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Open access

Alenka Marušič and Aleš Mrhar

Interakcije med Zdravili pri Bolnikih na Kirurškem Oddelku Splošne Bolnišnice Murska Sobota

Izhodišče: Interakcije med zdravili lahko predstavljajo težave. V literaturi zasledimo, da se klinično pomembne interakcije med zdravili pojavijo pri 7 % bolnikov, če jemljejo od 6 do 10 zdravil. Če se število sočasno predpisanih zdravil povečuje, se povečata tudi število in verjetnost klinično pomembnih interakcij med zdravili, ki lahko vplivajo tako na neučinkovitost zdravljenja kot na neželene ali toksične učinke zdravil. Interakcije med zdravili razvrščamo glede na klinično pomembnost v pet skupin: tip A, tip B, tip C, tip D in tip X.

Namen: Osnovni namen raziskave je bil analizirati delež interakcij tipa C, D in X pri bolnikih, ki med zdravljenjem v bolnišnici prejemajo osem ali več zdravil hkrati, in ugotoviti, pri katerih bolnikih in kombinacijah zdravil so se izrazile klinično pomembne interakcije.

Metode: V raziskavo smo vključili 53 bolnikov, ki so bili hospitalizirani na Kirurškem oddelku Splošne bolnišnice Murska Sobota v letih 2006-2009 in so prejemali osem ali več zdravil hkrati. Za vsakega bolnika smo izvedli farmakoterapijski pregled in s pomočjo programa Lexi-Comp OnlineTM pregledali terapijo z zdravili glede na interakcije med njimi. Analizirali smo delež predpisanih zdravil glede na ATC-klasifikacijo, delež interakcij tipa C, D in X ter ugotavljali, katere interakcije in kako so se pri bolnikih klinično izrazile.

Rezultati: Pri pregledu terapij smo med zdravili ugotovili 426 interakcij tipa C, 44 interakcij tipa D in eno interakcijo tipa X. Bolnikom je bilo predpisano 157 različnih učinkovin iz 11 različnih skupin po ATC-klasifikaciji. Iz anamneze ob sprejemu bolnika in pregleda farmakoterapije smo sklepali, da so se klinično pomembne interakcije izrazile pri 12 bolnikih (22,6 % vseh bolnikov).

Zaključek: Farmakoterapijski pregled je primerna metoda tako za identifikacijo posameznih interakcij med zdravili kot tudi za svetovanje pri prilagajanju oziroma zamenjavi farmakoterapije. Pri bolnikih, ki prejemajo osem ali več zdravil hkrati, bi se moral farmakoterapijski pregled, ki ga opravi klinični farmacevt, za zagotavljanje varne in učinkovite uporabe zdravil nujno uveljaviti na vseh bolnišničnih oddelkih.

Open access

Alenka Marušič, Igor Locatelli and Aleš Mrhar

Farmakokinetika Penicilinskih Antibiotikov: Preklop iz Intravenske na Peroralno Terapijo

Penicilinski antibiotiki delujejo baktericidno in spadajo med časovno odvisne antibiotike. Za večino penicilinov je značilna kratka razpolovna doba eliminacije. Benzilpenicilini se po peroralni aplikaciji ne absorbirajo, ampicilin in kloksacilin se sicer absorbirata, vendar slabo, medtem ko se amoksicilin skoraj v celoti absorbira. Pri slednjem je smotrno z intravenske terapije preklopiti na peroralno, če lahko s peroralno aplikacijo dosežemo plazemske koncentracije penicilina, primerljive s tistimi po intravenski aplikaciji, t. j. enako povprečno plazemsko koncentracijo penicilina v stacionarnem stanju. Posledično lahko pričakujemo enako učinkovitost obeh aplikacij. Smiselnost preklopne terapije je treba proučiti predvsem s stališča bolnika, saj ni primerna za bolnike, ki so v kritičnem stanju in imajo močno zvišano telesno temperaturo ali malabsorbcijski sindrom. Prednost preklopne terapije pa je v tem, da zmanjša pojavnost flebitisa in seps. V članku sta obravnavana dva primera preklopne terapije. Na osnovi farmakokinetičnih simulacij in indeksov učinkovitosti protibakterijskega zdravljenja je pokazana primerljivost intravenske terapije z ampicilinom in peroralne terapije z amoksicilinom, medtem ko preklopna terapija pri zdravljenju osteomielitisa s kloksacilinom ostaja nedorečena. Na podlagi predstavljenih primerov članek ilustrativno prikazuje, da ustrezna razlaga farmakokinetičnih parametrov bistveno pripomore k pravočasnemu preklopu z intravenske na peroralno terapijo s penicilinom. Takšna terapija je bolniku bolj prijazna, poleg tega pa prispeva k zniževanju stroškov za zdravljenje z zdravili v bolnišnicah ob še vedno varni in učinkoviti farmakoterapiji bakterijskih okužb.

Open access

Renata Rezonja, Lea Knez, Tanja Cufer and Aleš Mrhar

Abstract

Background. Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be at risk for excess toxicity.

Conclusions. The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient.

Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.

Open access

Renata Režonja, Lea Knez, Stanislav Šuškovič, Mitja Košnik and Aleš Mrhar

Comprehensive medication history: the need for the implementation of medication reconciliation processes

Introduction: Providing comprehensive medication history (CMH) upon hospital admission is of outmost importance for proper patient evaluation and prescription of drug treatment. The aim of this study was to evaluate the implementation of medication reconciliation in clinical practice.

Methods: Patients admitted to a teaching hospital in Slovenia were randomly selected and included in the study. For each patient a CMH was obtained by a research pharmacist using various sources of information. Next, the medication history in the hospital medical record was reviewed. The prescribed drugs were assessed for completeness of information, and possible discrepancies between both medication histories were recorded and classified.

Results: Overall, 108 patients with a median age of 73 years were included in the study. The research pharmacist recorded the use of 651 medicaments, with all relevant details being available for 94.9% of these drugs. Of the 464 medicines listed in the hospital medical record, only 42.0% were considered complete. A comparison of the medication history and the medical record with the CMH revealed at least one discrepancy in 72.4% of the drugs listed. The majority of the identified discrepancies were often present both in the medication order on the drug chart (76.2%) and in the discharge letter (69.9%). Most medication discrepancies were due to drug omissions (20.9%) and commissions (6.5%).

Conclusion: The high rate of discrepancies between the recorded drug history and CMH reported in our study stresses the need for the implementation of medication reconciliation. The participation of pharmacists in the reconciliation process, described in this study, resulted in more complete and accurate drug histories acquired.

Open access

Renata Rezonja Kukec, Iztok Grabnar, Tomaz Vovk, Ales Mrhar, Viljem Kovac and Tanja Cufer

Abstract

Background. Chemotherapy with platinum agent and etoposide for small-cell lung cancer (SCLC) is supposed to be associated with intermediate risk (10-20%) of febrile neutropenia. Primary prophylaxis with granulocyte colonystimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice febrile neutropenia is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of neutropenia and febrile neutropenia in advanced SCLC patients in the first cycle of standard chemotherapy. Furthermore, we explored the association between severe neutropenia and etoposide peak plasma levels in the same patients.

Methods. The case series based analysis of 17 patients with advanced SCLC treated with standard platinum/etoposide chemotherapy, already included in the pharmacokinetics study with etoposide, was performed. Grade 3/4 neutropenia and febrile neutropenia, observed after the first cycle are reported. The neutrophil counts were determined on day one of the second cycle unless symptoms potentially related to neutropenia occurred. Adverse events were classified according to Common Toxicity Criteria 4.0. Additionally, association between severe neutropenia and etoposide peak plasma concentrations, which were measured in the scope of pharmacokinetic study, was explored.

Results. Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient who did not receive primary prophylaxis the rates of both grade 3/4 neutropenia and febrile neutropenia were high (8/15 (53.3%) and 2/15 (13.3%), respectively), already in the first cycle of chemotherapy. One patient died due to febrile neutropenia related pneumonia. Neutropenic events are assumed to be related to increased etoposide plasma concentrations after a standard etoposide and cisplatin dose. While the mean etoposide peak plasma concentration in the first cycle of chemotherapy was 17.6 mg/l, the highest levels of 27.07 and 27.49 mg/l were determined in two patients with febrile neutropenia.

Conclusions. Our study indicates that there is a need to reduce the risk of neutropenic events in chemotherapy treated advanced SCLC, starting in the first cycle. Mandatory use of primary G-CSF prophylaxis might be considered. Alternatively, use of improved risk models for identification of patients with increased risk for neutropenia and individualization of primary prophylaxis based on not only clinical characteristics but also on etoposide plasma concentration measurement, could be a new, promising options that deserves further evaluation.