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Botulinum toxin in the treatment of migraine
No full textMigrena je kompleksni poremećaj središnjeg živčanog sustava opisan kao rekurentna, epizodična ili kronična glavobolja koja pogađa veliki dio svjetske populacije. Specifična manifestacija: visok intenzitet boli, preosjetljivost na svijetlo i zvuk, mučnina, povraćanje i trajanje napadaja do 72 h dovodi do nefunkcionalnosti pacijenata, a time negativno utječe i na kvalitetu života. Terapiju migrene čine lijekovi koji inhibiraju lučenje peptida i medijatora upale, vazodilataciju, sintezu prostaglandina, ekscitaciju trigeminalnog živca ili centar za povraćanje u produljenoj moždini. BoNT-A je kao analgetik posebnih svojstava (dugo djelovanje, minimalne nuspojave, smanjuje ili u potpunosti uklanja bol, smanjuje broj dana u mjesecu s glavoboljom) idealan za liječenje kronične migrene, a dodatna prednost mu je što u dozama koje se koriste nema sistemske apsorpcije pa tako ni sistemskih nuspojava. Velik broj studija potvrdio je njegovu učinkovitost na temelju čega je dobio odobrenje za ovu indikaciju. Kriteriji za terapiju BoNT-A su: više od 15 napadaja mjesečno u trajanju od 4 ili više sati te nedjelotvornost prve i druge linije liječenja migrene. Toksin se primjenjuje u obliku injekcija na 40 mjesta na području glave i vrata svaka 3 mjeseca. U budućnosti je potrebno standardizirati postupke unutar studija, validirati metode mjerenja rezultata eksperimenata i dizajnirati formulaciju BoNT-A koja bi ljudima bila prihvatljivija za primjenu. Time bi se povećao broj ljudi koji bi primjenjivali BoNT-A za liječenje migrene i drugih bolnih poremećaja te proširio dijapazon potencijalnih indikacija za koje još nije dobio odobrenje.Migraine is a complex disorder of central nerve system described as recurrent, episodic or chronic headache that affects large number of world population. Specific manifestation: high pain intensity, hypersensitivity to light and sound, nausea, vomiting and duration of attack up to 72 hours leads to disfunctionality of patients, a thus negatively affects quality of life. Migraine therapy consists of medications that inhibit secretion of peptides and inflammatory mediators, vasodilatation, prostaglandin synthesis, trigeminal nerve excitation or vomiting center in medulla oblongata. BoNT-A is, as analgesic with special properties (long duration, minimal side effects, reduces or removes pain completely, reduces number of days per month with headache) ideal for treating chronic migraine and his additional adventage is that he doesn't have systemic absorption in used doses, thus doesn't have systemic side effects. Large number od studies confirmed his efficiency on the basis of which he received approval for this indication. Criteria for BoNT-A therapy are: more than 15 attacks in duration of 4 or more hours and inefficiency of first and second migraine treatment. Toxin is administered in form of injections at 40 locations in head and neck region every 3 months. In the future is necessary to standardize procedure within studies, validate measurements of experimental results and design formulation of BoNT-A that would be more acceptable for application in humans. With that, number of people using BoNT-A for migraine and other pain disorders treatment would increase and diapason of potential indications, for which he didn't receive approval, would expand
Development of ophthalmic secondary cationic nanoemulsions with chitosan oligosaccharide
No full textBolest suhog oka bolest je površine oka koja je u današnje vrijeme česta pojava. Češće se javlja kod starijih osoba, žena, osoba koje su izložene niskoj vlažnosti zraka, osoba s autoimunim poremećajima, ali i kod mlađih osoba zbog svakodnevne dugotrajne uporabe digitalnih uređaja. Kationske nanoemulzije sa svojstvom mukoadhezivnosti stupaju u kontakt s mucinima na površini oka i namijenjene su liječenju bolesti površine oka zbog duljeg zadržavanja lijeka i veće bioraspoloživosti. U liječenju simptoma blagog oblika bolesti suhog oka dobre rezultate pokazuju kationske nanoemulzije pripravljene od sastavnica sličnih onima koje su fiziološki prisutne na površini oka. U sklopu ovog diplomskog rada uspješno su pripravljene formulacije koje sadrže 2,5% (m/m) polusintetske smjese srednjelančanih triglicerida, 0,05% (m/m) lecitina, 0,25% (m/m) makrogolglicerol ricinoleata 35, 0,05% (m/m) kitozana – polusintetskog kationskog polimera sa svojstvom mukoadhezivnosti, 2,5% (m/m) glicerola – alkohola neutralnog naboja prikladnog za izotonizaciju nanoemulzija i pročišćenu vodu do 100% (m/m). Pripravljenim formulacijama ispitana su fizičko-kemijska svojstva: prosječna veličina, raspodjela veličina te zeta-potencijal kapljica unutarnje faze. Također, ispitano je svojstvo mukoadhezivnosti reološkom metodom te određivanjem veličine kapljica, raspodjele veličina kapljica i zeta-potencijala nanoemulzija nakon miješanja s mucinom. Na temelju provedenih ispitivanja kao formulacija s potencijalom za daljnji razvoj ističe se sekundarna kationska nanoemulzija s oligomerom kitozana pripravljena dodavanjem otopine oligomera kitozana u smjesu prije priprave nanoemulzije procesom mikrofluidizacije.Dry eye disease is an ocular surface disease common in present times, more expressed in certain populations, such as senior citizens, women, people exposed to low humidity, patients with autoimmune diseases as well as younger people due to excessive everyday use of digital devices. Cationic nanoemulsions of mucoadhesive properties interact with mucins on the ocular surface and are intended for treatment of ocular surface diseases due to longer retention time of the drug and consequently its greater bioavailability. In treating symptoms of mild form of dry eye disease, cationic nanoemulsions composed of components similar to those found as constituents of the ocular surface show good results. Formulations prepared for purposes of this diploma thesis are composed of 2.5% (w/w) semisynthetic mixture of middle chain fatty acids, 0.05% (w/w) lecithin, 0.25% (w/w) macrogolglycerol ricinoleate 35, 0.05% (w/w) chitosan – semisynthetic cationic polymer with mucoadhesive properties, 2.5% (w/w) glycerol – neutrally charged alcohol suitable for nanoemulsion isotonisation and purified water to 100% (w/w). Formulations were tested for their physicochemical properties: average size, size distribution as well as zeta-potential of droplets of inner phase of nanoemulsions. In addition, mucoadhesive properties were also tested using rheological method and by measuring droplet size, size distribution and zeta-potential of nanoemulsions after the addition of mucin. Based on all conducted tests, formulation showing the potential for further development is secondary cationic nanoemulsion with chitosan oligosaccharide formed by adding a solution of chitosan oligosaccharide to the mixture before the process of microfluidisation
Lijekovi koji povećavaju rizik od padova u osoba starije životne dobi
No full textOlder people usually suffer from multiple diseases and consequently
are prescribed more medications. They are at higher
risk of therapeutic problems due to changes in the organism that occur with
aging. Such changes affect the pharmacokinetics and pharmacodynamics of
drugs. Falls and fractures are significant causes of mortality and morbidity in the
elderly. Falls are the result of a complex combination of different risk factors,
including fall-risk increasing drugs. The use of fall-risk increasing drugs increases
with the total number of chronic diseases and drugs, which is characteristic
for older age. Recently, Screening Tool of Older Persons Prescriptions in older
adults with high fall risk, was published, which aim is to identify fall-risk increasing
drugs for potential deprescribing
A cost of illness of COVID 19 patients in hospitalized patients
No full textKrajem 2019. godine u kineskom gradu Wuhan pojavio se virus SARS-CoV-2 koji izaziva bolest COVID-19. Nedugo nakon, u ožujku 2020. godine Svjetska zdravstvena organizacija (WHO) proglašava pandemiju bolesti COVID-19. Virus SARS-CoV-2 prvenstveno inficira dišne puteve, te uzrokuje različite simptome, od onih blažih poput umora, dispneje, gubitka okusa i mirisa, do težih kao sistemskih infekcija i upale pluća, a može dovesti do smrti. Kroz ovaj rad napravili smo analizu troška bolesti iz perspektiva bolnica za Republiku Hrvatsku. DTS koji se veže uz COVID-19 i korištenje respiratora je A06Z, Traheostomija ili ventilacija > 95 sati. To radno intenzivna skupina koja je na dan 4.6.2022. troškovno iznosila 123.552,00 kn. To je iznos koji bolnice fakturiraju HZZO-u. Prosječno trajanje bolničkog liječenja za skupinu A06Z je 15,67 dana, dok je broj trim dana 47. Prikazali smo koja je granica troškova materijala i lijekova preko koje ukoliko iznos prede, trošak epizode liječenja neće biti u potpunosti pokriven od strane HZZO-a. Od 2019 godine smo analizirali trajanje bolničkog liječenja, troškove materijala i lijekova i ostale troškove za skupinu A06Z. Od početka pandemije pa do kraja 2021. za troškove bolesti COVID-19 od strane HZZO-a izdvojeno je 4.150.106.390,36 kn. Na mnogobrojna testiranja potrošeno je 1.393.362.745,43 kn, a na cijepljenje protiv bolesti COVID-19 je potrošeno 594.618.516,00 kn. Bolest COVID-19 odnijela je mnogo života kroz dvije godine, te je zbog iste bilo potrebno socijalno distanciranje koje je uključivalo izolacije i samoizolacije. Sve to skupa veliki je trošak za zdravstveni sustav.The end of 2019 was marked by the arrival of SARS-CoV-2, the virus behind the disease called COVID-19. Shortly after, WHO announced the pandemic of the disease. The virus affects primarily the respiratory system, causing different symptoms ranging from mild exhaustion, dyspnea, loss of taste and smell, to life-threatening such as systematic infenction, lung infection and even death. In the following text we have analyzed the cost that COVID-19 put on the hospitals in the Republic of Croatia. COVID-19 and respirator-use related DRG is A06Z, tracheostomy or ventilation > 95 hours. That is the intense work group which, on June 6 2022, had the cost of 123.552 HRK. That is the amount that hospitals charge the HZZO. Average duration of hospital treatment for the A06Z group is 15,67 days, while the ×TRIM× is 47 days. Furthermore, we have shown what is the limit at which the HZZO will not cover further expenses fully. We made an analysis of the duration of hospital treatment, the cost of materials, medicines etc. since 2019 for the A06Z group. HZZO spent 4.150.106.390,36 HRK battling the disease from the beginning of the pandemic to the end of year 2021. Screening alone costed 1.393.362.745,43 HRK, while the vaccination carried the price of 594.618.516,00 HRK. Needless to say, COVID-19 took a much greater toll in human lives during those 2 years, in addition to social distancing and quarantining and self-quarantining. All that combined is a huge expense for the healthcare providers
Procjena potrebe za depreskripcijom inhibitora protonske pumpe u bolesnika starije životne dobi
No full textCilj istraživanja: Cilj je ovog istraživanja procijeniti racionalnost korištenja inhibitora protonske pumpe (IPP) kod bolesnika starije životne dobi i pomoću kriterija sastavljenih prema smjernicama Depreskripcija inhibitora protonske pumpe (Canadian family physician), odrediti udio bolesnika kojima bi depreskripcija IPP-a donijela korist.
Ispitanici i metode: Istraživanje je provedeno na uzorku 391 bolesnika starije životne dobi u sklopu EuroAgeism Horizon 2020 projekta. Podaci su prikupljeni u javnim ljekarnama pomoću upitnika razvijenog za potrebe ovog istraživanja. Na temelju smjernica za depreskripciju IPP-a (Depreskripcija inhibitora protonske pumpe, Canadian family physician) definirano je pet kriterija prema kojima se odlučivalo o potrebi za depreskripcijom IPP-a kod bolesnika koji su ih imali u terapiji.
Rezultati: U ispitivanju je sudjelovao 391 ispitanik (248 žena i 143 muškarca). Prosječna je dob ispitanika 74,33 (SD=10,65) godine, a u terapiji su imali prosječno šest lijekova. IPP je koristilo 122 (32,0%) ispitanika, a najčešće korišteni bio je pantoprazol. Pomoću kriterija za depreskripciju dobiveni su rezultati da bi 25 (20,5%) ispitanika moglo imati korist od depreskripcije IPP-a. Najviše ispitanika kandidati su za depreskripciju prema kriteriju C: Navedena indikacija za IPP je gastroprotekcija, ali ne postoji jasna potreba za njom, a iza njega slijedi kriterij B: indikacija je prisutna u bolesnikovoj anamnezi, ali ne uključuje dugotrajno korištenje IPP-a, te je trenutno trajanje terapije predugo.
Zaključak: Rezultati ovog istraživanja ukazali su na potrebu za racionalnijim korištenjem IPP-a u bolesnika starije životne dobi te su pokazali u kojim bi situacijama bolesnici od depreskripcije mogli imati koristi. Smjernice i kriteriji koji definiraju potrebu za depreskripcijom mogli bi biti vrijedan alat i pridonijeti racionalizaciji uporabe IPP-a.
Potencijalna korist depreskripcije bila bi povećanje racionalizacije farmakoterapije IPP-ovima; manji broj lijekova u terapiji, smanjenje mogućnosti pojave interakcija s drugim lijekovima ili nuspojava do kojih može doći zbog dugotrajne primjene te financijska ušteda za zdravstveni sustav i bolesnike.Objectives: The objective of this study was to determine rationality of proton pump inhibitor (PPI) use among older adults and to identify patients who would benefit from PPI deprescription based on deprescribing guidelines (Deprescribing proton pump inhibitors, Canadian Family Physician).
Patients and Methods: 391 older adult patients participated in the study which is part of EuroAgeism Horizon 2020 research. Data was collected in community pharmacies using a standardized questionnaire. Based on the deprescribing guidelines for PPI (Deprescribing proton pump inhibitors) five criteria for deprescribing were defined and used to determine the need for deprescribing PPI among the patients that use them.
Results: 391 patients participated in this study (248 women and 143 men). On average, they were 74,33 (SD=10,65) years old, and were prescribed on average 6 different medications. 122 patients had PPI in their therapy, and the most commonly used was pantoprazole. Based on deprescription criteria, 25 (20,5%) patients could benefit from deprescription of PPI. The majority of patients are candidates for deprescription primarily according to the criteria C: the indication for PPI use is gastroprotection, but there is no clear need for it, and secondarily criteria B: the indication is present in patient's history, but it doesn't include long-term use of PPI and it is used for too long.
Conclusion: The results of this research indicate the need for a more rational use of PPI in older patients and situations where deprescription is recommended and beneficial. Guidelines and criteria which define the need for deprescription could provide a valuable tool for the rationalisation of PPI use.
A potential benefit of deprescription would be an increase in rational use of PPI; fewer medications in therapy, reduced risk of interactions with other drugs or side effects that may occur due to long-term use, as well as financial benefits for the healthcare system and the patients
The effect of bisphenol A on oxidative stress parameters in onion (Allium cepa L.) roots
No full textCilj ovog rada bio je ispitati fitotoksičnost i oksidacijski stres kao mehanizam toksičnosti bisfenola A (BPA) u korjenčićima običnog luka (Allium cepa L.). Korjenčići lukovica luka (n = 10) bili su izloženi ili destiliranoj vodi (negativna kontrola) ili otopinama BPA (koncentracijski raspon 1-50 mg/l) kroz tri dana. Nakon trodnevne izloženosti, izvagana je masa svježeg tkiva korjenčića svake od lukovica te je pripremljen homogenat korjenčića luka u 5 % TCA (100 mg tkiva u 0,5 ml 5 % TCA). U supernatantu tako pripremljenog homogenata određeni su parametri oksidacijskog stresa: sadržaj reduciranog glutationa (GSH) i malondialdehida (MDA), a u talogu homogenata određen je sadržaj proteinskih karbonila. Sadržaj GSH određen je metodom prema Ellmanu (1959), MDA tiobarbituratnim testom, a proteinski karbonili metodom prema Levinu i sur. (1990), derivatizacijom karbonilne skupine proteina uz DNPH. Dobiveni rezultati statistički su obrađeni studentovim t-testom (Excell, MS Office). Masa svježeg tkiva korjenčića luka tretiranih otopinama BPA (1-50 mg/l) bila je niža u odnosu na negativnu kontrolu te je značajno smanjenje mase zabilježeno već nakon izloženosti BPA u koncentraciji 5 mg/l. Pad mase svježega tkiva s povećanjem koncentracije BPA ukazuje na fitotoksično djelovanje BPA na korjenčiće običnog luka. Sadržaj GSH bio je značajno niži u odnosu na kontrolu nakon izloženosti BPA u koncentraciji 1 mg/l. Značajan porast u odnosu na negativnu kontrolu sadržaja proteinskih karbonila zabilježen je nakon izloženosti BPA u koncentraciji 10 mg/l, a MDA nakon izloženosti 25 mg/l. Pad razine antioksidansa (GSH) i porast razine parametara oksidacijskog oštećenja lipida i proteina (MDA i proteinski karbonili) upućuju na to da je BPA izazvao oksidacijski stres u modelnom organizmu. Dobiveni rezultati pokazuju da BPA uzrokuje oksidacijsko oštećenje staničnih struktura te se može zaključiti da je oksidacijski stres jedan od mehanizama toksičnog učinka BPA.The aim of this study was to explore phytotoxicity and oxidative stress as a mechanism of bisphenol A (BPA) toxicity in onion roots (Allium cepa L.). Roots of onion bulbs (n = 10) were exposed to either distilled water (negative control) or BPA solutions (concentration range 1-50 mg/l) for three days. After a three-day exposure, the fresh root weight of each bulb was weighed, and in 5% TCA a homogenate of onion roots was prepared (100 mg of tissue in 0.5 ml of 5% TCA). In the supernatant of prepared homogenate oxidative stress parameters: the content of reduced glutathione (GSH) and malondialdehyde (MDA) was determined, and in the homogenate’s precipitate the content of protein carbonyls was assessed. The GSH content was determined based on the Ellman method (1959), MDA by using the thiobarbiturate test and the content of protein carbonyls was determined according to Levin et al. (1990), by derivatization of the proteins’ carbonyl group with DNPH. The obtained results were statistically analysed by student’s t-test (Excel, MS Office).The fresh tissue weight of onion roots treated with BPA (in concentration range 1-50 mg/l) was lower compared to the negative control, and a significant decrease in roots fresh weight was recorded already after exposure to BPA in concentration of 5 mg/l. The decrease in fresh tissue weight with increasing BPA concentration indicates that BPA had phytotoxic effect on onion roots. The exposure to BPA in concentration of 1 mg/l significantly decreased the content of GSH compared to the control. A significant increase compared to the negative control in the content of protein carbonyls was recorded after exposure to BPA in concentration of 10 mg/l, and MDA after exposure to BPA in concentration of 25 mg/l. A decrease in the level of antioxidants (GSH) and an increase in the level of lipid and protein oxidative damage parameters (MDA and protein carbonyls) indicate that BPA caused oxidative stress in the model organism. The obtained results imply that BPA caused oxidative damage to cellular structures, thus can be concluded that oxidative stress is one of the mechanisms of BPA toxicity
Topikalni pripravci za ublažavanje dermatoloških nuspojava antitumorskih lijekova
No full textCilj istraživanja
Specijalistički rad detaljno opisuje topikalne pripravke koji se koriste u prevenciji i liječenju
dermatoloških nuspojava povezanih s primjenom konvencionalne i biološke terapije kod onkoloških
pacijenata. U radu su opisane glavne karakteristike najučestalijih dermatoloških nuspojava, njihova
klinička slika, inicidencija te mogući mehanizmi nastanka. Također su opisani topikalni pripravci i
fizikalne metode te opće potporne mjere koji su obuhvaćeni literaturom prevencije i liječenja
dermatoloških nuspojava. Nuspojave obuhvaćene radom odnose se na sindrom šaka-stopalo,
papulopustularni osip, promjene na noktima, pruritus, kserozu, promjene u rastu dlake, fotoosjetljivost,
oralni mukozitis, pigmentacijske promjene, lihenoidni dermatitis, Raynaudov fenomen, flagelatni
dermatitis i ekstravazacijske ozljede. Spomenuti su i teški oblici kožnih reakcija koji zahtijevaju hitnu
hospitalizaciju.
Cilj ovog specijalističkog rada je sustavnim pregledom dostupnih topikalnih pripravaka i
fizikalnih metoda za ublažavanje dermatoloških nuspojava antitumorskih lijekova potaknuti izradu
smjernica za njihovo liječenje te osvijestiti pacijente i zdravstvene djelatnike o mogućnostima i važnosti
njege kože prije, tijekom i nakon procesa liječenja.
Materijal i metode
Materijal za izradu ovog specijalističkog rada sastoji se od relevantnih stručnih i znanstvenih
članaka koji obrađuju problematiku dermatoloških nuspojava povezanih s primjenom antitumorske
terapije i topikalne pripravke koji se koriste za njihovo ublažavanje. Osim stručnih članaka korišteni su i
podaci službenih web-stranica relevantnih za temu rada.
Literatura je pretraživana prema temi istraživanja, predmetu istraživanja, autorima i časopisu.
Pri proučavanju relevantnih članaka izdvojeni su najvažniji rezultati, rasprave i zaključci. Na
temelju proučavanih članaka izvedena su vlastita razmatranja proučavane problematike koja su
sastavni dio rasprave ovog specijalističkog rada.
Literatura je pretraživana putem baza podataka PubMed, Google Scholar i Cochrane Library
korištenjem sljedećih ključnih riječi: anticancer agents, cutaneous adverse reactions, management,
targeted therapies, topical preparations, vehicles.
Rezultati
Unatoč brojnim studijama koje se bave problematikom dermatoloških nuspojava nastalih uslijed
primjene antitumorskih lijekova, još uvijek za većinu njih nisu razvijene jasne smjernice i protokoli
liječenja. Nedostatak kliničkih studija najčešće je premali broj ispitanika i prekratko vrijeme njihova
provođenja. Pacijenti često ne prijavljuju dermatološke nuspojave, osobito kada se javljaju izvan
bolničkih uvjeta, te ih ne povezuju s terapijom.
Kod onkoloških pacijenata topikalni oblici liječenja imaju prednost pred sistemskom terapijom
zbog politerapije. Većina topikalnih lijekova koji su u receptnom režimu koristi se off-label, tj. izvan
odobrene indikacije, temeljem iskustva kliničara i brojnih studija u liječenju dermatoloških nuspojava,
kao što su topikalni kortikosteroidi, inhibitori kalcineurina, analozi vitamina D i retinoidi. Brojni kozmetički
i medicinski proizvodi, primjerice ovlaživači, keratolitici, fotozaštitna i antimikrobna sredstva, široko su
dostupni pacijentima u slobodnoj prodaji uz preporuku prethodnog savjetovanja s ljekarnikom ili drugim
zdravstvenim djelatnikom koji ga izdaje, u svrhu njihove racionalne i odgovorne primjene.
Nanotehnologija je omogućila razvoj suvremenih podloga i formulacija poboljšanih svojstava,
prije svega bioraspoloživosti, koje su prihvatljivije pacijentu i olakšavaju mu primjenu, što u konačnici
dovodi do terapijskog cilja.
Iako su mogućnosti prevencije i liječenja dermatoloških nuspojava antitumorskih lijekova doista
raznolike, još uvijek je zabilježena njihova relativno visoka incidencija.
Zaključak
Pravilnim odabirom topikalnog pripravka čiji je sastav prikladan oboljelom području kože uz
uvažavanje afiniteta pacijenta moguće je utjecati na pojavnost i tijek brojnih dermatoloških nuspojava
bez potrebe za prekidom ili prilagodbom osnovnih terapijskih postupaka.
S obzirom na konstantni porast broja onkoloških pacijenata, a time i primjene biološke terapije
koja je praćena većom incidencijom dermatoloških nuspojava, potrebno je na temelju što većeg broja
provedenih studija razviti opće smjernice za njihovu prevenciju i liječenje.Objectives
This expert thesis describes in detail the topical formulations used for prevention and treatment
of dermatological side effects associated with the application of conventional and biological treatment
with oncology patients. The paper describes the main characteristics of the most frequent dermatological
side effects, their clinical picture, incidence and possible mechanisms of occurrence. The topical
formulations and physical methods, as well as general support measures are also described, which are
encompassed with the literature for prevention and treatment of dermatological side effects. The side
effects included in this paper refer to the hand-foot syndrome, papulopustular rash, changes on the
fingernails, pruritus, xerosis, changes in hair growth, photosensitivity, oral mucositis, altered
pigmentation, lichenoid dermatitis, Raynaud's phenomenon, flagellate dermatitis, and extravasation
injuries. Severe forms of skin reactions which require urgent hospitalization are also mentioned.
The goal of this expert thesis is to, by systematic overview of available topical formulations and
physical methods for relieving dermatological side effects of anticancer medications, encourage the
development of guidelines for their treatment and to make patients and healthcare workers aware of the
possibilities and importance of skin care prior to, during, and after the treatment process.
Material and methods
The material for drafting this expert thesis is comprised of relevant expert and scientific articles
which address the issue of dermatological side effects associated with the application of anticancer
therapy and topical formulations which are used for their alleviation. Besides expert articles the data
from official websites relevant for the topic of the paper were used.
Literature was searched pursuant to the research topic, research subject, authors, and journal.
When studying relevant articles, the most important results, discussions, and conclusions were
extracted. Based on the studied articles, own considerations of the studied problematic were derived
which are an integral part of the discussion of this expert thesis.
Literature was searched through PubMed, Google Scholar, and Cochrane Library databases,
by using the following keywords: anticancer agents, cutaneous adverse reactions, management,
targeted therapies, topical preparations, vehicles.
Results
Despite numerous studies dealing with the issue of dermatological side effects caused by the
application of anticancer medications, for most of them clear treatment guidelines and protocols have
not yet been developed. The flaws of clinical studies are most often too few respondents and too short
time of their conduction. The patients often don't report dermatological side effects, especially when they
occur outside of hospital settings, and they don't link them with the treatment.
In oncology patients, topical forms of treatment have an advantage to systemic therapy due to
polytherapy. Most of topical medication which are in the prescription regime are used off-label, i.e.
beyond the approved indication, based on the experience of clinicians and numerous studies in treating
dermatological side effects, such as topical corticosteroids, calcineurin inhibitors, vitamin D analogues,
and retinoids.
Numerous cosmetic and medical products, for example moisturizers, keratolytics,
photoprotective and antimicrobial agents are widely available to patients in free sale with the
recommendation of previous consultation with a pharmacist or other healthcare professional who issues
it, for the purpose of their rational and responsible application.
Nanotechnology has enabled the development of modern foundations and formulations with
improved properties, primarily bioavailability, which are more acceptable to the patient and facilitate him
the application, which ultimately leads to the therapeutic goal.
Although the possibilities of prevention and treatment of dermatological side effects of
anticancer medications are truly diverse, their relatively high incidence is still recorded.
Conclusion
By choosing the right topical formulations whose composition is suitable for the affected area of
skin with respect to the affinity of the patient it is possible to influence the incidence and course of
numerous dermatological side effects without the need to interrupt or adjust basic therapeutic
procedures.
Given the constant increase in the number of oncology patients, and thus the application of
biological therapy accompanied by a higher incidence of dermatological side effects, it is necessary to
develop general guidelines for their prevention and treatment based on as many studies as possible
Antihypertensive drug usage in Croatia and pharmacoeconomic analysis
No full textOdabir antihipertenzivnog liječenja ima važne terapijske i financijske implikacije, a tek rijetke smjernice za liječenje arterijske hipertenzije (AH) uključuju farmakoekonomske analize. Cilj istraživanja je identificirati i analizirati: promjene u upotrebi lijekova za liječenje AH u Hrvatskoj od 2000. do 2016. godine, promjene u obrascima propisivanja, prosječne cijene po definiranoj dnevnoj dozi (DDD), te provesti analizu troška i učinkovitosti liječenja AH u usporedbi sa scenarijem bez intervencije (BI) lijekovima: diuretici (D), blokatori kalcijskih kanala (C), beta-blokatori (B), inhibitori angiotenzin konvertirajućeg enzima / blokatori angiotenzinskih receptora (A). Podaci o potrošnji lijekova prikupljeni su iz Intercontinental Medical Statistics (IMS) baze podataka. Analiza troška i učinkovitosti obuhvatila je pet zdravstvenih stanja u Markovljevom modelu, odvojeno za muškarce i žene u dobi od 65 godina. Rezultati su predstavljeni kao povećanje QALY-a i povezanih financijskih ušteda ili troškova u eurima (EUR) za svaku terapijsku opciju u usporedbi sa scenarijem BI. Od 2000. do 2016. godine potrošnja lijekova za KVB rasla je 150,81%, a financijski izdaci rasli su 47,32%. Najčešće propisivani bili su lijekovi koji djeluju na renin-angiotenzinski sustav. Analiza troška i učinkovitosti za muškarce pokazuju da je liječenje s D rezultiralo povećanjem QALY-ja za 0,76 i uštedom od 886 EUR, liječenje s C povećanjem od 0,74 QALY-ja i uštedom od 767 EUR, liječenje s A povećanjem od 0,69 QALY-ja i uštedom od 834 EUR, liječenje s B povećanjem od 0,40 QALY-ja, ali uz dodatni trošak od 41 EUR. Rezultati za žene (u usporedbi s BI): liječenje s D rezultiralo je povećanjem od 0,93 QALY-ja i uštedom od 987 EUR, liječenje s C povećanjem od 0,89 QALY-ja i uštedom od 855 EUR, liječenje s A povećanjem od 0,86 QALY-a i uštedom od 991 EUR, liječenje s B povećanjem od 0,48 QALY-a, ali uz dodatan trošak od 148 EUR. U Hrvatskoj je primijećena promjena obrazaca propisivanja lijekova za liječenje AH, što je rezultat: promjene zakonskih akata, utjecaja farmaceutske industrije i utjecaja smjernica za liječenje AH na propisivanje. Liječenje AH s D, C i A isplativo je u usporedbi sa scenarijem bez intervencije. Liječenje sa D predstavlja najisplativiju terapijsku opciju. Liječenje s B rezultiralo je povećanjem QALY-ja u usporedbi s BI ali uz dodatan trošak, pa na temelju rezultata istraživanja ova terapija nije preporučena kao prvi izbor u liječenju. Promjenom varijabli model može biti ponovno korišten, što može pridonijeti uvrštenju rezultata farmakoekonomskih analiza u nacionalne smjernice za liječenje AH, a time i racionalnijem liječenju AH u Hrvatskoj.The choice of pharmacologic treatment in people with arterial hypertension (AH) has important therapeutic and financial implications. Guidelines for treatment of hypertension often do not include outcomes of pharmacoeconomic evaluations. The aims of our study were to identify and analyze changes in the usage of drugs for treating AH in Croatia from 2000 to 2016, changes in prescribing patterns and mean prices per defined daily dose (DDD), evaluate cost-effectiveness comparing diuretics (D), beta-blockers (B), angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers (A) and calcium channel blockers (C) with no intervention (NI). Data on consumption were obtained from the International Medical Statistics (IMS) database. The pharmacoeconomic study included five health states in a Markov model separately for 65-year old men and women. The results were presented in terms of increase in QALYs and associated financial savings or costs in euros (€) for each therapeutic option comparing with NI. The consumption of drugs for cardiovascular disease in Croatia from 2000 to 2016 increased 150.81%, while financial expenditure in the same period increased 47.32%. The most frequently prescribed subgroup was Agents acting on the renin-angiotensin system (RAS). Results for men (compared with NI): treatment with D resulted in a QALY increase of 0.76 and €886 in savings, treatment with C in an increase of 0.74 QALYs and €767 in savings, treatment with A in an increase of 0.69 QALYs and €834 in savings, treatment with B resulted in an increase of 0.40 QALYs, but with an additional cost of €41. Results for women: treatment with D resulted in an increase of 0.93 QALYs and €987 in savings, treatment with C in an increase of 0.89 QALYs and savings of €855, treatment with A in an increase of 0.86 QALYs and savings of €991, treatment with B in an increase of 0.48 QALYs, but with an additional cost of €148. The prescribing patterns of antihypertensive drugs in Croatia have changed, which could be a result of a: changes in laws, pharmaceutical marketing, guidelines on hypertens
ion therapy. Treatment of AH with D, C and A is cost effective compared with the no-intervention scenario. Diuretics are the most cost-effective first-line treatment. The scenario with B resulted in additional QALY when compared with no intervention, but also additional costs; therefore, based on our results, this therapy would not be recommended as first-line treatment. By changing the variables, the model can be used again, which can contribute to the inclusion of the results of pharmacoeconomic analyzes in the national guidelines for the treatment of AH, and thus to a more rational treatment of AH in Croatia
Determining therapeutic problems of patients with diseases of the nervous system collected during vocational training
No full textCilj istraživanja: Cilj ovog diplomskog rada bio je utvrditi terapijske probleme i njihove uzroke prisutne kod pacijenata koji boluju od bolesti živčanog sustava te ih usporedit s terapijskim problemima i uzrocima terapijskih problema prepoznatih od strane studenata na Stručnom osposobljavanju u javnoj ljekarni tijekom pete godine studija farmacije na Farmaceutsko-biokemijskom fakultetu Sveučilišta u Zagrebu.
Ispitanici i metode: Provedena je opservacijska retrospektivna studija koja je uključivala analizu podataka prikupljenih od strane studenata u javnim ljekarnama za vrijeme Stručnog osposobljavanja u razdoblju od travnja 2019. do svibnja 2020. Prikupljeni su podaci o općim karakteristikama pacijenta, prisutnim komorbiditetima, lijekovima u terapiji, prepoznatim terapijskim problemima i njihovim uzrocima te o planu ljekarničke skrbi. Za identifikaciju terapijskih problema korišten je alat razvijen od strane Cipolle i suradnika. Nakon određivanja terapijskih problema i njihovih uzroka, procijenjena je uspješnost određivanja terapijskih problema od strane studenata.
Rezultati: Ukupno je obrađeno 70 pacijenata od kojih je 47 (60,14%) žena i 23 (32,85%) muškaraca. Srednja vrijednost životne dobi iznosila je 53,84±17,2, prosječan broj komorbiditeta 4,47±2,00, a prosječan broj lijekova u terapiji 6,27±2,38. Ukupno je prepoznato 215 terapijskih problema svaki pacijent imao je barem jedan terapijski problem dok je prosječan broj terapijskih problema iznosio 3,07±1,41. Najviše terapijskih problema utvrđeno je u kategoriji indikacija (n=80, 37,21%), zatim u kategoriji sigurnost (n=76, 35,35%), slijedi kategorija učinkovitost (n=35, 16,28%) te na posljednjem mjestu nalazila se kategorija suradljivost (n=24, 11,16%). Od ukupnog broja terapijskih problema studenti su prepoznali i ispravno kategorizirali njih 16 (7,44%), 60 terapijskih problema (27,91%) ostalo je u potpunosti neprepoznato, dok su ostali terapijski problemi bili prepoznati ali netočno klasificirani.
Zaključak: Iz svega navedenog možemo zaključiti da je kod pacijenata s bolestima živčanog sustava prisutan veliki broj terapijskih problema. Vrlo je važno pravovremeno prepoznati terapijske probleme i njihove uzroke te ih spriječiti kako bi se osigurali pozitivni ishodi liječenja i kako bi se smanjili troškovi u zdravstvu. S obzirom na uspješnost prepoznavanja terapijskih problema možemo zaključit da studenti nisu dovoljno upoznati s terapijskim problemima i njihovom kategorizacijom te da je potrebno dodatno se posvetiti njihovoj edukaciji s ciljem razvoja kompetentnih stručnjaka koji će nakon završetka fakulteta moći adekvatno pružati ljekarničku skrb.Research objectives: The objective of this study was to determine therapeutic problems and their causes present in patients with diseases of the nervous system and compare them with therapeutic problems and causes of therapeutic problems identified by students in vocational training in public pharmacy during the fifth year of pharmacy study on Faculty of Pharmacy and Biochemistry, University of Zagreb.
Subjects and methods: An observational retrospective study was conducted that included an analysis of data collected by students in public pharmacies during the vocational training in the period from April 2019 to May 2020. Data were collected on general patient characteristics, present comorbidities, drugs in therapy, identified therapeutic problems and their causes, and a pharmacy care plan. A tool developed by Cipolla et al. was used to identify therapeutic problems. After determining the therapeutic problems and their causes, the success of the determination of therapeutic problems by students was assessed.
Results: A total of 70 patients were treated, of which 47 (60.14%) were women and 23 (32.85%) were men. The mean age was 53.84 ± 17.2, the mean number of comorbidities was 4.47 ± 2.00, and the mean number of drugs in therapy was 6.27 ± 2.38. A total of 215 therapeutic problems were identified each patient had at least one therapeutic problem while the average number of therapeutic problems was 3.07 ± 1.41. Most therapeutic problems were found in the category of indications (n = 80, 37.21%), followed by the category of safety (n = 76, 35.35%), followed by the category of efficacy (n = 35, 16.28%) and the last place was the category of cooperation (n = 24, 11.16%). Of the total number of therapeutic problems, students recognized and correctly categorized 16 of them (7.44%), 60 therapeutic problems (27.91%) remained completely unrecognized, while other therapeutic problems were recognized but incorrectly classified.
Conclusion: From all the above we can conclude that patients with diseases of the nervous system have a large number of therapeutic problems. It is very important to identify therapeutic problems and their causes in a timely manner and to prevent them in order to ensure positive treatment outcomes and to reduce healthcare costs. Given the success of recognizing therapeutic problems, we can conclude that students are not sufficiently familiar with therapeutic problems and their categorization and that it is necessary to further dedicate themselves to their education in order to develop competent professionals who will be able to adequately provide pharmacy care
Development of ophthalmic secondary cationic nanoemulsions for incorporation of poorly soluble glucocorticoids
No full textNanoemulzije se ističu kao inovativni farmaceutski oblik s velikim potencijalom u liječenju bolesti suhog oka. Prednosti nanoemulzija temelje se na njihovoj strukturi i sastavu koje imaju učinak nadomještanja i stabilizacije suznog filma te na mogućnosti uklapanja slabo topljivih gluokokoritikoida kao što je loteprednol etabonat, djelatna tvar nedavno odobrena u liječenju blagih do umjerenog oblika bolesti suhog oka. Poseban potencijal imaju kationske nanoemulzije, zbog dobrih svojstava širenja po površini oka pri primjeni te produljenom zadržavanju na površini oka. Cilj ovog diplomskog rada bio je razviti sekundarnu kationsku U/V nanoemulziju s kitozanom pogodnu za uklapanje loteprednol etabonata. Nanoemulzije U/V tipa izrađene su visokoenergetskom metodom mikrofluidizacije. Kao ulja faza odabran je Capryol 90 zbog dobre topljivosti loteprednol etabonata u toj uljnoj fazi. Razvoj nanoemulzije proveden je u tri faze, (i) probir vrste i udjela neionske površinski aktivne tvari, (ii) probir vrste i udjela anionske površinski aktivne tvari te (iii) probir udjela niskomolekulskog kitozana. U svih fazama razvoja provedena je fizičko-kemijska karakterizacija nanoemulzija u vidu određivanja veličine i raspodjele veličina kapljica disperzne faze te zeta-potencijala. Na temelju provedene fizičko-kemijske karakterizacije sekundarna kationska nanoemulzija s 0,05 % (m/m) kitozana, 5 % (m/m) Capryola® 90, 0,25% (m/m) makrogol 15 hidroksistearata i 0,1% (m/m) lecitina Lipoid S75 ističe se kao vodeća formulacija s najvećim potencijalom za uklapanje loteprednol etabonata.Nanoemulsions stand out as an innovative dosage form with great potential in the treatment of dry eye disease. The benefits of nanoemulsions are based on (i) their structure and composition, which have the effect of replacing and stabilizing the tear film; and (ii) the ability to incorporate poorly soluble glucocorticoids such as loteprednol etabonate, an active substance recently approved in the treatment of mild to moderate dry eye disease. Cationic nanoemulsions have a unique potential due to their good spreading properties on the eye surface and prolonged retention on the eye surface. The aim of this thesis was to develop a secondary cationic O/W nanoemulsion with chitosan suitable for the incorporation of loteprednol etabonate. O/W type nanoemulsions are prepared by microfluidization. Capryol® 90 was chosen as the oil phase due to the good solubility of loteprednol etabonate in this oil phase. The development of the nanoemulsion was carried out in three phases, (i) screening of the type and content of nonionic surfactants, (ii) screening of the type and content of anionic surfactants, and (iii) screening of the content of low molecular weight chitosan. In all phases of development, physicochemical characterization of nanoemulsions was performed in the terms of determining the size and size distribution of droplets of the dispersed phase and zeta potential. Based on the performed physicochemical characterization, the secondary cationic nanoemulsion with 0.05% (w/w) chitosan, 5% (w/w) Capryola® 90, 0.25% (w/w) macrogol 15 hydroxystearate and 0.1% (w/w) Lecithin Lipoid® S75 stands out as the leading formulation with the greatest potential for incorporation of loteprednol etabonate