| Sažetak | Tijekom terapije antipsihoticima opisane su brojne nuspojave, koje, kada se pojave, nerijetko znakovito ometaju terapijske učinke i ugrožavaju funkcionalnost bolesnika na svim razinama. Zato je iznimno važno pravovremeno prepoznavanje i moguća predikcija nuspojava. Cilj ovog istraživanja je bio ocijeniti utjecaj antipsihotika prve i druge generacijena dinamiku nastanka laktata kao specifičnu nuspojavu. Daljnji cilj je bio odrediti acidobazno status (pH, BB, BE), plinove u krvi (pO2, pCO2, saturaciju O2), elektrolite (Na, K, Cl) i biokemijske parametre (GUK-i, ureu, kreatinin, CPK, kolesterol, trigliceride) u odnosu na promjene laktata kod osoba koje su na terapiji antipsihotikom. Sljedeći cilj je bio usporediti dinamiku promjene laktata sa pojavom ekstrapiramidnih nuspojava antipsihotika. Istraživanjem su bile obuhvaćene dvije skupine bolesnika sa psihotičnim smetnjama koji su u terapiji uzimali antipsihotike. Prethodno se svakog bolesnika upoznalo o sadržaju istraživanja i zatražilo njegov pristanak kojeg je i potpisao u obliku pisanog informiranog pristanka. U jednoj skupini su bili bolesnici (N=40) koji su u terapiji uzimali antipsihotik prve generacije-haloperidol, a u drugoj skupini (N=40) su bili bolesnici koji su u terapiji uzimali antipsihotik druge generacije-olanzapin. Svi bolesnici prethodno nisu bili liječeni antipsihotikom najmanje mjesec dana prije početka ispitivanja. Kroz cijelo vrijeme istraživanja (šest mjeseci), bolesnici su liječeni sa istom, ekvivalentnom dozom antipsihotika. Obe ispitivane skupine su bile homogenizirane s obzirom na kriterije uključenja i isključenja u ovo istraživanje. Istraživanje je trajalo šest mjeseci. Uključivanje bolesnika je započelo u lipnju 2008. i trajalo je do srpnja 2010. Svim ispitanicima se sukladno protokolu ispitivanja, uzimala i analizirala krv (prije početka liječenja-bazalno mjerenje, nakon mjesec dana, nakon tri mjeseca i nakon šest mjeseci) na laktate, acidobazni status (pH, BB, BE) i plinove (pO2 i pCO2), CPK, GUK-i, urea, kreatinin, trigliceride, kolesterol, Na, K, Cl te se mjerila tjelesna temperatura i težina ispitanika. ESRS (extrapiramidal symptom rating scale) standardiziranom ocjenskom ljestvicom ocjenjivale su se ekstrapiramidne nuspojave (EPS) i to četiri vrste poremećaja kretnji: parkinsonizam, akatizija, distonija i tardivna diskinezija. Rezultati ispitivanja su pokazali da razina laktata u krvi raste tijekom terapije antipsihoticima i to unutar granica puferske rezerve organizma.(2-4 mmom/l), statistički značajno više kod terapije APG haloperidolom nego ADG olanzapinom. Pozitivna povezanost EPS parkinsonizma i distonije sa dinamikom porasta laktata u obe skupine bolesnika, a posebice kod liječenih APG haloperidolom i to već nakon jednog mjeseca liječenja, ukazuje na izvjestan prediktivni značaj i potrebu za redovitim praćenjem plazmatske koncentracije laktata u odnosu na pojavnost EPS kod terapije antipsihoticima. Dinamika promjena ABS, plinova u krvi, biokemijskih parametara (urea, kreatinin, trigliceridi, kolesterol, GUK), elektrolita (Na, K, Cl), tjelesne težine, tjelesne temperature, frekvencije pulsa i disanja, u odnosu na promjene vrijednosti laktata nakon šest mjeseci istraživanja, su ostale unutar granica referentnih vrijednosti, bez kliničke značajnosti u obe ispitivane skupine bolesnika. Nađena je statistički značajna dinamika rasta CPK i značajna pozitivna povezanost razlike CPK i razlike laktata kod bolesnika liječenih APG haloperidolom nego kod bolesnika liječenih ADG olanzapinom, što je u korelaciji sa kliničkim stanjem mišićne kontrakcije i umorom koji se ispoljava kao ekstrapiramidna nuspojava parkinsonizma i distonije. Dobiveni rezultati iz ovog rada, uzimajući u obzir i relativna ograničenja istraživanja (trajanje studije, terapijska suradljivost bolesnika, uključeni samo muškarci), mogu ukazivati na izvjesnu predikciju ozbiljnim nuspojavama antipsihotika te tako utjecati na adekvatnije terapijsko promišljanje kada je u pitanju izbor i titriranje doze antipsihotika u liječenju psihotičnih stanja. Time se otvara prostor i potreba za daljnjim istraživanjem ove problematike. |
| Sažetak (engleski) | Numerous side-effects that can appear during the treatment with antipsychotics have been described in this study. When they appear they can significantly hinder the effects of the treatment und endanger patient's functionality on all levels. Therefore the recognition as well as the prediction of side-effects in due time are of an immense importance. The aim of this research was to evaluate the influence of antipsychotics of the first and second generation on the dynamics of lactate production as a specific side effect. Further aim was to establish the acid-base status (pH, BB, BE), blood gases (pO2, pCO2, saturation O2), electrolytes (Na, K, Cl) and biochemical parameters (GUK-i, urea, creatinine, CPK, cholesterol, triglyceride) in accordance to the lactate changes that affect patients taking the antipsychotics. The next step was to compare the dynamics of the lactate change with the appearance of the extrapyramidal side effects of antipsychotics. The research included two groups of patients with psychotic disorders who had antipsychotics as a part of their therapy. All the patients were preliminary acquainted with the research content and they were asked to sign the informed consent. In one group there were patients (N=40) who were taking the antipsychotic of the first generation-haloperidol during their treatment, and in the second group were (N=40) those who were taking antipsychotic of the second generation-olanzapine. All patients hadn't been exposed to any antipsychotic treatment one month before the examination started. During the research period (six months), patients were being treated with the same, equivalent dose of antipsychotics. Both groups were homogeneous according to the inclusion and exclusion criteria for this examination. The research lasted for six months. The inclusion of the patients started in June 2008 and lasted until July 2010. In accordance with the examination protocol all the examinees had their blood tested (before the beginning of the treatment – basal evaluation, after one month, three months and six months) in order to determine lactate values, acid-base status (pH, BB, BE) and gases (pO2 i pCO2) as well as CPK, GUK-i, urea, creatinine, triglyceride, cholesterol, Na, K, Cl. They also had their body temperature and weight examined. Using the standardised ESRS scale (extrapyramidal symptom rating scale) the extrapyramidal side effects (EPS) were determined - four movement disorders: parkinsonism, acathisia, dystonia and tardive dyskinesia. Examination results have shown that the level of lactates in blood rises during the treatment with antipsychotics and it rises within the limits of the buffer body reserve (2-4 mmol/L); according to the statistics – significantly more during the treatment with APG haloperidol rather than with ADG olanzapine. The positive connection between the EPS parkinsonism and dystonia with dynamic of the lactate raise among both groups of patients, and especially within those treated with APG haloperidol after only a month shows a certain predictive significance and a need to regularly follow the plasmatic concentration of lactates in accordance to the EPS appearance during the treatment with antipsychotics. After six months of research it is to conclude that the dynamic of ABS changes, blood gases, biochemical parameters (urea, creatinine, triglyceride, cholesterol, GUK), electrolytes (Na, K, Cl), body weight and temperature, pulse and breathing frequency in accordance to the changes of the lactate values are within the inner limits of the referential rates and without any clinical relevance in both groups of examinees. The statistically relevant CPK growth dynamic was discovered, as well as the significant positive connection of CPK and lactate differences among patients treated with APG haloperidol rather than among those treated with ADG olanzapine. This correlates with the clinical state of muscular contraction and fatigue manifested as an extrapyramidal side effect of parkinsonism and dystonia. The outcome of this research, considering certain limitations (duration of the study, therapeutic cooperation of patients, of which only men were involved), indicates possible prediction of some serious side effects of antipsychotics, which can surely help us reveal some more adequate treatment solutions, especially considering the choice and titration of doses of antipsychotics when treating psychotic conditions. Thus the need is being felt for a further research of this problem. |
