Brief Duration Of Action Research Articles

Nanomaterials: Recent Advances in Knee Osteoarthritis Treatment

AbstractOsteoarthritis (OA) of the knee is the most prevalent degenerative joint condition that places a substantial financial and medical burden on society. However, due to drawbacks such as inefficiency, adverse effects, and brief duration of action, the clinical efficacy of the current major therapies for knee OA is largely restricted. Therefore, novel medication development is highly required to address these issues. Numerous studies in recent years have established that nanomaterials can be a potential and highly effective way to overcome these challenges. In this review, the anatomical distinctions between healthy and OA knee joints, as well as novel advances in the field of nanomaterials for the treatment of knee OA are summarized. The limits of the present therapeutic strategies for treating knee OA are also highlighted, as well as the potential prospects of nanomaterials in the future.

Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aβ), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aβ and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aβ. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.

Ease of intubation: A randomized, double-blind study to compare two doses of rocuronium bromide for endotracheal intubation.

Context:Clinical need for a nondepolarizing agent with a rapid onset time and a brief duration of action has led to the development of rocuronium bromide.Aims:The aim of this study was to evaluate optimal dose of rocuronium bromide for intubation and to compare the onset time, duration of action, intubating conditions, and hemodynamic effects of two doses of rocuronium bromide.Settings and Design:A prospective, randomized, double-blind study.Materials and Methods:All the patients were divided in a randomized, double-blind fashion into two groups of twenty patients each. Group I patients received rocuronium bromide 0.6 mg/kg intravenously and intubated at 60 s, Group II patients received rocuronium bromide 0.9 mg/kg and intubated at 60 s. The neuromuscular block was assessed using single twitch stimulation of 0.1 Hz at adductor pollicis muscle of hand at every 10 s.Statistical Analysis Used:The results were compiled and analyzed statistically using Chi-square test for qualitative data and Student's t-test for quantitative data.Results:Time of onset was significantly shorter (P < 0.01) and duration of action was prolonged (P < 0.001) for Group II as compared to Group I. The intubating conditions were (excellent + good) in 100% patients of Group II and (excellent + good) in 80% of Group I. There was no significant change in pulse rate and mean arterial pressure from the baseline value after the administration of muscle relaxants in either of the two groups.Conclusions:Rocuronium bromide 0.9 mg/kg is a safer alternative to rocuronium bromide 0.6 mg/kg for endotracheal intubation with shorter time of onset and better intubating conditions.

Effectiveness of ondansetron as an adjunct to lidocaine intravenous regional anesthesia on tourniquet pain and postoperative pain in patients undergoing elective hand surgery: a systematic review protocol.

Review question/objective The objective of this quantitative systematic review is to determine the effects of ondansetron as an adjunct to lidocaine on the tourniquet pain and postoperative pain of American Society of Anesthesiologists class 1 or 2 adult patients undergoing elective hand surgery with intravenous regional anesthesia. Inclusion criteria Types of participants This quantitative systematic review will consider studies that included American Society of Anesthesiologists 1 or 2 patients aged 18 years or older who used ondansetron as an adjunct to lidocaine for intravenous regional anesthesia in elective hand surgery. Types of intervention(s)/phenomena of interest This quantitative systematic review will consider studies that evaluated the analgesic effectiveness of ondansetron admixed to lidocaine for intravenous regional anesthesia in patients undergoing elective hand surgery. Patients treated with the admixture of ondansetron and lidocaine for Intravenous regional anesthesia will be compared to those who were treated with lidocaine alone. Types of outcomes This quantitative systematic review will consider studies that include the following outcome measures: 1: Tourniquet pain as measured by time to onset of tourniquet pain; 2: Postoperative pain relief as measured by first analgesic requirement time. The first analgesic requirement time is defined as the time which has elapsed after tourniquet release to the first request by the patient for analgesic and is assessed via visual analogue score in two to six hour intervals up to 24 hours postoperatively.

Randomized comparison of recovery time after use of remifentanil alone versus midazolam and meperidine for colonoscopy anesthesia.

Although the combination of midazolam-meperidine has been widely used as a sedation regimen for colonoscopy, its residual effect which is longer than the duration of a colonoscopy procedure can delay patient recovery and discharge. Remifentanil, an ultra-short-acting opioid, has a very brief duration of action. We hypothesized that using remifentanil alone for colonoscopy would provide shorter recovery time compared with the midazolam-meperidine combination. Time to achieve Aldrete score = 10 was determined and compared in patients who were randomly allocated to receive remifentanil alone (group-R, n = 27) or a midazolam-meperidine combination (group-MM, n = 27) for colonoscopy. Intergroup differences in sedation, recall analgesia, cardio-respiratory profiles, and satisfaction of patient and endoscopist were also determined during and after colonoscopy. Group-R showed a significantly shorter recovery time than group-MM (median [25-75%], 0 [0-10] vs 30 [15-30] min, P < 0.001). Group-R showed significantly higher bispectral-index values during colonoscopy (92 [85-96] vs 84 [80-87], P = 0.001); a higher incidence of recall of explanations given during and after colonoscopy (100 vs 48% and 96 vs 52%, both P < 0.001); and a lower distress score (visual analog scale 30/100 vs 37/100 mm, P = 0.002), than did group-MM. Neither extent of pain, incidence of hemodynamic instability nor incidence of respiratory depression differed between the groups. Remifentanil for colonoscopy afforded faster recovery compared to midazolam-meperidine combination. It also provided greater patient-endoscopist communication and satisfaction with comparable patient analgesia and cardiorespiratory profile during colonoscopy.

Alcohol in essential tremor and other movement disorders

Many patients with essential tremor (ET) report transient improvement of symptoms after drinking alcohol. However, the brief duration of action, subsequent rebound, and the risk of developing alcohol addiction make the use of alcohol as a treatment for ET inappropriate. Whether excessive alcohol consumption is a risk for or a consequence of ET has been a subject of some controversy. In this review, we critically examine the mechanism of action of alcohol and its role in ET and other movement disorders.

Salvinorin A and derivatives: Protection from metabolism does not prolong short-term, whole-brain residence

Salvinorin A (SA) is a potent kappa opioid agonist with a brief duration of action. Consistent with this, our previous positron emission tomography (PET) studies of carbon-11 labeled SA showed that brain levels decrease rapidly after intravenous administration. SA is rapidly metabolized, giving the much less potent salvinorin B (SB), which is presumed to be responsible in part for SA's brief duration of action. To test this, we labeled the metabolically stable methyl ester of SA and SB with carbon-11 and compared their pharmacokinetics by PET imaging after intravenous administration to baboons. Labeling of salvinorin B ethoxymethyl ether (EOM-SB), a derivative with greater potency and resistance to metabolism, provided an additional test of the role of metabolism in brain efflux. Plasma analysis confirmed that SB and EOM-SB exhibited greater metabolic stability than SA. However, the three compounds exhibited very similar pharmacokinetics in brain, entering and exiting rapidly. This suggests that metabolism is not solely responsible for the brief brain residence time of SA. We determined that whole-brain concentrations of EOM-SB declined more slowly than SA after intraperitoneal administration in rodents. This is likely due to a combination in EOM-SB's increased metabolic stability and its decreased plasma protein affinity. Our results suggest that protecting salvinorin A derivatives from metabolism will prolong duration of action, but only when administered by routes giving slow absorption.

Pain, Transitions Are Palliative Care Challenges

Pain, Transitions Are Palliative Care Challenges

Sédation au pentobarbital par voie rectale pour enregistrement des PEA chez l'enfant

Objectives The aim of our study was to determine if rectal sedation with pentobarbital sodium provides safe and effective sedation for children undergoing auditory brainstem response (ABR) testing. Material and methods A prospective study was conducted in the ENT pediatric department of Robert Debre's hospital (APHP, Paris). 68 children under 8 years of age were given rectal pentobarbital for ABR testing at a dosage of about 5 mg/kg. Results 61 children of 68 (89.7%) were adequately sedated with rectal pentobarbital. The mean elapsed time from drug administration to full sedation was 36,1 minutes. No adverse event was reported in 84.1% of children. Conclusion Pentobarbital provides safe and effective sedation. Rectal administration is easy, painless and with brief duration of action. It's a good alternative to general anesthesia for young children undergoing ABR testing.

Neuromuscular block

Descriptions of the South American arrow poisons known as curares were reported by explorers in the 16th century, and their site of action in producing neuromuscular block was determined by Claude Bernard in the mid‐19th century. Tubocurarine, the most important curare alkaloid, played a large part in experiments to determine the role of acetylcholine in neuromuscular transmission, but it was not until after 1943 that neuromuscular blocking drugs became established as muscle relaxants for use during surgical anaesthesia. Tubocurarine causes a number of unwanted effects, and there have been many attempts to replace it. The available drugs fall into two main categories: the depolarising blocking drugs and the nondepolarising blocking drugs. The former act by complex mixed actions and are now obsolete with the exception of suxamethonium, the rapid onset and brief duration of action of which remain useful for intubation at the start of surgical anaesthesia. The nondepolarising blocking drugs are reversible acetylcholine receptor antagonists. The main ones are the atracurium group, which possess a built‐in self‐destruct mechanism that makes them especially useful in kidney or liver failure, and the vecuronium group, which are especially free from unwanted side effects. Of this latter group, the compound rocuronium is of especial interest because its rapid onset of action allows it to be used for intubation, and there is promise that its duration of action may be rapidly terminated by a novel antagonist, a particular cyclodextrin, that chelates the drug, thereby removing it from the acetylcholine receptors.British Journal of Pharmacology (2006) 147, S277–S286. doi:10.1038/sj.bjp.0706404

Pancreatic Amylin as a Centrally Acting Satiating Hormone

This review summarizes the present knowledge concerning the anorectic action of the pancreatic hormone amylin. It focuses mainly on the role of amylin as a short term satiating peptide. Since there is some evidence however that basal amylin levels might play a role in the long term control of food intake and/or body weight, this aspect will be discussed briefly towards the end of this review. Concerning amylin as a satiating hormone, it is well established that amylin is released during meals, and that exogenous amylin leads to a dose-related reduction in meal size. Amylin has a rapid onset and brief duration of action. The area postrema (AP) plays a predominant role in peripheral amylin's satiating effect, involving a direct activation of AP neurons by blood-borne amylin. The nucleus of the solitary tract (NTS) relays this effect to higher brain structures, the lateral parabrachial nucleus, and possibly the central nucleus of the amygdala and the bed nucleus of the stria terminalis. Amylin's anorectic effect may in part be due to reduced expression of orexigenic neuropeptides in the lateral hypothalamic area. The anorectic action of amylin is one important factor in amylin's overall role to control the influx of nutrients into the circulation. By reducing food intake, gastric acid secretion, limiting the rate of gastric emptying and diminishing pancreatic glucagon and digestive enzyme secretion, amylin regulates nutrient appearance and postprandial glucose concentration. Amylin seems to be a necessary and complementary factor to insulin, which regulates the rate of nutrient disappearance. In this sense, amylin and insulin are adjunct players in the control of nutrient fluxes, and amylin's role to control feeding is a pivotal factor in this regard.

Prolonged neuromuscular blockade as a result of malnutrition-induced pseudocholinesterase deficiency

Mivacurium is a short-acting neuromuscular blocking drug, ideal for short surgical procedures. The brief duration of action depends on rapid hydrolysis by plasma cholinesterase. An inherited or acquired deficiency of plasma cholinesterase can prolong the effect of mivacurium. We present an unusual case of unanticipated postoperative apnea following mivacurium administration, as a result of acquired plasma cholinesterase deficiency, in a patient with previous uneventful exposure to both mivacurium and suxamethonium (succinylcholine).

Tube digestif et toxine botulique

Introduction. – the aim of this work was to check literature to assess botulinum toxin injection efficacy in gastrointestinal motor disorders with special emphasis on controlled clinical trials. Methods. – literature was carried out with the Medline data bank. Results. – seventy three articles in French and in English including a recent general review were retained. Comparative clinical trials only concerned achalasia and anal fissure. The other gastrointestinal motor disorders only gave rise to open non-controlled trials assessed on clinical end points. Discussion. – this review of literature helps to determine usefullness and safety of Botulinum toxin injection in the treatment of esophageal achalasia and anal fissure. The main limitation is its brief duration of action. Studies concerning the others spastic motor disorders are based on unknown physiopathology and controlled trials are required to assess its efficacy. Conclusion. – botulinum toxin is increasingly used for gastrointestinal motor disorders with worthwhile results. Its efficacy has been yet established for only two disorders : it has a valuable palliative role in achalasia and may be curative for anal fissure.

Pharmacokinetics and pharmacodynamics of rapacuronium bromide.

Rapacuronium is an aminosteroidal nondepolarising neuromuscular blocking agent (NMBA). Its neuromuscular blocking effects have a different time course to those of most currently available agents. It also has lower potency than many of the other NMBAs. In doses consistent with short to medium duration of action, rapacuronium has rapid and complete onset. In some doses it gives tracheal intubating conditions that compare favourably with those produced by suxamethonium (succinylcholine) during rapid sequence induction of anaesthesia. Tracheal intubating conditions improve as dose increases, but adverse effects (including potentially severe bronchospasm) become more prominent. Rapacuronium has an active metabolite that is at least as potent as the parent compound and is eliminated much less efficiently. Consequently, the time course of action of rapacuronium is prolonged after multiple doses or an infusion. Its potency is similar across age ranges and its time course after single doses is little altered in patients with hepatic or renal insufficiency. At least in part because of its active metabolite, rapacuronium is highly cumulative in renal failure. In keeping with its rapid onset and short to medium duration of action, rapacuronium has a more rapid clearance than most other NMBAs. Values for clearance are in the range 0.26-0.67 L/h/kg, with most studies giving a value of approximately 0.45 L/h/kg. There is some evidence that clearance declines marginally with advanced age, and it is also reduced in children. A typical value for steady-state volume of distribution is 0.3 L/kg. This is similar to that of many other NMBAs, but is small compared with many other drugs, as expected with a highly polar compound. Pharmacokinetic parameters do not appear to differ markedly in hepatic insufficiency, but clearance is reduced by approximately 30% in renal failure. Rapacuronium equilibrates very rapidly between the plasma and the site of effect. This is the principal explanation behind its unusually rapid onset. It also appears to have a similar potency at the larynx compared with the adductor pollicis; most other NMBAs are less effective at the larynx. Because it gives rapid onset in a dose consistent with brief duration of action, it was hoped that rapacuronium might be a suitable alternative to suxamethonium. It does not have the problems associated with suxamethonium, but its use is associated with bronchospasm, the incidence of which is dose-related. Rapacuronium has been withdrawn from sale because of this adverse effect, and its future availability is uncertain.

Spinal anesthesia in infants

Spinal anesthesia is an extremely stable anesthetic in infants with minimal impact on cardiac and respiratory physiology. Initial reports centered on its use in minor surgical procedures such as inguinal hernia repair and circumcision. However, its applications have broadened considerably over the past decade. Spinal anesthesia has now been reported for use in major surgical procedures in neonates including upper abdominal and cardiac surgery. As experience with the technique spreads, its use will likely continue to increase. A limitation of spinal anesthesia in this ge group is its relatively brief duration of action and inability to provide analgesia into the postoperative period. Combined spinal and epidural techniques may be one solution to this problem.

A review of the use of fentanyl analgesia in the management of acute pain in adults.

A review of the use of fentanyl analgesia in the management of acute pain in adults.

Pulmonary Hypertension and Major Surgery

Pulmonary Hypertension and Major Surgery

Anti-allodynic actions of intravenous opioids in the nerve injured rat: potential utility of heroin and dihydroetorphine against neuropathic pain

Neuropathic pain has been suggested to be resistant to treatment with opiates. Such perceived lack of opioid responsiveness may be due to the dose-range over which specific opioid compounds have been studied as well as the efficacy of these compounds. Dihydroetorphine is a novel opiate that demonstrates significantly greater analgesic potency compared to morphine, and which also demonstrates diminished capacity for producing physical dependence in laboratory animals. The present study compared the intravenous (i.v.) efficacy, potency and duration of action of dihydroetorphine, fentanyl, heroin and morphine in producing anti-allodynic actions in a rat model of neuropathic pain (ligation of the L5/L6 nerve roots). All compounds produced significant anti-allodynic activity with dihydroetorphine being the most potent ( A 50 of 0.2 μg kg −1, i.v.). Morphine was approximately 7440 times less potent than dihydroetorphine while heroin and fentanyl were approximately 163.5 and 6.9 times less potent in producing anti-allodynic actions. Dihydroetorphine also showed a maximal effect at 0.6 μg kg −1 in all animals tested, while 100 μg kg −1 was required for heroin to produce a maximal effect. Fentanyl and morphine did not elicit a maximum anti-allodynic response (74 and 76%maximum possible effect (%MPE), respectively). As expected, fentanyl showed a relatively brief duration of action (approximately 20 min at the highest tested dose), while dihydroetorphine and morphine demonstrated anti-allodynic actions for up to 45 min. Heroin had the longest duration of action, producing significant anti-allodynic effects for up to 90 min. These data show that dihydroetorphine and heroin produce potent and long-lasting anti-allodynic actions in this model. Additionally, in contrast to morphine and fentanyl, both dihydroetorphine and heroin were able to achieve a maximal response. The remarkable potency, maximal efficacy and duration of action of these compounds, particularly dihydroetorphine, suggests that these compounds may warrant further examination as potential therapeutic treatments for neuropathic pain states.

Intranasal Lidocaine for Treatment of Migraine

<h3>To the Editor.</h3> —The suggested use of intranasal lidocaine 4% for the acute treatment of migraine is an interesting proposition that may offer hope as a useful analgesic option. However, the article by Dr Maizels and colleagues¹did not clearly address the use and dosage of this medication. In high doses, lidocaine can cause significant morbidity, resulting in confusion, agitation, seizures, and cardiac dysrhythmias. Intranasal lidocaine can be absorbed systemically and could be potentially toxic if the patient uses the agent excessively. The risk for toxicity due to frequent use is underscored by the brief duration of action of lidocaine and the high recurrence rate of acute migraine. Also, the authors note the high relapse rate for headache early after treatment. Further studies are essential to determine safe and judicious prescription labeling of lidocaine for treatment of acute migraine.

Section Review Cardiovascular &amp; Renal: Bradykinin degradation: potential pathways for cardiovascular therapeutic use

Bradykinin (BK) is a widely distributed nine amino acid peptide with potent cardiovascular effects. Physiologically, BK has a very brief duration of action due to rapid metabolism by a number of widely distributed enzymes, including carboxypeptidase N, angiotensin converting enzyme (ACE), endopeptidase 24.11 (EP24.11), en-dopeptidase 24.15 (EP24.15), and aminopeptidase P. The physiological importance of BK in cardiovascular regulation is beginning to be recognised, due to the development of inhibitors of these BK-degrading enzymes. ACE inhibitors have been used in clinical practice for a number of years for the treatment of cardiovascular diseases, but it has only been recognised recently that their beneficial effects are due to preservation of endogenous BK from metabolism, as well as by prevention of angiotensin II production. Inhibitors of EP24.11 have been tested in various animal models of cardiovascular diseases, and in human patients, and have been shown to have limited benefit when given alone. Wh...