PURPOSE: Pain after open urological procedures is often intense. The aim of the study was to compare the efficacy of intrathecal morphine with systemic analgesia approaches. DESIGN: Prospective, randomized, single-blind controlled study. METHODS: Patients undergoing open prostatectomy or nephrectomy were randomly divided into the intervention group or the control group. Patients in the intervention group received morphine 250 mcg in 2.5 mL saline intrathecally. Anesthesia was identical in both groups. All patients were admitted to the intensive care unit (ICU) postoperative and received paracetamol 1 g intravenously every 6 hours and diclofenac 75 mg intramuscularly every 12 hours. If postoperative pain exceeded four on the numeric rating scale, morphine 10 mg was administered subcutaneously. Pain intensity, time to first dose of morphine, morphine doses, and side effects were recorded. FINDINGS: In total, 41 patients were assigned to the intervention group and 57 to the control group. The time to administration of the first dose of morphine was significantly (P < .001) longer in the intervention group when compared to controls. This observation was also noted individually for patients undergoing nephrectomy (36.86 hours vs 4.06 hours) and prostatectomy (33.13 hours vs 4.5 hours). Many patients did not need opioids after surgery in the intervention group (nephrectomy 72% vs 3%, prostatectomy 75% vs 4.5%, P < .001). There was no significant difference in the incidence of side effects. CONCLUSIONS: The results of our study confirmed that preoperative intrathecal morphine provides long-lasting analgesia and reduces the need for postoperative systemic administration of opioids. Adverse effects are minor and comparable between groups.
- Klíčová slova
- analgesia, intrathecal morphine, nephrectomy, postoperative pain, prostatectomy,
- MeSH
- anestetika lokální aplikace a dávkování MeSH
- jednoduchá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- morfin * aplikace a dávkování MeSH
- nefrektomie * metody MeSH
- opioidní analgetika * aplikace a dávkování MeSH
- pooperační bolest * farmakoterapie prevence a kontrola MeSH
- prospektivní studie MeSH
- prostatektomie * metody MeSH
- senioři MeSH
- spinální injekce * metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- anestetika lokální MeSH
- morfin * MeSH
- opioidní analgetika * MeSH
We report on the case of a 46-year-old woman with generalized anxiety disorder, paranoid personality disorder, and mild reduction in glomerular filtration rate (GFR). She was treated with pregabalin, trazodone, hydroxyzine, and clonazepam before hospital admission. Pharmacotherapy for the patient was changed during her first week in the hospital. Dosing of hydroxyzine and clonazepam was gradually decreased, and then these two drugs were withdrawn. Treatment with amisulpride was started on the fourth day after admission, and amisulpride serum levels were then measured three times as a part of therapeutic drug monitoring (TDM). The serum concentration of amisulpride detected during concurrent use of trazodone and pregabalin was approximately twice the therapeutic range for amisulpride. When the dose of pregabalin was reduced by half, the serum concentration of amisulpride decreased to therapeutic serum levels. We hypothesize that an interaction between amisulpride and pregabalin was responsible for the increased amisulpride concentration since both drugs are almost exclusively excreted from the body by the renal route. Pregabalin-amisulpride interaction might also be influenced by concomitant therapy with trazodone or a mild reduction in GFR. However, we only have clinical evidence for an interaction between amisulpride and pregabalin because after we halved the dose of pregabalin, the amisulpride concentration decreased, and the C/D ratio normalized. This could be helpful information for psychiatrists in order to avoid drug-drug interactions between amisulpride and pregabalin. We recommend TDM of amisulpride in patients treated concomitantly with other drugs eliminated mainly by the kidneys.
- Klíčová slova
- amisulpride, case report, drug transporter, pharmacokinetic drug interaction, pregabalin, trazodone,
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Improvement in the prognosis of patients at risk of atherothrombotic events is based on three pillars - slowing down the process of atherogenesis (i.e. the development of atherosclerotic plaque), stabilizing the current atherosclerotic plaque, and reducing the risk of thrombotic occlusion in cases with unstable atherosclerotic plaque. The current prophylaxis has so far taken into consideration the adjustment of several risk factors, including dyslipidemia, arterial hypertension, smoking, and diabetes through lifestyle changes or pharmacological therapies. An essential part of prophylaxis is the anti-thrombotic strategy, especially anti-platelet therapy. Recently, a new pathway has been developed, based on reducing the activity of the inflammatory process with NLRP3 inflammasome, specifically a monoclonal antibody against interleukin 1beta (canakinumab). The efficacy and safety of this treatment, in secondary prevention, were documented in the CANTOS study. Other therapeutic procedures, including suppression of the inflammatory component of atherogenesis, are at the stage of clinical assessment.
- MeSH
- antiflogistika terapeutické užití MeSH
- aterosklerotický plát prevence a kontrola MeSH
- ateroskleróza farmakoterapie MeSH
- humanizované monoklonální protilátky farmakologie terapeutické užití MeSH
- interleukin-1beta antagonisté a inhibitory MeSH
- lidé MeSH
- makrofágy účinky léků fyziologie MeSH
- protein NLRP3 účinky léků fyziologie MeSH
- rizikové faktory MeSH
- trombóza prevence a kontrola MeSH
- zánět prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antiflogistika MeSH
- canakinumab MeSH Prohlížeč
- humanizované monoklonální protilátky MeSH
- IL1B protein, human MeSH Prohlížeč
- interleukin-1beta MeSH
- protein NLRP3 MeSH
Inosine pranobex (IP), commonly known as inosine acedoben dimepranol, isoprinosine and methisoprinol, has been proven to positively impact the host's immune system, by enhancing T-cell lymphocyte proliferation and activity of natural killer cells, increasing levels of pro-inflammatory cytokines, and thereby restoring deficient responses in immunosuppressed patients. At the same time, it has been shown that it can affect viral RNA levels and hence inhibit growth of several viruses. Due to its immunomodulatory and antiviral properties, and its safety profile, it has been widely used since 1971 against viral infections and diseases, among which subacute sclerosis panencephalitis, herpes simplex virus, human papilloma virus, human immunodeficiency virus, influenza and acute respiratory infections, cytomegalovirus and Epstein-Barr virus infections. Following an analysis of almost five decades of scientific literature since its original approval, we here summarize in vivo and in vitro studies manifesting the means in which IP impacts the host's immune system. We also provide a synopsis of therapeutic trials in the majority of which IP was found to have a beneficial effect. Lastly, positive results from limited studies, suggesting the putative future use of IP in new therapeutic indications are briefly described. In order to support use of IP against viral infections apart from those already approved, and to establish its use in clinical practice, further well-designed and executed trials are warranted.Funding: Ewopharma International.
- Klíčová slova
- Antiviral, HPV, Herpes, Immunomodulation, Infection, Influenza, Inosine pranobex, Isoprinosine, SSPE,
- MeSH
- adjuvancia imunologická terapeutické užití MeSH
- antivirové látky terapeutické užití MeSH
- chřipka lidská farmakoterapie MeSH
- HIV infekce farmakoterapie MeSH
- inosin pranobex farmakologie terapeutické užití MeSH
- lidé MeSH
- mediátory zánětu imunologie MeSH
- neinfekční nemoci farmakoterapie MeSH
- T-lymfocyty imunologie MeSH
- virové nemoci farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- adjuvancia imunologická MeSH
- antivirové látky MeSH
- inosin pranobex MeSH
- mediátory zánětu MeSH
OBJECTIVES: Carbamazepine and quetiapine are drugs that are used as mood stabilizers in the treatment of bipolar disorders. A series of studies has shown that concurrent use of carbamazepine decreases quetiapine serum level due to induction of CYP3A enzymes by carbamazepine. METHODS: In a 30-year-old bipolar patient with mania treated with quetiapine 1200 mg and carbamazepine 900 mg per day, we measured quetiapine serum level before and after carbamazepine withdrawal. RESULTS: No serum quetiapine was detected during concurrent use of carbamazepine and was lower than the therapeutic range almost 2 weeks after carbamazepine withdrawal. The patient suffered from sedation when her serum level of quetiapine was 181 ng/ml and because she was quiet we started slowly to decrease to a quetiapine dose of 600 mg. Her serum level (45 ng/ml) was again below therapeutic levels after 3 weeks of carbamazepine withdrawal. CONCLUSION: We hypothesize that induction of CYP3A lasts even after carbamazepine withdrawal. Our hypothesis was confirmed during the next treatment of mania. The patient had been off carbamazepine for 1 year and her serum level was four times higher (210 ng/ml) on 600 mg of quetiapine than 3 weeks after carbamazepine withdrawal. The influence of carbamazepine on CYP3A enzymes lasted at least 3 weeks after carbamazepine withdrawal which is in accordance with CYP3A de-induction lasting 3 weeks. This could be important information for psychiatrists to know that in some patients it is better to use a minimum washout period of 3 weeks for carbamazepine before new treatment with quetiapine.
- MeSH
- antimanika krev farmakokinetika terapeutické užití MeSH
- antipsychotika krev farmakokinetika terapeutické užití MeSH
- bipolární porucha krev farmakoterapie MeSH
- dospělí MeSH
- karbamazepin krev farmakokinetika terapeutické užití MeSH
- lékové interakce MeSH
- lidé MeSH
- quetiapin fumarát krev farmakokinetika terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- antimanika MeSH
- antipsychotika MeSH
- karbamazepin MeSH
- quetiapin fumarát MeSH
AIM: This study seeks to assess smoking habits, attitudes and intention to quit in students of the Third Faculty of Medicine of Charles University in Prague, Czech Republic. METHODS: A cross-sectional survey designed to obtain information on smoking history, current smoking status, cessation attempts, and attitudes towards smoking among health professionals was conducted in 452 students of the first and last years of a 6-year Master's Study Programme (General Medicine) and a 3-year Bachelor's Study Programme (Public Health). An anonymous questionnaire was administered during the classes in the course of academic years 2011-12 and 2012-13. RESULTS: 5.7% of the Master's Study Programme students (3.3% women and 9.0% men ) and 4.8% of the Bachelor's Study Programme students reported that they are regular smokers. The share of regular smokers was almost twice as big in students of the English Curriculum of the Master's Programme (10.7%) in comparison with the students of the Czech Curriculum (4.5%), and more than twice as big in students of the last years of both study programmes (3.9% in students of the 1st year and 10.8% in students of the 6th year of the Master's Programme; 3.2% in students of the 1st year and 7.0% in students of the 3rd year of the Bachelor's Study Programme). At the time of the research, 18.9% of students of the Master's Programme and 17.1% of students of the Bachelor's Programme were occasional smokers. 5.9% of students of the Master's Programme and 19.0% of students of the Bachelor's Programme reported that they quit smoking during their studies at the medical faculty; on the contrary, 9.8% of students of the Master's Programme and 14.3% of students of the Bachelor's Programme started smoking during that time. CONCLUSIONS: Smoking in health professionals undermines their significant role in health promotion and prevention of chronic diseases in their patients. Therefore, education at the medical faculty should focus on motivation of future health professionals towards non-smoking except providing knowledge on current research and guidance on early identification and further intervention in smokers.
- Klíčová slova
- education, health professions students, smoking cessation, tobacco use,
- MeSH
- dospělí MeSH
- kouření epidemiologie MeSH
- lidé MeSH
- odvykání kouření MeSH
- postoj ke zdraví * MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- studenti lékařství psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
Acyclic nucleoside phosphonates (ANPs) are potent antiviral agents effective against replication of DNA viruses and retroviruses including human immunodeficiency virus (HIV). Prototype compound 9-(R)-[2-(phosphonomethoxy)propyl]adenine (tenofovir) is a principal component of drugs widely used in the treatment of HIV infection (Viread, Truvada). Besides their antimetabolic mode of action, ANPs possess immunomodulatory properties. A number of them have been previously found to stimulate secretion of cytokines and anti-HIV effective chemokines. In the present pilot experiments we analysed the in vitro effects of ANPs on the expression of chemokine receptors CCR5 and CXCR4 that are co-receptors of HIV-1 entry in cells. The impact of ANPs was investigated at the level of gene transcription of mRNA in mouse lymphocytes and macrophages using the RT-PCR method. The following compounds were included in the study: 9-(R)-[2-(phosphonomethoxy) propyl]adenine (tenofovir), N6-cyclopropyl-(R)- 9-[2-(phosphonomethoxy)-propyl]2,6-diaminopurine, N6-cyclopentyl-(R)-9-[2-(phosphonomethoxy) propyl]2,6-diaminopurine, N6-dimethylaminoethyl-(R)-9-[2-(phosphonomethoxy)propyl]2,6-diaminopurine, N6-cyclopentyl-9-[2-(phosphonomethoxy) ethyl]2,6-diaminopurine, N6-isobutyl-9-[2-(phosphonomethoxy) ethyl]2,6-diaminopurine. Gene transcription of chemokine receptors CCR5 and CXCR4 was not affected after application of these acyclic nucleoside phosphonate antivirals.
- MeSH
- antivirové látky chemie farmakologie MeSH
- lymfocyty účinky léků metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- nukleosidy chemie farmakologie MeSH
- receptory CCR5 genetika metabolismus MeSH
- receptory CXCR4 genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antivirové látky MeSH
- messenger RNA MeSH
- nukleosidy MeSH
- receptory CCR5 MeSH
- receptory CXCR4 MeSH
OBJECTIVES: There is good evidence that opioids can potentiate analgesic activity of some older non-opioid analgesics (such as paracetamol or ibuprofen) but it is not known whether this also holds true for newer non-opioid analgesics that selectively inhibit cyclooxygenase 2 (coxibs). This study was undertaken to determine the nature of the interaction between codeine and celecoxib or etoricoxib in peritoneal irritation-induced visceral pain in mice. For comparison, interactions of codeine with paracetamol and ibuprofen were also tested using the same method. MATERIAL AND METHODS: A small volume of a weak acetic acid (0.6%) was injected into the peritoneal cavity and the number of writhes (contractions of abdominal muscles) was counted. All drugs were given orally. Their interaction was characterized using isobolographic analysis. RESULTS: Codeine, etoricoxib, celecoxib, ibuprofen and paracetamol all independently produced dose-dependent suppression of writhing. The isobolographic analysis carried out using equipotent dose ratios showed that the interactions between codeine and etoricoxib or celecoxib were sub-additive or additive, respectively. This was in contrast to combinations of codeine with ibuprofen or paracetamol, which were supra-additive. Interaction indexes γ, determined as a ratio between experimental and theoretical ED50 values of the mixture, were as follows: 2.7 for codeine + etoricoxib, 0.62 for codeine + celecoxib, 0.43 for codeine + ibuprofen and 0.33 for codeine + paracetamol. CONCLUSIONS: These and other results suggest that opioids do not seem to potentiate analgesic effects of selective COX-2 inhibitors, in contrast to nonselective COX inhibitors or paracetamol.
- MeSH
- bolest chemicky indukované farmakoterapie MeSH
- celekoxib MeSH
- etoricoxib MeSH
- ibuprofen terapeutické užití MeSH
- inbrední kmeny myší MeSH
- inhibitory cyklooxygenasy 2 terapeutické užití MeSH
- interpretace statistických dat MeSH
- kodein terapeutické užití MeSH
- kyselina octová škodlivé účinky MeSH
- lékové interakce MeSH
- modely u zvířat MeSH
- myši MeSH
- neopioidní analgetika terapeutické užití MeSH
- opioidní analgetika terapeutické užití MeSH
- paracetamol terapeutické užití MeSH
- pyrazoly terapeutické užití MeSH
- pyridiny terapeutické užití MeSH
- regresní analýza MeSH
- sulfonamidy terapeutické užití MeSH
- sulfony terapeutické užití MeSH
- synergismus léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- celekoxib MeSH
- etoricoxib MeSH
- ibuprofen MeSH
- inhibitory cyklooxygenasy 2 MeSH
- kodein MeSH
- kyselina octová MeSH
- neopioidní analgetika MeSH
- opioidní analgetika MeSH
- paracetamol MeSH
- pyrazoly MeSH
- pyridiny MeSH
- sulfonamidy MeSH
- sulfony MeSH
The aim of the present study was to evaluate and compare the analgesic activity and serum levels of meloxicam (CAS 71125-38-7) after administration of meloxicam associated with beta-cyclodextrin (BCD, CAS 7585-39-9) and unmodified meloxicam. The analgesic activity was measured using the plantar test (rats) and the writhing test (mice). In the plantar test, BCD-meloxicam (3 mg/kg and 10 mg/kg orally) showed higher analgesic activity than corresponding doses of meloxicam alone; in the writhing test BCD-meloxicam (7 mg/kg and 15 mg/kg orally) showed stronger analgesic activity than unmodified meloxicam. Serum levels of meloxicam were significantly higher, at 0.5 h and 1 h after administration of BCD-meloxicam orally than those of unmodified meloxicam (both dosed at 10 mg/kg). The present results suggest that association with beta-cyclodextrin increases the analgesic activity of meloxicam. This may be due to an icreased systemic bioavailability of meloxicam after oral administration of its complex with beta-cyclodextrin.
- MeSH
- analgetika farmakologie MeSH
- antiflogistika nesteroidní krev farmakologie MeSH
- beta-cyklodextriny krev MeSH
- bolest farmakoterapie MeSH
- hyperalgezie chemicky indukované MeSH
- karagenan MeSH
- krysa rodu Rattus MeSH
- meloxikam MeSH
- měření bolesti účinky léků MeSH
- myši MeSH
- potkani Wistar MeSH
- thiaziny krev farmakologie MeSH
- thiazoly krev farmakologie MeSH
- vény účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- analgetika MeSH
- antiflogistika nesteroidní MeSH
- beta-cyklodextriny MeSH
- betadex MeSH Prohlížeč
- karagenan MeSH
- meloxikam MeSH
- thiaziny MeSH
- thiazoly MeSH
OBJECTIVES: Paracetamol is converted to an active metabolite AM404 via fatty acid amide hydrolase (FAAH). The aim of the present study was to ascertain whether a FAAH inhibitor URB597 antagonizes paracetamol analgesic activity (and to asses by this way the role of FAAH in analgesic activity of paracetamol). METHODS: The interaction between a FAAH inhibitor URB597 and paracetamol was investigated in the writhing test in mice using an isobolographic analysis. RESULTS: URB597 or paracetamol alone and in combinations produced dose-dependent antinociceptive effects. ED50 values were estimated for the individual drugs and an isobologram was constructed. The observed ED50 value for the URB57-paracetamol combination was 0.097 (0.062-0.247) mg/kg. This value did not differ significantly from the theoretical additive ED50 value for the URB597-paracetamol combination which was 0.108 (0.059-0.198) mg/kg. Thus, inhibition of FAAH by URB597 was not followed by the lack of analgesic activity in paracetamol. CONCLUSION: The present results suggest that the analgesic activity of paracetamol is not dependent solely on FAAH metabolic conversion to AM404 and that paracetamol exerts analgesic activity also by additional mechanisms.
- MeSH
- amidohydrolasy antagonisté a inhibitory MeSH
- benzamidy farmakologie MeSH
- karbamáty farmakologie MeSH
- lékové interakce MeSH
- lineární modely MeSH
- měření bolesti účinky léků MeSH
- myši MeSH
- neopioidní analgetika farmakologie MeSH
- paracetamol farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amidohydrolasy MeSH
- benzamidy MeSH
- cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester MeSH Prohlížeč
- fatty-acid amide hydrolase MeSH Prohlížeč
- karbamáty MeSH
- neopioidní analgetika MeSH
- paracetamol MeSH
