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Preventivna medicina
No full textU kliničkoj praksi se relativno nedavno počelo pridavati više pozornost uzrocima bolesti nego simptomima,
dok znanost i tehnologija napreduju puno brže. P4 medicina predstavlja originalan pristup liječenju te
obuhvaća procese predikcije, prevencije, personalizacije i participacije. Koncept prevencije može se
primijeniti na razini pojedinca ili šire populacije, s ciljem promjene životnih navika koje dovode do razvoja
kroničnih degenerativnih bolesti. Na globalnoj razini pristupi prevenciji su raznoliki, od javnozdravstvenih
kampanja i edukativnih nastavnih programa do povećanja poreza na pojedine proizvode. Dob, spol,
metabolizam, razina fizičke aktivnosti i stresa te način prehrane bi se trebali uzimati u obzir pri određivanju
preventivnih opcija prilagođenih pacijentovim navikama, dijagnozi i terapiji. Dostupnost brze hrane i
rasprostranjenost zapadnjačkog načina prehrane predstavlja značajni rizik za razvoj hipertenzije, otpornosti
na inzulin i pretilosti. Unos hrane utječe na sastav crijevne mikrobiote i može poticati razvoj patogenih vrsta,
a posljedice se mogu odraziti na druge organske sustave (urogenitalni sustav, živčani sustav itd.). Uspješno
uvođenje koncepta prevencije i novih terapijskih mogućnosti u kliničku praksu ovisi o kvaliteti procesa
translacije i diseminacije, koji bi se trebali prilagoditi financijskim i obrazovnim mogućnostima ciljane
populacije. Novi pristupi zdravstvu trebali bi omogućiti pružanje najbolje moguće skrbi pacijentima te im
poboljšati kvalitetu i duljinu života, a ne težiti povećanju profita i marketingu. Uvođenje koncepta
preventivne medicine predstavlja etički, društveni, ekonomski i akademski izazov, ali može višestruko
doprinijeti unaprjeđenju zdravstvenog sustava.Clinical practice has recently started progressing towards treating the cause instead of symptoms of disease,
while research and technology are moving more rapidly. P4 medicine is an innovative approach to healthcare,
encompassing prediction, prevention, personalization and participation. Prevention strategies can be applied
to individual patients or the larger population, targeting lifestyle choices that increase the risk of developing
chronic diseases. Worldwide the approaches vary depending on the country, from public health campaigns
and school-based programs to higher health taxes. Various factors like age, gender and metabolism, physical
activity levels, stress and nutrition should be considered in the process of prevention, diagnosis and treatment.
The abundance of fast food and the widespread Western diet present a major risk factor for hypertension,
insulin resistance and obesity. Dietary intake affects gut microbial composition and potentially promotes the
growth of pathogenic species, which can have long lasting consequences for multiple organ systems
(urogenital tract, nervous system, etc.). Successful implementation of preventive strategies and therapeutic
options developed by researchers depends on the quality of translation and dissemination, so patients and
clinicians aren’t limited by financial and academic barriers. New initiatives should focus on optimal patient
care, improved survival and quality of life instead of profit and marketing. Introducing preventive medicine
to routine clinical practice presents an ethical, social, economic and intellectual challenge, but has the
potential to transform healthcare for the better
Preformulation studies in development of nanoemulsions loaded with ibuprofen
No full textBolest suhog oka karakterizirana je hiperosmolarnošću suznog filma i subakutnom upalom. Trenutno su glavne terapijske mogućnosti nadomještanje suznog filma, stimulacija stvaranja suza i topikalni protuupalni lijekovi. Protuupalna nesteroidna djelatna tvar ibuprofen ima potencijal za liječenje blagog do umjereno teškog oblika bolesti suhog oka. U/V nanoemulzije predstavljaju farmaceutski oblik pogodan za uklapanje ibuprofena, a zbog nadoknade i stabilizacije suznog filma koje osiguravaju pomoćne tvari nanoemulzija moguć je razvoj vrlo učinkovitog lijeka. Cilj ovog diplomskog rada bio je provesti ispitivanje topljivosti ibuprofena u uljima koja su odobrena ili velikog potencijala za oftalmičku primjenu te razviti preliminarne nanoemulzije U/V tipa s uklopljenim ibuprofenom. Topljivost ibuprofena ispitana je u četiri ulja: ricinusovo ulje, sezamovo ulje, sojino ulje te Miglyol® 812, od kojih ricinusovo ulje karakterizira najveća topljivost ibuprofena. U sljedećoj fazi izrade diplomskog rada ispitana je mogućnost izrade nanoemulzija s uklopljenim ibuprofenom. Uljnu fazu su činili ibuprofen i ricinusovo ulje, a vodenu fazu neionska površinski aktivna tvar Tween® 80, sredstvo za izotonizaciju glicerol te pročišćena voda. Nanoemulzije su pripravljene visokoenergetskom metodom mikrofluidizacije, nakon čega su im određena fizičko-kemijska svojstva uključujući veličinu kapljica i raspodjelu veličina te zeta-potencijal. Pripravljene preliminarne nanoemulzije karakterizira odgovarajuća uklopljenost ibuprofena, veličina kapljica i raspodjela veličina te zeta-potencijal, stoga predstavljaju dobar temelj za daljnji razvoj oftalmičke nanoemulzije s uklopljenim ibuprofenom za liječenje bolesti suhog oka.Dry eye disease is characterized by hyperosmolarity of the tear film and subacute inflammation. Currently, the main therapeutic options are tear replacement, stimulation of tear production and topical anti-inflammatory drugs. The anti-inflammatory non-steroidal active ingredient ibuprofen has the potential to treat mild to moderate dry eye disease. U/V nanoemulsions represent a dosage form suitable for loading ibuprofen and due to compensation and stabilization of the tear film provided by excipients of the nanoemulsions, development of a very effective drug is possible. The aim of this thesis was to test the solubility of ibuprofen in oils that are approved or have high potential for ophthalmic use and to develop preliminary o/w nanoemulsions loaded with ibuprofen. The solubility of ibuprofen was tested in four oils: castor oil, sesame oil, soybean oil and Miglyol® 812. Castor oil is characterized by the highest solubility of ibuprofen. In the next phase of this thesis, the possibility of preparing nanoemulsions loaded with ibuprofen was examined. The oil phase consisted of ibuprofen and castor oil, and the water phase consisted of the nonionic surfactant Tween® 80, an isotonizing agent glycerol and purified water. Nanoemulsions were prepared using a high energy microfluidization method, after which their physicochemical properties were determined, including droplet size, size distribution and zeta potential. The prepared preliminary nanoemulsions are characterized by appropriate incorporation of ibuprofen, droplet size, size distribution and zeta-potential, therefore they represent a good basis for further development of an ophthalmic nanoemulsion loaded with ibuprofen for the treatment of dry eye disease
Živa iz dentalnog amalgama - toksični, zdravstveni i ekološki aspekti
No full textDental amalgam has a long traditional use in dentistry. Thanks
to its durability, resistance, and, also its price, it is still one of the
most widespread materials used for dental cavities. In this review, the advantages and flaws of amalgam aplication are discribed in an objective and concise way.
Its main disadvantage is mercury toxicity which was controversial from the very
beginning of its synthesis. Mercuryis among the most toxic heavy metals with
diverse effects on neurological, cardiovascular and immune system. Although
mercury is realesed from dental amalgam during restauration, it has not shown
to be of any medical significance. One of the most important problem is disposal
of amalgam waste and its toxic effects on the environment. New conventional
materials are improving their quality while getting more available and are becoming
more suitable as an amalgam replacement
Antiviralni učinak prirodnih spojeva na Human alphaherpesvirus 1
No full textAntivirusni učinak antimikrobnih peptida bombinina H2 i H4, porijeklom iz kože žabe (Bombina variegata) testiran je na Herpes simplex virusu-1 (HHV-1), virusu s ovojnicom i dvolančanom DNA, a za usporedbu su korišteni drugi virusi za bolje razumijevanje mehanizma navedenih peptida, uključujući virus influence H1N1 koji je RNA virus s ovojnicom i JC Poliomavirus koji je dsDNA virus bez ovojnice. Potencijalni citotoksični učinak bombinina H2 i H4 ispitan je MTT testom. Na temelju rezultata MTT testa izabrane su koncentracije za pokuse u ovom istraživanju. Antivirusni učinak bombinina H2 i H4 na HHV-1 ispitan je “time-of-addition” testom. Naime, stanice su bile inficirane i tretirane s H2 ili H4 (10 i 20 μg/ml) u različito vrijeme infekcije: prije (PRE), tijekom (D) ili nakon (P) adsorpcije virusa na stanice domaćina ili tijekom i nakon (D +P, dvostruka doza) adsorpcijsku fazu i sljedeća 24 sata. Nadalje, radi provjere potencijalnog izravnog učinka bombinina na virione (virucidno djelovanje), virus je prethodno inkubiran sa svakim peptidom 1 sat na 37 ° C, a zatim su smjese korištene za inficiranje stanica. Iz ovih pokusa stanice su prikupljene i kasnije korištene za Western blot, a supernatanti su kasnije korišteni za standardno ispitivanje plakova. Prethodne studije provedene u našem laboratoriju pokazale su da temporin G (Tg) smanjuje infekciju HHV-1 kada se peptid doda tijekom faze adsorpcije virusa (podaci nisu objavljeni). Kako bi se proučio potencijalni sinergijski učinak primjene bombinina H2 i Tg na životni ciklus HHV-1, stanični monoslojevi inficirani su virusom prethodno inkubiranim bombininima, a također su tretirani s Tg-om 1 sat tijekom adsorpcije virusa na stanice domaćina. Nakon 24 sata, supernatanti su prikupljeni i korišteni za izvođenje standardnog testa na plak. Isti pokus je izravno ponovljen na ploči s 96 jažica radi izvođenja Unutar staničnog-Western blota (ICW). Peptidi su zatim testirani na H1N1 virusu influence A isti način kao i na HHV-1, ali na stanicama A549. Umjesto testa plaka korištena je metoda ICW, a stanice su korištene za Western blot. Kako bi se potvrdila virucidna svojstva bombinina na ovojnici virusa, sljedeći je eksperiment bio usmjeren na ispitivanje bombinina na virus bez ovojnice. U tu svrhu odabran je JC poliomavirus (JCPyV). Stanice SVGp12, bile su zaražene 48 sati virusom prethodno tretiranim bombininima, kako je ranije opisano za virucidne testove HHV-1 i IAV. Kako bi se dobila šira slika i bolji pregled informacija, provedeno je ispitivanje “time-of-addition” na isti način kao na HHV-1. Prikupljeni supernatanti i DNA, ekstrahirana iz stanica, korišteni su za Q-PCR analizu. Bombinin H2 i H4 korišteni su u dozama 10 i 20 μg/mL koje nisu pokazale toksični učinak tijekom MTT testa. Rezultati testa plaka i Western blot pokazuju virucidni učinak bombinina H2 u dozama od 10 μg/ml (p <0,001) i 20 μg/ml (p <0,0001) μg/ml i H4 u dozama od 10 μg/ml (p <0,01) i 20 μg/ml (p <0,001) na HHV-1. Bombinin H2 pokazuje snažniji virucidni učinak od oko 2 log smanjenja u usporedbi s infekcijom koja odgovara 99% inhibiciji replikacije HHV-1. Bombinin H2 dodan izravno na HHV-1 u dozi od 10 μg/ml pokazuje aditivni učinak s peptidom temporinom G u dozi od 50 μg/ml tijekom faze adsorpcije. Rezultati Western blota i ICW-a pokazuju da bombinin H2 ima virucidan učinak na H1N1 virus influence. Rezultati dobiveni Q-PCR-om pokazuju da bombinin H2 smanjuje infekciju JC poliomavirusa za 2-log ako su stanice prethodno tretirane peptidom (pre-tretman). Bombinin H2 pokazuje smanjenje infekcije za 1-log ako se doda u drugim stadijima infekcije ili izravno na polimiovirus JC. Bombinin H4 ne pokazuje antivirusni učinak na JC Poliomavirus. Prema našim saznanjima ovo je prvo izvješće o antivirusnom djelovanju bombinina H2 i H4.Antiviral effect of antimicrobial peptides bombinin H2 and H4 originated from frog skin (Bombina variegata) was tested on enveloped, dsDNA, Human aplhaherpesvirus-1 (HHV-1) and for comparison other viruses were used to understand the mechanism of peptides better, including H1N1 influenza virus which is an enveloped RNA virus and JC Polyomavirus which is non-enveloped dsDNA virus. MTT assay was used to test possible cytotoxicity of bombinin H2 and H4 as well as to choose appropriate concentrations for further experiments.. To test antiviral effect of bombinin H2 and H4 on HHV-1 time of addition assays were performed. Cells were infected and treated with H2 or H4 (10 and 20 μg/ml) at different times of infection: before (PRE), during (D) or after (P) the virus adsorption to the host cells or during and after (D+P, double dose) the adsorption phase and for the following 24 h. Moreover, to verify the potentially direct effect of bombinins on virions (a virucidal action), virus was preincubated with each peptide for 1 h at 37°C, and then the mixtures were used to infect the cells. From these experiments cells were collected and later used for Western blot and supernatants later used for plaque assay. Previous studies performed in our lab demonstrated that temporin G (Tg) reduces HHV-1 infection when the peptide is added during the viral adsorption phase (data not published). To study the potential synergic effect of bombinins and Tg administration on HHV-1 life cycle, cellular monolayers were infected with virus preincubated with bombinins and were also treated with Tg for 1 h during the virus adsorption to the host cells. After 24 h, supernatants were collected and used to perform a standard plaque assay. The same experiment was directly repeated in a 96-well plate to perform an Odyssey assay. To conclude are bombinins H2 and H4 virucidal on other viruses than HHV-1 Influenza A virus was tested in the same manner as for HHV-1 but on A549 cells. Instead of plaque assay used method was ICW and cells were used for Western blot. To verify the virucidal properties of bombinins on viral envelope, the next experimentation was addressed to test bombinins against a non-enveloped virus. To this aim, JC polyomavirus (JCPyV) was chosen. SVGp12 cells, were infected for 48 h with bombinins-pretreated virus, as described earlier for HHV-1 and IAV virucidal tests. To get a broad picture, time-of-addition assay was performed as on HHV-1. Collected supernatants and DNA extracted from cells were used for Q-PCR analysis. Bombinin H2 and H4 were used in doses of 10 and 20 μg/mL which do not show toxic effect during MTT assay. Results obtained from plaque assay and Western blot show virucidal effect of bombinin H2 in doses of 10 μg/ml (p<0,001) and 20 μg/ml (p<0,0001) μg/ml and H4 in doses of 10 μg/ml (p<0,01) and 20 μg/ml (p<0,001) on HHV-1. Bombinin H2 shows stronger virucidal effect of about 2-log decrease in comparison to infection which corresponds to 99% inhibition of HHV-1 replication. Bombinin H2 added directly to HHV-1 in dose of 10 μg/ml shows additive effect with temporin G added in the dose of 50 μg/ml during adsorption phase. Results from Western blot and ICW show that bombinin H2 is virucidal on H1N1 influenza virus. Results obtained from Q-PCR show that bombinin H2 reduces infection of JC Polyomavirus for 2-log if cells are pretreated with the peptide. Bombinin H2 shows 1-log reduction of infection if added in other stages of infection or directly to the JC Polyomavirus. Bombinin H4 does not show antiviral effect on JC Polyomavirus. To our knowledge this is a first report on antiviral activity of bombinin H2 and H4
Biological activity of black medick (Medicago lupulina L.) glycerol extracts
No full textOksidativni stres ima važnu ulogu u procesu starenja kože i razvoju kroničnih bolesti povezanih sa
starenjem. S obzirom da polifenoli imaju snažno antioksidativno djelovanje te smanjuju učinak
oksidativnog stresa na starenje kože, česti su sastojci dermatoloških i kozmetičkih proizvoda. Cilj
istraživanja bio je spektrofotometrijski odrediti sadržaj ukupnih polifenola, flavonoida te fenolnih
kiselina u glicerolnim ekstraktima zeleni hmeljaste vije. Kako bi se utvrdilo potencijalno korištenje
ekstrakata u topičkim pripravcima, korištene su metode za određivanje antioksidativne aktivnosti.
Ispitana je antiradikalna aktivnost korištenjem DPPH reagensa te kelirajuća aktivnost prema Fe2+
ionima. Biološka aktivnost inhibicije tirozinaze u svrhu potencijalnog korištenja biljke protiv
poremećaja pigmentacije na koži ispitana je enzimskom metodom. Istraživanje je pokazalo da
ekstrakt pripremljen u 60 %-tnom glicerolu kao ekstrakcijskom otapalu ima bolju kelirajuću
aktivnost te je bogatiji fenolnim kiselinama u odnosu na ekstrakt pripremljen u 90 %-tnom glicerolu.
Ekstrakt pripremljen u 90 %-tnom glicerolu nešto je bogatiji flavonoidima te ima bolje antiradikalno
djelovanje. Ekstrakti su pokazali zanemarivo inhibirajuće djelovanje na tirozinazu. S obzirom na
relativno dobru antioksidativnu aktivnost, M. lupulina ima potencijal za korištenje u dermatološke i
kozmetičke svrhe, no potrebna su daljnja istraživanja kako bi se utvrdile njezine značajke u odnosu
na druge biljne vrste koje se koriste u kozmetičke svrhe.Oxidative stress plays an important role in the aging process of the skin and the development of
chronic diseases associated with aging. Since polyphenols have a strong antioxidant effect and
reduce the effect of oxidative stress on skin aging, they are common ingredients in dermatological
and cosmetic products. The aim of the study was to spectrophotometrically determine the content of
total polyphenols, flavonoids, and phenolic acids in glycerol extracts of black medick aerial parts.
Methods for determining antioxidant activity were used to determine the potential use of extracts in
skin products. Antiradical activity using DPPH reagent and chelating activity against Fe2+ ions were
investigated. The biological activity of tyrosinase inhibition for the potential use of plant against
skin pigmentation disorders was investigated by an enzymatic method. The study showed that the
extract prepared in 60 % glycerol as an extraction solvent has better chelating activity and is richer
in phenolic acids compared to the extract prepared in 90 % glycerol. The extract prepared in 90 %
glycerol is slightly richer in flavonoids and has better antiradical effect. The extracts showed
negligible inhibitory activity on tyrosinase. Due to its relatively good antioxidant activity, M.
lupulina has the potential to be used for dermatological and cosmetic purposes, but further research
is needed to assess its activity in comparison with other species that are used for cosmetic purposes
Nuspojave lijekova kod osoba starije životne dobi
No full textCilj istraživanja: Glavni cilj istraživanja bio je pregled problematike nuspojava lijekova kod
osoba starije životne dobi, kao i pregled prijava nuspojava podnesenih Hrvatskoj agenciji za
lijekove i medicinske proizvode o broju i vrsti nuspojava koje zahvaćaju stariju populaciju u
Republici Hrvatskoj.
Materijal i metode: Materijali korišteni za izradu ovog rada obuhvaćali su podatke Hrvatske
agencije za lijekove i medicinske proizvode o prijavljenim nuspojavama od 1993. godine do
21.2.2021. koji se odnose na osobe starije od 65 godina. Nadalje, podaci iz ovog rada dobiveni
su i iz Popisa stanovništva, kućanstva i stanova 2011., iz Izvješća o smrtnosti prema listi
odabranih uzroka u 2019., iz Izvješća o potrošnji lijekova u Republici Hrvatskoj 2020. godine,
iz Potrošnje lijekova u Republici Hrvatskoj u 2019. godini i iz Izvješća o nuspojavama u 2019.
godini. Naposljetku, materijale za izradu ovog rada činili su znanstveni radovi pronađeni na
web stranici PubMed kao i znanstveni radovi na koje se prethodni referiraju. Izrazi korišteni za
pronalazak radova su: „Adverse effect“, „Ageing“, „Chronic disease“, „Drug“, „Elderly“,
„Polypharmacy“ i „Potentially inappropriate drugs“.
Rezultati: Znanstveni radovi ukazuju da starenjem slabe homeostatski sustavi i dolazi do
pojave kroničnih bolesti. Istraživanja ukazuju da značajan broj oboljelih starijih od 65 godina
ima rastući broj komorbiditeta i u zamjetnom postotku koriste potencijalno neodgovarajuće
lijekove. Politerapija je prisutna u značajnom udjelu bolesnika. Navedeni čimbenici pogoduju
nastanku nuspojava. Pregled podataka HALMED-a o nuspojavama daje informaciju da se
nuspojave češće javljaju kod žena, u dobi od 65-74 godine. 29,2% nuspojava karakterizirano je
kao ozbiljno. Od 11528 prijava 3623 se odnosilo na lijekove s djelovanjem na srce i krvožilje,
a 1689 na lijekove s djelovanjem na probavni sustav i mijenu tvari što približno odgovara
potrošnji tih skupina lijekova. 29,2% nuspojava pogađalo je gastrointestinalni sustav. Opće
reakcije i reakcije na mjestu primjene su 27,5%, poremećaji kože i potkožnog tkiva 23,5%, a
poremećaji središnjeg živčanog sustava 18,1% svih nuspojava. Među lijekovima koji su
najčešće prijavljivani za sumnju izazivanja nuspojava su acetilsalicilna kiselina, amlodipin,
atorvastatin, varfarin i rivaroksaban. Široka primjena acetilsalicilne kiseline može objasniti
veliki broj prijava. Broj prijava amlodipina je srazmjeran njegovoj potrošnji, no čini se da u
usporedbi s drugim blokatorima kalcijevih kanala ne nosi viši rizik izazivanja nuspojava. Broj
prijava varfarina nije srazmjeran njegovoj potrošnji, ali se može objasniti njegovom
farmakokinetikom i uskom terapijskom širinom. Rivaroksaban i novi oralni antikoagulansi
imaju velik broj prijava iako nisu u širokoj primjeni. Acetilsalicilna kiselina i varfarin su
lijekovi čije korištenje alati za određivanje PNL-ova smatraju rizičnim. Važna je prevencija
nuspojava. Uz liječničke intervencije ljekarnici mogu razgovorom s pacijentima i pregledom
uzimanih lijekova i preparata uočiti potencijalne probleme i uz to pružiti odgovore na pitanja
pacijenta s ciljem poboljšanja adherencije čime se smanjuje rizik nuspojava.
Zaključak: Politerapija i korištenje potencijalno neodgovarajućih lijekova je rašireno u starijoj
populaciji. Iako ima mjesta za napredak prijavljivanje nuspojava lijekova u Republici Hrvatskoj
je na zadovoljavajućoj razini. Broj prijava nuspojava lijekova je uglavnom proporcionalan
njihovoj potrošnji. Samo oralni antikoagulansi imaju značajno veći broj prijava nuspojava
lijekova usprkos njihovoj relativno maloj potrošnji. Općenito je većina nuspojava blaga.
Potreban je daljnji razvitak mjera za prevenciju nuspojava koje mogu uključivati ljekarnike u
javnim ljekarnama.Objectives: The main objective of this research will be overview of adverse drug effects in the
elderly as well as overview of adverse drug effects reported to Croatian agency for medicines
and medicinal products which encompass number and type of adverse effects in Croatian
elderly population.
Materials and Methods: Materials used for this overview encompass data from Croatian
agency for medicines and medicinal products on reported adverse effects from 1993. to
21.2.2021 in population older than 65. Furthermore, data in this overview was obtained from
Population census of 2011, Report of mortality in 2019; Annual Report on Drug Utilization for
2020; document of Drug Utilization in Republic of Croatia in 2019. and Adverse Drug Reaction
Report of 2019. Finally, materials used in this overview are scientific papers found on the webpage Pubmed and scientific papers which they refer to. Keywords used to find scientific papers
are: „Adverse effect“, „Ageing“, „Chronic disease“, „Drug“, „Elderly“, „Polypharmacy“ i
„Potentially inappropriate drugs“.
Results: Scientific papers indicate that ageing weakens homeostatic systems, which leads to
chronic diseases. Research shows that a notable number of people older than 65 have a growing
number of comorbidities and use potentially inappropriate drugs in a significant percentage.
Polypharmacy is found in a significant number of patients. These factors all contribute to side
effects. Overview of data from HALMED on adverse effects gives us information that side
effects are more common in women, in people aged 65-74. 29,2% of adverse effects are
characterized as serious. Of 11528 reports, 3623 reports were about cardiovascular medicines
and 1689 reports were about digestive and metabolic medicines which roughly corresponds to
their respective utilization. 29,2% of adverse effects involved the gastrointestinal system.
General reactions and local reactions are 27,5% of all adverse effects. Skin reactions and
reactions of underlying tissue are 23,5% of all adverse reactions. Central nervous system
disorders are 18,1% of all adverse effects. The most commonly reported medicines are
acetylsalicylic acid, amlodipine, atorvastatin, warfarin, and rivaroxaban. A large number of
reports on acetylsalicylic acid can be explained by its wide utilisation. The number of reports
on amlodipine is proportional to its utilization, but it seems that it does not carry a greater risk
of adverse effects. The number of reports on warfarin is not proportional to its utilization but
can be explained by its pharmacokinetics and narrow therapeutic width. Rivaroxaban and new
oral anticoagulants have large numbers of reports despite not being widely used. Acetylsalicylic
acid and warfarin are characterized as potentially inappropriate drugs by tools to determine such
medicines. Prevention of adverse effects is important. In addition to doctor's interventions
pharmacists can, through patient interview and review of utilized medicines and supplements,
find potential problems and offer answers to any question patients may have with a goal of
improving adherence which may reduce the risk of adverse effects.
Conclusions: Polypharmacy and the utilization of potentially inappropriate drugs is widespread
in the elderly population. Although there is space for improvement reporting of adverse drug
reactions in Republic of Croatia is on satisfactory level. The number of reports on adverse drug
effects is generally proportionate to drug utilization. Only oral anticoagulants have significantly
more reports of adverse drug effects despite their relatively small utilization. Generally, most
adverse effects are mild. Further development of measures for the prevention of adverse drug
effects is necessary and those may include pharmacists in public pharmacies
HSS-GC-FID analysis of residual solvents in food supplements used in the treatment of inflammatory bowel disease
No full textUpalne bolesti crijeva su kronične upalne bolesti gastrointestinalnog trakta karakterizirane rekurentnim upalama segmenata probavnog trakta koje se manifestiraju kao nadutost, abdominalna bol, grčevi, krvarenje te kronični proljev. U ovu skupinu bolesti spadaju dva podtipa, a to su Cronhova bolest i ulcerozni kolitis. Unatoč sigurnim i efektivnim farmakološkim metodama liječenja, koje uklučuju aminosalicilate, kortikosteroide, imunosupresive te biološku terapiju, mnogi pacijenti koji pate od ovih složenih bolesti posežu za rješenjima svojih tegoba u drugim područjima. Tako ih sve više efektivne odgovore na svoje probleme traži u dodacima prehrani. Neki od njih mogu predstavljati javnozdravstvenu opasnost zbog prisutnosti neprijavljenih ostatnih otapala u svojem sastavu. Ostatna otapala su hlapljivi organski spojevi koji se koriste ili nastaju u proizvodnji medicinskih proizvoda. Klasificiraju se od klase 1 do klase 3 ovisno o opasnosti koje predstavljaju za ljudsko zdravlje. Kako bi se odredila prisutnost ostatnih otapala u dodacima prehrani namijenjenim za liječenje upalnih bolesti crijeva korištena je analitička metoda definirana člankom Američke farmakopeje. 44 uzoraka s hrvatskog tržišta je pripremljeno i analizirano koristeći HSS-GC-FID za identifikaciju analita te onda uspoređeno s kromatogramima analiziranih standardnih otopina koji sadrže ostatna otapala klase 2 i klase 3. Analizom je određena prisutnost ostatnih otapala u 21 od 44 ispitanih uzoraka no u svim tim uzorcima koncentracije detektiranih ostatnih otapala bile su unutar prihvatljivih granica za ljudsku upotrebu.Inflammatory bowel diseases are chronic inflammatory diseases of the gastrointestinal tract characterised by recurring inflammations of particular segments of the gastrointestinal tract, the clinical manifestation of which include bloatedness, abdominal pains, cramps, bleeping and chronic diarrhea. Two diseases belong to this group: Crohn's disease and ulcerative colitis. Despite safe and effective pharmacological treatment options, which include aminosalicylates, corticosteroids, immunosuppressives and biological therapy, many patients suffering from these complex diseases are seeking solutions to their medical issues in food supplements. Some of these food supplements may pose public health risks due to the presence of residual solvents in them not being properly reported. Residual solvents are volatile organic chemical substances that may have been used or produced in the preparation of a medicinal product. They are classified from Class 1 to Class 3 based on their potential dangers to human health. In order to determine the presence of residual solvents in food supplements used for the treatment of inflammatory bowel disease, method defined by the United States Pharmacopeia was used. Multiple samples from the Croatian market were prepared and analysed using HSS-GC-FID and then compared with chromatograms of analysed standards containing Class 2 and Class 3 residual solvents. Using this method, the presence of residual solvents was determined in 21 out of 44 analysed samples, with all of the detected residual solvents being within acceptable limits, making them safe for human use
Analysis of the safety profile of JAK inhibitors based on the received reports of suspected side effects
No full textCitokini i faktori rasta su proteini koji posreduju aktivnost i preživljavanje brojnih stanica u organizmu. Jedan od
načina kojim se to posredovanje odvija je i JAK/STAT signalizacijski put. Citokini se vežu za svoje receptore na
površini stanica, konformacijskom promjenom se pokreće signalizacijska kaskada te nastavlja fosforilacijom. Janus
(JAK) kinaze su unutarstanične tirozin kinaze, vezane uz citokinske receptore, zadužene za uzastopnu fosforilaciju
nizvodnih molekula. Obzirom na širok utjecaj kojeg JAK/STAT put ima na imunosne i krvne stanice, ne čudi da su
Janus kinaze postale atraktivna terapijska meta u liječenju autoimunih i hematoloških bolesti. Velik broj nizvodnih
ciljeva na koje utječe inhibicija Janus kinaza ima i jednu manu, a to je sigurnosni profil ovih potentnih lijekova. Cilj
ovog rada bio je analizirati nuspojave JAK inhibitora prijavljene Agenciji za lijekove i medicinske proizvode u
razdoblju od 1. siječnja 2013. godine do 11. srpnja 2021. godine te povećati svijest o sigurnosnom profilu ovih
lijekova, kao i mjerama minimizacije rizika. Zaprimljene prijave sumnji na nuspojave analizirane su u odnosu na
ukupan broj zaprimljenih prijava u zadanom razdoblju, prema vrsti prijavitelja, dobi i spolu pacijenta, ozbiljnosti
reakcije, kriteriju ozbiljnosti, najčešće prijavljenim rekacijama, pripadnosti prema klasifikaciji organskih sustava
Medicinskog rječnika za regulatorne poslove (MedDRA) te najčešće istodobno primijenjivanim lijekovima. Dobiveni
rezultati i znanje o sigurnosnom profilu JAK inhibitora te mjerama minimizacije rizika omogućuju dodatnu edukaciju
zdravstvenih radnika o učinkovitijoj prevenciji, otkrivanju i liječenju mogućih nuspojava, a sve sa svrhom poboljšanja
kvalitete života pacijenata.Cytokines and growth factors are proteins that mediate the activity and survival of many cells in human body. One of the ways in which this mediation takes place is via JAK / STAT signaling path. Cytokines bind to their receptors on the cell surface and, by conformational change, trigger a signaling cascade which is continued by phosphorylation. Janus (JAK) kinases are intracellular tyrosine kinases which are associated with cytokine receptors. Kinases are responsible for the consequential phosphorylation of downstream molecules. Given the wide range of effects that JAK / STAT pathway has on immune and blood cells, the fact that Janus kinases have become an attractive therapeutic target in the treatment of autoimmune and hematological diseases is not surprising. A number of downstream targets affected by Janus kinase inhibition also has one disadvantage which is the safety profile of these potent drugs. The aim of this study was to analyze the side effects of JAK inhibitors reported to the Agency for Medicinal Products and Medical Devices of Croatia in the period from 1 January 2013 to 11 July 2021. Also, another intention was to increase awareness of the safe profile of these drugs and risk minimization measures. Received reports of suspected adverse reactions were analyzed in relation to the total number of received reports in a given period, reporter qualification, age and sex of the patient, seriousness of reactions, seriousness criteria, most commonly reported reactions, reported reactions by MEdDRA organic classification (Medical Dictionary for Regulatory Affairs) and most commonly applied medicines.The obtained results and knowledge about the safe profile of JAK inhibitors and risk minimization measures enable additional education of healthcare professionals on effective prevention, detection and treatment of possible side effects, all with the purpose of improving the quality of life of patients
Analysis of adverse drug reactions reported by elderly cardiovascular patients in a primary care setting
No full textLijekovi danas manifestiraju sve brojnije pozitivne kliničke učinke te su uvelike doprinijeli smanjenju mortaliteta pacijenata, produljenju njihovog životnog vijeka te poboljšanju njihove kvalitete života. S druge strane, isti ti lijekovi povećavaju učestalost neželjenih reakcija, s obzirom da su upravo starija životna dob, prisutnost višestrukih komorbiditeta i polifarmacija jedni od najvažnijih čimbenika rizika za razvoj nuspojava lijekova. Premda je prijavljivanje nuspojava zakonska obveza svih zdravstvenih radnika, studije pokazuju kako se prijavljuje samo oko 6 % svih nuspojava. S obzirom na ograničenost podataka o epidemiologiji nuspojava, cilj ovog istraživanja bio je odrediti učestalost te klasificirati nuspojave kod pacijenata starijih od 65 godina s dijagnozom hipertenzije i barem jedne kardiovaskularne bolesti na razini primarne zdravstvene zaštite. Dodatno, cilj je bio utvrditi postoji li utjecaj sveobuhvatne usluge upravljanja farmakoterapijom (engl. Comprehensive Medication Management (CMM) services) na smanjenje učestalosti nuspojava. Provedeno je prospektivno, prije- i poslijeintervencijsko istraživanje s dvogodišnjim kontroliranim praćenjem pacijenata koji su uz uobičajenu skrb pruženu od strane drugih zdravstvenih radnika primili i CMM uslugu. Učestalost sumnji na nuspojave lijekova analizirana je s obzirom na redni broj konzultacije, dob, spol, broj komorbiditeta i broj lijekova pacijenata. Zabilježene nuspojave klasificirane su prema MedDRA (engl. Medical Dictionary for Regulatory Activities – Medicinski rječnik za regulatorne poslove) PT-u (engl. Preferred Term – Preporučeni pojam), MedDRA SOC-u (engl. System Organ Class – Klasifikacija organskih sustava), mehanizmu nastanka, ozbiljnosti i očekivanosti. Kod ukupno 65 pacijenata uključenih u ovo istraživanje zabilježeno je 596 sumnji na nuspojave lijekova (po pacijentu 9,2 ± 16,9). Uočena je snažna i statistički značajna povezanost između porasta broja korištenih lijekova i porasta broja nuspojava (r = 0,823; p = 0,000). Prema MedDRA PT-u predvodile su hipotenzija (42), glavobolja (29) i neučinkovitost lijeka (27), dok su prema MedDRA SOC-u predvodili Opći poremećaji i reakcije na mjestu primjene (103), Krvožilni poremećaji (71) i Poremećaji probavnog sustava (68). Prema mehanizmu nastanka, najveći udio u ukupnom broju nuspojava činile su nuspojave tipa A (75 %). Ozbiljne i neočekivane nuspojave činile su manji udio u ukupnom broju nuspojava (12 %, odnosno 19 %). Dodatno, uočen je pozitivan i statistički značajan utjecaj CMM usluge na smanjenje učestalosti nuspojava (p < 0,001). U svjetlu sve kompleksnijih terapija, povećanja broja korištenih lijekova, kao i broja zdravstvenih radnika koji mogu propisivati lijekove (često bez znanja što je drugi zdravstveni radnik propisao) s jedne strane te nedostatka kontrole nad propisivanjem i primjenom lijekova s druge strane, CMM usluga pažljivim bi odabirom i redovitim kontroliranjem propisane terapije mogla odgovoriti na problem kliničkog i financijskog tereta nuspojava te osigurati povećanje učinkovitosti i sigurnosti primjenjivanih lijekova.Today, medications are manifesting ever more numerous positive clinical effects and have greatly contributed to a lowered mortality rate, prolonged life span and increased quality of life of patients. On the other hand, an increase in unwanted adverse effects of these medications is being marked due to old age, an overabundance of comorbidities and polypharmacy being some of the most important risk factors for the manifestation of the adverse drug reactions (ADRs). Although reporting ADRs is a legal obligation of all healthcare workers, studies show that only around 6 % of ADRs are actually reported. As a consequence, limited data exists on the epidemiology of ADRs. Bearing this in mind, the goal of this research was to determine the frequency of ADRs in a primary care setting and to classify them based on cases of patients that are older than 65 with a diagnosis of hypertension and at least one other underlying cardiovascular disease. An additional goal was to determine the effect of Comprehensive Medication Management (CMM) service on the frequency of ADRs. In the span of two years, a prospective pre-post study on continuously monitored patients that were receiving CMM service was conducted. The frequency of ADRs was analysed based on the sequence number of the patient and their age, sex, number of comorbidities and number of medications taken. The noticed ADRs were classified according to MedDRA (Medical Dictionary for Regulatory Activities) PT (Preferred Term), MedDRA SOC (System Organ Class), occurrence mechanism, seriousness and expectedness. In a total of 65 patients involved in this study, 596 suspicions of ADRs were noted (9,2 ± 16,9 per patient). A strong and statistically notable connection was found between the number of reported ADRs and the number of medications the patient is taking (r = 0,823; p = 0,000). According to MedDRA PT, the leading ADRs were hypotension (42), headache (29) and drug ineffectiveness (27), while according to MedDRA SOC, the leading ADRs were General disorders and administration site conditions (103), Vascular disorders (71) and Gastrointestinal disorders (68). Based on occurrence mechanism, the majority of the total number of reported ADRs was made up of type A ADRs (75 %). Serious and unexpected ADRs represented a lower ratio of the total number of ADRs (12 % and 19 %, respectfully). Additionally, a positive and statistically noticeable effect on the reduction of the frequency of ADRs was observed following the implementation of CMM service (p < 0,001). Taking into consideration both the ever more complex therapy regimens, the increasing number of medications being taken and the increasing number of healthcare workers that can prescribe medications (often without knowing what other healthcare workers have prescribed) and the lack of control over the prescription and consumption of medications, through more careful prescription methods and control of a patient’s therapy, CMM services could serve as a solution to the problem caused by the clinical and financial burden of ADRs, while increasing the efficacy and safety of the use of the prescribed medications
In vitro evaluation of nasal deposition of donepezil-loaded microspheres
No full textAlzheimerova bolest (AB) je kronična i progresivna bolest središnjeg živčanog sustava (SŽS) s kompleksnim patološkim mehanizmima u podlozi. Glavna skupina lijekova koji se koriste u liječenju AB-a su inhibitori acetilkolinesteraze (donepezil, rivastigmin, galantamin). Unatoč velikom napretku u neuroznanosti i novim neuroterapeuticima, učinkovitost liječenja bolesti SŽS-a je ograničena postojanjem krvno moždane barijere. Iz tog
razloga je smanjena učinkovitost sistemski primijenjenog lijeka u mozgu. Nazalna primjena lijekova pruža
mogućnost izravne dostave u SŽS. Odlikuju ju brz nastup djelovanja, neinvazivnost te zaobilaženje probavnog sustava i prvog prolaska kroz jetru. Cilj ovog rada bio je pripraviti i karakterizirati mikrosfere s donepezilom građene od kitozana i manitola te ispitati utjecaj parametara primjene (kut primjene u odnosu na horizontalnu ravninu i protok udahnutog zraka) na nazalnu depoziciju pripravljenih mikrosfera. Mikrosfere s donepezilom
zadovoljile su kriterije za primjenu u nosnoj šupljini s obzirom na prikladnu uspješnost uklapanja, sadržaj lijeka,
sadržaj vlage, površinski naboj i reološka svojstva. Pri ispitivanju depozicije u nosnoj šupljini, korišten je 3D
printani model nosne šupljine, respiratorna pumpa (za simulaciju disanja) i UDSP uređaj razvijen za ciljanje olfaktorne regije. Mikrosfere s donepezilom uspješno su dostavljene u ciljnu (olfaktornu) regiju nosne šupljine. Smanjenjem kuta primjene uređaja u odnosu na horizontalnu ravninu rastao je udio lijeka dostavljen u olfaktornu
regiju. Primjena UDSP uređaja uz zadržavanje daha rezultirala je većom depozicijom lijeka u ciljnoj olfaktornoj
regiji, te manjom depozicijom u anteriornoj i posteriornoj regiji, u odnosu na primjenu uz udah.Alzheimer’s disease (AD) is a chronic and progressive disease of the central nervous system (CNS) with complex underlying pathological mechanisms. The main group of medications used in the AD treatment are acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine). Despite great advances in neuroscience and
new neurotherapeutics, the effectiveness of CNS disease treatment is primarily limited by the existence of a bloodbrain barrier. Thus, brain bioavailability of a systemically administrated drug is reduced. Nasal administration
enables direct CNS delivery of the drug. It is characterized by rapid onset of action, non-invasiveness, bypass of the gastrointestinal tract and first-pass metabolism. The aim of this study was to prepare and characterize
chitosan/mannitol based donepezil-loaded microspheres and to examine the influence of administration parameters
(administration angle in relation to the horizontal plane and inspiratory flow rate) on nasal deposition of prepared microspheres. Donepezil-loaded microspheres met the criteria for nasal application with respect to appropriate entrapment efficiency, drug loading, moisture content, surface charge, and rheological properties. In nasal deposition studies, a 3D printed nasal cavity model, a respiratory pump (for simulating breathing) and a UDSP
delivery device were used. Donepezil-loaded microspheres were successfully delivered to the targeted (olfactory)
region of the nasal cavity. By reducing the administration angle in relation to the horizontal plane, the proportion of drug delivered to the olfactory region increased. The use of the device at breath-hold resulted in higher drug
deposition in the targeted olfactory region, and lower deposition in the anterior and posterior regions, compared to
application under breathing conditions