Ceska A Slovenska Neurologie A Neurochirurgie, 2019
Souhrn Cil : urcit ucinnost antiagregacni lecby aspirinem v sekundarni prevenci v přisně selektov... more Souhrn Cil : urcit ucinnost antiagregacni lecby aspirinem v sekundarni prevenci v přisně selektovanem souboru pacientů po ischemicke cevni mozkove přihodě. Soubor a metodika : do souboru bylo zahrnuto 106 pacientů s minimalizaci možných faktorů, ktere by mohly ovlivnit efekt aspirinu. Compliance byla potvrzena laboratornim vysetřenim kyseliny salicylove v plazmě, embolizacni přihody minimalizovany peclivým vysetřenim srdce a karotických tepen. Přisna vylucovaci kriteria jsou uvedena niže. U vsech pacientů uživajicich 100mg kyseliny acetylsalicylove denně jsme vysetřili serove koncentrace 11-dehydrotromboxanu B2. Výsledky : i v tomto přisně selektovanem souboru ucinnou supresi tromboxanu (95% a vice) dosahlo jen 76 pacientů, ale u dalsich 24 suprese dosahovala 80-94,9% a pouze u sesti pacientů byla jestě mensi. Pacienti s neucinnou supresi tromboxanu měli statisticky významně vyssi BMI, cholesterol a LDL cholesterol a kyselinu mocovou. Zavěr : aspirin vedl k výrazne supresi tromboxan...
The compliance of patients receiving long-term acetylsalicylic acid therapy was tested by determi... more The compliance of patients receiving long-term acetylsalicylic acid therapy was tested by determining plasma levels of salicylic acid by HPLC. The same determination was performed in a control group of untreated patients. Almost 20 % of the examined patients were not using the prescribed therapy.
OBJECTIVE The aim of our study was to establish whether or not tinnitus patients have higher plat... more OBJECTIVE The aim of our study was to establish whether or not tinnitus patients have higher platelet activity, as measured by plasma 11-dehydro-thromboxane B2 levels, compared with individuals without tinnitus. METHODS The study group included patients without documented organic causes of tinnitus or a cause of non-vascular hearing impairment. Laboratory tests included complete blood count, biochemistry, coagulation activity, and thromboxane levels. To exclude a pathology in the cerebellopontine angle, CT and MRI were performed together with an X-ray scan of cervical vertebrae. For the purpose of this study, blood samples were screened for 11-dehydro-thromboxane B2 levels using commercial kits. RESULTS A comparison of the main marker of increased platelet activity i.e., thromboxane levels of tinnitus patients with those of a control group, showed increased thromboxane levels in the former. The average plasma concentrations of 11-dehydro-thromboxane B2 were 2.0234±1.80 ng/ml in the ...
OBJECTIVE: The aim of our study was to establish whether or not tinnitus patients have higher pla... more OBJECTIVE: The aim of our study was to establish whether or not tinnitus patients have higher platelet activity, as measured by plasma 11-dehydro-thromboxane B2 levels, compared with individuals without tinnitus. METHODS: The study group included patients without documented organic causes of tinnitus or a cause of non-vascular hearing impairment. Laboratory tests included complete blood count, biochemistry, coagulation activity, and thromboxane levels. To exclude a pathology in the cerebellopontine angle, CT and MRI were performed together with an X-ray scan of cervical vertebrae. For the purpose of this study, blood samples were screened for 11-dehydro-thromboxane B2 levels using commercial kits. RESULTS: A comparison of the main marker of increased platelet activity i.e., thromboxane levels of tinnitus patients with those of a control group, showed increased thromboxane levels in the former. The average plasma concentrations of 11-dehydro-thromboxane B2 were 2.0234±1.80 ng/ml in t...
Autoři pojednavaji o soucasných možnostech v lecbě dny (akutni dnavý zachvat, profylaxe, hypourik... more Autoři pojednavaji o soucasných možnostech v lecbě dny (akutni dnavý zachvat, profylaxe, hypourikemicka lecba) a asymptomaticke hyperurikemie. Poukazuji na rozdily v jednotlivých doporucených postupech z hlediska spektra použivaných leků, jejich preferenci, davkovani, titrovani davek, cilech lecby, i na odlisný přistup v otazkach asymptomaticke hyperurikemie. Diskutuji o novějsich poznatcich o kyselině mocove a jejim vztahu k některým neurologickým a kardiovaskularnim nemocem. Zmiňuji se take o zcela odlisných doporucených postupech amerických praktických lekařů a jejich principech. Zavěrem konstatuji, že odpovědi na některe sporne otazky v lecbě dny daji jen výsledky spravně zadaných a provedených klinických studii.
Poškození šlach patří mezi méně známé nežádoucí účinky některých léčiv. Donedávna byly známé jen ... more Poškození šlach patří mezi méně známé nežádoucí účinky některých léčiv. Donedávna byly známé jen u glukokortikoidů a fluorochinolonů. Dnes známe i další léčiva, která mohou způsobit poškození šlach (statiny, inhibitory aromatáz, anabolické steroidy a další). Autoři pojednávají o nejčastější klinické manifestaci, diagnostice a léčbě i novinkách z experimentálních prací k této problematice. Nejčastěji postiženou bývá šlacha Achillova, ale postiženy mohou být kterékoliv šlachy v organizmu. Lékový původ tendinopatie bychom měli zvažovat vždy, pokud máme pacienta s onemocněním šlachy, který užívá nebo nedávno užíval uvedené léky. Klíčová slova: anabolické steroidy-fluorochinolony-glukokortikoidy-inhibitory aromatáz-poškození šlach-statiny Drug induced tendon injury Summary Tendon injury belongs to the less known side effects of some drugs, reported until recently only for glucocorticoids and fluoroquinolones. To date, some other classes of drugs such as statins, aromatase inhibitors, anabolic steroids, potentially causing tendon injury, have been added to the list. The authors discuss the most common clinical presentations, diagnosis, and management as well as latest experimental data regarding this issue. The most often, the Achilles tendon is affected, however, nearly every tendon of the entire body may be affected. Tendon rupture or drug induced tendinopathy should be strongly considered in those who have a tendon injury and have recently taken these drugs.
Farmakologické a kardiologické minimum Citalopram patří mezi nejpoužívanější léčiva v léčbě depre... more Farmakologické a kardiologické minimum Citalopram patří mezi nejpoužívanější léčiva v léčbě deprese. Patří do skupiny tzv. selektivních inhibitorů zpětného vychytávání serotoninu (selective serotonin reuptake inhibitors-SSRI). Citalopram je racemická směs
Ústav farmakologie 2. LF UK, Praha Polymedikace je spojena s vyšším výskytem negativních zdravotn... more Ústav farmakologie 2. LF UK, Praha Polymedikace je spojena s vyšším výskytem negativních zdravotních ukazatelů včetně pádů, morbidity i mortality. I přes vynakládanou snahu je řešení této problematiky stále neuspokojivé. Dvě hlavní příčiny polymedikace jsou stárnutí populace a její polymorbidita, a na druhé straně rozvoj farmakoprůmyslu a dostupnost širokého spektra léčiv. Obě příčiny, tj. stárnutí populace i dostupnost léčiv, mají každoročně stoupající trend. Autoři pojednávají o hlavních nedostatcích při zkoumání uvedené problematiky, jako jsou nejednotně používaná terminologie, metodologické nedostatky při získávání dat, neexistence doporučených postupů pro léčbu polymorbidních pacientů apod. Diskutují o tom, zda polymedikace je příčinou nebo markerem zvýšené křehkosti, pádů a mortality. V závěru kriticky hodnotí možné řešení polymedikace v budoucnu-personalizovanou medicínu. Klíčova slova: polymedikace, polymorbidita, doporučené postupy, personalizovaná medicína. Pitfalls of solving polypharmacy problems Polymedication is associated with a higher incidence of negative health indicators including falls, morbidity and mortality. Despite efforts, the solution to this problem is still unsatisfactory. The two main causes of polymedication are population aging and polymorbidity and, on the other hand, the development of the pharmaceutical industry and the availability of a wide range of medicines. The authors discuss the main shortcomings in the investigation of this issue, such as inconsistent terminology used, methodological shortcomings in data acquisition, lack of recommended guidelines for the polymorbid patients treatment, etc. They discuss whether polymedication is the cause or marker of increased falls, frailty and mortality. In the end they critically evaluate possible solution of polymedication in future-personalised medicine.
Current Reviews in Clinical and Experimental Pharmacology, 2021
Background: The prevalence of cholelithiasis in developed countries is high and its cause is mult... more Background: The prevalence of cholelithiasis in developed countries is high and its cause is multifactorial, with a negligible proportion of drug-induced cholelithiasis. Methods: Relevant studies were identified by PubMed, Google Scholar and Science Direct. Reference lists of retrieved articles were also reviewed. The most relevant and up-to-date information was incorporated. Results: There is a wide range of drugs that can induce lithiasis. While the risk of developing lithiasis is high with some drugs (ceftriaxone, atazanavir, somatostatin analogues), it is lower or even questionable with others. Some drugs precipitate in the bile and may account for up to 100% of the weight of the stone. Conclusion: Cholelithiasis can be induced by a wide range of drugs with different mechanisms of action. The aim of the article is to draw attention to this lesser known fact and the need to take into account the risk of developing lithiasis prior to therapy initiation.
Činnost lékaře v každodenní praxi výrazným způsobem ovlivňují doporučené postupy. Na jednu nemoc ... more Činnost lékaře v každodenní praxi výrazným způsobem ovlivňují doporučené postupy. Na jednu nemoc však mohou existovat víceré doporučené postupy, které vypracují různé odbornosti, výzkumné skupiny apod. Dna je onemocněním spadajícím do oboru revmatologie, ale v praxi více než 90 % pacientů s dnou léčí ve světě praktičtí lékaři nebo internisté. Jednotlivé doporučené postupy se mohou lišit, ale doposud to nebylo nic zásadního, malé odlišnosti byly i u národních doporučení a většinou šlo o preferenci jednotlivých léků a jejich dávkování [1-4]. Největší rozdíly se týkaly hypourikemické léčby. K zásadním odlišnostem došlo až při vypracování doporučených postupů pro léčbu dny americkými praktickými lékaři-The American College of Physicians (ACP) publikovaných nedávno [5]. Zatímco doporučené postupy amerických a evropských revmatologů [6-10] možno označit jako "léčbu k cíli", doporučené postupy ACP jsou označovány jako "léčba symptomů", což autoři zdůvodňují chyběním důkazů pro jiný postup. Dále poukážeme na rozdíly v léčbě akutního dnavého záchvatu, prováděné profylaxe, hypourik emické léčby a asymptomatické hyperurikemie v posuzovaných doporučených postupech ve světě (tab). Akutní dnavý záchvat V léčbě se uplatňují 3 skupiny látek: nesteroidní antirevmatika (NSA), kolchicin a glukokortikoidy. Všechny tyto skupiny pokládáme za léky první volby. Jejich preference v léčbě je v jednotlivých zemích různá. Ve výběru se lékař rozhoduje na základě současných komorbidit pacienta. V britských doporučených postupech se lékař řídí preferencí pacienta, stavem renálních funkcí a přítomností ostatních komorbidit [10]. Správný výběr léku může být u polymorbidního pacienta obtížný i pro zkušeného lékaře. V práci Keenana et al [11] mělo aspoň jednu kontraindikaci pro použití NSA více než 90 % pacientů, pro kolchicin jen 30 %. Kolchicin V Evropě je od roku 2016 [8] preferovaným lékem pro léčbu akutního dnavého záchvatu kolchicin, pokud je léčba zahájena do 12 hod od vzniku symptomů a u pacienta nejsou
Česká a slovenská neurologie a neurochirurgie, 2019
Laboratory ef cacy test ing of acetylsalicylic acid treatment in secondary prevention of ischemic... more Laboratory ef cacy test ing of acetylsalicylic acid treatment in secondary prevention of ischemic stroke Souhrn Cíl: Určit účin nost antiagregační léčby kyselinou acetylsalicylovou v sekundární prevenci v přísně selektovaném souboru pa cientů po ischemické CMP. Soubor a metody: Do souboru bylo zahrnuto 106 pa cientů s minimalizací možných faktorů, které by mohly ovlivnit efekt kyseliny acetylsalicylové. Compliance byla potvrzena laboratorním vyšetřením kyseliny salicylové v plazmě, embolizační příhody minimalizovány pečlivým vyšetřením srdce a karotických tepen. U všech pa cientů užívajících 100 mg kyseliny acetylsalicylové den ně jsme vyšetřili sérové koncentrace 11-dehydrotromboxanu B2. Výsledky: I v tomto přísně selektovaném souboru k účin né supresi tromboxanu (95 % a více) došlo jen u 76 pa cientů, ale u dalších 24 suprese dosahovala 80-94,9 % a pouze u šesti pa cientů byla ještě nižší. Pa cienti s neúčin nou supresí tromboxanu měli statisticky významně vyšší body mass index, cholesterol a LDL cholesterol a kyselinu močovou. Závěr: Kyselina acetylsalicylová vedla k výrazné supresi tromboxanu u všech pa cientů, požadovaný stupeň suprese nedosáhla více než čtvrtina souboru pa cientů. V souladu s nejnovějšími poznatky je pravděpodobné, že zdánlivě nedostatečná suprese tromboxanu je způsobena produkcí tromboxanu z mimodestičkových zdrojů.
declare that they have no conflict of interest. The present study was approved by the respective ... more declare that they have no conflict of interest. The present study was approved by the respective Ethics Committees and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All procedures performed were in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients included in the study.
Scandinavian journal of clinical and laboratory investigation, 2015
Citalopram, a selective serotonin reuptake inhibitor (SSRi), is widely used to treat major depres... more Citalopram, a selective serotonin reuptake inhibitor (SSRi), is widely used to treat major depression. Patients treated with SSRIs suffer more frequently from bleeding disorders caused by the antiplatelet effect of SSRIs. To investigate the potential suppressive effect of citalopram treatment on plasma thromboxane B2 levels and its possible correlation with actual plasma concentration of citalopram. Plasma concentrations of thromboxane B2 and citalopram were examined in a cohort of 77 aspirin-treated geriatric patients before and in the third week of citalopram therapy. Citalopram therapy led to a significant decrease of plasma concentrations of thromboxane B2 compared to its levels before initiation of the therapy. Furthermore, we have shown negative correlation in thromboxane B2 levels and actual plasma concentration of citalopram. Actual plasma concentrations of citalopram were significantly higher compared to younger adult patients treated with similar dose. In this study we hav...
Serotonin syndrome is a potentially serious clinical condition. In this article, the authors put ... more Serotonin syndrome is a potentially serious clinical condition. In this article, the authors put serotonin syndrome into historical context, discuss its pathophysiology, review in detail its clinical presentations, diagnostic criteria, differential diagnosis and treatment. Special attention is given to drugs that most often cause serotonin syndrome, and the gene polymorphisms involved in the metabolism of these drugs.
The authors present an overview of the most often discussed questions concerning citalopram, i.e.... more The authors present an overview of the most often discussed questions concerning citalopram, i.e. its proven effect on the QT interval and related dose reductions. They discuss citalopram's antiplatelet effect including the most recent data and draw attention to serotonin syndrome as its incidence is still underestimated. They go on to discuss hyponatremia pointing out that this condition may develop even in those taking low doses of citalopram. Finally, the authors provide a brief overview of the latest findings on osteoporosis and the serotonergic mechanism inducing it in individuals treated with a selective serotonin reuptake inhibitor.
Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11-dTxB2) are widely used as pro... more Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11-dTxB2) are widely used as prognostic risk markers of platelet activation in cardiovascular diseases. The main errors in TxB2 and 11-dTxB2 determination include either low concentrations of circulating TxB2 (1 - 2 pg/mL) and 11-dTxB2 (0.9 - 4.3 pg/mL) or rather high transiency (mean TxB2 half-life is approximately 5 minutes) as well as an incorrect pre-analytical phase set up. The aim of this study was to investigate the impact of a widely used purification step on the results of enzyme immunosorbent assay (EIA)--based measurement of the two selected thromboxanes. For the purpose of this study, 20 plasma samples (10 healthy donors, 10 patients under treatment with acetylsalicylic acid) were screened for TxB2 and 11-dTxB2 concentrations using commercial competitive EIA kits (Cayman Chemicals, Tallinn, Estonia; Neogen, Lexington, KY, USA) with or without the introduction of the purification procedure. The purification ...
Production of endothelial nitric oxide declines with advancing age. On the other hand, ageing its... more Production of endothelial nitric oxide declines with advancing age. On the other hand, ageing itself is associated with a mild degree of chronic inflammation. Besides, asymptomatic infectious and non-infectious inflammation is frequent in old age. All this may lead to an increased formation of nitric oxide via inducible nitric oxide synthase. The plasma levels of nitric oxide metabolites in older age groups are not known. The aim of our study was to determine the plasma levels of metabolites of nitric oxide (nitrite and nitrate) and to correlate them with the levels of inflammation markers in clinically healthy individuals aged over 80. The plasma levels of nitrite/nitrate as well as erythrocyte sedimentation rate, and the levels of C-reactive protein and tumor necrosis factor alpha were determined in a group of 30 clinically healthy individuals aged over 80 years. Results were compared with those obtained in a control group. Nitrate levels were increased and the levels of inflammat...
Aspirin administered early after coronary artery bypass grafting surgery (CABG) improves graft pa... more Aspirin administered early after coronary artery bypass grafting surgery (CABG) improves graft patency and patients survival. However, the antiplatelet effect of aspirin seems to be variable and aspirin resistance is currently still being discussed. The aim of the study was to assess aspirin efficacy in the early postoperative period. Forty patients undergoing elective CABG surgery (20 in on-pump and 20 in off-pump) were enrolled in the study. Functional and biochemical responses to aspirin were evaluated by arachidonic acid (ARA)-induced platelet aggregation and urine 11-dehydro Thromboxane B2 metabolite excretion. Samples were collected before surgery (baseline; > or =7 days after aspirin withdrawal) and on days 1, 2 and 5 after surgery. Median baseline ARA aggregability was 55%. On day 1, platelet aggregability decreased (12%, P < 0.001). On day 2, despite the aspirin administration, platelet aggregability exceeded the values from day 1 (38%, P < 0.001). Only on day 5, sufficient inhibition of platelet aggregation was achieved (8%, P < 0.001). Median preoperative urine concentration of 11-dehydroTxB2 was 106 ng/mmol of creatinine. On day 1, the concentration decreased only slightly and insignificantly (97 ng/ml, P = NS), similarly as on day 2 (86 ng/ml, P = NS). Only on day 5, significant decrease in concentration of thromboxane metabolite was achieved compared to preoperative values (46 ng/ml, P = 0.001). Aspirin did not sufficiently inhibit platelet aggregation and thromboxane formation in the early postoperative period. Thus, antiplatelet treatment strategy should be intensified or modified in patients early after bypass surgery.
Journal of Cardiothoracic and Vascular Anesthesia, 2012
Aspirin therapy decreases mortality and ischemic complication rates after coronary artery bypass ... more Aspirin therapy decreases mortality and ischemic complication rates after coronary artery bypass grafting (CABG). However, platelet inhibition after oral aspirin seems to be insufficient in the early postoperative period. There are incomplete data reporting aspirin efficacy early after CABG. The aim of this study was to assess the pharmacologic effect of aspirin on platelets in the first postoperative days using the most specific laboratory tests for the evaluation of aspirin efficacy. A prospective study. A clinical study in one cardiac surgery center and measurements in two pharmacologic institutions. Thirty patients. Postoperative aspirin efficacy (200 mg/d) was assessed by the suppression of serum thromboxane B(2) (TxB(2)) and by arachidonic acid-induced aggregometry using the MULTIPLATE analyzer. Samples were collected before surgery and on postoperative days 1-5. The median baseline value (range) of serum TxB(2) was 1.6 ng/mL (1.4-1.9). The median TxB(2) inhibition >90% (the value required for full platelet inhibition) was not achieved until day 5 (-91%, 0.13 ng/mL [0.08-0.22], p < 0.001) and in only 55% of patients. The median baseline ASPI value was 805 (640-975) aggregation units (AU)*min. A significant decrease in aspirin insufficiency was not seen before postoperative day 5 (390 [243-621], p < 0.003) and only 34% of patients reached an effective platelet inhibition on day 5 (cutoff < 300 AU*min). The effect of aspirin on inhibition of TxB(2) production and arachidonic acid-induced platelet aggregation is impaired during the first postoperative days after CABG. A more effective antiplatelet strategy presumably could increase early graft patency and improve clinical outcomes after CABG.
Ceska A Slovenska Neurologie A Neurochirurgie, 2019
Souhrn Cil : urcit ucinnost antiagregacni lecby aspirinem v sekundarni prevenci v přisně selektov... more Souhrn Cil : urcit ucinnost antiagregacni lecby aspirinem v sekundarni prevenci v přisně selektovanem souboru pacientů po ischemicke cevni mozkove přihodě. Soubor a metodika : do souboru bylo zahrnuto 106 pacientů s minimalizaci možných faktorů, ktere by mohly ovlivnit efekt aspirinu. Compliance byla potvrzena laboratornim vysetřenim kyseliny salicylove v plazmě, embolizacni přihody minimalizovany peclivým vysetřenim srdce a karotických tepen. Přisna vylucovaci kriteria jsou uvedena niže. U vsech pacientů uživajicich 100mg kyseliny acetylsalicylove denně jsme vysetřili serove koncentrace 11-dehydrotromboxanu B2. Výsledky : i v tomto přisně selektovanem souboru ucinnou supresi tromboxanu (95% a vice) dosahlo jen 76 pacientů, ale u dalsich 24 suprese dosahovala 80-94,9% a pouze u sesti pacientů byla jestě mensi. Pacienti s neucinnou supresi tromboxanu měli statisticky významně vyssi BMI, cholesterol a LDL cholesterol a kyselinu mocovou. Zavěr : aspirin vedl k výrazne supresi tromboxan...
The compliance of patients receiving long-term acetylsalicylic acid therapy was tested by determi... more The compliance of patients receiving long-term acetylsalicylic acid therapy was tested by determining plasma levels of salicylic acid by HPLC. The same determination was performed in a control group of untreated patients. Almost 20 % of the examined patients were not using the prescribed therapy.
OBJECTIVE The aim of our study was to establish whether or not tinnitus patients have higher plat... more OBJECTIVE The aim of our study was to establish whether or not tinnitus patients have higher platelet activity, as measured by plasma 11-dehydro-thromboxane B2 levels, compared with individuals without tinnitus. METHODS The study group included patients without documented organic causes of tinnitus or a cause of non-vascular hearing impairment. Laboratory tests included complete blood count, biochemistry, coagulation activity, and thromboxane levels. To exclude a pathology in the cerebellopontine angle, CT and MRI were performed together with an X-ray scan of cervical vertebrae. For the purpose of this study, blood samples were screened for 11-dehydro-thromboxane B2 levels using commercial kits. RESULTS A comparison of the main marker of increased platelet activity i.e., thromboxane levels of tinnitus patients with those of a control group, showed increased thromboxane levels in the former. The average plasma concentrations of 11-dehydro-thromboxane B2 were 2.0234±1.80 ng/ml in the ...
OBJECTIVE: The aim of our study was to establish whether or not tinnitus patients have higher pla... more OBJECTIVE: The aim of our study was to establish whether or not tinnitus patients have higher platelet activity, as measured by plasma 11-dehydro-thromboxane B2 levels, compared with individuals without tinnitus. METHODS: The study group included patients without documented organic causes of tinnitus or a cause of non-vascular hearing impairment. Laboratory tests included complete blood count, biochemistry, coagulation activity, and thromboxane levels. To exclude a pathology in the cerebellopontine angle, CT and MRI were performed together with an X-ray scan of cervical vertebrae. For the purpose of this study, blood samples were screened for 11-dehydro-thromboxane B2 levels using commercial kits. RESULTS: A comparison of the main marker of increased platelet activity i.e., thromboxane levels of tinnitus patients with those of a control group, showed increased thromboxane levels in the former. The average plasma concentrations of 11-dehydro-thromboxane B2 were 2.0234±1.80 ng/ml in t...
Autoři pojednavaji o soucasných možnostech v lecbě dny (akutni dnavý zachvat, profylaxe, hypourik... more Autoři pojednavaji o soucasných možnostech v lecbě dny (akutni dnavý zachvat, profylaxe, hypourikemicka lecba) a asymptomaticke hyperurikemie. Poukazuji na rozdily v jednotlivých doporucených postupech z hlediska spektra použivaných leků, jejich preferenci, davkovani, titrovani davek, cilech lecby, i na odlisný přistup v otazkach asymptomaticke hyperurikemie. Diskutuji o novějsich poznatcich o kyselině mocove a jejim vztahu k některým neurologickým a kardiovaskularnim nemocem. Zmiňuji se take o zcela odlisných doporucených postupech amerických praktických lekařů a jejich principech. Zavěrem konstatuji, že odpovědi na některe sporne otazky v lecbě dny daji jen výsledky spravně zadaných a provedených klinických studii.
Poškození šlach patří mezi méně známé nežádoucí účinky některých léčiv. Donedávna byly známé jen ... more Poškození šlach patří mezi méně známé nežádoucí účinky některých léčiv. Donedávna byly známé jen u glukokortikoidů a fluorochinolonů. Dnes známe i další léčiva, která mohou způsobit poškození šlach (statiny, inhibitory aromatáz, anabolické steroidy a další). Autoři pojednávají o nejčastější klinické manifestaci, diagnostice a léčbě i novinkách z experimentálních prací k této problematice. Nejčastěji postiženou bývá šlacha Achillova, ale postiženy mohou být kterékoliv šlachy v organizmu. Lékový původ tendinopatie bychom měli zvažovat vždy, pokud máme pacienta s onemocněním šlachy, který užívá nebo nedávno užíval uvedené léky. Klíčová slova: anabolické steroidy-fluorochinolony-glukokortikoidy-inhibitory aromatáz-poškození šlach-statiny Drug induced tendon injury Summary Tendon injury belongs to the less known side effects of some drugs, reported until recently only for glucocorticoids and fluoroquinolones. To date, some other classes of drugs such as statins, aromatase inhibitors, anabolic steroids, potentially causing tendon injury, have been added to the list. The authors discuss the most common clinical presentations, diagnosis, and management as well as latest experimental data regarding this issue. The most often, the Achilles tendon is affected, however, nearly every tendon of the entire body may be affected. Tendon rupture or drug induced tendinopathy should be strongly considered in those who have a tendon injury and have recently taken these drugs.
Farmakologické a kardiologické minimum Citalopram patří mezi nejpoužívanější léčiva v léčbě depre... more Farmakologické a kardiologické minimum Citalopram patří mezi nejpoužívanější léčiva v léčbě deprese. Patří do skupiny tzv. selektivních inhibitorů zpětného vychytávání serotoninu (selective serotonin reuptake inhibitors-SSRI). Citalopram je racemická směs
Ústav farmakologie 2. LF UK, Praha Polymedikace je spojena s vyšším výskytem negativních zdravotn... more Ústav farmakologie 2. LF UK, Praha Polymedikace je spojena s vyšším výskytem negativních zdravotních ukazatelů včetně pádů, morbidity i mortality. I přes vynakládanou snahu je řešení této problematiky stále neuspokojivé. Dvě hlavní příčiny polymedikace jsou stárnutí populace a její polymorbidita, a na druhé straně rozvoj farmakoprůmyslu a dostupnost širokého spektra léčiv. Obě příčiny, tj. stárnutí populace i dostupnost léčiv, mají každoročně stoupající trend. Autoři pojednávají o hlavních nedostatcích při zkoumání uvedené problematiky, jako jsou nejednotně používaná terminologie, metodologické nedostatky při získávání dat, neexistence doporučených postupů pro léčbu polymorbidních pacientů apod. Diskutují o tom, zda polymedikace je příčinou nebo markerem zvýšené křehkosti, pádů a mortality. V závěru kriticky hodnotí možné řešení polymedikace v budoucnu-personalizovanou medicínu. Klíčova slova: polymedikace, polymorbidita, doporučené postupy, personalizovaná medicína. Pitfalls of solving polypharmacy problems Polymedication is associated with a higher incidence of negative health indicators including falls, morbidity and mortality. Despite efforts, the solution to this problem is still unsatisfactory. The two main causes of polymedication are population aging and polymorbidity and, on the other hand, the development of the pharmaceutical industry and the availability of a wide range of medicines. The authors discuss the main shortcomings in the investigation of this issue, such as inconsistent terminology used, methodological shortcomings in data acquisition, lack of recommended guidelines for the polymorbid patients treatment, etc. They discuss whether polymedication is the cause or marker of increased falls, frailty and mortality. In the end they critically evaluate possible solution of polymedication in future-personalised medicine.
Current Reviews in Clinical and Experimental Pharmacology, 2021
Background: The prevalence of cholelithiasis in developed countries is high and its cause is mult... more Background: The prevalence of cholelithiasis in developed countries is high and its cause is multifactorial, with a negligible proportion of drug-induced cholelithiasis. Methods: Relevant studies were identified by PubMed, Google Scholar and Science Direct. Reference lists of retrieved articles were also reviewed. The most relevant and up-to-date information was incorporated. Results: There is a wide range of drugs that can induce lithiasis. While the risk of developing lithiasis is high with some drugs (ceftriaxone, atazanavir, somatostatin analogues), it is lower or even questionable with others. Some drugs precipitate in the bile and may account for up to 100% of the weight of the stone. Conclusion: Cholelithiasis can be induced by a wide range of drugs with different mechanisms of action. The aim of the article is to draw attention to this lesser known fact and the need to take into account the risk of developing lithiasis prior to therapy initiation.
Činnost lékaře v každodenní praxi výrazným způsobem ovlivňují doporučené postupy. Na jednu nemoc ... more Činnost lékaře v každodenní praxi výrazným způsobem ovlivňují doporučené postupy. Na jednu nemoc však mohou existovat víceré doporučené postupy, které vypracují různé odbornosti, výzkumné skupiny apod. Dna je onemocněním spadajícím do oboru revmatologie, ale v praxi více než 90 % pacientů s dnou léčí ve světě praktičtí lékaři nebo internisté. Jednotlivé doporučené postupy se mohou lišit, ale doposud to nebylo nic zásadního, malé odlišnosti byly i u národních doporučení a většinou šlo o preferenci jednotlivých léků a jejich dávkování [1-4]. Největší rozdíly se týkaly hypourikemické léčby. K zásadním odlišnostem došlo až při vypracování doporučených postupů pro léčbu dny americkými praktickými lékaři-The American College of Physicians (ACP) publikovaných nedávno [5]. Zatímco doporučené postupy amerických a evropských revmatologů [6-10] možno označit jako "léčbu k cíli", doporučené postupy ACP jsou označovány jako "léčba symptomů", což autoři zdůvodňují chyběním důkazů pro jiný postup. Dále poukážeme na rozdíly v léčbě akutního dnavého záchvatu, prováděné profylaxe, hypourik emické léčby a asymptomatické hyperurikemie v posuzovaných doporučených postupech ve světě (tab). Akutní dnavý záchvat V léčbě se uplatňují 3 skupiny látek: nesteroidní antirevmatika (NSA), kolchicin a glukokortikoidy. Všechny tyto skupiny pokládáme za léky první volby. Jejich preference v léčbě je v jednotlivých zemích různá. Ve výběru se lékař rozhoduje na základě současných komorbidit pacienta. V britských doporučených postupech se lékař řídí preferencí pacienta, stavem renálních funkcí a přítomností ostatních komorbidit [10]. Správný výběr léku může být u polymorbidního pacienta obtížný i pro zkušeného lékaře. V práci Keenana et al [11] mělo aspoň jednu kontraindikaci pro použití NSA více než 90 % pacientů, pro kolchicin jen 30 %. Kolchicin V Evropě je od roku 2016 [8] preferovaným lékem pro léčbu akutního dnavého záchvatu kolchicin, pokud je léčba zahájena do 12 hod od vzniku symptomů a u pacienta nejsou
Česká a slovenská neurologie a neurochirurgie, 2019
Laboratory ef cacy test ing of acetylsalicylic acid treatment in secondary prevention of ischemic... more Laboratory ef cacy test ing of acetylsalicylic acid treatment in secondary prevention of ischemic stroke Souhrn Cíl: Určit účin nost antiagregační léčby kyselinou acetylsalicylovou v sekundární prevenci v přísně selektovaném souboru pa cientů po ischemické CMP. Soubor a metody: Do souboru bylo zahrnuto 106 pa cientů s minimalizací možných faktorů, které by mohly ovlivnit efekt kyseliny acetylsalicylové. Compliance byla potvrzena laboratorním vyšetřením kyseliny salicylové v plazmě, embolizační příhody minimalizovány pečlivým vyšetřením srdce a karotických tepen. U všech pa cientů užívajících 100 mg kyseliny acetylsalicylové den ně jsme vyšetřili sérové koncentrace 11-dehydrotromboxanu B2. Výsledky: I v tomto přísně selektovaném souboru k účin né supresi tromboxanu (95 % a více) došlo jen u 76 pa cientů, ale u dalších 24 suprese dosahovala 80-94,9 % a pouze u šesti pa cientů byla ještě nižší. Pa cienti s neúčin nou supresí tromboxanu měli statisticky významně vyšší body mass index, cholesterol a LDL cholesterol a kyselinu močovou. Závěr: Kyselina acetylsalicylová vedla k výrazné supresi tromboxanu u všech pa cientů, požadovaný stupeň suprese nedosáhla více než čtvrtina souboru pa cientů. V souladu s nejnovějšími poznatky je pravděpodobné, že zdánlivě nedostatečná suprese tromboxanu je způsobena produkcí tromboxanu z mimodestičkových zdrojů.
declare that they have no conflict of interest. The present study was approved by the respective ... more declare that they have no conflict of interest. The present study was approved by the respective Ethics Committees and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All procedures performed were in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients included in the study.
Scandinavian journal of clinical and laboratory investigation, 2015
Citalopram, a selective serotonin reuptake inhibitor (SSRi), is widely used to treat major depres... more Citalopram, a selective serotonin reuptake inhibitor (SSRi), is widely used to treat major depression. Patients treated with SSRIs suffer more frequently from bleeding disorders caused by the antiplatelet effect of SSRIs. To investigate the potential suppressive effect of citalopram treatment on plasma thromboxane B2 levels and its possible correlation with actual plasma concentration of citalopram. Plasma concentrations of thromboxane B2 and citalopram were examined in a cohort of 77 aspirin-treated geriatric patients before and in the third week of citalopram therapy. Citalopram therapy led to a significant decrease of plasma concentrations of thromboxane B2 compared to its levels before initiation of the therapy. Furthermore, we have shown negative correlation in thromboxane B2 levels and actual plasma concentration of citalopram. Actual plasma concentrations of citalopram were significantly higher compared to younger adult patients treated with similar dose. In this study we hav...
Serotonin syndrome is a potentially serious clinical condition. In this article, the authors put ... more Serotonin syndrome is a potentially serious clinical condition. In this article, the authors put serotonin syndrome into historical context, discuss its pathophysiology, review in detail its clinical presentations, diagnostic criteria, differential diagnosis and treatment. Special attention is given to drugs that most often cause serotonin syndrome, and the gene polymorphisms involved in the metabolism of these drugs.
The authors present an overview of the most often discussed questions concerning citalopram, i.e.... more The authors present an overview of the most often discussed questions concerning citalopram, i.e. its proven effect on the QT interval and related dose reductions. They discuss citalopram's antiplatelet effect including the most recent data and draw attention to serotonin syndrome as its incidence is still underestimated. They go on to discuss hyponatremia pointing out that this condition may develop even in those taking low doses of citalopram. Finally, the authors provide a brief overview of the latest findings on osteoporosis and the serotonergic mechanism inducing it in individuals treated with a selective serotonin reuptake inhibitor.
Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11-dTxB2) are widely used as pro... more Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11-dTxB2) are widely used as prognostic risk markers of platelet activation in cardiovascular diseases. The main errors in TxB2 and 11-dTxB2 determination include either low concentrations of circulating TxB2 (1 - 2 pg/mL) and 11-dTxB2 (0.9 - 4.3 pg/mL) or rather high transiency (mean TxB2 half-life is approximately 5 minutes) as well as an incorrect pre-analytical phase set up. The aim of this study was to investigate the impact of a widely used purification step on the results of enzyme immunosorbent assay (EIA)--based measurement of the two selected thromboxanes. For the purpose of this study, 20 plasma samples (10 healthy donors, 10 patients under treatment with acetylsalicylic acid) were screened for TxB2 and 11-dTxB2 concentrations using commercial competitive EIA kits (Cayman Chemicals, Tallinn, Estonia; Neogen, Lexington, KY, USA) with or without the introduction of the purification procedure. The purification ...
Production of endothelial nitric oxide declines with advancing age. On the other hand, ageing its... more Production of endothelial nitric oxide declines with advancing age. On the other hand, ageing itself is associated with a mild degree of chronic inflammation. Besides, asymptomatic infectious and non-infectious inflammation is frequent in old age. All this may lead to an increased formation of nitric oxide via inducible nitric oxide synthase. The plasma levels of nitric oxide metabolites in older age groups are not known. The aim of our study was to determine the plasma levels of metabolites of nitric oxide (nitrite and nitrate) and to correlate them with the levels of inflammation markers in clinically healthy individuals aged over 80. The plasma levels of nitrite/nitrate as well as erythrocyte sedimentation rate, and the levels of C-reactive protein and tumor necrosis factor alpha were determined in a group of 30 clinically healthy individuals aged over 80 years. Results were compared with those obtained in a control group. Nitrate levels were increased and the levels of inflammat...
Aspirin administered early after coronary artery bypass grafting surgery (CABG) improves graft pa... more Aspirin administered early after coronary artery bypass grafting surgery (CABG) improves graft patency and patients survival. However, the antiplatelet effect of aspirin seems to be variable and aspirin resistance is currently still being discussed. The aim of the study was to assess aspirin efficacy in the early postoperative period. Forty patients undergoing elective CABG surgery (20 in on-pump and 20 in off-pump) were enrolled in the study. Functional and biochemical responses to aspirin were evaluated by arachidonic acid (ARA)-induced platelet aggregation and urine 11-dehydro Thromboxane B2 metabolite excretion. Samples were collected before surgery (baseline; > or =7 days after aspirin withdrawal) and on days 1, 2 and 5 after surgery. Median baseline ARA aggregability was 55%. On day 1, platelet aggregability decreased (12%, P < 0.001). On day 2, despite the aspirin administration, platelet aggregability exceeded the values from day 1 (38%, P < 0.001). Only on day 5, sufficient inhibition of platelet aggregation was achieved (8%, P < 0.001). Median preoperative urine concentration of 11-dehydroTxB2 was 106 ng/mmol of creatinine. On day 1, the concentration decreased only slightly and insignificantly (97 ng/ml, P = NS), similarly as on day 2 (86 ng/ml, P = NS). Only on day 5, significant decrease in concentration of thromboxane metabolite was achieved compared to preoperative values (46 ng/ml, P = 0.001). Aspirin did not sufficiently inhibit platelet aggregation and thromboxane formation in the early postoperative period. Thus, antiplatelet treatment strategy should be intensified or modified in patients early after bypass surgery.
Journal of Cardiothoracic and Vascular Anesthesia, 2012
Aspirin therapy decreases mortality and ischemic complication rates after coronary artery bypass ... more Aspirin therapy decreases mortality and ischemic complication rates after coronary artery bypass grafting (CABG). However, platelet inhibition after oral aspirin seems to be insufficient in the early postoperative period. There are incomplete data reporting aspirin efficacy early after CABG. The aim of this study was to assess the pharmacologic effect of aspirin on platelets in the first postoperative days using the most specific laboratory tests for the evaluation of aspirin efficacy. A prospective study. A clinical study in one cardiac surgery center and measurements in two pharmacologic institutions. Thirty patients. Postoperative aspirin efficacy (200 mg/d) was assessed by the suppression of serum thromboxane B(2) (TxB(2)) and by arachidonic acid-induced aggregometry using the MULTIPLATE analyzer. Samples were collected before surgery and on postoperative days 1-5. The median baseline value (range) of serum TxB(2) was 1.6 ng/mL (1.4-1.9). The median TxB(2) inhibition >90% (the value required for full platelet inhibition) was not achieved until day 5 (-91%, 0.13 ng/mL [0.08-0.22], p < 0.001) and in only 55% of patients. The median baseline ASPI value was 805 (640-975) aggregation units (AU)*min. A significant decrease in aspirin insufficiency was not seen before postoperative day 5 (390 [243-621], p < 0.003) and only 34% of patients reached an effective platelet inhibition on day 5 (cutoff < 300 AU*min). The effect of aspirin on inhibition of TxB(2) production and arachidonic acid-induced platelet aggregation is impaired during the first postoperative days after CABG. A more effective antiplatelet strategy presumably could increase early graft patency and improve clinical outcomes after CABG.
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Papers by Zoltán Paluch