Medizinische Monatsschrift fur Pharmazeuten最新文献

With an incidence of approximately 60,000 per year prostate cancer is the most common malignant neoplasm in men with a relatively low mortality rate and a high mean age of primary diagnosis of about 70 years. The disease remains usually clinically occult over a long period of time and generally manifests primarily in a locally advanced or metastasized stage. Due to screening using the PSA level (prostate specific antigen) in blood serum, diagnosis and therapy nowadays are oftentimes possible at an early stage. The prostate carcinoma is classified using risk groups based on the level of PSA, the local tumor spread and the histological degree of differentiation (Gleason score). If no metastases are detected during staging a local curative therapy is indicated, provided that the patient is eligible for this due to age, comorbidity and life expectancy. Depending on the risk group of the patient, radical prostatectomy, percutaneous radiotherapy, brachytherapy or active surveillance are available as curative therapy concepts. Focal therapies such as HIFU, electrovaporization or cryotherapy are currently considered to be experimental. If metastases are already present at primary diagnosis, palliative, systemic therapy can be performed with an androgen deprivation therapy and chemotherapy. At an advanced and hormone refractory stage, treatment with an osteotropic radiotracer or palliative radiotherapy can reduce bone metastases and alleviate respective symptoms.

The clinical evaluation of medicinal drugs follows strict guidelines both concerning the clinical as well as the pharmaceutical implementation perspective. Furthermore, it underlies similarly rigid implementation guidelines from the medical biometry perspective, pertaining from the choice of minimum necessary patient numbers to the primary statistical evaluation concept. The latter, however, require the explicit parameterization of clinical endpoints, alongside which efficacy and effectiveness of the drug under investigation will then be tested for the trial at hand. In most settings, the choice of these endpoints directly arises from the clinical rationale of the investigation, but is then complemented with a rather rigid recommendation from the trial statistician’s perspective, that is the restriction to only one primary clinical endpoint. The use of several parallel clinical endpoints cannot only end up in inconsistent or even contradictory clinical decision rules, but can also have crucial impact on the overall number of patients necessary in the statistical analysis of the clinical trial under consideration. Although the combination of multiple parallel endpoints may provide a solution in some clinical trial settings, the most effective recommendation can be seen in specifying only one primary clinical endpoint of maximum clinical relevance for the therapeutic intention at hand.

Pharmacological neuroenhancement and mood enhancement are gaining tremendous importance in society. The main motivation for neuroenhancement and mood enhancement is the anticipated increase in attention and vigilance, better performance in learning and memory and mood stability to meet the complex demands of an exacerbating meritocracy. Most users apply drugs originally designated for attention disorders, sleep disorders or dementia. Application of related drugs in terms of enhancement strategies in healthy individuals is off-label per se, the acquisition and distribution illegal. Here, we first provide an overview of the basic physiological mechanisms underlying vigilance, learning and memory, and emotional states. We then present the different pharmacological classes, i. a. purines and methylxanthines, phenylethylamine, modafinil, nootropics and antidepressants and elaborate their pharmacodynamics profile. Special attention will be paid to the norepinephrine/dopamine and cholinergic receptors and transporter systems but also to functional interaction with adenosine, serotonine and the glutamate receptor systems. Metaanalysis revealed that efficacy reported in, e. g. ADHD or dementia patients cannot be translated to healthy individuals. A validated positive effect on attention and vigilance has only been reported for some phenylethylamines and modafinil. It is likely that new developments, particularly in the field of antidementives will dramatically enhance neuroenhancement and mood enhancement. Drug regulatory actions, public and political discussions are necessary to meet the ethical and legal challenges of neuroenhancement and mood enhancement in the future.