Ş Ş AimsThe impact of a short postgraduate course on rational pharmacotherapy planning behaviour of general practitioners (GP) was investigated via a face-to-face interview with 25 GPs working at health centres in Istanbul. MethodsGPs were randomly allocated to control and intervention g roups. Intervention group attended a 3-day-training program preceded and followed by a written exam to plan treatment for simulated cases with a selected indication. The participants' therapeutic competence was also tested at the post-test for an unexposed indication to show the transfer effect of the course. In addition, patients treated by these GP's were interviewed and the prescriptions were analysed regarding rational use of drugs (RUD) principles at the baseline, 2 weeks and 4 months after the course. ResultsAt the baseline there was not any significant difference between the control and intervention groups in terms of irrational prescribing habits. The questionnaires revealed that the GPs were not applying RUD rules in making their treatment plans and they were not educating their patients efficiently. Training produced a significant improvement in prescribing habits of the intervention group, which was preserved for 4 months after the course. However, very low scores of the pretest indicate the urgent necessity for solutions. ConclusionsTraining medical doctors on RUD not only at the under-but also at the postgraduate level deserves attention and should be considered by all sides of the problem including academia, health authorities and medical associations.

The present study demonstrated that the final-year medical students (interns) markedly benefited from undergraduate RPE at the medical school in developing rational prescribing skills compared with their classmates from a medical school with traditional pharmacology education. Interestingly, they got higher scores than not only RPE(-) interns, but also than the GPs participating in this study, indicating the urgent need for continuous medical education programs in this field throughout the country for practicing GPs.

The present study aims to assess the short- and mid-term post-graduation impact of a pharmacotherapy course in the fifth year at Marmara University School of Medicine by an objective (OSCE) and a subjective (questionnaires) evaluation. Statistical comparison of pretest, posttest-exposed case and posttest-unexposed case scores indicated both a retention and a transfer effect of training. The post-course questionnaire revealed that 95%of the students found the course useful and necessary; 97% reported that they will apply a rational pharmacotherapy approach using this model and communicate better with their patients. The post-graduation questionnaire also showed that the majority of them have learned general principles of rational pharmacotherapy(90%), gained good prescribing (90%) and communication skills (87.5%), and understood the importance of non-pharmacological treatment alternatives (100%). In general, they stated that they would apply the principles during their medical practice and they believed their colleagues would do too. In conclusion, the present study demonstrates the benefit of a clinical pharmacology programme focused on rational pharmacotherapy during the clinical years of medical education.

The reduction of amphotericin B (AmB)-induced renal tubular apoptosis and nephrotoxicity by N-acetylcysteine (NAC) in a murine model was evaluated. Four groups of rats were treated with AmB for 5 days, and each group concomitantly received two doses of 30, 60, or 120 mg of NAC/kg of body weight/day or sterile water for 5 days. Groups that received concomitant NAC at any dose had significantly decreased levels of apoptosis compared to that in animals receiving AmB only (48.8% versus 27.4, 23.6, or 23.5%, respectively; P < 0.001).Nephrotoxicity is the major dose-limiting side effect of amphotericin B (AmB) deoxycholate (14,16,34). AmB-induced nephrotoxicity is usually reversible; however, up to 15% of patients may require dialysis, resulting in extended hospital stays and increased mortality (3,34). Nephrotoxicty is secondary to renal vasoconstriction, which leads to tubular damage and a decreased glomerular filtration rate (GFR) (11,14,15). The mechanism of renal tubular damage has not been fully elucidated; however, AmB has been suggested previously to induce dose-dependent renal tubular cell apoptosis (32).Several approaches to decreasing the incidence of AmB nephrotoxicity have been proposed. These approaches include prehydrating the drug formulation with saline and prolonging the infusion time (10, 18), infusing the drug in a fat emulsion (Intralipid) solution (7,19,21,25,27), and coadministering the drug with mannitol (6); however, none of these approaches have proven to be effective. While lipid formulations of AmB were found to be less nephrotoxic than other formulations of the drug, these formulations do not completely eliminate nephrotoxicity (9,17,23,35).Recently, Varlam et al. demonstrated that AmB causes a dose-dependent apoptotic effect in rat renal tubular cells, with ensuing nephrotoxicity (32). They also showed that AmB-induced apoptosis and the resulting nephrotoxicity can be reduced by the concomitant use of recombinant human insulinlike growth factor 1 (rhIGF-1), an antiapoptotic agent.N-Acetylcysteine (NAC) is an antiapoptotic and antioxidant drug, and NAC administration prior to the administration of radiocontrast agents prevents the nephrotoxicity associated with these agents (4, 5, 30). The purpose of our study was to evaluate the effect of the concomitant administration of NAC on AmB-induced renal tubular cell apoptosis.(An abstract describing this study was presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, 2006 [22].)Three-week-old male Sprague-Dawley rats weighing 100 g on average were maintained in individual cages. The animals had free access to a standard diet and received water ad libitum. Prior to the experiments, rats were randomized and divided into four groups consisting of 10 animals each. Animals in each of the groups (A, B, C, and D) were treated with 10 mg of intraperitoneal (i.p.) AmB deoxycholate (Bristol-Myers Squibb)/kg of body weight/day for 5 days. In addition to AmB, group A was given i.p. sterile water and groups B, C, and D were ...

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Immunosuppressive therapy is the most crucial treatment of organ-transplanted patients. Both cyclosporin and tacrolimus have become a part of the standard immunosuppressive therapy for prevention of rejection. However, lower levels of these drugs are associated with insufficient therapy and eventually result in rejection of the organ, and, on the contrary, higher levels are associated with toxicity to certain organs such as liver and kidneys. Therefore, the levels of these drugs in body fluids should be monitored for the prevention of unwanted situations. In this retrospective study, the authors evaluated the 18-month profile of blood drug concentrations of cyclosporin and tacrolimus in patients admitted to the TDM Unit of the Marmara University Hospital (Istanbul, Turkey) between June 2000 and November 2001. A total of 578 blood samples (347 cyclosporin and 231 tacrolimus) from 134 patients (88 for cyclosporin, 46 for tacrolimus) were evaluated in this period. The therapeutic trough ranges were accepted as 100-350 ng/mL for cyclosporin and 5-20 ng/mL for tacrolimus, and levels below or above the identified levels were accepted to be subtherapeutic or toxic. Most of the results were found within the range of therapeutic levels (67.48% for cyclosporin and 82.71% for tacrolimus). Subtherapeutic levels were found in 19.92% of all cyclosporin and 10.53% of all tacrolimus assays, whereas toxic levels were seen in 12.60% and 6.77% of cyclosporin and tacrolimus results, respectively. In conclusion, this study gives information about the TDM practice in institutional clinical laboratory and also indicates the importance of critical information such as sampling time for individual decision making in dosage regiment.

The online version of the original article can be found at http:// dx

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