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    Synthesis and characterization of harmicines

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    Harmin i derivati cimetne kiseline pokazuju širok spektar farmakološkog djelovanja, među kojima je i antimalarijsko djelovanje. Njihovim povezivanjem nastaju harmicini te je cilj ovog rada bila sinteza i karakterizacija dva nova hibrida harmina i derivata cimetne kiseline povezana karbamatnom skupinom. Sintetski put uključivao je alkiliranje harmina i uklanjanje zaštitne skupine kako bi se dobio željeni amin 2, sintezu odgovarajućeg alkohola 5 te sintezu harmicina 6 i 7 pomoću CDI-a (Shema). Svim novosintetiziranim spojevima struktura je potvrđena uobičajenim analitičkim i spektroskopskim metodama (IR, 1H i 13C NMR, MS) te im je određena temperatura tališta. U daljnjim ispitivanjima, koja nadilaze okvir ovog rada, sintetiziranim derivatima ispitat će se antimalarijsko djelovanje.Harmine and cinnamic acid derivatives (CAD) show a wide range of pharmacological activities, including antimalarial activity. Harmicines represent hybrids composed of harmine and CAD moieties and the aim of this thesis was the synthesis and characterization of two new carbamatetype harmicines. The synthetic pathway included alkylation of harmine and removal of the Bocprotecting group to obtain the desired amine 2, synthesis of the alcohol 5 and finally, synthesis of harmicines in the presence of CDI. The structures of the newly synthesized compounds were confirmed using conventional analytical and spectroscopic methods (IR, 1H i 13C NMR, MS) and their melting points were determined. Subsequent studies, which surpass this thesis, will determine antimalarial activity of the synthesized derivatives

    Phytochemical composition and antioxidant activity of cornelian cherry fruit (Cornus mas L.)

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    U okviru ovog diplomskog rada istraženi su fitokemijski sastav i antioksidacijska svojstva ploda vrste Cornus mas. Metodom tankoslojne kromatografije u drogi je dokazana prisutnost fenolnih kiselina i antocijana. Spektrofotometrijskim metodama određeno je da ekstrakt drijenovog ploda sadrži 0,32 % fenolnih kiselina, 0,06 % antocijana, 0,21 % trjeslovina te 0,03% flavonoida. Antioksidacijski potencijal ekstrakta drijenovog ploda vrednovan je na temelju sposobnosti hvatanja slobodnih radikala i uspoređen s aktivnošću referentnih antioksidansa (askorbinska kiselina i kvercetin). Utvrđeno je da etanolno-vodeni ekstrakt droge posjeduje sposobnost hvatanja slobodnih DPPH radikala te ostvaruje 50%-tnu učinkovitost pri koncentraciji 76,14 μg/mL. Za razliku od čistih antioksidansa, ispitivani ekstrakt drijenovog ploda nije pokazao značajnu sposobnost hvatanja NO radikala. Dobiveni rezultati doprinose znanstvenim spoznajama o bioaktivnim sastavnicama i antioksidacijskom potencijalu drijena koji raste u Hrvatskoj.In this work, phytochemical composition and antioxidant properties of Cornus mas fruit were studied. Thin-layer chromatography revealed the presence of phenolic acids and anthocyanins in the studied fruit. It was determined by spectrophotometric methods that the cornelian cherry fruit extract contains 0.32% phenolic acids, 0.06% anthocyanins, 0.21 % tannins and 0.03% flavonoids. The antioxidant potential of the extract was evaluated based on the ability to scavenge free radicals and was compared with the activity of reference antioxidants (ascorbic acid and quercetin). It was established that the cornelian cherry fruit extract posses the ability to scavenge DPPH free radicals and achieves 50% efficiency at concentration 7 6.14 μg/mL. In contrast to reference antioxidants, the investigated plant extract did not show significant ability to scavenge NO radicals. The obtained results contribute to scientific knowledge on the bioactive compounds and antioxidant potential of cornelian cherry fruit originating from Croatia

    Study o α-glucosidase inhibition by selected polyphenols

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    Šećerna bolest kronični je metabolički poremećaj sa sve većim brojem oboljelih. Kao jedan od vodećih uzroka smrtnosti u svijetu predstavlja značajan javnozdravstveni problem. Prevencija, rano otkrivanje te adekvatna terapija su ključne za sprječavanje progresije bolesti i njezinih komplikacija. Bioakivne tvari iz biljaka se sve više istražuju zbog potencijalnih antidijabetičkih svojstava, a manje neželjenih učinaka u odnosu na konvencionalno dostupne antidijabetike. Sposobnost inhibicije α-glukozidaze jedno je od tih poželjnih svojstava budući da smanjivanjem i usporavanjem apsorpcije glukoze doprinosi kontroli postprandijalne hiperglikemije. Cilj ovog rada bio je provesti usporedno ispitivanje sposobnosti odabranih polifenola da inhibiraju aktivnost enzima α-glukozidaze te pronaći poveznicu između učinka i strukturnih obilježja ispitivanih spojeva. Među flavonoidima, najučinkovitijim su se pokazali flavonoli koji imaju dvostruku C2=C3 vezu, hidroksilnu skupinu na C-3 i karbonilnu skupinu na C-4 u središnjem heterocikličnom prstenu C te hidroksilirani aromatski prsten B. Flavonol miricetin (IC50 63,84 μg/mL), kao jedini ispitani 3',4',5'-trihidroksilirani spoj, pokazao se snažnijim inhibitorom enzima u odnosu na di- i monohidroksilirane flavonoide u prstenu B. Fenolne kiseline su se pokazale značajno slabijim inhibitorima enzima u usporedbi s flavonoidima, a na učinak je utjecao stupanj hidroksilacije i metoksilacije aromatskog prstena. Od svih ispitivanih polifenola, stilben resveratrol je pokazao najveću sposobnost inhibicije α-glukozidaze.Diabetes is a chronic metabolic disease with an increasing number of patients. As one of the leading causes of death worldwide, it is a significant public health problem. Prevention, early detection and appropriate therapy are key to prevent the progression of the disease and its complications. Therefore, bioactive plant compounds are increasingly being investigated for their potential antidiabetic properties, with fewer side effects compared to conventional antidiabetic drugs. The ability to inhibit α-glucosidase is one of these desirable properties, as it contributes to the control of postprandial hyperglycemia by reducing and slowing the absorption of glucose uptake. The aim of this study was to comparatively investigate the ability of selected polyphenols to inhibit the activity of the α-glucosidase enzyme and to establish a link between the effect and the structural properties of the compounds. Among flavonoids, flavonols with a C2=C3 double bond, a hydroxyl group at C-3 and a carbonyl group at C-4 in the central heterocyclic ring C and the hydroxylated aromatic ring B were found to be the most effective inhibitors. The flavonol myricetin (IC50 63.84 μg/mL), proved to be the only 3',4',5'-trihydroxylated compound tested, as a more potent inhibitor of the enzyme compared to di- and monohydroxylated flavonoids at ring B. Phenolic acids were much weaker enzyme inhibitors compared to flavonoids, and the effect was influenced by the degree of hydroxylation and methoxylation of the aromatic ring. Of all the polyphenols studied, stilbene resveratrol showed the greatest ability to inhibit α-glucosidase

    Posebnosti primjene antipsihotika kod djece i adolescenata

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    Cilj istraživanja: Cilj ovog rada je ukazati na posebnosti primjene antipsihotika kod djece i adolescenata te naglasiti činjenicu da djeca nisu “odrasli u malom” nego populacija s različitim stupnjem neurorazvoja i različitim farmakokinetskim i farmakodinamičkim svojstvima lijekova koji se pritom i značajno mijenjaju od dojenačke dobi do srednje i kasne adolescencije. U radu je iznesen pregled antipsihotika odobrenih za primjenu kod djece i adolescenata temeljem relevantnih znanstvenih istraživanja.Također rad će se osvrnuti na važnost uloge koju ljekarnici, kao najdostupniji zdravstveni djelatnici, mogu imati prilikom primjene antipsihotika u navedenoj populaciji. Metode: Napravljen je sustavni i retrospektivni pregled znanstvene i stručne literature, pretražene su trenutno važeće terapijske smjernice, publikacije stručnih udruga i institucija, baza lijekova Agencije za lijekove i medicinske proizvode te drugi raspoloživi izvori prema ključnim riječima od interesa. Rezultati: U ovom radu dan je pregled antipsihotika odobrenih za primjenu kod djece i adolescenata. Istaknute su specifičnosti vezane uz primjenu pojedinih lijekova te pripadajuća relevantna znanstvena istraživanja uz svaki lijek. Naglašena je važnost uključivanja kliničkih farmaceuta kako bi se poboljšali ishodi liječenja. Zaključak: Djeca i adolescenti čine posebnu i osjetljivu skupinu u ukupnoj populaciji ponajprije zbog lijekova koji imaju različita farmakokinetička svojstva u odnosu na odrasle osobe. Međutim, mali je broj relevantih randomiziranih kontroliranih kliničkih ispitivanja koji su bitni za sigurnost i učinkovitost primjene pojedinog lijeka u ovakvoj populaciji. Potrebno je naglasiti bitnu ulogu kliničkog farmaceuta koji sa svojim stručnim kompetencijama može biti od velike pomoći u pružanju informacija o lijeku (doziranje, nuspojave, interakcije) roditeljima i skrbnicima, koji naposlijetku svojim pristankom odobravaju primjenu lijeka djetetu. Nužno je i potrebno kliničke farmaceute stalno usavršavati kako bi uz liječnika činili jedan snažan i učinkovit tim potreban za brojne izazove koje im struka iz dana u dan zadaje.Aim: The aim of this paper is to point out the particularities of the use of antipsychotics in children and adolescents and to emphasize the fact that children are not "small adults" but a population with a completely different level of neurodevelopment and different pharmacokinetic and pharmacodynamic properties that change significantly from infancy to middle and late adolescence. The paper presents an overview of antipsychotics approved for use in children and adolescents in the Republic of Croatia, along with related relevant scientific research. The study will also look at the importance of the role that pharmacists, as the most accessible healthcare professionals, can play when administering antipsychotics in the aforementioned population. Subjects and method: For this purpose, a systematic and retrospective review of scientific and professional literature was made, currently valid therapeutic guidelines, publications of professional associations and institutions, the drug database of the Agency for Medicines and Medical Products and other available sources were searched. Results: This paper provides an overview of antipsychotic drugs approved for use in children and adolescents in the Republic of Croatia. The specifics related to the use of certain drugs in children and adolescents and the associated relevant scientific research with each drug are highlighted. The importance of involving clinical pharmacists in order to improve adherence was emphasized. Conclusion: Children and adolescents constitute a special and sensitive group in the total population, primarily due to different pharmacodynamic and pharmacokinetic properties compared to adults. Accordingly, there is a small number of relevant randomized controlled clinical trials that are essential for the safety and effectiveness of the use of a particular drug in this population. We must not forget the important role of the clinical pharmacist, who with his professional competences can be of great help in providing information about the drug (dosage, side effects, interactions) to the parents, who ultimately approve the administration of the drug to the child with their consent. It is necessary and necessary to constantly train clinical pharmacists so that, together with the doctor, they form a strong and efficient team necessary for the numerous challenges that the profession gives them every day

    Optimization of MEKC-MS/MS detection conditions for the simultaneous determination of six drugs in breast cancer therapy

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    Rak dojke najčešća je zloćudna bolest kod žena. U današnje vrijeme mortalitet mu opada zbog novih terapijskih metoda, unatoč trajnom porastu incidencije. Kako bi se osiguralo pravilno doziranje terapije koje će osigurati najbolju učinkovitost lijeka te njegove nuspojave svesti na minimum, važno je pratiti koncentracije lijekova u plazmi. Kod ispitivanja bioloških uzoraka, važno je da metoda bude osjetljiva kako bi mogla detektirati analite niskih koncentracija te ih također učinkovito razdvojiti od interferencija koje su također prisutne. U ovome radu, analiti su bili šest lijekova za rak dojke: ribociklib, abemaciklib i palbociklib kao CDK4/6 inhibitori, anastrozol i letrozol kao nesteroidni inhibitori aromataze te fulvestrant kao kompetitivni antagonist ER. U literaturi još nije opisana uporaba MEKCMS/MS u analizi ovih lijekova. Cilj ovoga rada bio je odrediti optimalne MS/MS uvjete kako bismo osigurali zadovoljavajuću osjetljivost metode i kvantifikaciju ovih lijekova. Optimizirani uvjeti bili su: temperatura (75- 250 °C) i protok pomoćnog plina (3-11 L/min), protok (2-12 μL/min) i sastav pomoćne tekućine - prikladno organsko otapalo (metanol, izopropanol, etanol, acetonitril), njegov udio (50-80%, v/v) i sadržaj mravlje kiseline (0-0,5%, v/v). Također su optimizirani napon mlaznice (0-2000 V) i napon kapilare (2000-4000 V). Parametri plina u ESI izvoru koji su optimizirani uključuju temperaturu (200-350 °C), protok (5-11 L/min) i tlak plina za raspršivanje (6-14 psi). Dobiveni su sljedeći rezultati: optimalna temperatura pomoćnog plina je 250°C, a njegov protok 5 L/min. Kao najbolje organsko otapalo u sastavu pomoćne tekućine pokazao se metanol i to u udjelu od 70%. Optimalni udio mravlje kiseline u pomoćnoj tekućini je 0,2%, a protok pomoćne tekućine 1 mL/min. Optimalni napon mlaznice je 2000 V, a napon kapilare 2500 V. Parametri plina u ESI izvoru su: temperatura 350 °C, protok 9 L/min i tlak plina za raspršivanje 12 psi.Breast cancer is the most common malignant disease in women. Nowadays, its mortality rate is decreasing due to new therapeutic methods, despite a continuous increase in incidence. To ensure proper dosing of therapy that will maximize drug efficacy and minimize side effects, it is important to monitor drug concentrations in plasma. When analyzing biological samples, it is essential for the method to be sensitive enough to detect analytes at low concentrations and effectively distinguish them from interfering substances that are also present. In this study, the analytes were six breast cancer drugs: ribociclib, abemaciclib, and palbociclib as CDK4/6 inhibitors, anastrozole and letrozole as non-steroidal aromatase inhibitors and fulvestrant as a competitive ER antagonist. The use of MEKCMS/MS in the analysis of these drugs has not yet been described in the literature. The aim of this study was to determine the optimal MS/MS conditions to ensure satisfactory method sensibility and quantification of these drugs. The optimized conditions were: temperature (75-250 °C) and sheath gas flow (3-11 L/min), flow rate (2-12 μL/min) and sheath liquid composition - suitable organic solvent (methanol, isopropanol, ethanol, acetonitrile), its proportion (50-80%, v/v) and formic acid content (0-0.5%, v/v). Nozzle voltage (0-2000 V) and capillary voltage (2000-4000 V) were also optimized. The ESI source gas parameters which were optimized are temperature (200-350 °C), flow (5-11 L/min) and nebulizing gas pressure (6-14 psi). The following results were obtained: the optimal sheath gas temperature is 250°C, with a flow rate of 5 L/min. Methanol at a concentration of 70% proved to be the best organic solvent in the composition of the sheath liquid. The optimal formic acid content in the sheath liquid is 0.2%, with a sheath liquid flow rate of 1 mL/min. The optimal nozzle voltage is 2000 V, while the capillary voltage is 2500 V. The ESI source gas parameters are: temperature 350°C, flow rate 9 L/min, and nebulizing gas pressure 12 psi

    Novel pharmacotherapy possibilities for treatment of Alzheimer disease

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    Alzheimerova bolest (AD) je progresivna neurodegenerativna bolest koja uzrokuje značajan pad kognitivnih funkcija i kvalitete života oboljelih. Ovaj diplomski rad istražuje farmakoterapijske mogućnosti liječenja AD-a, uključujući postojeće i nove pristupe. Rad se fokusira na nekoliko ključnih aspekata: 1. Inhibitori acetilkolinesteraze: Donepezil, rivastigmin i galantamin su odobreni lijekovi koji djeluju povećanjem razine acetilkolina u mozgu, što može privremeno poboljšati ili stabilizirati simptome AD-a. 2. Antagonisti NMDA receptora: Memantin je lijek koji se koristi za liječenje umjerene do teške AD-a, djelujući na glutamatni sustav kako bi se smanjila neurotoksičnost. 3. Prirodni nootropici: Istraženi su prirodni spojevi poput ginka, ginsenga, bakope i kurkume, koji imaju potencijalne neuroprotektivne učinke. 4. Novija saznanja iz kliničkih studija: Proučeni su novi lijekovi poput adukanumaba, lekanemaba, donanemaba i AXS-05 koji ciljaju različite patofiziološke mehanizme AD-a, uključujući smanjenje amiloidnih plakova i upalnih procesa. Zaključno, unatoč trenutnom nedostatku lijeka koji bi mogao zaustaviti ili preokrenuti tijek AD-a, istraživanja u farmakoterapiji pružaju nadu za budućnost u smislu boljeg upravljanja simptomima i poboljšanja kvalitete života oboljelih. Potrebna su daljnja istraživanja kako bi se razvili učinkoviti tretmani koji bi ciljali temeljne uzroke bolesti.Alzheimer's disease (AD) is a progressive neurodegenerative disorder that significantly impairs cognitive functions and quality of life. This thesis explores the pharmacotherapeutic options for treating AD, including existing and emerging approaches. The study focuses on several key aspects: 1. Acetylcholinesterase inhibitors: Donepezil, rivastigmine, and galantamine are approved drugs that work by increasing acetylcholine levels in the brain, which can temporarily improve or stabilize AD symptoms. 2. NMDA receptor antagonists: Memantine is used for moderate to severe AD, acting on the glutamate system to reduce neurotoxicity. 3. Natural nootropics: Natural compounds such as ginkgo, ginseng, bacopa, and turmeric are explored for their potential neuroprotective effects. 4. Recent findings from clinical studies: New drugs like aducanumab, lecanemab, donanemab, and AXS-05 are studied, targeting various AD pathophysiological mechanisms, including reducing amyloid plaques and inflammatory processes. In conclusion, despite the current lack of a cure to halt or reverse AD progression, pharmacotherapy research offers hope for better symptom management and improved quality of life for patients. Further research is needed to develop effective treatments targeting the underlying causes of the disease

    Izolacija i identifikacija eteričnog ulja sredozemnog smilja - Helichrysum italicum (Roth) G. Don

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    Cilj istraživanja Cilj je ovog specijalističkog rada provesti izolaciju i identifikaciju eteričnog ulja sredozemnog smilja - Helichrysum italicum (Roth) G. Don s različitih lokacija na hrvatskim otocima. Materijali i metode Sadržaj eteričnog ulja u osušenim cvjetovima sredozemnog smilja određen je metodom destilacije pomoću vodene pare. Identifikacija izoliraronog eteričnog ulja provedena je primjenom plinske kromatografije i spektrometrije masa (GC-MS). Rezultati Iz cvjetova sredozemnog smilja s otoka Visa, Paga i Cresa izolirano je 2,5-4 mL/kg eteričnog ulja. Identificirano je 70 sastavnica koje su činile 89,96-98,05% pojedinog eteričnog ulja. Glavne sastavnice eteričnog ulja uzorka s otoka Visa bili su -pinen (26,80 %) i -kurkumen (20,33 %). Uzorak s otoka Paga sadržavo je najviše -pinena (11,91 %) i neril-acetata (11,13 %). Najveći udio neril-acetata (16,03 %) određen je u eteričnom ulju s otoka Cresa koje je sadržavalo i značajne količine -selinena (11,98 %). Zaključci Ustanovljene razlike u udjelima i kromatografskim profilima analiziranih eteričnih ulja najvjerojatnije su vezane za određeni genotip, razvojni stadij biljke, vegetacijsko razdoblje u kojem je prikupljen biljni materijal te su posljedica klimatskih i ekoloških čimbenika na lokacijama sabiranja kao i primijenjene metode izolacije.Objectives The aim of this study is to isolate and identify the essential oil of immortelle - Helichrysum italicum (Roth) G. Don from different locations on the Croatian islands. Materials and methods The essential oil content of the dried immortelle flowers was determined by steam distillation. The essential oil Immortelle was identified by gas chromatography and mass spectrometry (GC-MS). Results From the flowers of immortelle collected on the islands of Vis, Pag and Cres, 2.5-4 mL/kg of essential oil was isolated. Seventy components were identified, accounting for 89.96-98.05% of each essential oil. The main components of the essential oil sample from the island of Vis were -pinene (26.80 %) and -curcumene (20.33 %). The sample from the island of Pag contained the most -pinene (11.91 %) and neryl acetate (11.13 %). The highest proportion of neryl acetate (16.03 %) was found in the essential oil from the island of Cres, which also contained significant amounts of -selinene (11.98 %). Conclusion The observed differences in the yields and chromatographic profiles of the essential oils analysed are most likely related to a specific genotype, the developmental stage of the plant and the growing season in which the plant material was collected, and are a consequence of the climatic and environmental factors at the place of collection and the isolation method used

    Software comparison in the molecular analysis of Fragile X Syndrome

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    Sindrom fragilnog X kromosoma najčešći je nasljedni oblik mentalne retardacije i poteškoća u razvoju. Posljedica je dinamičke mutacije u FMR1 genu X kromosoma koja se očituje ekspanzijom CGG ponavljajućeg slijeda u 5'-nekodirajućoj regiji gena. S obzirom na broj CGG ponavljanja, razlikuju se četiri klase alela: normalni (5-44 CGG), intermedijarni (45-54 CGG), premutacijski (55-200 CGG) te aleli s punom mutacijom (>200 CGG). U sindromu fragilnog X karakterističan je i mozaicizam, prisutnost različitih alela u različitim subpopulacijama stanica. Cilj ovog rada bio je usporediti rezultate dobivene pomoću GeneMapper i AmplideX Reporter softwarea te utvrditi može li automatizirani AmplideX Reporter zamijeniti GeneMapper software u rutinskoj dijagnostici. Analizirano je ukupno 130 uzoraka, uključujući 129 uzoraka pacijenata i 1 negativan kontrolni uzorak. Analizirani uzorci obuhvaćali su sve četiri kategorije alela, dok je u 3 uzoraka utvrđen mozaicizam. U 41 uzorku pronađene su razlike u broju ponavljanja za 1 ili 2 CGG tripleta između dva programa što, međutim, ne predstavlja klinički značajnu razliku. U AmplideX Reporter softwareu uočen je rascjep alela u 19 uzoraka te su detektirani dodatni pikovi u 11 uzoraka. Usporedbom je utvrđena veća osjetljivost i specifičnost AmplideX Reporter softwarea u otkrivanju mozaicizama zbog automatskog izračuna broja CGG ponavljanja s obzirom na CGG profil i ROX ljestvicu veličine te razmatranja kontrole kvalitete prilikom analize. Potrebna je optimizacija sustava kako bi u potpunosti bila zadovoljena kontrola kvalitete svakog analiziranog uzorka te se osigurala točnost dobivenih rezultata.Fragile X syndrome is the most common inherited form of mental retardation and developmental disorders. It results from a dynamic mutation in the FMR1 gene on the X chromosome, characterized by the expansion of a CGG repeat sequence in the 5'-untranslated region of the gene. Based on the number of CGG repeats, four allele classes are distinguished: normal (5-44 CGG), intermediate (45-54 CGG), premutation (55-200 CGG), and full mutation (>200 CGG). The syndrome is also characterized by mosaicism, the presence of different alleles in different subpopulations of cells. The aim of this study was to compare the results obtained using GeneMapper and AmplideX Reporter software and to determine whether the automated AmplideX Reporter can replace GeneMapper software in routine diagnostics. A total of 130 samples were analysed, including 129 patient samples and 1 negative control sample. The analysed samples covered all four categories of alleles, and mosaicism was detected in 3 samples. Differences in the number of repeats by 1 or 2 CGG triplets between the two programs were found in 41 samples but with no significance in clinical interpretation. In the AmplideX Reporter software, allele splitting was observed in 19 samples, and additional peaks were detected in 11 samples. The comparison showed greater sensitivity and specificity of the AmplideX Reporter software in mosaicism detection due to its automatic calculation of the number of CGG repeats based on the CGG profile and ROX size ladder, as well as its consideration of quality control during the analysis. System optimization is needed to fully satisfy the quality control requirements for each analysed sample and to ensure the accuracy of the obtained results

    The safety of the use of multivitamin-mineral dietary supplements

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    Multivitaminsko-mineralni (MVM) dodaci prehrani popularni su i široko korišteni dodaci prehrani u općoj populaciji. Sadrže vitamine i minerale različitih sastava, količina sastavnica i karakteristika te se koriste kao pomoć u dodatnom unosu esencijalnih mikronutrijenata u organizam te za podržavanje specifičnih funkcija u organizmu kod određenih stanja pacijenata ili u posebnim skupinama pacijenata. Iako su vrlo popularni, primjena MVM dodataka prehrani nije u potpunosti bez rizika za zdravlje pacijenata. Poznato je da vitamini i minerali, kao sastavnice MVM dodataka prehrani, mogu ulaziti u različite interakcije s lijekovima i zdravstvenim stanjima pacijenata. Također, važno je imati na umu raspon doza optimalnog unosa vitamina i minerala te sigurnost primjene istih u posebnim skupinama pacijenata što uključuje djecu, trudnice i dojilje. Sve navedeno može uzrokovati smanjenje ili povećanje učinaka lijekova ili sastavnica MVM dodataka prehrani ili može povećati rizik od nastanka štetnih ishoda kod pacijenata. U ovom diplomskom radu pružen je sustavni pregled i detaljna objašnjenja najvažnijih interakcija vitamina i minerala, kao sastavnica MVM dodataka prehrani, s lijekovima i zdravstvenim stanjima pacijenata te sigurnost primjene istih kod djece, trudnica i dojilja. Rad također naglašava ključnu ulogu ljekarnika u savjetovanju pacijenata o primjeni MVM dodataka prehrani.Multivitamin/mineral (MVM) dietary supplements are popular and widely used dietary supplements in the general population. They contain vitamins and minerals of different compositions, amounts of components, and characteristics. They are used to help with additional intake of essential micronutrients in the body and to support specific functions in the body in certain patients' conditions or special groups of patients. Although they are very popular, the use of MVM dietary supplements is not entirely without risk to patient's health. It is known that vitamins and minerals, as components of MVM dietary supplements, can interact with drugs and different patients' health conditions. Also, it is important to take into account the range of doses for optimal intake of vitamins and minerals and the safety of their use in special groups of patients including children, pregnant women, and breastfeeding women. All of the above can cause a decrease or increase in the drug effect or MVM dietary supplement components or may increase the risk of patient's adverse outcomes. This diploma thesis provides a systematic overview and detailed explanations of the most important interactions of vitamins and minerals, as components of MVM dietary supplements, with drugs and patients' health conditions, as well as the safety of their use in children, pregnant women, and breastfeeding women. The thesis also emphasizes the key role of the pharmacist in the counseling of patients on the use of MVM dietary supplements

    Pharmacotherapy opportunities in the treatment of dystonia

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    Distonija je poremećaj pokreta uzrokovan trajnim ili povremenim nevoljnim mišićnim kontrakcijama koje dovode do abnormalnih položaja i pokreta tijela. Terapija distonije je uglavnom simptomatska te je nužan multidisciplinaran pristup u liječenju. Terapiji distonije prethodi pravilna dijagnoza i klasifikacija bolesti. Prva linija liječenja je botulinum toksin koji se može kombinirati s preostalom terapijom koju čine oralni lijekovi i kirurški zahvati te fizikalna terapija. Oralni lijekovi koji se koriste su antikolinergici, dopaminergici, benzodiazepini i baklofen. Od kirurških zahvata zlatni standard u liječenju je duboka stimulacija mozga, dok su ostale metode poput selektivne periferne denervacije i ablativnih metoda rijetko u upotrebi. Uz farmakoterapiju znatno poboljšanje je vidljivo uz istovremenu provedbu fizikalne i potporne terapije. Distonija, često praćena i nemotornim simptomima, kao što su bol, anksioznost, nesanica i dr. znatno ograničava svakodnevni život te je liječenje iznimno važno za olakšanje simptoma i mogućnost ponovnog obavljanja svakodnevnih aktivnosti, poput hodanja, pisanja, vožnje automobila, sviranja instrumenta i govora.Dystonia is a movement disorder caused by persistent or intermittent muscle contractions that result in abnormal body positions and movements. Therapy for dystonia is primarily symptomatic, requiring a multidisciplinary approach to treatment. Proper diagnosis and classification of the disease precede dystonia therapy. The first-line treatment is botulinum toxin, which can be combined with other therapies including oral medications, surgical procedures and physical therapy. Oral medications used include anticholinergics, dopaminergics, benzodiazepines, and baclofen. The gold standard in surgical treatment is deep brain stimulation, while other methods such as selective peripheral denervation and ablative techniques are rarely used. Significant improvement is often observed with pharmacotherapy alongside physical and ocupational therapy. Dystonia symptoms significantly limit everyday life, making treatment crucial for alleviating symptoms and enabling individuals to resume activities like walking, writing, driving, playing instruments, and speaking

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