Specifičnosti farmakokinetike kod starijih pacijenata

Aging represents a very complex biological process that implies specific changes in body composition and physiological functions. Aging can affect drug absorption, distribution, metabolism, and excretion leading to significant changes in plasma drug concentrations, and consequently in drug efficacy and safety profile. Since usually elderly patients suffer from different diseases which require polypharmacy, clinically significant drug interactions are common. When considering setting up the initial or modified drug regimen, individual pharmacokinetic parameters' values are needed. In this article, the newest information regarding clinical pharmacokinetics of drugs in geriatric population of patients is presented.Starenje predstavlja složen biološki proces, koji podrazumeva specifične promene u sastavu i fiziološkim funkcijama organizma. Starost može uticati na procese resorpcije, raspodele, metabolizma i izlučivanja leka uslovljavajući tako značajne promene u koncentraciji leka, a samim tim i promene u efikasnosti i bezbednosti terapije. Kako su u populaciji starijih pacijenata često prisutne pridružene bolesti, od kojih neke zahtevaju hroničnu terapiju, pacijenti su primorani na kombinovanu hroničnu terapiju, što povećava rizik od klinički značajnih interakcija lekova. Pri razmatranju potrebe za postavljanjem ili korigovanjem režima doziranja lekova, neophodna je procena individualnih vrednosti farmakokinetičkih parametara kod pacijenta. U ovom radu su predstavljena dosadašnja saznanja u oblasti kliničke farmakokinetike u gerijatrijskoj populaciji pacijenata

Farmakokinetički aspekti doziranja lekova u pedijatriji

Clinical trials in paediatric patients are limited due to certain practical, ethical and regulatory aspects. Accordingly, after performing pharmacokinetic (PK) and efficacy/safety clinical trials in adults, clinical trials in paediatrics might be carried on by taking into consideration physiological characteristics of neonates, infants, children and adolescents. Physiological changes are reflected in maturation of functional organs and they change PK processes in quantitatively and/or qualitatively manner in comparison to adults that affect drug dosing regimen. The major differences in PK are observed in neonates and infants, while PK in children and adolescents are approaching those in adults and they are easier to predict. When defining dosing regimen both PK characteristics of drug and specific pharmacodynamic features has to be considered. Values of PK parameters, as well as doses are usually based on age, body weight and body surface area. In clinical practice it is recognised concomitant use of age and body weight based dosing regimens. However, clinical practice revealed an evidence for the need to individually adjust dosing regimen to each patient according to his physiological and disease characteristics.Određena praktična, etička i regulatorna ograničenja postoje kada su u pitanju kliničke studije koje uključuju pedijatrijsku populaciju pacijenata. Zbog toga se studije uobičajeno sprovode nakon ispitane farmakokinetike (FK) i efikasnosti/bezbednosti leka u odraslih uz razmatranje fizioloških karakteristika novorođenčadi, odojčadi, dece i/ili adolescenata u zavisnosti od podgrupe pacijenata kojoj je lek namenjen. Fiziološki procesi koji obuhvataju sazrevanje funkcionalnih organa utiču na FK procese i njihov uticaj može biti kvantitativno i kvalitativno različit u odnosu na odrasle, utičući tako na režim doziranja leka. Najveće razlike u FK procesima u odnosu na odrasle pacijente uočene su kod novorođenih beba i odojčadi, dok se kod dece FK procesi približavaju procesima kod adolescenata i odraslih, i lakše ih je predvideti. Specifičnosti u FK leka neophodno je uzeti u obzir prilikom definisanja optimalnog režima doziranja leka, uz razmatranje eventualnih specifičnosti u farmakodinamici leka kod pedijatrijskih pacijenata. Vrednosti FK parametara i režimi doziranja se najčešće definišu na osnovu godina, telesne mase ili površine tela. U kliničkoj praksi se pri definisanju početnih režima doziranja leka koriste godine i telesna masa. Međutim, prepoznata je potreba da se pacijent prati i da se režim doziranja individualno prilagodi svakom pacijentu prema njegovim fiziološkim i karakteristikama bolesti

Clinical and Demographic Characteristics of Patients with Molluscum Contagiosum Treated at the University Dermatology Clinic Maribor in a 5-year period

Molluscum contagiosum virus (MCV) is a common skin pathogen in both adults and children. In this prospective study, we clinically evaluated consecutive patients with molluscum contagiosum (MC) who had been examined during a 5-year period at the second-largest dermatology clinic in Slovenia and described their main demographic and clinical characteristics, concomitant diseases, and treatment success. The study included 188 patients, of which 121 (64%) were men and 67 (36%) were women. A total of 135 (72%) patients were adults, with lesions that were most commonly located in the anogenital region (98%) and were probably sexually acquired. Two adult patients were diagnosed with concurrent human immunodeficiency virus (HIV) infection. Fifty-three (28%) patients were children with a mean age of 5.7 years, most commonly presenting with lesions on the torso and extremities (85%). In adults, the infection most commonly occurred in male patients, while in children it was slightly more common in female patients. At presentation, 58% of patients had more than 5 MC lesions. A total of 30% of the included children had concomitant atopic dermatitis. We did not observe an increased occurrence of MCV infection in patients with atopic dermatitis. All patients were treated with curettage of the lesions. The cure rate at the first follow-up visit after 2 months was relatively high (63%), and recurrences were not associated with the number or site of lesions at presentation or with concomitant atopic dermatitis. </p

Gojaznost kao faktor farmakokinetičke varijabilnosti

Increased prevalence of obesity of the population in the recent years suggests that health professionals will be, in the near future, in a position to provide daily health care services to the obese patients. This population of patients represents a major challenge for health systems, because obese patients are, unfortunately, often excluded from the clinical trials during drug development, and the data on the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs in this population of patients are scarce and incomplete. Since different degrees of obesity may qualitatively and/or quantitatively change the PK of drug, clearly there is a need for the descriptors of size of the organism that best describes the changes in the composition of the organism in obese patients. It is also necessary to define the scalar descriptor that gave the best prediction values of the key PK parameters dosage regimen. This paper provides an overview of the different ways to assess the degree of obesity that are legitimate from the aspects of the PK, then physiological changes that are reflected on the PK processes, and finally this paper gives the examples of individualization of dosage regimen of certain drugs in the obese patients.Povećana prevalenca gojaznosti stanovništva poslednjih godina ukazuje da će zdravstveni radnici u skoroj budućnosti biti u situaciji da svakodnevno pružaju usluge zdravstvene zaštite gojaznim pacijentima. Ova populacija pacijenata predstavlja veliki izazov za zdravstveni sistem, jer su nažalost gojazni pacijenti često isključeni iz kliničkih studija tokom razvoja leka, te su podaci o farmakokinetici (FK) i farmakodinamici (FD) lekova u ovoj populaciji pacijenata malobrojni i nepotpuni. Imajući u vidu činjenicu da različit stepen gojaznosti može na kvalitativno i/ili kvantitativno drugačiji način da utiče na FK karakteristike lekova, jasno se javlja potreba za poznavanjem deskriptora veličine organizma koji na najbolji način opisuje promene u sastavu organizma u gojaznih pacijenata. Takođe je neophodno poznavati koji bi skalarni deskriptor dao najbolje predviđanje vrednosti ključnih FK parametara režima doziranja. U ovom radu dat je osvrt na različite načine procene stepena gojaznosti koje su sa FK aspekta opravdane, potom patofiziološke promene kao rezultat gojaznosti koje se odražavaju na FK procese i na kraju rada su dati primeri individualizacije režima doziranja pojedinih lekova u gojaznih pacijenata

Klinička farmakokinetika inhalacionih kortikosteroida

Corticosteroids, as anti-inflammatory drugs, represent the cornerstone of asthma treatment. Inhalation route provides rapid local effect with simultaneous elimination or minimization of systemic side effects that are associated with oral or parenteral administration. Pharmacokinetic characteristics are of a great importance for efficient and safe therapy. Among individual inhaled corticosteroids the bioavailability from gastrointestinal tract and lungs differ, and these parameters influence systemic bioavailability and hence potential for adverse drug reactions. Besides, pharmacokinetic characteristics that enhance safety profile of these drugs include on-site activation, high protein binding and rapid systemic clearance. Moreover, liposolubility and lipid esterification are pharmacokinetic characteristics affect pulmonary retention time, and hence are important for the efficacy.Kortikosteroidi, kao antiinflamatorni lekovi, predstavljaju okosnicu terapije astme. Inhalacionim putem se obezbeđuje brzo postizanje lokalnog delovanja na ciljnom mestu uz istovremeno izbegavanje ili smanjenje sistemskih neželjenih reakcija u poređenju sa per os ili parenteralnim putem primene. Poznavanje farmakokinetičkih karakteristika inhalacionih kortikosteroida je od velikog značaja za efikasnu i bezbednu terapiju. Između pojedinačnih lekova ove grupe razlikuju se vrednosti stepena resorpcije iz gastrointestinalnog trakta i pluća koje utiču na sistemsku biološku raspoloživost i tako na potencijal leka za ispoljavanje neželjenih reakcija. Osim toga farmakokinetičke karakteristike od značaja za bezbednost inhalacionih kortikosteroida obuhvataju aktivaciju leka na nivou mesta delovanja, visok stepen vezivanja leka za proteine plazme i visoke vrednosti ukupnog klirensa. Razmatranje farmakokinetičkih karakteristika u svetlu efikasnosti pokazuje da liposolubilnost i masna esterifikacija inhalacionih kortikosteroida utiču na duže vreme zadržavanja leka na nivou pluća

Integrated process planning and scheduling in dynamic environment: The state-of-the-art

U ovom radu je dat detaljan pregled stanja u oblasti istraživanja jedne od funkcija inteligentnih tehnoloških sistema (ITS) - integrisano planiranje i terminiranje tehnoloških procesa u dinamičkim uslovima (DIPPS). U tom smislu, datje opis DIPPSproblema, razmatrani su kriterijumi na osnovu kojih se vrši odabir optimalanog plana terminiranja, definisane su usvojene pretpostavke i predstavljen je matematički model ovog problema. Takođe, detaljno su razmatrani i sledeći poremećajni faktori koji se mogu javiti u okviru tehnoloških sistema: (i) prestanak rada mašine alatke, (ii) dolazak novog dela u sistem i (iii) otkaz obrade dela. Analizirani su pristupi za rešavanje DIPPS problema bazirani na multiagentnim sistemima, kao i pristupi bazirani na algoritmima. Kada su u pitanju pristupi bazirani na algoritmima, fokus u ovom radu je na biološki inspirisanim algoritmima optimizacije i to: evolucionim algoritmima, algoritmima baziranim na inteligenciji roja, kao i hibridnim pristupima. Kritičkom analizom stanja u ovoj oblasti istraživanja može se zaključiti da biološki inspirisane tehnike veštačke inteligencije imaju veliki potencijal u optimizaciji pomenute funkcije ITS-a.This paper gives a detailed state-of-the art in the research area o f the important function o f Intelligent Manufacturing Systems (IMS) - integrated process planning and scheduling o f manufacturing systems in dynamic environment (DIPPS). Referring to this, description o f the DIPPS problem is given, the criteria on the basis o f which the optimal rescheduling plan are formulated and considered, the adopted assumptions are defined and the mathematical model o f this problem is presented. Furthermore, the disturbances that occur in manufacturing systems are considered in detail: (i) machine breakdown, (ii) arrival of a new job and (iii) job cancellation. Approaches for solving DIPPS problems based on multiagent systems as well as approaches based on algorithms are analyzed. When it comes to approaches based on algorithms, the focus of this paper is on biologically inspired optimization algorithms: evolutionary algorithms, swarm intelligence based algorithms as well as hybrid approaches. The critical analysis within this research area is shown in order to conclude that biologically inspired artificial intelligence techniques have great potential in optimizing the considered IMS function

Integrated process planning and scheduling in dynamic environment: The state-of-the-art

U ovom radu je dat detaljan pregled stanja u oblasti istraživanja jedne od funkcija inteligentnih tehnoloških sistema (ITS) - integrisano planiranje i terminiranje tehnoloških procesa u dinamičkim uslovima (DIPPS). U tom smislu, datje opis DIPPSproblema, razmatrani su kriterijumi na osnovu kojih se vrši odabir optimalanog plana terminiranja, definisane su usvojene pretpostavke i predstavljen je matematički model ovog problema. Takođe, detaljno su razmatrani i sledeći poremećajni faktori koji se mogu javiti u okviru tehnoloških sistema: (i) prestanak rada mašine alatke, (ii) dolazak novog dela u sistem i (iii) otkaz obrade dela. Analizirani su pristupi za rešavanje DIPPS problema bazirani na multiagentnim sistemima, kao i pristupi bazirani na algoritmima. Kada su u pitanju pristupi bazirani na algoritmima, fokus u ovom radu je na biološki inspirisanim algoritmima optimizacije i to: evolucionim algoritmima, algoritmima baziranim na inteligenciji roja, kao i hibridnim pristupima. Kritičkom analizom stanja u ovoj oblasti istraživanja može se zaključiti da biološki inspirisane tehnike veštačke inteligencije imaju veliki potencijal u optimizaciji pomenute funkcije ITS-a.This paper gives a detailed state-of-the art in the research area o f the important function o f Intelligent Manufacturing Systems (IMS) - integrated process planning and scheduling o f manufacturing systems in dynamic environment (DIPPS). Referring to this, description o f the DIPPS problem is given, the criteria on the basis o f which the optimal rescheduling plan are formulated and considered, the adopted assumptions are defined and the mathematical model o f this problem is presented. Furthermore, the disturbances that occur in manufacturing systems are considered in detail: (i) machine breakdown, (ii) arrival of a new job and (iii) job cancellation. Approaches for solving DIPPS problems based on multiagent systems as well as approaches based on algorithms are analyzed. When it comes to approaches based on algorithms, the focus of this paper is on biologically inspired optimization algorithms: evolutionary algorithms, swarm intelligence based algorithms as well as hybrid approaches. The critical analysis within this research area is shown in order to conclude that biologically inspired artificial intelligence techniques have great potential in optimizing the considered IMS function

Interakcije kardiovaskularnih lekova u terapiji ishemijske bolesti srca

Treatment of ischaemic heart disease usually comprises concomitant use of several drugs and therefore, the potential of drug interactions in this patient population is substantial. If non-prescription drugs are reviewed, as well, it is clear that the efficacy and/or safety of therapy may be jeopardized in many patients. Studies show that much more attention should be paid to the problem of interactions and their consequences in clinical practice, since the majority of patients with ischaemic disease are prescribed at least one interacting combination of drugs. Due to knowledge and competencies it is primarily the role of pharmacist within the health care team, to identify and manage drug interactions in association with other health care professionals. It is also the role of pharmacist to educate the patient how to manage potential interactions appropriately. In this work, clinically significant cardiovascular drug interactions will be outlined as well as their underlying interaction mechanism and management for providing efficient and safe pharmacotherapy.Pacijenti sa ishemijskom bolesti srca često primenjuju više lekova istovremeno čime je potencijal lek-lek interakcija u ovoj populaciji značajan. Ukoliko se u razmatranje uzmu i lekovi koji se izdaju bez recepta, jasno je da su efikasnost i bezbednost farmakoterapije kod velikog broja pacijenata potencijalno ugrožene. Studije pokazuju da se problemu interakcija lekova i posledicama koje usled takvih interakcija mogu nastati, posvećuje nedovoljna pažnja u kliničkoj praksi, s obzirom da većina pacijenata na terapiji ishemijske bolesti srca primenjuje najmanje jednu kombinaciju lekova koji stupaju u interakciju. Kompetencije u identifikaciji i prevenciji klinički značajnih interakcija kardiovaskularnih i drugih lekova u značajnoj meri pripadaju farmaceutu u saradnji sa ostalim članovima zdravstvenog tima. Takođe je uloga farmaceuta da pacijentu pruži odgovarajuće informacije u cilju prevencije negativnih posledica interakcija. U okviru ovog rada biće detaljnije reči o klinički značajnim interakcijama kardiovaskularnih lekova, mehanizmima njihovog nastanka kao i intervencijama neophodnim kako bi se obezbedila efikasna i bezbedna farmakoterapija

Towards development of DC servo motor intelligent control by applying artificial neural networks

U radu je prikazan mogući pristup inteligentnog upravljanja servo motora jednosmerne struje korišćenjem veštačkih neuronskih mreža. Pored primene jedne od najzastupljenijih tehnika veštačke inteligencije, u radu je predloženo i dato matematičko modelovanje ovog široko zastupljenog objekta automatskog upravljanja. Takođe, u cilju prevazilaženja nedostataka vezanih za konvencionalno upravljanje servo motora jednosmerne struje, u radu su iskorišćene sposobnosti veštačkih neuronskih mreža da mogu da generalizuju i aproksimiraju izlaze ovog objekta primenom mašinskog učenja kroz proces njihovog obučavanja. Predloženi pristup, prvo je analiziran putem simulacije, a potom je i eksperimentalno verifikovan na primeru dva od četiri modela koji su razmatrani.In this paper the possible approach of DC servo motor intelligent control is presented by using artificial neural networks. Besides the application of one of the most important techniques of artificial intelligence, this paper suggests and gives the mathematical modelling of widely used object of automatic control. Also, this paper uses abilities of artificial neural networks in order to generalize and approximate the outputs of this object by applying machine learning through the process of its training, aiming to overcome the faults connected to the conventional control of the DC servo motor. The suggested approach, was analyzed firstly by simulation, and then it was experimentally verified in two out of four models which were taken into consideration

Klinički značajne interakcije antibiotika i antimikotika sa drugim lekovima

Antibiotics (AB) and antifungals are large, heterogeneous, and commonly prescribed groups of drugs. Even thou, their use in therapy are considered to be safe, during concomitant use with other drugs the result can be clinically important interaction. Certain classes of AB or antifungal drugs are known to interact with many other drugs, but the interaction potential of them is not uniform among members of the class. Therefore, choosing the appropriate drug allows the possibility to avoid potentially dangerous drug-drug interactions.Antibiotici (AB) i antimikotici predstavljaju velike, heterogene i često propisivane grupe lekova. Iako se smatraju za relativno bezbedne lekove, pri istovremenoj primeni sa drugim lekovima mogu da stupe u klinički značajne interakcije. Određene grupe AB i antimikotika su poznate da stupaju u interakcije, ali potencijal za stupanje u interakcije unutar istih klasa lekova je različit, što pruža mogućnost da se odgovarajućim odabirom AB odnosno antimikotika izbegnu potencijalno štetne lek-lek interakcije