Adrenergic Agonist Drugs Research Articles

Safe use of opioids

Background: Opioids are effective analgesics for cancer pain and refractory non-cancer pain. Although they are essential medication, problematic issues on aberrant behavior and adverse events have rapidly emerged as social problems in Korea. This study aimed to describe the mechanisms, efficacy, and adverse events, especially how to deal with opioid dependency.Current Concepts: Opioid-induced aberrant behavior includes physical and psychological dependences (addiction), abuse, and diversion (giving prescribed opioids to another person). Most physicians are unfamiliar with how to handle patients presenting these problematic issues. Physical and psychological dependences develop through different pathophysiologic mechanisms, i.e., noradrenergic and dopaminergic pathways, respectively. Motivational enhancement therapy, psychosocial support, substitution therapy with buprenorphine, and adjunctive medications, including alpha-2 adrenergic agonist, antidepressants, and non-steroidal antiinflammatory drugs, are the mainstay of treatment for opioid dependency. Constipation, nausea/vomiting, drowsiness/sedation, delirium, itching sensation, voiding difficulty, dry mouth, opioid-induced hyperalgesia, and respiratory depression are well-known physical side effects of opioid consumption.Discussion and Conclusion: Research on the development history, epidemiology of opioid dependency, and its treatment are warranted to avoid an opioid crisis in Korea. Above all, thorough knowledge for physicians and patients is urgently needed.

Synthesis and Structural Characterization of Process Related Impurities of Mirabegron: A Beta-3 Adrenergic Agonist Drug

In the synthesis of active pharmaceutical ingredient and the development of pharmaceutical products, the impurities profiling plays a significant role. The control of impurities is essential for producing the quality, safe and efficient drug products for therapeutic use. Few works reported for the synthesis of potential impurities and further characterized to support the synthesis route and purity of the synthesized compound. Hence in present study, five impurities of mirabegron such as impurity 3, 4, 6, 8 and 9 were synthesized and structural characterization was carried using NMR, IR and mass spectral studies. Based on the results, it was confirmed that the route of synthesis established in the study was simple, convenient and economical and can be useful for the products of potential impurities of mirabegron. By characterizing each of these impurities, the regulatory need has been met. Additionally, the analytical method development and validation studies have utilized the generated impurity standards. This effort helped with the process development’s optimization stage and made it possible to identify the crucial parts of the process. The production method for mirabegron was carefully adjusted to eliminate or reduce the formation of impurities, which is helpful for the creation of safe pharmaceutical goods.

Stress cardiomyopathy (Takotsubo syndrome) in patients who received adrenergic agonist drugs: A pharmacovigilance study using the Japanese Adverse Drug Event Report (JADER) database

IntroductionStress cardiomyopathy, or Takotsubo syndrome (TTS), is an acute and reversible syndrome developing in strong association with psychological or physiological stressors. While a surge in the circulating catecholamine level is suspected as one of its pathophysiologies, the contribution of treatment with sympathomimetic drugs to the development of TTS remains uncertain. MethodsWe conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database containing more than 500,000 patient cases recorded between April 2004 and March 2019, to detect TTS (‘stress cardiomyopathy’) as adverse event signals associated with adrenergic agonist drugs usage by calculating reporting odds ratio (ROR). ResultsAmong 306 TTS cases reported to JADER, we identified 58 TTS cases with exposure to adrenergic agonist drugs, predominantly of women (52/58, 89.7%) and those in the median age-decades of the 70s. After adjusting for age in decades and sex, most of the intravenous catecholamines showed significantly higher reporting (lower 95% ROR > 1) for TTS, including adrenaline, noradrenaline, dobutamine, dopamine, phenylephrine, and ephedrine. In addition, peroral midodrine, transdermal tulobuterol, inhaled salbutamol, and inhaled procaterol also showed significantly higher ROR for TTS. We also identified a small number of TTS cases with Parkinson's disease taking midodrine or droxidopa, but not receiving other adrenergic agonists. ConclusionThe current pharmacovigilance study showed significantly higher RORs for TTS following the use of some of the adrenergic drugs, being mostly consistent with the TTS-related adrenergic drugs reported in earlier literature. A potential association of taking midodrine or droxidopa with the development of TTS was also suggested.

Evaluation of potential anti-RNA-dependent RNA polymerase (RdRP) drugs against the newly emerged model of COVID-19 RdRP using computational methods

IntroductionDespite all the efforts to treat COVID-19, no particular cure has been found for this virus. Since developing antiviral drugs is a time-consuming process, the most effective approach is to evaluate the approved and under investigation drugs using in silico methods. Among the different targets within the virus structure, as a vital component in the life cycle of coronaviruses, RNA-dependent RNA polymerase (RdRP) can be a critical target for antiviral drugs. The impact of the existence of RNA in the enzyme structure on the binding affinity of anti-RdRP drugs has not been investigated so far. MethodsIn this study, the potential anti-RdRP effects of a variety of drugs from two databases (Zinc database and DrugBank) were evaluated using molecular docking. For this purpose, the newly emerged model of COVID-19 (RdRP) post-translocated catalytic complex (PDB ID: 7BZF) that consists of RNA was chosen as the target. ResultsThe results indicated that idarubicin (IDR), a member of the anthracycline antibiotic family, and fenoterol (FNT), a known beta-2 adrenergic agonist drug, tightly bind to the target enzyme and could be used as potential anti-RdRP inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These outcomes revealed that due to the ligand-protein interactions, the presence of RNA in this structure could remarkably affect the binding affinity of inhibitor compounds. ConclusionIn silico approaches, such as molecular docking, could effectively address the problem of finding appropriate treatment for COVID-19. Our results showed that IDR and FNT have a significant affinity to the RdRP of SARS-CoV-2; therefore, these drugs are remarkable inhibitors of coronaviruses.

Side effects of mirabegron studied on ants as models

The overactive bladder syndrome (OAB) affects the quality of life. It is most often treated with anticholinergic drugs, but at the cost of many unwanted effects. In the last decade to date, mirabegron, an adrenergic receptor agonist drug used to relieve OAB has appeared in the pharmacopoeia. It works through a different mechanism than antimuscarinic drugs, with apparently fewer side effects. In the same way that we have examined the adverse effects of the anticholinergic oxybutynin on the ant Myrmica sabuleti used as a biological model, here we examine the side effects of mirabegron. Unlike oxybutynin, mirabegron had no adverse effect on ants, except that it increased their meat consumption, reduced their sugar water intake and decreased their general activity. No adaptation was observed for this last- mentioned effect, which may correspond to the tiredness reported in humans. The ants did not become dependent on the consumption of mirabegron, whose effect on general activity decreased very slowly and disappeared about 52 hours after weaning. Patients are advised to take mirabegron daily though its elimination half-life is 50 hours, and fatigue is one of the side effects of the treatment. In the event that patients under mirabegron medication show a decrease in activity over their treatment, it would be careful to space out the medication or to add an appropriate stimulant or to alternate mirabegron with an anticholinergic drug that does not affect the patient’s level of activity. The kind of antimuscarinic drug that could be used together with mirabegron, the respective dosage and the timing of each drug should be defined depending on their combined efficacy and side effects, and taking into account their elimination time.

Side effects of mirabegron studied on ants as models

The overactive bladder syndrome (OAB) affects the quality of life. It is most often treated with anticholinergic drugs, but at the cost of many unwanted effects. In the last decade to date, mirabegron, an adrenergic receptor agonist drug used to relieve OAB has appeared in the pharmacopoeia. It works through a different mechanism than antimuscarinic drugs, with apparently fewer side effects. In the same way that we have examined the adverse effects of the anticholinergic oxybutynin on the ant Myrmica sabuleti used as a biological model, here we examine the side effects of mirabegron. Unlike oxybutynin, mirabegron had no adverse effect on ants, except that it increased their meat consumption, reduced their sugar water intake and decreased their general activity. No adaptation was observed for this last- mentioned effect, which may correspond to the tiredness reported in humans. The ants did not become dependent on the consumption of mirabegron, whose effect on general activity decreased very slowly and disappeared about 52 hours after weaning. Patients are advised to take mirabegron daily though its elimination half-life is 50 hours, and fatigue is one of the side effects of the treatment. In the event that patients under mirabegron medication show a decrease in activity over their treatment, it would be careful to space out the medication or to add an appropriate stimulant or to alternate mirabegron with an anticholinergic drug that does not affect the patient’s level of activity. The kind of antimuscarinic drug that could be used together with mirabegron, the respective dosage and the timing of each drug should be defined depending on their combined efficacy and side effects, and taking into account their elimination time.

Dexmedetomidine modulates transient receptor potential vanilloid subtype 1

Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist and novel sedative drug with minimal respiratory suppression, have shown anti-nociceptive activity in various pain models by poorly understood mechanisms. Because alpha-2 adrenergic receptor is co-localized with TRPV1 polymodal nociceptive receptor in dorsal root ganglion neurons and up-regulated in neuropathic pain animal models, the analgesic activity might be mediated through inhibition of TRPV1 in the peripheral nervous system. In an effort to elucidate whether modulatory effect of dexmedetomidine on TRPV1 activity could be the potential peripheral mechanism underlying the antinociceptive effect of dexmedetomidine, intracellular calcium concentration after capsaicin application was investigated in mice dorsal root ganglion (DRG) neurons, with and without pretreatment of dexmedetomidine. Dexmedetomidine (10 μM) reduced capsaicin-induced calcium responses by 29.7 ± 7.39% (n = 34, p < 0.0001), in dose-dependent manner. Higher level of inhibition was observed with increased dose of dexmedetomidine (50 μM, 45.1 ± 8.58%, n = 15, p = 0.0002), and lower inhibition by decreased dose (1 μM, 18.8 ± 1.48%, n = 148, p = 0.004). RT-PCR analysis revealed expression of TRPV1 and alpha-2A, alpha-2B and alpha-2C subtypes of adrenergic receptor in mice DRG neurons, and immunocytochemical analysis revealed co-expression of TRPV1 and alpha-2A receptors in primary cultured DRG neurons. In summary, these results suggested the inhibition of TRPV1 expressed in the primary sensory neurons as a potential mechanism that contributes to the anti-nociceptive action of dexmedetomidine.

Adrenergic and cholinergic influence on the production of reactive oxygen species in human neutrophils

To determine and compare the effect of adrenergic and cholinergic agonist drugs on the production of reactive oxygen species (ROS) in neutrophils of healthy individuals. Whole blood samples were taken from five participants to purify neutrophils using the gelatin method. The production of chemiluminescent (QLM) ROS was measured using a scintillation counter and phorbol-12-myristat-13-acetate (PMA) as a stimulus. Non-PLA tests were also conducted to measure spontaneous production. Subsequently, with the same method, ROS formation was measured in the presence of nicotine (cholinergic agonist), salbutamol, and clonidine (adrenergic agonists), each in concentrations of 10-2 M, 10-3 M, 10-4 M, and 10-5 M. The area integrated under the QLM curves was calculated and the percentage of inhibition or stimulation was found as the case may be. The effect of the drugs was compared with their corresponding controls and statistical analysis was carried out. A decrease in the production of ROS was obtained as an effect of the substances studied with a significant difference between the controls and the effect produced at 10-2 M, 10-3 M, and 10-4 M . This effect increased in intensity as drug concentration increased. The highest percentages of inhibition were shown at 10-2 M and 10-3 M. Salbutamol presented the maximum values with all the concentrations with a significant difference between its inhibition and that generated by the other drugs. Adrenergic and cholinergic stimuli have an inhibitory effect on the production of ROS in neutrophils of healthy individuals.

Dexmedetomidine provides better hemodynamic stability compared to clonidine in spine surgery

Introduction: Spine surgery presents a number of challenges to the anesthesiologist. The a2 adrenergic agonist drugs are commonly used in such cases to provide hemodynamic and sympathoadrenal stability. Dexmedetomidine (DEX) is one of the most potent and highly selective a2-adrenergic receptor agonists. Another a2 adrenergic agonist drug that is used widely is clonidine. The study aims to compare both drugs in terms of hemodynamic stability in spine surgeries. Patients and Methods: 30 patients underwent spinal surgery were classified into one of the following group: DEX group (received DEX 1 mcg/kg in 10 minutes followed by 0.5 mcg/kg/hour during the course of the surgery) or CLO group (received clonidine 1 mcg/kg in 10 minutes followed by 1 mcg/kg/hour during surgery), by consecutive sampling. All other treatments and medications were similar in both groups. The systolic and diastolic blood pressure, mean arterial pressure, and heart rate were recorded every 5 minutes. Data was then analyzed by SPSS. Result: The patients in the DEX group had a better mean arterial pressure (p=0.002) and heart rate (p=0.018) stability compared to those in the CLO group. Conclusion: The administration of dexmedetomidine provides a better hemodynamic stability compared to clonidine in patients underwent spinal surgery.

Spectrofluorimetric determination of certain adrenergic agonist drugs in their pure forms and pharmaceutical formulations: Content uniformity test application.

A new, simple, sensitive and rapid spectrofluorimetric method has been developed for determination of certain adrenergic agonists such as isoxsuprine hydrochloride, ritodrine hydrochloride and etilefrine hydrochloride in their pure forms and pharmaceutical dosage forms. The method depends on micellar enhancement of the native fluorescence of investigated drugs by using 2% w/v sodium dodecyl sulfate (SDS) as an anionic surfactant. The enhanced fluorescence intensity of investigated drugs was measured at 305nm after excitation at 278nm. The interaction of studied drugs with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of investigated drugs. The relative fluorescence intensity-concentration plots were rectilinear over the range 0.15-3.00μgml-1 , with low quantification limits of 0.132, 0.123 and 0.118μgmL-1 for isoxsuprine, ritodrine and etilefrine, respectively. The proposed method was successfully applied for determination of studied drugs in their pharmaceutical formulations. Moreover, the high sensitivity of the proposed method allows performing the content uniformity testing of the studied drugs in their tablets by using the official United States Pharmacopeia (USP) guidelines. Statistical comparisons of the results with those of the reported methods revealed excellent agreement and indicated no significant difference in accuracy and precision.

Dexmedetomidine induces conditioned place preference in rats: Involvement of opioid receptors

Dexmedetomidine (DEX) is an alpha-2 adrenergic agonist drug recently introduced to anesthesia practice. Certain agents used in anesthesia practice have been associated with abuse and addiction problems; however, few studies have investigated the role of DEX on addictive processes. Here, the effects and possible mechanisms of action of DEX on conditioned place preference (CPP), a model used for measuring the rewarding effects of drug abuse in rats, was investigated. The CPP apparatus was considered “biased” as the animals preferred the grid side to the mesh side. Male Wistar albino rats weighing 250–300g were divided into several groups, including control (saline), morphine (10mg/kg), DEX (2.5–20μg/kg), naloxone alone (0.5mg/kg) and a combination (0.5mg/kg naloxone plus 20μg/kg DEX) (n=7–8 for each group). The CPP effects of morphine, DEX, saline and the combination were evaluated. All the drug and saline administrations except naloxone were performed by intraperitoneal (ip) injections. Naloxone was injected subcutaneously (sc) when given alone or in combination with DEX. Morphine (10mg/kg) and DEX (5–20μg/kg) produced CPP that were statistically significant relative to saline-injected rats. DEX-induced CPP was significantly reversed by pretreatment with naloxone, an opioid antagonist. Naloxone alone treatment did not cause any significant effect on CPP. Our results suggest that DEX produces CPP effects similar to morphine in rats and that opioidergic mechanism may be responsible for DEX-induced CPP. Thus, DEX might have the potential to be addictive, and this possibility should be considered during clinical application of this drug.

A comparative evaluation of the effect of intravenous dexmedetomidine and clonidine on intraocular pressure after suxamethonium and intubation.

Background:In patients with penetrating eye injury and a full stomach, suxamethonium is still used for rapid sequence induction of anesthesia. But its use is associated with the rise in intraocular pressure (IOP) and this can result in permanent vision loss in these patients. Dexmedetomidine and clonidine are two alpha-2 adrenergic agonist drugs which prevent the rise in IOP. The aim of this study is to compare the efficacy of intravenous (i.v.) dexmedetomidine and clonidine in preventing an increase in IOP after administration of suxamethonium and tracheal intubation.Materials and Methods:Sixty patients undergoing elective nonophthalmic surgery under general anesthesia were included in this clinical study. Patients were randomly assigned into three groups to receive 0.5 mcg/kg dexmedetomidine (Group D), 2 mcg/kg clonidine (Group C) or normal saline (Group S) as premedication i.v. over a period of 10 min before induction. IOP, heart rate, and mean arterial pressure were recorded before and after premedication, after suxamethonium, after intubation and then after 5 min.Results:Following administration of dexmedetomidine and clonidine IOP decreased in both groups. After suxamethonium IOP increased in all three groups but it never crossed the baseline in Group D and C. After laryngoscopy and intubation IOP again increased in all three groups but in dexmedetomidine group it never crossed the baseline whereas in clonidine group it was significantly higher than the baseline.Conclusion:Single i.v. dose of dexmedetomidine premedication (0.5 mcg/kg) blunt the IOP and hemodynamic response to suxamethonium injection and tracheal intubation more effectively than single i.v. dose of clonidine premedication (2 mcg/kg).

PGE&lt;sub&gt;2&lt;/sub&gt; Generation in Myocardium from Isolated Rat Atrium under Hypoxia and Reoxygenation Conditions. Effect of Anti-&lt;i&gt;β&lt;/i&gt;&lt;sub&gt;1&lt;/sub&gt; IgG from Patients with Chronic Severe Periodontitis

Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, on isolated myocardium from rat atria contractility. We used an ELISA assay to measure the generation of PGE2 in vitro after the addition of either the antibody or the adrenergic agonist. We analyzed the myocardium histopathologically in the presence of both the antibody and/or the adrenergic agonist drug during normoxia, hypoxia and reperfusion conditions. Results: PGE2 generation increased during the hypoxia and was unchanged during reoxygenation period compared with the production of this prostanoid in atria during normoxia condition. A β1 specific adrenoceptor antagonist atenolol and the β1 synthetic peptide abrogated the increment of the prostanoid in the presence of pIgG but only atenolol due to it in the presence of xamoterol. The increment of PGE2 was dependent on the activation of cox-1 and cox-2 isoforms. Moreover, cox-2 was more active and produced more increments in the production of PGE2 in the presence of the pIgG than cox-1 activation. Histopathologically, studies of myocardium specimens during these different periods of the experimental protocol: basal (B), hypoxia (H) and reoxygenation (R), were also performed and showed tissue necrosis and edematization at the myocardium level. Conclusion: The phenomenon studied here supports the notion that PGE2 may be responsible for tissue edematization. PGE2 maybe acts as a beneficial modulator in the myocardium and prevents a major injury of it. The inflammation damage to the heart organ and cardiomyocytes caused by the actions of the antibodies in the course of heart lesions provoked by cardiovascular autoimmune disease, explains some of these results obtained in the present experiments. Further studies will be needed to establish the real role of PGE2 during hypoxia injury of the heart in the course of autoimmune diseases.

ChemInform Abstract: Synthesis of Differentially Substituted 2‐Aminoimidazolidines via a Microwave‐Assisted Tandem Staudinger/Aza‐Wittig Cyclization.

A new route for the construction of 2-aminoimidazolidines including analogues of the α2 adrenergic agonist drug clonidine is elaborated. The key step is an intramolecular microwave-assisted Staudinger/aza-Wittig cyclization of an in situ generated urea intermediate (formed by the reaction of β-amino azide and isocyanate) upon treatment with Bu3P or polymer-supported phosphine reagent, allowing the introduction of various substituents at the N1 and the 2-amino function. Furthermore, a useful one-pot Staudinger/aza-Wittig/Buchwald–Hartwig protocol leading to bicyclic guanidines has been elaborated.

Synthesis of Differentially Substituted 2-Aminoimidazolidines via a Microwave-Assisted Tandem Staudinger/Aza-Wittig Cyclization

A new route for the construction of 2-aminoimidazolidines including analogues of the α2 adrenergic agonist drug clonidine is elaborated. The key step is an intramolecular microwave-assisted Staudinger/aza-Wittig cyclization of an in situ generated urea intermediate (formed by the reaction of β-amino azide and isocyanate) upon treatment with Bu3P or polymer-supported phosphine reagent, allowing the introduction of various substituents at the N1 and the 2-amino function. Furthermore, a useful one-pot Staudinger/aza-Wittig/Buchwald-Hartwig protocol leading to bicyclic guanidines has been elaborated.

Is Elevated Norepinephrine an Etiological Factor in Some Cases of Alzheimers Disease?

Loss of norepinephrine (NE) releasing neurons, in the locus coeruleus of the brainstem, is well documented to occur in Alzheimer's disease (AD). However, this process does not necessarily result in decreased release of NE, since compensatory mechanisms may produce increased release of this neurotransmitter. Independent of potential loss of locus coeruleus cells, brain NE levels may be elevated in some persons with AD, both before and during disease progression. Here I examine evidence that elevated, endogenous brain NE is an etiological factor in some cases of AD, and not merely an epiphenomenon of the disease. To explore this etiological hypothesis in AD, I examine the following eight lines of evidence: 1) direct evidence of elevated NE or its metabolites in AD; 2) studies of tricyclic antidepressants, which may principally boost NE; 3) studies of clonidine and other alpha2 adrenergic agonist drugs, which may principally lower the concentration of NE; 4) studies of beta adrenoceptor blocking drugs, including propranolol; 5) comorbidity of AD and bipolar disorder, where both disorders may involve elevated NE; 6) comorbidity of AD and hypertension; 7) comorbidity of AD and obesity; and 8) potential interaction between AD and psychological stress, where stressors are known to release NE. These lines of evidence tend to support the elevated NE etiological hypothesis.

Adsorption of Beta-Adrenergic Agonists Used in Sport Doping on Metal Nanoparticles: A Detection Study Based on Surface-Enhanced Raman Scattering

The adsorption of beta(2)-adrenergic agonist (βAA) drugs clenbuterol, salbutamol, and terbutaline on metal surfaces has been investigated in this work by means of surface-enhanced Raman scattering (SERS). To assist in this investigation, a previous vibrational (IR and normal Raman) characterization of these drugs was performed, supported by ab initio density functional theory calculations. The application of SERS was aimed to apply this highly sensitive technique, based on localized surface plasmon resonance, in the detection of βAA at trace concentrations and as a possible alternative method which can be postulated in routine antidoping analysis. The adsorption of these drugs was studied in depth at different experimental conditions: on Au and Ag, at different pHs, and with varying adsorbate concentration. Moreover, plasmon resonance spectroscopy was employed to investigate the adsorption of these drugs on the metal nanoparticles as well as their aggregation. It was found that the adsorption of these molecules is more effective on gold nanoparticles and at acidic pH, based on the direct interaction of the aromatic or aliphatic moieties through ionic or coordination bonds with the metal. These drugs followed a Langmuir adsorption model from which the adsorption constant and the limit of detection can be determined.

Opioid consumption in total intravenous anesthesia is reduced with dexmedetomidine: a comparative study with remifentanil in gynecologic videolaparoscopic surgery

Study Objective To evaluate the capacity of dexmedetomidine (DEX), an α 2 adrenergic agonist drug, as a substitute for remifentanil (REM), a potent opioid, in total intravenous anesthesia (TIVA), in patient undergoing gynecologic videolaparoscopy. Design Randomized, single-blinded study. Setting University-affiliated hospital. Patients 30 ASA physical status I and II women, patients (22-56 yrs), scheduled for gynecologic videolaparoscopy. Interventions Patients were anesthetized with DEX or REM in continuous venous infusion, associated with propofol, in a target-controlled infusion. Measurements Heart rate, mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma glucose, and cortisol were determined before anesthetic induction, 5 minutes after tracheal intubations and 30 minutes after initial surgical incision. Extubation and orientation times, and postanesthesia care unit (PACU) discharge times were noted. Main Results Blood cortisol levels were higher in the DEX group than in the REM group at 30minutes after surgical incision. Cortisol levels decreased as a function of time in the REM group, whereas intheDEX group they decreased in the second sample and returned to basal levels at 30minutes. Hyperglycemia was higher in DEX than in REM during the second and third sample collection. However, glucose increased as a function of time in both groups. Analysis of MBP and DBP indicated adecrease in blood pressure at 5 minutes after tracheal intubations in both groups. At 30minutes afterincision, MBP and DBP returned to basal levels in the DEX group, whereas the variables were significantly lower in the REM group. There were significant differences between groups for systolic blood pressure and heart rate at 5 and 30 minutes after incision with a greater decrease in REM. The extubation and orientation times were significantly increased in the DEX group, when compared with those of the REM group. There were no differences in postanesthesia care unit discharge times between groups. Conclusions Dexmedetomidine was a clinically effective drug as a REM substitute in TIVA, during minimally invasive video gynecologic surgical procedures; however, patients anesthetized with DEX showed a more prolonged recovery time for some parameters such as orientation and extubation times.

Risk factors of acute renal failure after liver transplantation

The objective of this study was to determine the risk factors of postoperative acute renal failure (ARF) in orthotopic liver transplantation (OLT). We reviewed 184 consecutive OLT. Postoperative ARF was defined as a persistent rise of 50% increase or more of the S-creatinine (S-Cr). The patients were classified as early postoperative ARF (E-ARF) (first week) and late postoperative ARF (L-ARF) (second to fourth week). Preoperative variables were age, sex, comorbidity, indication for OLT, Child-Pugh stage, united network for organ sharing status, analysis of the blood and urine, and donor's data. Intraoperative variables were systolic arterial pressure, mean arterial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance index. Surgical technique, number of blood products transfused, need for adrenergic agonist drugs, and intraoperative complications were also important. Postoperative variables were duration of stay in the intensive care unit, time on mechanic ventilation, liver graft dysfunction, need for adrenergic agonist drugs, units of blood products infused, episodes of acute rejection, re-operations, and bacterial infections. Firstly we carried out a univariate statistical analysis, and secondly a logistic regression analysis. The risk factors for E-ARF were: pretransplant ARF (odds ratio (OR)=10.2, P=0.025), S-albumin (OR=0.3, P=0.001), duration of treatment with dopamine (OR=1.6, P=0.001), and grade II-IV dysfunction of the liver graft (OR=5.6, P=0.002). The risk factors for L-ARF were: re-operation (OR=3.1, P=0.013) and bacterial infection (OR=2.9, P=0.017). The development of E-ARF is influenced by preoperative factors such as ARF and hypoalbuminemia, as well as postoperative factors such as liver dysfunction and prolonged treatment with dopamine. The predicting factors of L-ARF differ from E-ARF and correspond to postoperative causes such as bacterial infection and surgical re-operation.

Adrenergic drugs for urinary incontinence in adults

Adrenergic drugs have been used for the treatment of urinary incontinence. However, they have generally been considered to be ineffective or to have side effects which may limit their clinical use. To determine the effectiveness of adrenergic agonists in the treatment of urinary incontinence in adults. We searched the Cochrane Incontinence Group specialised trials register (searched 9 March 2005) and the reference lists of relevant articles. Randomised or quasi-randomised controlled trials in adults with urinary incontinence which included an adrenergic agonist drug in at least one arm of the trial. Two reviewers independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook. Twenty-two eligible randomised trials were identified, of which 11 were crossover trials. The trials included 1099 women with 673 receiving an adrenergic drug (phenylpropanolamine in 11 trials, midodrine in two, norepinephrine in three, clenbuterol in another three, terbutaline in one, eskornade in one and Ro-115-1240 in one). No trials included men. The limited evidence suggested that an adrenergic agonist drug is better than placebo in reducing the number of pad changes and incontinence episodes, as well as improving subjective symptoms. In two small trials, the drugs also appeared to be better than pelvic floor muscle training, possibly reflecting relative acceptability of the treatments to women but perhaps due to differential withdrawal of women from the trial groups. There was not enough evidence to evaluate the use of higher compared to lower doses of adrenergic agonists nor the relative merits of an adrenergic agonist drug compared with oestrogen, whether used alone or in combination. Over a quarter of women reported adverse effects. There were similar numbers of adverse effects with adrenergics, placebo or alternative drug treatment. However, when these were due to recognised adrenergic stimulation (insomnia, restlessness and vasomotor stimulation) they were only severe enough to stop treatment in 4% of women. There was weak evidence to suggest that use of an adrenergic agonist was better than placebo treatment. There was not enough evidence to assess the effects of adrenergic agonists when compared to or combined with other treatments. Further larger trials are needed to identify when adrenergics may be useful. Patients using adrenergic agonists may suffer from minor side effects, which sometimes cause them to stop treatment. Rare but serious side effects, such as cardiac arrhythmias and hypertension, have been reported.