples of 6-week-old Socs2−/− mice. These studies emphasise the critical role of SOCS2 in controlling the local GH anabolic bone effects. We provide compelling evidence implicating SOCS2 in the regulation of GH osteoblast signalling and ultimately bone accrual, which maybe via mechanisms that are independent of IGF1 production in vivo

Aluminum toxicity in childhood

Aluminum intoxication is an iatrogenic disease caused by the use of aluminum compounds for phosphate binding and by the contamination of parenteral fluids. Although organ aluminum deposition was noted as early as 1880 and toxicity was documented in the 1960s, the inability to accurately measure serum and tissue aluminum prevented delineation of its toxic effects until the 1970s. Aluminum toxicity has now been conclusively shown to cause encephalopathy, metabolic bone disease, and microcytic anemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47831/1/467_2004_Article_BF00869743.pd