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Synthesis and characterization of harmicines
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.)
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
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
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
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
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
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
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
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
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