Person: KARAALP, ATİLA
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KARAALP
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ATİLA
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Publication Open Access Impact of a short postgraduate course in rational pharmacotherapy for general practitioners: Rational pharmacotherapy course: impact on GPs(2003-11-14) AKICI, AHMET; Akici, Ahmet; Kalaça, Sibel; Ugurlu, M. Ümit; Karaalp, Atila; Çali, Şanda; Oktay, ŞulePublication Metadata only Distinct functional muscarinic receptors in guinea-pig gallbladder, ileum and atria(ACADEMIC PRESS LTD, 1999) AKICI, AHMET; Karaalp, A; Akici, A; Akbulut, H; Ulusoy, NB; Oktay, SObjective. The contractile responses of guinea-pig gallbladder smooth muscle cells have been suggested to be mediated by M-3 and M-4 muscarinic receptors by different research groups. Therefore, in the present study, several pharmacological properties of cholinergic functions in guinea-pig gallbladder, guinea-pig ileum (mediated via M-3 receptors), and guinea-pig and rat atria (mediated via Mt receptors) were compared, Methods: The isometric contractions of isolated guinea-pig ileum, guinea-pig gallbladder, guinea-pig and rat atrial strips in in vitro organ bath were recorded on a polygraph and the effects of carbachol, oxotremorine, McN-A-343, and clozapine have been investigated. Results: Three muscarinic receptor agonists, carbachol, oxotremorine and McN-A-343 showed different order of potencies in their negative inotropic effects and contractile actions in guinea-pig gallbladder suggesting that functional muscarinic receptors in the gallbladder are distinct from those in the atria, and similar to M-4-subtypes. Clozapine which was shown to have antagonistic affinity for muscarinic M-1, M-2, M-3 and M-5, but partial agonistic affinity for muscarinic M-4 receptors, contracted gallbladder concentration-dependently. On the other hand, clozapine antagonised carbachol-induced ileal and gallbladder contractions and negative inotropic effects indicating that it acts like a partial agonist in the gallbladder. Conclusion: It was concluded that the contractile muscarinic receptors of guinea-pig gallbladder are distinct from those of atria (M-2) and ileum (M-3), but seem to be of M-4 subtype. (C) 1999 Academic Press.Publication Metadata only What do graduates think about a two-week rational pharmacotherapy course in the fifth year of medical education?(CARFAX PUBLISHING, 2003) AKICI, AHMET; Karaalp, A; Akici, A; Kocabasoglu, YE; Oktay, SThe 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.Publication Metadata only Impact of a short postgraduate course in rational pharmacotherapy for general practitioners(WILEY, 2004) AKICI, AHMET; Akici, A; Kalaca, S; Ugurlu, MU; Karaalp, A; Cali, S; Oktay, SAims The 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. Methods GPs were randomly allocated to control and intervention groups. 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. Results At 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. Conclusions Training 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.Publication Metadata only Comparison of rational pharmacotherapy decision-making competence of general practitioners with intern doctors(SPRINGER HEIDELBERG, 2004) AKICI, AHMET; Akici, A; Kalaca, S; Goren, MZ; Akkan, AG; Karaalp, A; Demir, D; Ugurlu, U; Oktay, SObjective. The aim of this study was to compare rational pharmacotherapy decision-making competency of interns (final-year medical students) who had received rational pharmacotherapy education (RPE), with their classmates at another medical school and general practitioners (GPs) who had not been exposed to RPE. Design. A written, objective, structured clinical examination (OSCE), consisting of open and structured questions, was given to all participants. The participants were expected to make a treatment plan and prescribe for simple, uncomplicated beta-hemolytic streptococcal tonsillitis and mild-to-moderate essential hypertension patients, explain their proposed treatment plans and reasons affecting their drug choice. After the OSCE, a questionnaire to assess knowledge of the rational use of drugs was given to the participants. Results. Fifty RPE(+) interns, 54 RPE(-) interns and 53 GPs participated in the study. Mean scores of RPE(+) interns were higher than those of GPs, which were in turn found to be higher than those of RPE(-) interns for all cases. The RPE(+) interns scored the highest regarding all components of rational pharmacotherapy process for all cases of both indications. However, participants in all groups had higher scores for the structured questions compared with the corresponding open ones for both diseases. Prescription analysis also revealed better results for RPE(+) interns regarding the number of drugs/prescription and treatment costs. Conclusion. 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.Publication Metadata only Further evidence for the heterogeneity of functional muscarinic receptors in guinea pig gallbladder(2000) AKICI, AHMET; Akici, A.; Karaalp, A.; Iskender, E.; Christopoulos, A.; El-Fakahany, E. E.; Oktay, S.Previous studies have suggested the presence of multiple muscarinic receptor subtypes in guinea pig gallbladder smooth muscle, although the relative abundance and functional role of these subtypes remains an area of significant research efforts. The present study utilized both radioligand kinetic and functional experiments to further probe the nature of the muscarinic receptors in gallbladder smooth muscle and their mode of coupling to intra- and extra-cellular Ca(2+) sources. Dissociation kinetic studies using [3H]N-methylscopolamine ([3H]NMS) indicated that the binding profile in guinea pig gallbladder smooth muscle could not be reconciled with that expected for a single muscarinic receptor subtype, the latter determined in parallel experiments conducted on the cloned muscarinic M(1)-M(5) subtypes in Chinese hamster ovary (CHO) cells. Furthermore, comparison of the gallbladder data with the dissociation characteristics of [3H]NMS in guinea pig urinary bladder revealed a significantly different kinetic profile, with the urinary bladder, but not the gallbladder, demonstrating biphasic radioligand dissociation kinetics. In functional experiments, carbachol caused a concentration-dependent contraction of guinea pig gallbladder smooth muscle strips in Ca(2+)-free or 5 mM Sr(2+)-substituted physiological salt solutions (PSS) with amplitudes of the maximal contractions corresponding to 45.8+/-8.0% and 33.2+/-6.6% of control responses in normal PSS, respectively. Furthermore, the stimulus-response characteristics of carbachol-mediated contraction appeared significantly altered in Ca(2+)-free PSS relative to normal or Sr(2+)-substituted PSS. The antagonist, methoctramine (1x10(-7)-3x10(-5) M), exerted only a slight inhibition of carbachol (10(-5) M)-induced contractions in 5 mM Sr(2+)-substituted medium, whereas it was significantly more potent in antagonizing gallbladder contractions in response to 10(-5) M carbachol in the absence of extracellular Ca(2+). Both atropine and tripitramine were equipotent in antagonizing carbachol-induced contractions in Ca(2+)-free (pIC(50): 6.85+/-0.11 for atropine and 5.75+/-0.32 for tripitramine) and Sr(2+)-substituted media (pIC(50): 6.88+/-0.25 for atropine and 5.70+/-0.16 for tripitramine), and pirenzepine was only slightly more potent in Ca(2+)-free PSS (pIC(50): 5.66+/-0.23) than in Sr(2+)-substituted PSS (pIC(50): 5.33+/-0.21). Taken together, our data indicate that carbachol contracts guinea pig gallbladder by stimulating two distinct muscarinic receptor subtypes linked to extracellular Ca(2+) influx and intracellular Ca(2+) release. These two subtypes may represent the muscarinic M(3) and M(4) receptors, although the presence of the muscarinic M(2) receptor subtype is also suggested from the binding data.Publication Metadata only Muscarinic M-2 receptors are not primarily involved in the contraction of guinea-pig gallbladder smooth muscle(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 1999) AKICI, AHMET; Akici, A; Karaalp, A; Iskender, E; El-Fakahany, EE; Oktay, SThe presence of M-1-M-4 receptors in guinea-pig gallbladder smooth muscle cells has been reported recently. The majority of these receptors are said to be of M-2 subtype. However, there are controversial reports about the functional muscarinic receptors that mediate contraction in this tissue. Similar to gallbladder, it was claimed that M-4 receptors mediate guinea-pig uterine contractions, but these receptors have appeared to be of M-2 subtypes later. Therefore, the antagonistic affinities of three M-2-selective muscarinic antagonists were determined in contraction and radioligand binding experiments in guinea-pig gallbladder in the present study. The antagonistic affinity Values (pK(i)) of gallamine, tripitramine and imperialine were as follows, respectively: 6.28+/-0.15, 8.65+/-0.10 and 6.55+/-0.07 against 0.250 nM [H-3]QNB binding. All three antagonists displaced the concentration-response curves to carbachol to the right in parallel without affecting the maximum responses. The pA(2) values obtained from constrained Schild plots (-log K-B) were 4.14+/-0.18 for gallamine, 6.79+/-0.09 for tripitramine, and 7.02+/-0.09 for imperialine. The antagonistic affinity values of gallamine, tripitramine and imperialine for M-2 receptors are reported to be 6.3, 9.6, 7.7, respectively. The pA(2) values obtained in this study clearly indicate that the primary muscarinic receptors involved in carbachol-induced guinea-pig gallbladder contraction are not of M-2 subtype. The poor correlation between the antagonistic affinity values of these antagonists obtained at radioligand binding (pK(i)) and contraction (pA(2)) experiments also support the conclusion that the majority of muscarinic receptors which have been reported to be of M-2 do not mediate the contractile responses. (C) 1999 Academic Press.Publication Metadata only Therapeutic drug monitoring of immunosuppressant drugs in Marmara University Hospital(LIPPINCOTT WILLIAMS & WILKINS, 2004) AKICI, AHMET; Karaalp, A; Demir, D; Goren, MZ; Akici, A; Iskender, E; Yananli, HR; Ozyurt, H; Ozkaynakci, A; Berkman, K; Oktay, S; Onat, FImmunosuppressive 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.Publication Metadata only The role of nitric oxide in the reversal of hemorrhagic shock by oxotremorine(2001) AKICI, AHMET; Gören, M. Z.; Akici, A.; Karaalp, A.; Aker, R.; Oktay, S.In the present study, the effect of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methylester (L-NAME), on the antishock actions of oxotremorine was investigated in rats subjected to hemorrhagic shock under urethane anesthesia. L-citrulline production in the AV3V region, as an indicator of nitric oxide (NO) synthesis, was assayed by high-performance liquid chromatography (HPLC) with fluorescent detection throughout the experiment. The rats were pretreated with either intravenous (i.v.) physiological saline or L-NAME (2.5 mg/kg) before bleeding. L-NAME potentiated the reversal of hypotension by oxotremorine (25 microg/kg, i.v.). However, oxotremorine either alone or in combination with L-NAME did not produce any significant change in 60-min survival rate at this low dose. Analysis of microdialysis samples collected from the AV3V region showed that L-citrulline concentration increased during bleeding and that this increase was abolished by L-NAME pretreatment. These results may suggest that nitric oxide production contributes to hypotension in rats bled to shock since nitric oxide levels in the AV3V region increased in response to bleeding and nitric oxide synthase (NOS) inhibition abolished this increase and potentiated the oxotremorine-induced reversal of hypotension.