Onečišćenja u ljekovitom bilju i biljnim proizvodima

Medicinal plants have a long history of use in therapy throughout the world and still make an important part of traditional medicine. Thus, medicinal plants and herbal products must be safe for the patient (consumer). This review addresses biological contaminants (microbes and other organisms) and chemical contaminants (mycotoxins, toxic elements such as heavy metals, and pesticide residues) as major common contaminants of medicinal herbs and herbal products. To prevent and screen for contamination and ensure safety and conformity to quality standards, medicinal herbs and herbal products should be included in appropriate regulatory framework.Ljekovito bilje i biljni proizvodi već tisućljećima nalaze široku primjenu u različitim sustavima tradicionalnog liječenja. Stoga je njihova neškodljivost, ponajprije uvjetovana kakvoćom biljne sirovine, od izuzetne važnosti za javno zdravstvo. Od mogućih čimbenika koji utječu na kakvoću ljekovitog bilja i biljnih proizvoda ovaj pregledni rad osvrće se na najčešće prisutna biološka (mikroorganizmi) i kemijska onečišćenja (mikotoksini, toksični elementi poput teških metala te ostaci pesticida). S ciljem postizanja ujednačenih standarda kakvoće te osiguranja sigurnosti primjene biljnih proizvoda od vitalne su važnosti zakonski propisi koji moraju u odgovarajućim regulatornim okvirima obuhvatiti ovu skupinu proizvoda s naglaskom na sprječavanju i ispitivanju njihovih mogućih onečišćenja

Polyphenolic Profiling of Croatian Propolis and Wine

Polifenoli su široko rasprostranjeni prirodni spojevi, koji uz farmakološko djelovanje imaju i bakteriostatski/baktericidni, antifungalni, protuupalni, kemopreventivni, citostatski, imunomodulacijski i antioksidacijski učinak. Upotrebljavaju se kao funkcionalna hrana u svakodnevnoj prehrani, a u većoj su količini prisutni u propolisu, vinu i različitom ljekovitom bilju. U ovom su radu opisani postupci kemijske analize (spektrofotometrija, visokodjelotvorna tekućinska kromatografija, visokodjelotvorna tankoslojna kromatografija, vezani sustav plinske kromatografije i spektrometrije masa, itd.) polifenola, tj. udjela flavonoida i fenolnih kiselina za određivanje autentičnosti i porijekla propolisa i vina. Navedene su analize osnova za kontrolu kvalitete propolisa, vina i ostalih prehrambenih dodataka koji pozitivno utječu na zdravlje.Polyphenols are ubiquitous natural compounds that show chemopreventive, cytostatic, immunomodulatory, bacteriostatic/bactericidal, antifungal, anti-inflammatory, antioxidant and many other pharmacological activities. Propolis, wine and many medicinal plants used in everyday life as functional food present rich sources of polyphenols. In this paper we focus on their production, chemical analysis (spectrophotometry, HPLC, HPTLC, GC/MS, etc.) of flavonoids and phenolic acids, all of which enable authentication and geographical traceability of propolis and wine. This represents the basis for quality control and regulatory framework for any dietary supplement claiming to have beneficial health effectiveness

Nuspojave antidijabetika prijavljene Hrvatskoj agenciji za lijekove i medicinske proizvode

Uvod. Šećerna bolest (ŠB) je kronična i progresivna bolest, zahvaća sve dobne skupine i u stalnom je porastu. Komplikacije dovode do trajnih invalidnosti, poskupljenja zdravstvene skrbi i preuranjene smrti. Upravo iz tih razloga rano otkrivanje i pravovremeno liječenje ŠB mogu donijeti velike uštede u zdravstvu kao i osigurati bolju kvalitetu života bolesnika. Zbog progresivnog tijeka ŠB monoterapija se obično proširuje na liječenje dvojnom ili trojnom kombinacijom antidijabetika kako bi se kroz dulji period održala zadovoljavajuća kontrola glikemije. Dodatno se mora posvetiti pažnja liječenju komorbiditeta, a nerijetko i već nastalih komplikacija, čime se povećava rizik od nuspojava i interakcija te negativno utječe na suradljivost pacijenta. S ciljem optimizacije terapije, liječenje oboljelih zahtijeva individualiziran pristup i kontinuiran nadzor svih čimbenika rizika. Cilj istraživanja. Mogućnosti liječenja oboljelih posljednih su godina proširene dostupnošću novih antidijabetika čiji sigurnosni profil treba još dodatno razjasniti. Poznavanje nuspojava lijekova, osobito u pojedinih skupina bolesnika s posebnim rizicima, jedan je od osnovnih uvjeta za planiranje racionalne farmakoterapije. Stoga je cilj ovog rada prikazati karakteristike nuspojava antidijabetika (ATK skupina A10) prijavljenih Hrvatskoj agenciji za lijekove i medicinske proizvode (HALMED) tijekom sedmogodišnjeg razdoblja (2010.–2016.) te ih usporediti s njihovom nacionalnom potrošnjom u istom periodu. Materijal i metode. Nacionalne sigurnosne prijave pojedinačnih slučajeva nuspojava antidijabetika pretražene su u razdoblju od 01. siječnja 2010. do 31. prosinca 2016. god. pomoću programskog alata VigiLyze svjetske baze nuspojava VigiBase. Slučajevi nuspojava analizirani su do pete razine ATK-a s obzirom na učestalost prijavljivanja, dob i spol bolesnika, pripadnost nuspojave prema klasifikaciji organskih sustava i ozbiljnost nuspojave. Dodatno su razmatrane prijave nuspojava za koje je prijavitelj naznačio da su potencijalno posljedica interakcije lijekova u istodobnoj primjeni, a pritom je korišten interakcijski program Micromedex. Također je dan pregled najvažnijih sigurnosnih regulatornih mjera poduzetih za pojedine antidijabetike u navedenom razdoblju prema podacima iz godišnjih Izvješća o nuspojavama lijekova i arhivi Pisama zdravstvenim radnicima na mrežnim stranicama HALMED-a. Istraživanje kretanja nacionalne potrošnje antidijabetika u istom razdoblju provedeno je na temelju rutinski prikupljenih podataka HALMED-a iz javnih i bolničkih ljekarni o broju izdanih originalnih pakiranja pojedinog lijeka. Podaci o potrošnji iskazani su brojem definiranih dnevnih doza na 1000 stanovnika na dan (DDD/TSD) i financijski u kunama (kn), t e s u u spoređeni s v ažećim h rvatskim terapijskim smjernicama. Rezultati. U ispitivanom razdoblju zabilježeno je 620 prijava sumnji na nuspojave antidijabetika, od čega je 130 ozbiljnih prijava. Uočeni porast prijavljivanja nuspojava antidijabetika može se povezati s nekoliko farmakoepidemioloških pokazatelja, od kojih su najznačajniji porast prevalencije bolesti i posljedično kontinuirani rast ukupne potrošnje antidijabetika (osobito novih kombinacija oralnih antidijabetika). Najzastupljeniji su očekivani probavni poremećaji (27,8 %), a sporadično se bilježe i neke rijetke nuspojave, primjerice laktacidoza (metformin), trombocitopenija (repaglinid), dijabetička ketoacidoza (empagliflozin), pankreatitis (linagliptin, liraglutid, metformin/sitagliptin, metformin/vildagliptin), karcinom gušterače (linagliptin, metformin/vildagliptin) i karcinom mokraćnog mjehura (pioglitazon). Najveći broj slučajeva nuspojava antidijabetika očekivano se bilježi u starijoj populaciji (≥ 65 godina) zbog prisutnih komorbiditeta, politerapije i općenito više prevalencije pretežite ŠBT2. Nešto više nuspojava antidijabetika zabilježeno je u bolesnica (56,6 %) što se pripisuje općenitom obrascu raspodjele učestalosti nuspojava lijekova prema spolu pacijenta. Usklađenost propisivanja antidijabetika s hrvatskim terapijskim smjernicama najviše se uočava iz podataka o potrošnji metformina, derivata sulfonilureja i inzulinskih pripravaka, što se odražava i na isto kretanje broja prijava njihovih nuspojava (primjerice, metformin je kao prva linija liječenja ŠBT2 kroz cijelo razdoblje stabilno na prvom mjestu u potrošnji i prijavama nuspojava antidijabetika). Sigurnost primjene lijekova novog mehanizma djelovanja intenzivno se prati pa je i povećano prijavljivanje nuspojava unatoč manjoj potrošnji od standardnih antidijabetika. Za novije antidijabetike razmatran je i velik broj sigurnosnih signala proizašlih iz spontanih prijava nuspojava, od kojih su neki doveli do izmjena u informacijama o lijeku (pioglitazon i karcinom mokraćnog mjehura, vildagliptin i mialgija, SGLT2 inhibitori i dijabetička ketoacidoza) ili povlačenja lijeka s tržišta (roziglitazon i kardiovaskularni rizik). U prijavljenim slučajevima potencijalno uzrokovanim interakcijama lijekova kao najučestalija reakcija prepoznata je hipoglikemija bilo zbog aditivnog učinka kombiniranih antidijabetika ili istodobne primjene s lijekovima u terapiji komorbiditeta (većinom s ramiprilom). Zaključak. Racionalna farmakoterapija i dobro poznavanje sigurnosnog profila antidijabetika ključni su za unaprjeđenje zdravstvene skrbi osoba sa šećernom bolešću. U ovom opservacijskom istraživanju kretanja potrošnje i prijavljivanja nuspojava antidijabetika moguće je prepoznati glavne obrasce propisivanja te potencijalne rizike primjene antidijabetika. Poznavanjem nuspojava antidijabetika u znatnoj se mjeri mogu spriječiti neželjeni učinci i poboljšati ishodi liječenja bolesnika.Background. Diabetes mellitus (DM) is a chronic and progressive metabolic disorder affecting all age groups at epidemic levels worldwide. The complications of DM are the main cause of patient disability, while also leading to an increase in health care costs and premature death. It is therefore important to provide early diagnosis and timely treatment of DM and, in doing so, contribute to achieving significant savings in health care costs and improved quality of life for the patients. Due to the progressive natural course of the disease, in order to maintain glycaemic control over a longer period of time, the monotherapy for DM is commonly intensified by introducing a combination o f t wo o r t hree antidiabetics. Furthermore, treatment of comorbidities and complications is frequently needed which increases the risk of drug use side effects and interactions, and may negatively affects the patient adherence. In order to optimize the therapy for DM, an individualized approach with continuous monitoring of all possible risk factors should be applied in the treatment of DM patients. Objectives. The pharmacotherapeutic options for treating DM have recently been expanded thanks to the emergence of new antidiabetics. However, the safety profiles of such drugs have not been established yet and are subject to additional monitoring. Awareness of possible adverse drug reactions (ADRs), in particular with regard to different groups of patients with special risks, is one of the basic preconditions for planning rational pharmacotherapy. The main objective of this study was therefore to present the characteristics of ADRs of antidiabetic drugs (ATC group A10) reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) during a seven-year period (from 2010 to 2016) and to compare the observed ADRs with related drug utilization rates recorded in the same period at the national level. Material and Methods. For the purposes of this study, antidiabetic drug related Individual Case Safety Reports (ICSRs), submitted in the period from January 1, 2010 to December 31, 2016, were searched using VigiLyze, a tool that allows overview and analysis of national data from the global ICSR database - VigiBase. The reported ADRs were analysed up to the fifth level of ATC system in respect of frequency of reporting, age and sex of the patient, system organ class into which the relevant ADR is classified, and the seriousness of the same. The ADRs indicated by reporting person as potentially caused by drug interactions were also included in the analysis, for which purpose the Micromedex interaction application was used. The paper also provide a review of the most important safety-related regulatory measures, implemented within the observed period for particular antidiabetic drug, according to the data from Annual ADR Reports prepared by HALMED and the archive of Direct Healthcare Professional Communication letters available on HALMED's website. The national antidiabetic drug utilization trends recorded in the same period were analyzed on the basis of the data that HALMED routinely collects from public and hospital pharmacies concerning the number of original packaging dispensed for individual drug. The antidiabetic drug utilization data, expressed in the number of defined daily doses per 1000 inhabitants per day (DDD/TID) and financially in kunas (HRK), were compared with current Croatian therapeutic guidelines. Results. In the observed period, 620 suspected antidiabetic drug related ADRs were reported, of which 130 serious ones. The observed increase in the number of ADR reports can be ascribed to several pharmacoepidemiological indicators. The most significant among such indicators are the increasing prevalence of the disease and the consequent continuous increase in total antidiabetic drug utilization rates (in particular with regard to the new combinations of oral antidiabetics). The most commonly reported ADRs were gastrointestinal disorders (27.8 %) while some rare and serious ADRs, such as lactacidosis (metformin), thrombocytopenia (repaglinid), diabetic ketoacidosis (empagliflozin), pancreatitis (linagliptin, liraglutide, metformin/sitagliptin, metformin/vildagliptin), pancreatic cancer (linagliptin, metformin/vildagliptin) and urinary bladder cancer (pioglitazone), were recorded in sporadic cases. Most ADRs were reported in the elderly (aged 65 and above), which was expected considering the frequent presence of comorbidities, polypharmacy and the greater prevalence of the predominant DMT2. Slightly more ADRs were recorded in female patients (56.6 %), following the general pattern of patient sex distribution of ADRs. Compliance with the Croatian therapeutic guidelines in prescribing antidiabetics was most evident from the data on the use of metformin, sulfonylureas and insulin preparations, and the related ADR reporting trends were analogous (e.g. metformin, as the first-line treatment choice for DMT2, steadily recorded the highest figures in terms of both utilization and ADR reporting). Despite their lower drug utilization, increased ADR reporting was noticed for antidiabetics with new mechanisms of action as they are medicines under additional safety monitoring. Based on the spontaneous ADR reports, a large number of safety signals in the observed period were identified for these new antidiabetics, some of which resulted in the modification of product information (pioglitazone and bladder cancer, vildagliptin and myalgia, SGLT2 inhibitors and diabetic ketoacidosis) or even withdrawal of the drug from the market (rosiglitazone and cardiovascular risk). Among the ADRs indicated in the reports as potentially caused by drug interactions, hypoglycemia was identified as the most frequently occurring adverse reaction due to either the additive effect of combined antidiabetic drugs or the concurrent use of antidiabetics with drugs in therapy of comorbidities (mostly ramipril). Conclusion. Rational pharmacotherapy and in-depth understanding of the safety profiles of antidiabetics is crucial for improving the health care of patients suffering from DM. This observational study of trends in antidiabetic drug utilization and ADR reporting has helped identify the main patterns applied in prescribing antidiabetics and the potential safety risks associated with such drugs. Awareness of adverse reactions to antidiabetic drugs can significantly contribute to the prevention of unwanted effects and improvement of treatment outcomes

Kakvoća homeopatskih proizvoda

Homeopathic medicinal product is any medicine prepared in accordance with a homeopathic manufacturing procedure described by a pharmacopoeia in official use or other officially recognized documents. Starting from variety of source materials (medicinal plants, animal and human materials, pathogens as well as minerals and chemicals), the homeopathic manufacturing procedure includes potentization or dilution of the product into different grades or potencies. Nowdays, the use of homeopathic medicines for self-healing is widespread not only in the European region but also in south Asian countries and North and Souch American countries. With the rapid expansion of their global market, the safety and the quality of homeopathic medicines has become a major concern for the public health. The safety of the homeopathic medicines largely depends on their quality. Two issues are decisive for the quality of homeopathic medicine: determining the authenticity and the origin of the starting materials according to the homeopathic tradition, and defining the manufacturing procedure. Because of the wide range of processing techniques and manufacturing methods in the different pharmacopoeias, the final homeopathic products may show marked variability. Second, the specific nature of homeopathic medicines have as consequence that some of the methods for quality control and some test systems that are mandatory in pharmaceutical regulation, may at times be inapplicable or irrelevant. These include identification and quantification of active substance contained in the final homeopathic product at high potency. In such cases the quality should be demonstrated by complete validation of the manufacturing and dilution process, and also by quality control of the starting material and of the least diluted source employed for potentization (e.g. mother tincture). As long as the identity and purity of starting materials and the reproducibility of the manufacturing process are given, the consistency of quality of homeopathic medicines is assured allowing their safe use

Granični biljni proizvodi

Given that herbal products can have medical, food (nutritional) and cosmetic purposes, the aim of this paper is to show the complexity of their regulatory classification into groups, and the importance of setting harmonized legal framework. Many herbal products due to their characteristics belong t o various regulatory groups so we consider them to be herbal borderline products. Both at European and national level, there are still no clear standards or equal access to herbal products and their classification is not unambiguous since there is still no harmonized legal framework that would allow the same criteria for herbal borderline products. In this paper the examples of classification for some herbal borderline products are shown: herbal medicine - food supplement, herbal medicine - medical device. Also, this paper points out the importance of implementing a harmonized approach to herbal borderline products, so that all of them are released to the market having proven quality and safety for a presented purpose. It can be concluded that since a particular berbal product can be found on the EU market registered in various regulatory groups there is a need for adoption of harmonized legal framework for borderline products on European Union level. Harmonized legal framework for borderline products would define common criteria for classification and therefore facilitate the registration of borderline products. Also, only products of acceptable quality, safety and purpose would be available to consumers and patients

Kakvoća biljnog lijeka

A lot of factors such as temperature, light exposure, water availability, nutritients, period and site of collection, age and part of plant collected, method of collection, processing (drying, chemical/radioactive treatment, ... ), storage and distribution of starting herbal material, etc., can greatly affect the quality and consequently the therapeutic value of herbal medicines. Therefore, it is essential to produce starting material under Good Agriculture and Collection Practice (GACP) conditions. Because of plant's genetic and chemical content variations, the site and date should be recorded for each collection. The production of starting materials by cultivation would normally lead to more consistent herbal products due to greater genetic uniformity. Furthermore, cultivation permits monitoring of active constituents and defining of the best period for harvesting. Whether field collected from the wild or produced by cultivation, botanical authentication of plant species and identification by their binomial Latin names are necessary to insure that the correct herbal material is obtained. Also, care must be taken to free the targeted starting material of undesirable plant parts, soil, insects, animal excreta and other contaminants. During post-collection treatments microbial, agrochemical residues and toxic metals contamination should be reduced to a minimum. The harvested starting material must be processed to produce the finished herbal product under Good Manufacture Practices (GMPs) which are similar to those employed for the manufacture of conventional drugs. Frequent variability in the composition of herbally based medicines can be avoided by proper standardization of herbal drugs/preparations and their quality control using pharmacopoeial and/ or validated testing methods. ln the cases where the active principles are unknown, marker substance(s) should be established for analytical purposes. lndependently on traditional use of HMP, all data concerning the quality ))from the seeds to the final product« should be provided in the application dossier for marketing authorisation. Post-marketing surveillance by regulatory agencies is further pivotal step in the permanent quality assurance of HMP

Farmakoterapija šećerne bolesti tipa 2

Although normoglycemia for most diabetic patients is hard to achieve, any therapy that contributes to glucose regulation may delay the development of complications and improve the quality of life for the patients. While therapy of type 1 diabetes is primarily focused on maintaining good glycemic control, in patients with type 2 diabetes attention should also be paid to the treatment of comorbidities. Polypharmacy in type 2 diabetes increases the risk of adverse drug reactions (ADRs) and negatively affects patient adherence. In order to attain optimal treatment outcomes, an individualized approach with awareness of possible ADRs should be applied in the pharmacotherapy of diabetic patients. The risks of long-term use of new antidiabetics are not fully clarified and spontaneous reporting of their suspected ADRs resulted in a series of safety signals in post-approval phase. This paper reviewed the available literature on the pharmacotherapeutic options for the treatment of type 2 diabetes and lists current knowledge on the safety profile of antidiabetic drugs