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

Benzodiazepines have been widely used in clinical praxis for many decades. They act as GABAA receptor agonists and possess muscle-relaxant, hypnotic-sedative, anticonvulsant, and anxiolytic properties. Flumazenil acts as a benzodiazepine receptor antagonist (subunits α1, α2, α3, and α5) or partial agonist (subunits α4 and α6). It competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex, thereby reversing the effects of benzodiazepines. In our experiments, administration of flumazenil in rabbits was surprisingly associated with anxiolytic effects similar to those of midazolam. Additionally, flumazenil significantly and dose-dependently decreased the total number of vocalizations in rats, i.e. it was anxiolytic. These observations seem to be in contrast to the effect of flumazenil in humans, where it is believed to produce mainly anxiogenic effects. It seems that in individuals, who exhibit anxiogenic behavior or in individuals with anticipation anxiety, flumazenil acts as an anxiolytic agent, while in individuals without any signs of anxiety, flumazenil can also act as anxiogenic agent. Thus, we hypothesize that flumazenil is associated with decreased intensity of anticipatory anxiety due to occupancy of benzodiazepine binding sites by an endogenous ligand with inverse agonistic properties.

• MeSH
• antagonisté receptorů GABA-A aplikace a dávkování   farmakologie   MeSH
• anxiolytika aplikace a dávkování   farmakologie   MeSH
• benzodiazepiny antagonisté a inhibitory   metabolismus   MeSH
• biologické modely * MeSH
• flumazenil aplikace a dávkování   farmakologie   MeSH
• králíci MeSH
• lidé MeSH
• ligandy MeSH
• úzkost farmakoterapie   MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté receptorů GABA-A MeSH
• anxiolytika MeSH
• benzodiazepiny MeSH
• flumazenil MeSH
• ligandy MeSH

GC with nitrogen phosphorus detection and HPLC with UV detection were used to determine midazolam (MDZ) levels in rabbit plasma following ocular and nasal administration. For GC with nitrogen phosphorus detection, the analyte was extracted from the plasma using a three-step liquid-liquid extraction including extraction with an isopropanol/butyl chloride mixture in an alkaline solution, followed by extractions with 1 M HCl, and finally with an alkaline solution of butyl chloride. The recovery of MDZ was dependent on the sample alkalization time prior to the final extraction. The procedure increased the recovery of MDZ up to 99.6%. Improved sample preparation led to a significant increase in the sensitivity of the determination by GC with nitrogen phosphorus detection. The achieved detection limit was 0.34 ng/mL, which is ten times lower than that obtained using HPLC with UV detection. The small plasma volume was another advantage of the GC with nitrogen phosphorus detection method (200 μL per assay). Both administration routes of the anesthetic (nasal and ocular) resulted in comparable plasma MDZ levels. Kinetic simulation of the MDZ plasma was performed for both administration routes.

• Klíčová slova
• Fentanyl, Midazolam, Nasal administration, Nitrogen phosphorus detection, Ocular administration,
• MeSH
• aplikace intranazální MeSH
• aplikace oční MeSH
• chromatografie plynová metody   MeSH
• hypnotika a sedativa aplikace a dávkování   krev   MeSH
• králíci MeSH
• limita detekce MeSH
• midazolam aplikace a dávkování   krev   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hypnotika a sedativa MeSH
• midazolam MeSH

BACKGROUND: Dental procedures on intellectually disabled patients represent a clinical challenge. The oral administration of sedating drugs can remediate the problems with cooperation and enable the medical procedures to take place. Standard guidelines are lacking for oral sedation of the intellectually disabled. OBJECTIVE: To compare two oral combinations of sedating drugs in terms of time to the onset and achievement of full sedation, vital signs, behavioral measures and safety. METHODS: In a group of 29 intellectually disabled patients we compared two oral combinations for analgosedation: ketamine (5 mg/kg) - clonidine 2 µg/kg - midazolam 0.3 mg/kg (N=17) or ketamine 5 mg/kg - midazolam 0.3 mg/kg (N= 12 patients). Drugs were dissolved in a sweet drink. RESULTS: Full sedation was achieved within 25 min. in 27 patients and serious side effects were not detected. Clonidine in combination with ketamine and midazolam did not exert any significant effect by means of the onset of sedation, time to the achievement of full sedation, vital signs and behavioral measures of sedation (Vancouver Interaction and Calmness Scale) and agitation (Pittsburgh Agitation Scale). CONCLUSIONS: Our study is the first to document that oral administration of ketamine and midazolam in low doses represents a safe and effective method of premedication in intellectually disabled patients indicated for dental procedures. Clonidine co-administration did not exert any substantial benefit and should be left out in this clinical setting.

• MeSH
• clonidin aplikace a dávkování   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fixní kombinace léků MeSH
• hypnotika a sedativa aplikace a dávkování   MeSH
• ketamin aplikace a dávkování   MeSH
• klinické protokoly MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mentální retardace MeSH
• midazolam aplikace a dávkování   MeSH
• postižení MeSH
• premedikace anestezie metody   MeSH
• stomatologická péče pro postižené metody   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zubní anestezie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• clonidin MeSH
• fixní kombinace léků MeSH
• hypnotika a sedativa MeSH
• ketamin MeSH
• midazolam MeSH

OBJECTIVE: To develop a safe and effective immobilization protocol in rhesus monkeys, which is not based on dissociative anaesthetic agent. STUDY DESIGN: Prospective, randomised, experimental trial. ANIMALS: Twenty rhesus monkeys, weighing 2.6-8.0 kg, 1-3 years of age, of both sexes. METHODS: The monkeys received 50 μg kg(-1) medetomidine, 0.25 mg kg(-1) midazolam and 5 μg kg(-1) fentanyl with 150 IU hyaluronidase intramuscularly (IM). The animals were closely observed for behavioural changes and reaction to sound stimulus. Pulse rate and oxygen saturation of haemoglobin (SpO(2) ) were monitored every 5 minutes, for 20 minutes. After this period, 250 μg kg(-1) atipamezole or a placebo was administered IM and behavioural changes were closely observed. RESULTS: Full immobilization was observed after mean 269 ± SD 116 seconds. Ten minutes after injection mean arterial oxygen saturation of haemoglobin was 94 ± 4%, but did not fall significantly further. The median pulse rate was 116 beats minute(-1) 5 minutes after the administration of the drug. This level further decreased to a median level of 108 beats minute(-1) 20 minutes after the drug's administration. The median time to recover from immobilization was significantly shorter after atipamezole administration when compared to placebo (2.7 versus 55 minutes). All animals awoke smoothly and no side effects such as vomiting or agitation were observed. CONCLUSIONS: Short term and reversible pharmacological immobilization was achieved using combination of midazolam, medetomidine, and fentanyl. CLINICAL RELEVANCE: The present study demonstrates that 20-minute pharmacological immobilization with a combination of midazolam, medetomidine, and fentanyl is feasible in rhesus monkeys with minimal effect on heart rate.

• MeSH
• analýza krevních plynů veterinární   MeSH
• časové faktory MeSH
• fentanyl * aplikace a dávkování   farmakologie   MeSH
• hypnotika a sedativa * aplikace a dávkování   farmakologie   MeSH
• imobilizace metody   veterinární   MeSH
• injekce intramuskulární veterinární   MeSH
• kombinovaná farmakoterapie veterinární   MeSH
• Macaca mulatta * MeSH
• medetomidin * aplikace a dávkování   farmakologie   MeSH
• midazolam * aplikace a dávkování   farmakologie   MeSH
• srdeční frekvence účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fentanyl * MeSH
• hypnotika a sedativa * MeSH
• medetomidin * MeSH
• midazolam * MeSH

BACKGROUND: The aim of this study was to compare cardiorespiratory and behavioral profile of a new alpha 2-adrenoceptor ligand naphthylmedetomidine with medetomidine in rhesus monkeys. METHODS: Naphthylmedetomidine or medetomidine (50 microg/kg) together with ketamine (3 mg/kg) and hyaluronidase (150 IU/kg) i.m was administered to 35 rhesus monkeys. Behavioral changes were then observed together with blood pressure, heart rate and oxygen saturation of hemoglobin. RESULTS: The onset of sedation, ataxia, and reduction of aggression was similar in both treatment groups. Immobilization was observed only in medetomidine treated animals, while in naphthylmedetomidine treated animals loss of aggressiveness was observed but the animals never completely lost mobility. Naphthylmedetomidine showed less prominent effects on cardiorespiratory functions compared with medetomidine. CONCLUSIONS: Our results suggest that naphthylmedetomidine can be used to induce sedation in primates and other small animals while avoiding the serious side effects observed after administration of the currently used full alpha(2)-AR agonists.

• MeSH
• agonisté adrenergních alfa-receptorů farmakologie   MeSH
• alfa-2-adrenergní receptory - agonisté * MeSH
• anestetika disociativní aplikace a dávkování   farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• hemoglobiny metabolismus   MeSH
• hyaluronoglukosaminidasa aplikace a dávkování   farmakologie   MeSH
• ketamin aplikace a dávkování   farmakologie   MeSH
• Macaca mulatta fyziologie   MeSH
• medetomidin aplikace a dávkování   analogy a deriváty   farmakologie   MeSH
• srdeční frekvence účinky léků   MeSH
• triclosan metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4-(1-(1-naphthyl)ethyl)imidazole MeSH Prohlížeč
• agonisté adrenergních alfa-receptorů MeSH
• alfa-2-adrenergní receptory - agonisté * MeSH
• anestetika disociativní MeSH
• hemoglobiny MeSH
• hyaluronoglukosaminidasa MeSH
• ketamin MeSH
• medetomidin MeSH
• triclosan MeSH

OBJECTIVE: The aim of this study was to investigate the effect of a novel alpha-2-adrenoceptor (alpha(2)-AR) agonist, naphthylmedetomidine, on cardiorespiratory function and sedation in rabbits in comparison with medetomidine. STUDY DESIGN: Prospective, randomized, experimental trial. ANIMALS: Forty-two chinchilla rabbits of both sexes, weighing 2.5-4.5 kg. METHODS: The rabbits received 350 microg kg(-1) naphthylmedetomidine (n = 21) or medetomidine (n = 21) intramuscularly according to a randomization scheme. Arterial blood pressure (AP), oxygen saturation of haemoglobin (SpO(2)), pulse rate (PR) and righting reflex were monitored for 20 minutes after injection. RESULTS: Both drugs significantly decreased PR. The effect of medetomidine was significantly greater than that of naphthylmedetomidine and was evident within 1 minute. The decrease in PR after naphthylmedetomidine administration first appeared after 4 minutes. Medetomidine decreased the SpO(2) after 3 minutes but there was no effect after naphthylmedetomidine. Medetomidine decreased the mean, systolic and diastolic AP within 5 minutes of administration but naphthylmedetomidine had no effect. The mean time to loss of righting reflex was 185 and 714 seconds after the administration of medetomidine and naphthylmedetomidine respectively. CONCLUSIONS AND CLINICAL RELEVANCE: These results provide the first description of the effects of naphthylmedetomidine on cardiovascular and psychomotor functions in rabbits. Further work is required to reveal the anaesthetic sparing, analgesic or sedative effect of partial naphthylmedetomidine.

• MeSH
• alfa-2-adrenergní receptory - agonisté * MeSH
• hypnotika a sedativa farmakologie   MeSH
• imidazoly farmakologie   MeSH
• králíci fyziologie   MeSH
• krevní tlak účinky léků   MeSH
• medetomidin analogy a deriváty   farmakologie   MeSH
• neopioidní analgetika farmakologie   MeSH
• srdeční frekvence účinky léků   MeSH
• zvířata MeSH
• Check Tag
• králíci fyziologie   MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• 4-(1-(1-naphthyl)ethyl)imidazole MeSH Prohlížeč
• alfa-2-adrenergní receptory - agonisté * MeSH
• hypnotika a sedativa MeSH
• imidazoly MeSH
• medetomidin MeSH
• neopioidní analgetika MeSH

Alpha-2 adrenoceptors (alpha(2)-ARs) are critically involved in regulating neurotransmitter release from sympathetic nerves and neurons and play an important role in the regulation of awareness, arousal and vigilance. In our recent study, dexmedetomidine, a full alpha(2)-AR agonist, produced antiaggressive effects in the social conflict test in mice at doses that were twice smaller than those producing sedation. The aim of this study was to ascertain antiaggressive effect of a novel drug naphthylmedetomidine, with a more selective alpha(2)-AR activity. Behavioral effects of naphthylmedetomidine (150-1200 microg/kg i.p.) were studied in the activity cage and in the social conflict tests in mice. Naphthylmedetomidine dose dependently decreased aggressive behavior during social conflict in aggressive mice with significant reduction already at the lowest doses tested (150 microg/kg), whereas locomotion and social investigation were significantly decreased only after four times bigger dose of naphthylmedetomidine (600 microg/kg) in aggressive mice. Naphthylmedetomidine had no effect on aggression in nonaggressive mice. Naphthylmedetomidine reduced locomotion in the activity cage significantly only at the highest doses tested (600 and 1200 microg/kg), and this effect was only partially reversed by administration of high doses of an alpha-2 antagonist atipamezole (3 and 10 mg/kg). In nonaggressive mice, the difference between the dose reducing dominant social behavior (social investigation) and locomotion (150 and 300 microg/kg, respectively) was smaller than in aggressive mice. In conclusion, naphthylmedetomidine showed a very strong and selective antiaggressive effect in aggressive mice, which was devoid of locomotion-inhibiting/sedative effect. This study suggests that naphthylmedetomidine may have clinical potential as antiaggressive drug.

• MeSH
• agonisté adrenergních alfa-receptorů farmakologie   MeSH
• agonistické chování účinky léků   MeSH
• agrese účinky léků   MeSH
• alfa-2-adrenergní receptory - agonisté * MeSH
• arousal účinky léků   MeSH
• dominance a subordinace MeSH
• medetomidin analogy a deriváty   farmakologie   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pohybová aktivita účinky léků   MeSH
• sociální chování MeSH
• sociální izolace MeSH
• sociální prostředí 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
• agonisté adrenergních alfa-receptorů MeSH
• alfa-2-adrenergní receptory - agonisté * MeSH
• medetomidin MeSH

Dexmedetomidine is a highly specific alpha2-adrenoreceptor agonist, which is now clinically used to induce sedation in patients in the intensive care units. Behavioural effects of dexmedetomidine have been little studied so far. The drug was reported to reduce behaviour such as locomotion or measures of anxiety or aggression in animals. The aim of the present study was to ascertain whether dexmedetomidine inhibits behaviour uniformly or with respect to particular stimuli or situations. Therefore, behavioural effects of dexmedetomidine were studied in the social conflict test in male mice (after three weeks of individual housing), which provides a wide spectrum of behavioural activities in two types of animals (aggressive and sociable mice) as well as in the activity cage. Dexmedetomidine (5-40 microg/kg i.p.) decreased locomotion in the activity cage and this effect was fully antagonized by atipamezole, a selective alpha2-adrenereceptor antagonist. However, dexmedetomidine did not reduce locomotion during social conflict. The only significant effects during social conflict were a selective and dose-dependent antiaggressive effect in aggressive mice and a selective reduction of social investigation ('sociability') in sociable mice. Thus, dexmedetomidine appears to inhibit predominantly dominant behaviour evoked by biologically important stimuli. The ability of dexmedetomidine to reduce aggression might be utilized for treatment of aggressive states. Sedation caused by dexmedetomidine can be easily disrupted and thus the drug may have an advantage over benzodiazepines or neuroleptics, which are used in this indication.

• MeSH
• agonisté adrenergních alfa-receptorů aplikace a dávkování   farmakologie   MeSH
• agrese účinky léků   MeSH
• alfa blokátory aplikace a dávkování   farmakologie   MeSH
• alfa-2-adrenergní receptory účinky léků   MeSH
• analýza rozptylu MeSH
• chování zvířat účinky léků   MeSH
• dexmedetomidin aplikace a dávkování   farmakologie   MeSH
• imidazoly aplikace a dávkování   farmakologie   MeSH
• konflikt (psychologie) MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pohybová aktivita účinky léků   MeSH
• sociální chování * 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
• srovnávací studie MeSH
• Názvy látek
• agonisté adrenergních alfa-receptorů MeSH
• alfa blokátory MeSH
• alfa-2-adrenergní receptory MeSH
• atipamezole MeSH Prohlížeč
• dexmedetomidin MeSH
• imidazoly MeSH