Bisoprolol is a second-generation, highly selective beta-1 adrenergic receptor antagonist with various beneficial effects in patients with heart failure. Interindividual variability in response to bisoprolol is known, and finding the optimal dose for individual patients with heart failure is still challenging. This pilot study included patients treated with bisoprolol for chronic heart failure with reduced ejection fraction. Between November 2022 and November 2023, one to six blood samples were collected from these patients to determine the trough serum concentration of bisoprolol. At the same time, the values of selected clinical variables were recorded. Bisoprolol concentrations ranged from 1.1 to 65.0 μg/L and correlated with both the daily dose and the dose per kilogram of body weight. However, wide variability in measured serum concentrations of bisoprolol was observed at the same daily dose and in apparent weight-adjusted clearance. Patients classified as NYHA III-IV received a 33% higher dose per kilogram of body weight than patients in NYHA I-II but achieved 165% higher serum concentrations of bisoprolol. An inverse correlation was found between diastolic blood pressure and dose per kilogram of body weight, and a positive correlation between N-terminal pro-B-type natriuretic peptide and both dose per kilogram of body weight and serum bisoprolol concentration. A wide variability in patients' serum concentrations of bisoprolol achieved after taking the same dose has been observed. A significantly higher concentration-to-dose ratio and a significantly lower weight-adjusted apparent clearance were demonstrated in patients with reduced cardiac function, reduced renal function, and taking the combination with amiodarone. These patients may be more prone to overdose with bisoprolol.
- MeSH
- Adrenergic beta-1 Receptor Antagonists * blood administration & dosage pharmacokinetics therapeutic use MeSH
- Bisoprolol * blood administration & dosage pharmacokinetics therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Drug Monitoring MeSH
- Pilot Projects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Failure * drug therapy blood physiopathology MeSH
- Stroke Volume drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Drug consumption rooms (DCRs) are harm reduction facilities providing safer and hygienic setting for supervised administration of drugs aimed at decreasing negative health and social consequences of drug use. The first DCR in Czechia was opened in September 2023 in city of Brno in a mobile form operating in a socially excluded area (SEA). A research project informed the implementation of the DCR. METHODS: A mixed methods design was applied in the following phases: desk review, research before and after the launch of the mobile DCR, and routine monitoring of programme performance. Two cross-sectional questionnaire surveys among PWUDs (n = 131 and 135), ethnographic observation, focus group (n = 19), interviews with PWUDs (n = 26 and 19), with personnel of addiction services and local officials (n = 16 and 12), and residents (n = 7 and 6) were performed prior to and after the launch of the DCR. Thematic analysis of qualitative data, descriptive and regression analyses of quantitative data were performed. RESULTS: There was a need and high willingness to use the DCR among potential clients. The significant predictors were opioid use (adjusted odds ratio, AOR = 3.4 in survey 1 and 3.9 in survey 2), drug injection in the last 30 days (AOR 4.3 in survey 1), being in the probationary period during the previous 30 days (AOR 10.0 in survey 1), witnessing an overdose in the past 30 days (AOR 8.5 in survey 2), HCV positivity ever in life (AOR 2.9 in survey 2), living in SEA (AOR 2.7 in survey 2) and Roma ethnicity (AOR 2.8 in survey 2). The beginnings of the DCR were relatively slow with low initial number of clients and drug administrations. However, with time, and programme adjustments following research results, the attendance at the facility has grown. CONCLUSIONS: Research was instrumental in shaping the DCR in Brno before and during its implementation. The DCR showed a potential to attract the most vulnerable PWUDs from SEA. Despite a slow start, the DCR has become an integral part of low-threshold services for PWUDs in Brno and has proven its feasibility in the Czech settings.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Mobile Health Units * organization & administration MeSH
- Substance-Related Disorders * MeSH
- Cross-Sectional Studies MeSH
- Surveys and Questionnaires MeSH
- Harm Reduction * MeSH
- Drug Users * statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Úvod: Injekční užívání drog je spojeno se závažnou zdravotní zátěží, a to zejména díky vysokému riziku krví přenosných infekcí, jako jsou virová hepatitida typu C (VHC) nebo infekce virem lidské imunodeficience (HIV). Mezi doporučované intervence v prevenci a kontrole infekcí spojených s užíváním drog patří služby aplikačních místností (AM). AM je odborná adiktologická služba, kde si mohou lidé užívající drogy (PWUDs) aplikovat přinesenou drogu za bezpečnějších a hygienicky nezávadných podmínek. První AM v ČR byla otevřena v Brně v září 2023 v mobilní formě (MAM) v sociálně vyloučené lokalitě (SVL) s vysokým výskytem injekčního užívání heroinu a jiných opioidů, zejména v místní romské komunitě. Její spuštění provázel výzkum zaměřený na analýzu potřeb a nastavení služby. Tato práce představuje analýzu části kvantitativních dat zaměřenou na rizikové chování a další charakteristiky u potenciálních klientů programu. Materiál a metodika: Dvě dotazníkové průřezové studie (n = 131 a n = 135) provedené těsně před spuštěním a po spuštění MAM na souborech PWUDs zařazených do studie namátkovým výběrem prostřednictvím spolupracujících služeb a peer pracovníků v Brně. Analýza byla zaměřena na charakteristiky klientů v SVL, kde MAM působí. Párové souvislosti mezi příslušností k SVL a dalšími proměnnými byly analyzovány pomocí chí-kvadrát testu a t-testu. U statisticky významných prediktorů z párové analýzy byla provedena logistická regresní analýza s adjustací na pohlaví a věk. Výsledky jsou prezentovány jako adjusted odds ratio (AOR). Výsledky: V obou souborech tvořili 2/3 muži, průměrný věk byl kolem 37 let (36,5 let v prvním a 37,5 let ve druhém souboru), většinu tvořili lidé užívající drogy injekčně s poměrně častým výskytem rizikového chování. Ve druhém souboru bylo více osob, které se považují za Romy (50,7 % vs. 20,3 %), a více osob, jejichž primární drogou jsou opioidy (39,7 % vs. 27,5 %). Mezi respondenty žijícími v SVL bylo v prvním souboru statisticky významně častější užívání heroinu (AOR = 8,2) a opioidů (4,7) v posledním roce, aplikace drog ve vnitřním veřejném prostoru v posledních 30 dnech (3,6), častěji byli svědky předávkování (2,5) a byli odvezeni zdravotnickou záchrannou službou (2,6) v posledních 12 měsících. Respondenti ze SVL byli častěji klienty adiktologických služeb v posledním roce (2,8), především opiátové substituční léčby (4,6), ale vykazovali statisticky významně více bariér pro vstup do léčby. V souboru po spuštění MAM se potvrdila vyšší míra užívání opioidů (2,9) a nižší míra užívání pervitinu (0,3) a ukázal se vyšší výskyt VHC diagnostikované někdy v životě (3,0) mezi klienty ze SVL. V souboru před otevřením MAM měli klienti ze SVL menší povědomí o aplikačních místnostech obecně (0,4), ale v souboru po zahájení MAM uváděli větší ochotu ji využít (2,7). Závěr: Spuštění MAM v Brně bylo odůvodněné, neboť výskyt injekčního užívání drog včetně aplikace ve veřejném prostoru a výskyt dopadů s ním spojených je značný. Umístění MAM je vhodné, neboť PWUDs v SVL, kde působí, vykazují vyšší míru rizikového chování a zranitelnosti. Současně vykazují vyšší ochotu službu MAM využít. Nastavení a dopady MAM v Brně na zdravotní a sociální situaci mezi klienty a na komunitu je vhodné dále sledovat.
Background: Injecting drug use is associated with a high disease burden, particularly due to the high risk of blood-borne infections such as viral hepatitis C (HCV) and human immunodeficiency virus (HIV) infection. Interventions recommended for the prevention and control of infections associated with drug use include so-called drug consumption rooms (DCRs). A DCR is a professional addiction service where people who use drugs (PWUD) can consume the drug they bring under safer and hygienic conditions. In September 2023, the first DCR in the Czech Republic was opened in Brno as a mobile setting (MDCR) in a socially excluded location (SEL) with a high prevalence of heroin and other opioids injecting, especially in the local Roma community. Its launch involved mixed methods research aimed at needs analysis and service set-up. This paper presents an analysis of quantitative data focusing on risk behaviours and other characteristics of potential clients of the programme. Material and methods: Two cross-sectional questionnaire surveys (n=131 and n=135) were conducted just before and after the launch of the programme among PWUD recruited through convenience sampling by collaborating services and peer workers in Brno. The analysis addressed the characteristics of clients in the SEL where the MDCR operates. Pairwise associations between the SEL affiliation and other variables were analysed using the chi-square test and t-test. For statistically significant predictors from the pairwise analysis, logistic regression analysis was performed, with adjustment for gender and age. Results are presented as adjusted odds ratios (AOR). Results: In both surveys, two thirds were male, mean age around 37 years (36.5 years in survey 1 and 37.5 years in survey 2). Most of them were people who injected drugs with a relatively high rate of risk behaviours. In survey 2, more people self-reported Roma ethnicity (50.7% versus 20.3%) and opioids as their primary drug (39.7% versus 27.5%). Respondents from survey 1 living in the SEL were more likely to have used heroin (AOR=8.2) and opioids (4.7) in the past year, to have injected drugs in an indoor public space in the past 30 days (3.6), to have witnessed an overdose (2.5), and to have been taken by emergency services (2.6) in the past 12 months. SEL respondents were more likely to have been clients of addiction services in the past year (2.8), especially opioid agonist treatment (4.6), but on the other hand, showed significantly more barriers to treatment. The survey after the MDCR launch confirmed higher rates of opioid use (2.9) and lower rates of methamphetamine use (0.3) and showed a higher prevalence of ever-diagnosed HCV (3.0) among SEL respondents. Prior to the opening of the MDCR, SEL respondents were in general less aware of the DCR (0.4) but reported greater willingness to use it after its launch (2.7). Conclusion: The launch of the mobile DCR in Brno was justified due to the high prevalence of injecting drug use and the presence of associated risks, including injecting in public. The location of the DCR is appropriate as PWUDs in the SEL where it operates exhibit higher levels of risk behaviour and vulnerability. At the same time, they show a higher willingness to use the DCR. The set-up of DCR in Brno and its impacts on the health and social situation of clients and the community should be further monitored.
V článku je uveden přehled současných poznatků o vitaminu D z klinického hlediska. Jsou shrnuta základní fakta o jeho formách, fyziologických účincích a metabolismu. Z klinického hlediska se článek věnuje stavu zásobení vitaminem D, deficitu vitaminu D a jeho klinickým projevům a léčbě. V části věnované léčbě jsou shrnuty současné poznatky o používaných formách vitaminu D, jejich indikacích, strategiích léčby a doporučeném dávkování.
The article reviews current knowledge about vitamin D from the clinical point of view. The basic facts about its forms, physiological effects and metabolism are summarized. From clinical point of view the article deals with the state of supply of vitamin D, vitamin D deficiency and its clinical signs, symptoms and therapy. In paragraphs devoted to the treatment the current knowledge about forms of vitamin D, their indication, doses and dosage regimens are summarized.
- MeSH
- Diabetes Mellitus etiology MeSH
- Clinical Laboratory Techniques methods MeSH
- Humans MeSH
- Vitamin D Deficiency etiology pathology prevention & control MeSH
- Osteomalacia drug therapy prevention & control MeSH
- Drug Overdose MeSH
- Rickets diagnosis etiology drug therapy MeSH
- Vitamin D * administration & dosage physiology metabolism MeSH
- Recommended Dietary Allowances MeSH
- Check Tag
- Humans MeSH
RATIONALE: Cabergoline (CAB) is an ergot derivative typically prescribed for the treatment of hyperprolactinemia. It suppresses the release of prolactin through agonist actions on dopamine (DA) D2 receptors; however, it possesses binding affinity for other DA and 5-HT receptors. Side effects that exacerbate valvular heart disease can occur with high doses. OBJECTIVE: The present study examined the acute, subchronic, and chronic dose-response effects of CAB and a derivative dimethylcabergoline (DMC) which acts as an antagonist instead of agonist at 5-HT 2B receptors, on appetitive and consummatory sexual behaviors of male rats. METHODS: CAB (0, 0.03, 0.15, or 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 68 days. Sexual behavior was tested every 4 days during this period for a total of 16 trials. On the 17th trial, rats were administered their dose of CAB, and 4 h after were overdosed with sodium pentobarbital, perfused intracardially, and their brains processed for Fos immunohistochemistry. DMC (0, 0.03, 0.15, 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 36 days. Sexual behavior was tested every 4 days for a total of 9 trials. RESULTS: CAB increased anticipatory level changes, intromissions, and ejaculations significantly across all timepoints, with the medium and high doses being most potent. The medium and high doses also increased Fos protein significantly within the medial preoptic area, whereas in the nucleus accumbens shell, the low and medium doses decreased Fos protein but the high dose increased it significantly from control. Similar to CAB, the medium and high doses of DMC increased the number of ejaculations significantly. Rats in all drug dose groups appeared healthy for the duration of the experiments. CONCLUSIONS: Both CAB and DMC facilitate ejaculations, and CAB further facilitates measures of anticipatory sexual motivation and intromissions. These data suggest that both could be used as treatments for sexual arousal disorders and ejaculation/orgasm disorders with little or no untoward side effects at low doses.
- MeSH
- Cabergoline pharmacology MeSH
- Copulation * MeSH
- Rats MeSH
- Motivation MeSH
- Brain MeSH
- Gonadal Steroid Hormones MeSH
- Receptors, Dopamine D2 MeSH
- Sexual Behavior, Animal * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
N-acetylcysteín (ACC) je acetylovaný variant aminokyseliny L-cysteín a primárne sa používa ako špecifické antidotum pri predávkovaní paracetamolom. Ďalšie indikácie jeho aplikácie zahŕňajú prevenciu exacerbácie chronickej obštrukčnej choroby pľúc, zmiernenie príznakov chrípky, liečbu pľúcnej fibrózy, liečbu neplodnosti u pacientok so syndrómom polycystických ovárií rezistentným na klomifén, ďalej pri liečbe autizmu, Alzheimerovej choroby, bipolárnej afektívnej poruchy, schizofrénie, obsesívno-kompulzívnej poruchy a drogovej závislosti. Okrem toho ACC môže zohrávať úlohu aj ako chemoprevencia malignít, doplnok pri eradikácii Helicobacter pylori a pri profylaxii straty sluchu vyvolanej podávaním gentamicínu u hemodialyzovaných pacientov. Napriek určitej kontroverzii sa ACC odporúča aj na prevenciu poškodenia obličiek vyvolaného kontrastom počas zobrazovacích procedúr. Podľa súčasných odporúčaní sa ACC má profylaticky podať pred vyšetrením, resp. výkonom s použitím kontrastnej látky u pacientov, ktorý majú chronickú obličkovú chorobu a najmenej jedno z nasledujúceho: diabetes mellitus, srdcové zlyhávanie, vek viac ako 74 rokov, užívajú nefrotoxické liečivá, čaká ich perkutánna koronárna intervencia alebo objem kontrastnej látky, ktorá im má byť podaná, je viac ako 19 ml.
N-acetylcysteine (ACC) is an acetylated variant of the amino acid L-cysteine and is primarily used as a specific antidote for paracetamol overdose. Other indications for its application include prevention of exacerbation of chronic obstructive pulmonary disease, relief of flu symptoms, treatment of pulmonary fibrosis, treatment of infertility in patients with polycystic ovary syndrome resistant to clomiphene, moreover, in the treatment of autism, Alzheimer's disease, bipolar affective disorder, schizophrenia, obsessive-compulsive disorder and drug addiction. In addition, ACC may also play a role as a chemoprevention of malignancies, an adjunct in the eradication of Helicobacter pylori and in the prophylaxis of gentamicin-induced hearing loss in hemodialysis patients. Despite some controversy, ACC is also recommended for the prevention of contrast-induced renal injury during imaging procedures. According to current recommendations, ACC should be given prophylactically before the examination, or procedure with the use of contrast material in patients who have chronic kidney disease and at least one of the following: diabetes mellitus, heart failure, age over 74 years, are taking nephrotoxic drugs, are awaiting percutaneous coronary intervention, or the volume of contrast material to be administered, is more than 19 ml.
OBJECTIVE: The cytochrome P450 2D6 (CYP2D6) is an enzyme involved in the oxidative biotransformation of various widely used drugs, including paroxetine, a substrate and strong inhibitor of the enzyme. The aim is to report on a case of protracted intoxication with paroxetine after a single overdose in a genotype-predicted intermediate CYP2D6 metabolizer. OBSERVATION: A 49-year-old man was receiving chronic treatment for more than 6 years with paroxetine 60 mg/day for an indication of agoraphobia. The patient ingested fifty 20 mg tablets of paroxetine in a suicide attempt. The toxic plasma level, accompanied by delirium, persisted for approximately 1 month after the overdose. According to the genotype profile, the patient was evaluated as an intermediate metabolizer with reduced CYP2D6 enzyme activity. CONCLUSION: As a consequence of the suicide attempt with overdose and the chronic paroxetine treatment that preceded it, phenoconversion to a poor metabolizer with very low CYP2D6 enzyme activity is suggested as contributing to an extremely long intoxication accompanied by delirium. Prolonged monitoring over a standard 24 h of both physical symptoms and drug plasma levels, together with a genetic profile assessment and phenoconversion consideration, is recommended after a single overdose in patients chronically treated with paroxetine.
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Obezita představuje rostoucí společenský a zdravotnický problém, její prevalence v posledních desetiletích významně roste. Patofyziologické změny spojené s obezitou mohou měnit farmakokinetiku (PK) podávaných antiinfektiv a vést tak k subterapeutickým hladinám a selhání léčby. Vzhledem ke komplexním změnám distribučního objemu a eliminačních funkcí však prostý přepočet dávky na tělesnou hmotnost může naopak vést k předávkování pacienta a toxicitě. I díky řadě PK studií hodnotících použití antibiotik u kriticky nemocných a dedikovaným studiím u obézních pacientů se v posledních letech podařilo získat více informací o vhodném dávkování u této populace. Přesto pro celou řadu běžně používaných antibiotik validní informace stále chybí a tam, kde k dispozici jsou, se často jedná o doporučení založené na nepřímých důkazech bez klinické validace. Tato práce se snaží přinést základní přehled dostupných informací a doporučení pro úpravu dávek tam, kde jsou k dispozici.
Obesity is a growing societal and population health problem the prevalence of which has increased significantly in the recent decades. Pathophysiological changes associated with obesity can alter the pharmacokinetics (PK) of antiinfective drugs and result in subtherapeutic levels and treatment failure. Due to complex changes in distribution volume and elimination functions, a simple correction based on total body weight would often lead to overdosing and risk of toxicity. Thanks to a number of PK studies evaluating antibiotic doses in the critically ill and thanks to dedicated studies in the obese we have gained new insights into adequate dosing in the recent years. Despite this, the information is still lacking for many of the most commonly prescribed antibiotics and where it is available, the recommendations are often based on indirect evidence rather than clinical validation. This paper offers a comprehensive look at the current evidence and recommendations (where available) for dose adjustments in the obese patient.
V důsledku obezity dochází ke změnám farmakokinetických parametrů a hladin podávaných léků v krvi, což může významně komplikovat farmakoterapii obézních pacientů. Zpravidla dochází ke zvětšování distribučního objemu, tyto změny však nejsou vždy přímo úměrné nárůstu celkové tělesné hmotnosti, uplatňuje se relativní zvýšení množství tukové hmoty oproti hydrofilnímu kompartmentu. Vlivem obezity mohou být ovlivněny i eliminační orgány, což vede ke změnám clearance léčiv. Prosté navýšení dávek podle celkové tělesné hmotnosti by u mnohých pacientů mohlo vést k předávkování, naopak fixní dávky mohou být spojeny s nedostatečným efektem. Změny tělesného složení a eliminace se však u různých léčiv neprojeví stejným způsobem. Nelze tedy jednoznačně určit univerzální postup úpravy dávek pro všechna léčiva. Specifickou problematikou je dávkování léčiv po bariatrických operacích, kdy je nutné zohlednit jak změny biodostupnosti a jejich postupnou úpravu v čase od výkonu, tak dramatickou redukci hmotnosti vyžadující pravidelné přehodnocování farmakoterapie. Přestože je obezita celosvětově narůstajícím problémem, stále se potýkáme s nedostatečným množstvím spolehlivých dat a klinických studií zabývajících se problematikou dávkování léčiv u obézních pacientů. Předložený článek uvádí na základě dostupných informací základní principy dávkování u obézních pacientů.
Obesity is related to changes in pharmacokinetic parameters and blood levels of administered drugs, which can significantly complicate the pharmacotherapy of obese patients. An increase in the volume of distribution is generally expected, but due to a relative increase in the amount of fat mass compared to the hydrophilic compartment, this change is not always directly proportional to the increase in total body weight. The elimination organs may also be affected by obesity, leading to changes in drug clearance. Simply increasing doses according to total body weight could lead to overdose in many patients, whereas fixed doses may be associated with insufficient therapeutic effect. However, changes in body composition and elimination are not consistent for different drugs. Therefore, an unambiguous recommendation for dose adjustment of all drugs cannot be made. Drug dosing after bariatric surgery presents a unique challenge, when it is necessary to assess changes in bioavailability and their gradual adjustment over time from the procedure, as well as dramatic weight reduction requiring regular reassessment of pharmacotherapy. Although obesity is a growing problem worldwide, we still face an insufficient amount of reliable data and clinical studies dealing with drug dosing in obese patients. Based on the available information, this article describes the basic principles of dosing in obesity.
BACKGROUND AND OBJECTIVE: Theophylline has been used for decades in human medicine for its psychostimulant, anti-inflammatory, and bronchodilator effects. Historically, in pulmonary medicine, theophylline has been used in the treatment of obstructive pulmonary diseases such as bronchial asthma (BA) or chronic obstructive pulmonary disease (COPD). This review aims to determine whether theophylline still has its place in the therapy of obstructive pulmonary diseases or whether we can even extend its use to other diagnoses such as atropine-resistant cardiac arrests, apnea of prematurity, or others. Moreover, we also aim to determine if there is a rationale for using low-dose theophylline due to its immunomodulatory and anti-inflammatory effect, or if the future of methylxanthines lies in newly synthesized derivates of theophylline such as bamifylline, or doxofylline. METHODS: The narrative review is based on a literature search of the articles indexed in the PubMed database in 2023. We searched the database since the year 2009 using the MeSH terms "theophylline", "aminophylline", and "methylxanthines" and we included original articles in the English language. KEY CONTENT AND FINDINGS: Theophylline has a number of adverse drug reactions (ADRs), the most serious of which is its effect on the cardiovascular system. It can cause severe arrhythmias or even cardiac arrest when overdosed. On the other hand, there is still a substantial amount of its applications in current clinical practice. CONCLUSIONS: There is considerable controversy associated with its use in current medicine, which can be attributed both to its narrow therapeutic range and its mentioned cardiotoxic effect. Herein, we summarize the current state-of-art of theophylline and its use in human medicine.
- Publication type
- Journal Article MeSH
- Review MeSH
