ArticleLiterature Review

From Cocaine to Ropivacaine: The History of Local Anesthetic Drugs

Authors:
  • Hôpital du Jura, CH-2800 Delémont JU, Switzerland
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Abstract

In 1850, about three centuries after the conquest of Peru by Pizzaro, the Austrian von Scherzer brought a sufficient quantum of coca leaves to Europe to permit the isolation of cocaine. As suggested by his friend Sigmund Freud, descriptions of the properties of the coca prompted the Austrian Koller to perform in 1884 the first clinical operation under local anesthesia, by administration of cocaine on the eye. The use of cocaine for local and regional anesthesia rapidly spread throughout Europe and America. The toxic effects of cocaine were soon identified resulting in many deaths among both patients and addicted medical staff. Local anesthesia was in a profound crisis until the development of modern organic chemistry which led to the synthesis of pure cocaine in 1891. New amino ester local anesthetics were synthesized between 1891 and 1930, such as tropocaine, eucaine, holocaine, orthoform, benzocaine, and tetracaine. In addition, amino amide local anesthetics were prepared between 1898 and 1972 including nirvaquine, procaine, chloroprocaine, cinchocaine, lidocaine, mepivacaine, prilocaine, efocaine, bupivacaine, etidocaine, and articaine. All of these drugs were ostensibly less toxic than cocaine, but they had differing amounts of central nervous system (CNS) and cardiovascular (CV) toxicity. Bupivacaine is of special interest because of its long duration of action and history of clinical application. Synthesized in 1957, the introduction of bupivacaine on the market in 1965 paralleled the progressive and cumulative reports of CNS and CV toxicity, leading to the restriction of its use and the identification of a special therapy-resistant CV toxicity. Numerous experimental studies were conducted to identify the fine cellular mechanism of this toxicity, which refines our understanding of the action of local anesthetics. The identification of optically active isomers of the mepivacaine family led to the selection of ropivacaine, a pure S-(-) enantiomer, whose toxicology was selectively and extensively studied before its introduction on the market in 1996. During the rapid and extensive use of ropivacaine in the clinic, unwanted side-effects have been found to be very limited.

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... Organs dependent on aerobic metabolism, such as the heart and brain, are especially susceptible to toxic injury resulting in cardiovascular collapse. Lipid emulsion therapy is the mainstay treatment of LAST [1]; however, it may inadvertently cause lipid-induced necrotizing pancreatitis due to high amounts of serum triglycerides. Management of lipid-induced pancreatitis is similar to the treatment of pancreatitis in general, requiring adequate intravenous hydration and pain control with analgesia. ...
... We present a case of a 71-year-old female with a non-contributory past medical history who presented for 1 an elective open reduction and internal fixation (ORIF) of the right wrist after suffering a traumatic fall in her backyard one week prior. Plain radiographs of the right extremity, obtained on the day of the fall, demonstrated a comminuted fracture of the distal radius, which extended to the articular surface, and an ulnar styloid fracture. ...
... The use of local anesthesia for pain control has come a long way since 1884 when the first clinical operation under local anesthesia was performed using cocaine administration [1]. Although effective as an anesthetic, cocaine abuse and misuse ran rampant among patients and healthcare workers [1]. ...
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Although rare, local anesthetic use has been associated with adverse central nervous system and cardiovascular adverse events. One complication is local anesthetic systemic toxicity (LAST), wherein the anesthetic agent inadvertently enters systemic circulation resulting in widespread inhibition of fast-gated sodium channels. Organs dependent on aerobic metabolism, such as the heart and brain, are especially susceptible to toxic injury resulting in cardiovascular collapse. Lipid emulsion therapy is a mainstay treatment of LAST; however, it may inadvertently cause lipid-induced necrotizing pancreatitis. We present a 71-year-old female with a non-contributory past medical history who presented for elective open reduction and internal fixation (ORIF) of the right wrist after a fall onto the right hand one week prior. A supraclavicular brachial plexus block was planned to deliver regional analgesia for ORIF of the right wrist. Shortly after the introduction of the local anesthetic agent, our patient became bradycardic and hypotensive. The patient's heart rate and systolic blood pressure remained in the low 45s and 50s, respectively, refractory to multiple doses of phenylephrine and ephedrine. Suspicion for LAST syndrome was high and lipid emulsion therapy was started. Once stabilized, the patient was transported to the ICU requiring manual ventilation, where she later reported flank pain. Labs drawn were notable for elevated triglyceride, lipase, and amylase levels of over 3000, 600, and 700, respectively. CT imaging confirmed acute necrotizing pancreatitis. The patient's ICU stay was uncomplicated with stabilization of vitals and discharge 10 days later. A follow-up with gastroenterology (GI) was scheduled after two weeks. Since discharge, the patient noted intermittent abdominal aches. Magnetic resonance cholangiopancreatography (MRCP) and MRI were performed after liver function tests (LFTs) were found to be elevated during her follow-up appointment. MRI showed liquefaction necrosis of 80% of the pancreas, with a 14-centimeter fluid collection pushing on the distal common bile duct, causing extrinsic obstruction. MRCP revealed no stones. Advanced GI performed a transgastric cystogastrostomy with lumen apposing metal stent placement in the common bile duct, and drained the fluid from the obstructing cyst. Cytopathology came back as virtually acellular. Liver enzymes began to downtrend appropriately and the patient was discharged soon after. Follow-up at two and four days post-discharge confirmed resolution of symptoms.
... It is the S-enantiomer of bupivacaine hydrochloride and is currently marketed in several countries, including the United States, Japan, and China. It is widely used in clinical practice for local anesthesia during surgical and obstetric procedures and postoperative pain management [3][4][5]. Research has shown that the R-enantiomer of bupivacaine hydrochloride exhibits significant cardiac toxicity [6]. during surgical and obstetric procedures and postoperative pain management [3][4][5]. ...
... Research has shown that the R-enantiomer of bupivacaine hydrochloride exhibits significant cardiac toxicity [6]. during surgical and obstetric procedures and postoperative pain management [3][4][5]. Research has shown that the R-enantiomer of bupivacaine hydrochloride exhibits significant cardiac toxicity [6]. Therefore, levobupivacaine hydrochloride (21), with its lower cardiac toxicity, expands the safety margin for patients. ...
... The new synthetic route of levobupivacaine hydrochloride (21) (overall yield 45%). (5) In order to obtain a higher purity of (2S)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (5), we attempted the chiral separation of the readily available and cost-effective (R,S)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (28) following a patented method [13]. During this process, we utilized L-(−)-dibenzoyl tartaric acid (29) as the resolving agent and successfully obtained the crude product of (2S)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (5). Subsequently, based on our refined solvent screening results (Table 1), we ultimately chose to purify it in ethyl acetate (EA) due to higher yields and purity. ...
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In this study, we not only optimized and improved the synthesis process of levobupivacaine hydrochloride (21) but also conducted a comprehensive exploration of critical industrial-scale production details, and a novel high-performance liquid chromatography (HPLC) analysis method was developed. Starting with the readily available and cost-effective (R,S)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (28) as the initial material and utilizing l-(–)-dibenzoyl tartaric acid (29) for chiral separation, and then through substitution and a salting reaction, levobupivacaine hydrochloride (21) was obtained with high purity (chemical purity of 99.90% and enantiomeric excess (ee) values of 99.30%). The total yield of the three steps was 45%. Structures of intermediates and the final product were confirmed using nuclear magnetic resonance (NMR) (1H NMR, 13C NMR), mass spectrometry (MS), and elemental analysis. The crystal structure of the final product was determined through differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Furthermore, we evaluated the risk of the substitution reaction using a reaction calorimeter and accelerating rate calorimetry (ARC). This process offers the advantages of simple operation, greenness, safety, controllable quality, and cost-effectiveness. It provides reliable technical support for the industrial-scale production of levobupivacaine hydrochloride (21), which is of significant importance in meeting clinical demands. Pilot-scale production has already been successfully completed by China National Medicines Guorui Pharmaceutical Co., Ltd., with a production scale of 20 kg.
... Local anesthetics are a category of drugs that were introduced initially back in the 19th century for the purpose of analgesia. 1 They are the most commercially used drugs by dentists; it was estimated that in the United States, more than 300 million cartridges are being annually used by dentists alone, 2 while another estimation stated that in Ontario, 13 million cartridges had been used in the year 2007. 3 After being developed originally from Cocaine, in order to reduce toxicity many derivatives are being used daily nowadays, such as lidocaine and mepivacaine. ...
... The operating dentist now has the choice to use any of them basing their decision on multiple factors, such as procedure, cost, availability, and pharmacological characteristics. 1,[4][5][6][7] Proper dose calculation for local anesthetics is of critical importance as over-administration of local anesthetics could lead to serious complications. Local anesthetic systemic toxicity LAST is a severe, life-threatening complication when the local anesthetic agent being administered reaches a significant level in the systemic circulation. ...
... The leading causes of LAST include injection of the drug into a highly vascular area or directly into the bloodstream, incorrect calculation of the therapeutic dose MRD, and exceeding the absolute maximum. 1 Prevention of LAST and most adverse reactions of local anesthesia is a multifactorial process; careful obtaining of the medical history, proper dose calculation, and having the adequate knowledge of the LA preparation being administered, such as its half-life, the concentration of the local anesthetic in the carpule, the presence of a vasoconstriction and how to minimize the LA systemic absorption, are important for the prevention of LAST. 2 Practitioners' knowledge and awareness of the local anesthetics' calculations and LAST, and how it could be recognized and managed, is significant for patient safety. One of the earliest publications that touched on this topic was by Kirova et al., 7 and it assessed which LA is being used the most by dentists, as well as the management of medically-compromised patients. ...
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Objectives: This study aims to assess the knowledge level, behavior, and attitude of dental practitioners regarding the absolute maximum dose of local anesthetics, their MRD, and systemic complications. Materials & Method: An electronic survey was distributed through social media platforms to dental practitioners in Jeddah. The survey consisted of 4 sections: demographic information, knowledge, behavior, and attitude. Cronbach’s alpha was used to test for the validity 0.86. Results: A total of 403 participants completed the questionnaire, with a response rate of 60%. Of all, 55.8% were females. The majority were undergraduate students 42.4%, and below the age of 25 44.9%. For the question “what is the MRD/ kg for 2% lidocaine with Epinephrine?” we found a statistically significant difference between the professional rankings p=0.001. Although the undergraduate dentists were the least group to answer the questions “What does a 2% local anesthetic solution mean?”, there was no statistically significant difference between those who answered correctly. Conclusion: We found many of our participants to have false knowledge regarding the topics of LA, MRD/kg, and LAST. We believe that the current levels are not acceptable, and that more efforts must be made to raise the knowledge pertaining to this topic
... Further advancements led to the development of tetracaine, a long-acting ester anesthetic widely used in spinal and ophthalmic anesthesia, and prilocaine, an amide anesthetic known for its reduced toxicity and application in regional anesthesia. These were followed by bupivacaine, renowned for its prolonged action, and ropivacaine, which maintained bupivacaine's efficacy while significantly reducing cardiotoxicity [32]. These innovations marked a critical evolution in locoregional anesthesia, addressing safety concerns while expanding clinical applications such as epidural analgesia during childbirth, nerve blocks for postoperative pain, and infiltration anesthesia in outpatient settings [27]. ...
... The shift from ester-based to amide-based anesthetics reflects a pivotal milestone in the history of anesthetic development, highlighting the pursuit of agents that optimize safety, efficacy, and convenience [32]. While ester-based LAs remain useful for specific scenarios, amide-based agents dominate contemporary practice due to their superior pharmacokinetic and pharmacodynamic properties [54]. ...
Article
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Local anesthetics (LAs) have been indispensable in clinical pain management, yet their limitations, such as short duration of action and systemic toxicity, necessitate improved delivery strategies. Hydrogels, with their biocompatibility, tunable properties, and ability to modulate drug release, have been extensively explored as platforms for enhancing LA efficacy and safety. This narrative review explores the historical development of LAs, their physicochemical properties, and clinical applications, providing a foundation for understanding the integration of hydrogels in anesthetic delivery. Advances in thermoresponsive, stimuli-responsive, and multifunctional hydrogels have demonstrated significant potential in prolonging analgesia and reducing systemic exposure in preclinical studies, while early clinical findings highlight the feasibility of thermoresponsive hydrogel formulations. Despite these advancements, challenges such as burst release, mechanical instability, and regulatory considerations remain critical barriers to clinical translation. Emerging innovations, including nanocomposite hydrogels, biofunctionalized matrices, and smart materials, offer potential solutions to these limitations. Future research should focus on optimizing hydrogel formulations, expanding clinical validation, and integrating advanced fabrication technologies such as 3D printing and artificial intelligence-driven design to enhance personalized pain management. By bridging materials science and anesthetic pharmacology, this review provides a comprehensive perspective on current trends and future directions in hydrogel-based LA delivery systems.
... Ropivacaine was first synthesized in the late 1970s and early 1980s to create safer alternatives to established local anesthetics such as bupivacaine. Initial investigations concentrated on understanding its pharmacological characteristics and evaluating its potential for clinical application [2]. ...
Article
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Ropivacaine, a widely used regional anesthetic also used for pain management, has been increasingly used in recent years due to its increased efficacy and improved safety compared to similar anesthetics. Biomonitoring of ropivacaine and its metabolites during and after anesthesia is an essential process for ensuring therapeutic efficacy and safe usage for patients. The most useful biomonitoring tool in recent years has been liquid chromatography coupled with mass spectrometry (LC-MS/MS), which offers selectivity, sensitivity, as well as accuracy of measurements. The current manuscript summarizes and discusses the existing liquid chromatographic methods described in the literature, as well as the personal experience with developing bioanalytical and analytical methods for the quantification of ropivacaine in biological samples for clinical applications. It is focused on methodological aspects, recent advancements, challenges, and future perspectives, highlighting the importance of LC-MS/MS techniques in ropivacaine analysis.
... Bupivacaine was discovered in 1957 and became available commercially in 1965. Its closely related compound, ropivacaine, underwent clinical trials starting in 1990 and was introduced clinically in 1996 [5]. ...
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BACKGROUND Intrathecal bupivacaine is the traditional anesthetic drug used in spinal anesthesia for caesarean sections (CSs), but ropivacaine has emerged as a potential alternative. This meta-analysis compares the efficacy and safety of intrathecal hyper-baric bupivacaine vs hyperbaric ropivacaine for cesarean sections.
... Lidocaine, another member of the amide group, has approximately half the action duration of bupivacaine. [28][29][30] This observation aligns with our study's findings, which identified a significant difference in the onset and maintenance of anesthesia between patient groups injected with ropivacaine and lidocaine. The ropivacaine group experienced quicker anesthesia onset and longer maintenance periods. ...
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Introduction This study aims to compare the efficacy of ropivacaine and lidocaine in the treatment of temporomandibular joint (TMJ) disorders, with the goal of exploring a more effective treatment for TMJ disorders. Methods Patients with Wilkes stage III and IV unilateral TMJ disorders were enrolled in the study. 0.5% ropivacaine was used for local anesthesia in group A, 2% lidocaine was used in group B. Sodium hyaluronate was injected after supra-articular lavage in both groups. The patients’ general conditions, pain scores, and maximum opening before and after treatment were collected, the time of onset and maintenance of anesthesia, and the levels of inflammatory factors IL-1β and IL-6 in the joint lavage fluid were detected. Results Study showed that the onset of anesthesia was faster and longer maintained in group A. The decrease in IL-1β was more pronounced in group A (16.08 ± 3.10) than in group B (18.03 ± 2.84), p < 0.05. At 2 months after treatment, the joint clicking rate was higher in group A (75%) compared to group B (35%), p < 0.05. At 3 months after treatment, the joint clicking rate was higher in group A (76.69%) compared to group B (40%) and the maximum mouth opening was greater in group A (45.00 ± 2.38) compared to group B (41.73 ± 4.18), p < 0.05. There were no statistically significant differences in VAS score and lateral excursion in group A compared with group B at 2 months and 3 months after treatment. Conclusions Compared with lidocaine, the application of ropivacaine combined with sodium hyaluronate supra-articular lavage for the treatment of temporomandibular joint disorder is more clinically effective. Clinical trials Registration Number ChiCTR2300075241 (30/08/2023).
... Lidocaine was developed in 1943 and bupivacaine in 1957. Ropivacaine was developed in 1996 and serves to be more potent than lidocaine with less cardio-and chondrotoxicity (15,16). ...
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Spine procedures are commonly performed to diagnose and treat various spinal conditions, ranging from degenerative disc disease to vertebral fractures. These procedures often involve the use of pharmaceutical agents to enhance the efficacy of the intervention and improve patient outcomes. This review provides an overview of the pharmaceuticals commonly utilized in spine procedures, including corticosteroids, anesthetics, antibiotics, radiographic contrast, neurolytic agents, and materials used in kyphoplasty and vertebroplasty. This review summarizes the utilization of these pharmaceutical agents in spine procedures in an effort to optimize patient outcomes. Understanding the pharmacological properties and appropriate uses of these pharmaceuticals is essential for interventionalist and healthcare providers involved in the care of patients undergoing spinal interventions.
... He first applied topical cocaine to the eye of a frog and when the frog did not move in response to touching of its cornea, regional anesthesia was truly born. 3 He practiced ophthalmology with regional anesthesia for the remainder of his career. The concept of Spinal anesthesia was pioneered by Leonard Corning, a New York neurologist, but first carried out by August Bier in Germany in 1889. ...
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In this review article, the current challenges for development of regional anesthesia in Nepal and their solutions are described. With brief historical background the review covers development of general and regional anesthesia from landmark techniques, along with utilization of ultrasound to the application of artificial intelligence. Safety concerns and quality indicators are essential as there is an increase in practice of perioperative pain services and chronic pain management services. The scope and reason of regional anesthesia in diverse facilities, including its contribution to point of care, Enhanced Recovery After Surgery protocols(ERAS), and Perioperative Surgical Home model (PSHM) are described. This review also elaborates a practice triangle to promote regional anesthesia practice in Nepal including curriculum strengthening, research publication, and the establishment of a national registry.
... Cocaine ( Figure 1) is a plant-derived compound (mainly from plants of the Erythroxylum genus [29]) and is the parent compound of the local anesthetic superfamily, which primarily targets voltage-gated sodium channels on the surface of nerve cells [30,31]. Besides its local anesthetic properties, cocaine's main behavioral effect in vertebrates is through its interaction with neurotransmitter transporters, particularly the dopamine transporter [32]. ...
Article
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The freshwater planarian is an emerging animal model in neuroscience due to its centralized nervous system that closely parallels closely parallels the nervous system of vertebrates. Cocaine, an abused drug, is the ‘founding member’ of the local anesthetic family. Parthenolide, a sesquiterpene lactone, acts as a behavioral and physiological antagonist of cocaine in planarians and rats, respectively. Previous work from our laboratory showed that both parthenolide and cocaine reduced planarian motility and that parthenolide reversed the cocaine-induced motility decrease at concentrations where parthenolide does not affect the movement of the worms. However, the exact mechanism of the cocaine/parthenolide antagonism is unknown. Here, we report the results of a Schild analysis to explore the parthenolide/cocaine relationship in the planarian Girardia tigrina. The Schild slopes of a family of concentration–response curves of parthenolide ± a single concentration of cocaine and vice versa were −0.55 and −0.36, respectively. These slopes were not statistically different from each other. Interestingly, the slope corresponding to the parthenolide ± cocaine (but not the cocaine ± parthenolide) data set was statistically different from −1. Our data suggest an allosteric relationship between cocaine and parthenolide for their effect on planarian motility. To the best of our knowledge, this is the first study about the mechanism of action of the antagonism between cocaine and parthenolide. Further studies are needed to determine the specific nature of the parthenolide/cocaine target(s) in this organism.
... Since they are both more effective and have significantly lower systemic toxicity than other local anesthetics on the market, lidocaine and articaine are the amides and esters that are most frequently used in dentistry. 14 The short duration of anesthesia, low anesthetic efficiency, and side effects are just a few of the drawbacks that all local anesthetics have. 15 The pH of the solution determines when anesthesia starts to work and how well it works. ...
... [5][6][7][8] This led to the identification of pure S-enantiomer ropivacaine with a prolonged action mechanism. [9] Ropivacaine and bupivacaine are nearly identical in quality, onset, and sensory blockade duration. Still, ropivacaine produces a shorter duration of motor blockade and is safer. ...
... One of the most used banned substances is cocaine, being extensively manufactured, distributed, marketed, and consumed globally. The history of cocaine alongside humans, and its use as a substance capable of invigorating the spirit and body, in addition to revitalizing the soul and bringing it closer to the gods, dates to pre-Columbian cultures 1,2 throughout the Andean region 3,4 . Its use in humans was first recorded and described by Amerigo Vespucci, and its isolation from coca leaves was documented in 1860 by Albert Niemann, with its chemical formula elucidated in 1865 by Wilhelm Lossen 5 . ...
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Introduction: The global crisis of illicit substance consumption, particularly cocaine, extends beyond individual users, impacting social, cultural, and institutional levels. Cocaine use is associated with a myriad of illicit activities and significantly affects public health, especially in underdeveloped countries. This study examines the cardiovascular risks linked to cocaine use, focusing on conditions such as chest pain and acute myocardial infarction. Methodology: A comprehensive review of the literature was conducted to explore the epidemiology, pathophysiology, and treatment strategies for cocaine-associated cardiovascular events. Data on cocaine use prevalence and related cardiovascular incidents were analyzed, alongside mechanisms of cocaine-induced myocardial damage and treatment protocols. Results: Cocaine use has increased, particularly among young adults, leading to higher prevalence rates of cardiovascular events, including acute myocardial infarction. Cocaine induces vasoconstriction, arrhythmias, and oxidative stress, contributing to myocardial ischemia and infarction. The literature reveals a significant incidence of severe coronary atherosclerosis and multivessel disease among young cocaine users experiencing acute myocardial infarction. Immediate intervention strategies, including dual antiplatelet therapy and percutaneous coronary intervention, are essential but must be tailored to the unique challenges posed by cocaine's effects. Conclusions: Cocaine elevates the risk of severe cardiovascular events, necessitating targeted prevention and treatment strategies. The management of acute myocardial infarction in cocaine users requires a personalized approach, considering the drug's complex impact on cardiovascular health. Preventive measures and early intervention are crucial to mitigating the heightened risk of myocardial infarction and other cardiac events in this population.
... This helps to hasten the postoperative recovery [3] . Since its introduction into market in 1996, Ropivacaine has been put to extensive use in epidural, intrathecal and peripheral nerve blocks [4] . Various adjuvants have been added to Ropivacaine to shorten the onset of block and to augment the clinical efficiency and duration of analgesia. ...
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Background: Ropivacaine also showed the advantage of lesser motor blockade making it preferable when early mobilization is suggested. This helps to hasten the postoperative recovery [3]. Since its introduction into market in 1996, Ropivacaine has been put to extensive use in epidural, intrathecal and peripheral nerve blocks. Objectives: To measure, compare and analyse the below mentioned parameters at regular intervals among subjects undergoing lower abdominal and lower limb surgeries. Material & Methods: A prospective, randomized, comparative study. The study was conducted in the Department of Anesthesiology, Malla Reddy Institute of Medical Sciences a tertiary care centre in Hyderabad. All the patients who were undergoing the elective lower abdominal and limb surgeries in the department of anesthesiology during the study period. Study consisted of 60 cases. Simple random method. All the patients meeting the inclusion criteria were taken into the study. A pre- designed, pre-tested, semi structured and pre-coded proforma was used for recording all the findings. After obtaining Ethical clearance from the Institutional Ethical Committee, study was conducted. Results: Comparison of the Modified Ramsay Sedation Score between the two groups shows that Modified Ramsay Sedation Score at 30, 120, 150 and 180 mins is higher in GROUP-N and is statistically not significant with a p value of > 0.05. Comparison of the Modified Ramsay Sedation Score between the two groups shows that Modified Ramsay Sedation Score at 60 and 90 mins is higher in GROUP-N and is statistically significant with a p value of < 0.001. Conclusion: To conclude, Nalbuphine (500μg) seems to be an attractive alternative to 25μg Fentanyl as an adjuvant to spinal ropivacine in surgical procedures as it provides good quality of intraoperative analgesia, hemodynamically stable conditions, and excellent quality of postoperative analgesia as per our study.
... Clinically, many phytochemicals like galantamine (memory enhancer) (Loy et al., 1996), risperidone (antipsychotic) (Hunter et al., 1996), cocaine (CNS stimulant and local anesthetic) (Isenschmid, 2020;Ruetsch et al., 2001), ergotamine (migraine) (Graham & Wolff, 1938;Tfelt-Hansen et al., 2000), and opioids (pain) (McQuay, 1999) were approved for the management of a variety of neurological diseases. ...
Article
Neurological disorders incidences are increasing drastically due to complex pathophysiology, and the nonavailability of disease‐modifying agents. Several attempts have been made to identify new potential chemicals to combat these neurological abnormalities. At present, complete abolishment of neurological diseases is not attainable except for symptomatic relief. However, dietary recommendations to help brain development or improvement have increased over the years. In recent times, cruciferous vegetables and their phytochemicals have been identified from preclinical and clinical investigations as potential neuroprotective agents. The present review highlights the beneficial effects and molecular mechanisms of phytochemicals such as indole‐3‐carbinol, diindolylmethane, sulforaphane, kaempferol, selenium, lutein, zeaxanthin, and vitamins of cruciferous vegetables against neurological diseases including Parkinson's disease, Alzheimer's disease, stroke, Huntington's disease, autism spectra disorders, anxiety, depression, and pain. Most of these cruciferous phytochemicals protect the brain by eliciting antioxidant, anti‐inflammatory, and antiapoptotic properties. Regular dietary intake of cruciferous vegetables may benefit the prevention and treatment of neurological diseases. The present review suggests that there is a lacuna in identifying the clinical efficacy of these phytochemicals. Therefore, high‐quality future studies should firmly establish the efficacy of the above‐mentioned cruciferous phytochemicals in clinical settings.
... Such an example, morphine, a potent analgesic drug isolated from the juice (latex) of the unripe seedpod of Papaver somniferum L. (poppy plant), led to the development of not only morphinomimetic compounds with improved analgesic properties, but also to other chemically modified derivatives, such as dextromethorphan and loperamide, which retained only the antitussive or constipating activities [7,8]. Similarly, the local anaesthetic effect of cocaine, an alkaloid isolated from the leaves of Erythroxylon coca L., allowed to obtain local anaesthetic drugs by structural modifications [9], while the discovery of salicine, a phenolic glycoside from the bark of the willow tree Salix alba L., led to the synthesis of the wellknown anti inflammatory drug aspirin [10]. ...
Article
Introduction: Exploring the chemical diversity and molecular mechanisms of natural products continues to be an important research area for identifying novel promising therapeutic approaches for fighting cancer. This is a complex disease and poses important challenges, which require not only targeted interventions to improve chemotherapy efficacy and tolerability, but also adjuvant strategies to counteract chemoresistance development and relapses. Areas covered: After a brief description of the recent literature on the anticancer potential of natural compounds, we searched for patents following the PRISMA guidelines, filtering the results published from 2019 onwards. In addition, some relevant publications from the overall scientific literature were also discussed. Expert opinion: This review comprehensively covers and analyzes the most recent advances on the anticancer mechanism of licensed natural compounds and their chemical optimization. Patentability of natural compounds was discussed according to the recent legislation in the U.S.A. and Europe.
... However, its use was restricted due to its high toxicity after absorption. 22 Common local anesthetics have a chemical structure composed of three parts: a lipophilic benzene ring, an intermediate carboxylic ester (-COO-) or amide (-NCO-) chain for linkage, and a hydrophilic tertiary or secondary amine group (Scheme 1). 23 The mechanism of action for traditional local anesthetics involves the inhibition of voltage-gated sodium channels, which are responsible for conducting neuronal impulses. ...
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Anesthetics, which include both local and general varieties, are a unique class of drugs widely utilized in clinical surgery to alleviate pain and promote relaxation in patients. Although numerous anesthetics and their traditional formulations are available in the market, only a select few exhibit excellent anesthetic properties that meet clinical requirements. The main challenges are the potential toxic and adverse effects of anesthetics, as well as the presence of the blood-brain barrier (BBB), which makes it difficult for most general anesthetics to effectively penetrate to the brain. Loading anesthetics onto nanocarriers as anesthetic nanomedicines might address these challenges and improve anesthesia effectiveness, reduce toxic and adverse effects, while significantly enhance the efficiency of general anesthetics passing through the BBB. Consequently, anesthetic nanomedicines play a crucial role in the field of anesthesia. Despite their significance, research on anesthetic nanomedicines is still in its infancy, especially when compared to other types of nanomedicines in terms of depth and breadth. Although local anesthetic nanomedicines have received considerable attention and essentially meet clinical needs, there are few reported instances of nanomedicines for general anesthetics. Given the extensive usage of anesthetics and the many of them need for improved performance, emerging anesthetic nanomedicines face both unparalleled opportunities and considerable challenges in terms of theory and technology. Thus, a comprehensive summary with systematic analyses of anesthetic nanomedicines is urgently required. This review provides a comprehensive summary of the classification, properties, and research status of anesthetic nanomedicines, along with an exploration of their opportunities and challenges. In addition, future research directions and development prospects are discussed. It is hoped that researchers from diverse disciplines will collaborate to study anesthetic nanomedicines and develop them as a valuable anesthetic dosage form for clinical surgery.
... Local anesthetics (LA) are used in several medical conditions, from stitches to surgeries. Since the first use of cocaine for eye surgery in 1884, several molecules have been synthesized the most common being lidocaine [1]. LA bind to voltage-gated sodium channels of nerve cells, preventing the entry of sodium ions. ...
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Purpose To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes. Methods Spontaneous reports notified to the French Pharmacovigilance Network were retrieved and followed by a case-by-case review, according to the following criteria: LA as suspected drug, age < 18 years, adverse drug reactions related to nervous system, cardiac, respiratory, psychiatric or general disorders. Multivariate logistic regression analysis was performed to identify factors leading to life-threatening reaction (i.e. continuous seizures or cardiorespiratory arrest). Results Among 512 cases retrieved, 64 LAST cases were included (neonates 11%, infants 30%, children 36%, adolescents 23%) mainly involving lidocaine (47%), lidocaine + prilocaine (22%) and ropivacaine (14%). Toxicity profiles were neurological (58%), cardiac (11%) or mixed (20%) and 7 patients (11%) developed methemoglobinemia. LAST was life-threatening for 23 patients (36%) and 2 patients died. Doses were above recommendations in 26 patients (41%) and were not different between life-threatening and non-life-threatening cases. The context of use (general and orthopedic surgery, p = 0.006) and the type of LA agent (lidocaine, p = 0.016) were independently associated with a life-threatening outcome. Conclusion In this national retrospective analysis, LAST in children appear to be a rare event. Neurological and cardiac signs were the most frequently reported reactions. LAST in children can be life-threatening, even at therapeutic doses. Although a fatal outcome may anecdotally occur, the vast majority of patients recovered after appropriate medical care.
... However, cocaine is highly toxic to corneal epithelial cells and is no longer used for anesthesia. Since then, local anesthetics for ophthalmic use have changed to tetracaine, proparacaine, and lidocaine [16,17]. ...
Chapter
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Alkaloids can have a variety of effects on the eyes. Some alkaloids are used as a treatment for eye diseases, such as keratoconjunctivitis, but they are also toxic to the retina. Other alkaloids are known to protect neuroretina from damage caused by oxidative stress. Numerous ophthalmic drugs, such as glaucoma and antibiotic eye drops, have long been developed through alkaloids. In this chapter, we will introduce the beneficial and detrimental effects of alkaloids on the eye. In addition, the action of alkaloids as existing eye drops and the possibility of developing them as drugs in the future will be discussed.
... Unlike general anesthetic drugs, local anesthetic drugs numb only a small portion of the body during surgical procedures like deep-cut suturing, repairing a broken bone, skin biopsies, and breast biopsies. Prior to the discovery of P.HCl, cocaine was widely used for local anesthesia because of its ability to act as a vasoconstrictor [4,5]. However, prolonged use of cocaine resulted in severe local and systemic toxicities, because of which the introduction of P.HCl into the field of anesthesia soon became widely accepted owing to its less hazardous nature than cocaine. ...
Article
Procaine hydrochloride (P.HCl) is one of the earliest and most well-established local anesthetic drugs used in medicine. Though it is employed frequently for effective clinical nerve blocks during surgeries, its immoderate administration has often shown reports of systemic toxicity. To prevent such repercussions, developing a sensor for the drug is crucial to enable real-time monitoring of the drug and assist in quality control procedures during its industrial preparations. Thus, in this work, we have fabricated a simple yet highly selective and sensitive amperometric sensor for P.HCl detection based on a Barium-oxide multi-wall carbon nanotube-modified carbon paste electrode (BaO-MWCNT/CPE). Herein, we have adopted a novel approach devoid of sophisticated procedures and pretreatments for rapidly determining P.HCl. Furthermore, experimental conditions, including supporting electrolytes, pH, and scan rate, were optimized to achieve a well-defined P.HCl anodic peak current at 631 mV, which is lower than the previously reported peak potentials, indicating an advantage of reduced overpotential. Besides, a striking 66-fold rise in current responsiveness to P.HCl was achieved upon modification with BaO-MWCNT. Such an intense signal enhancement upon electrode modification compared to bare CPE was due to the strong electrocatalytic feature of BaO-MWCNT, which was verified using surface morphology studies with scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Additionally, the charge transfer kinetics analyzed via electrochemical impedance spectroscopy (EIS) justified the enhancement of electrocatalytic activity upon electrode modification. The developed sensor exhibited a remarkable analytical performance over a wide linear dynamic range of 2.0-100.0 µM with a detection limit of 0.14 µM. Moreover, a significant merit of this sensor is its excellent selectivity towards P.HCl even in the presence of various common interferants. Finally, the versatility of the sensor was further validated by implementing it for the trace analysis of urine and blood serum real samples.
... Ropivacaine, bupivacaine, and lidocaine are amide local anesthetics synthesized in the 1900s [8]. They reduce sodium ion permeability in nerve cell membranes, reversibly blocking nerve impulse conduction [9]. ...
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Pain relief in hip fracture patients may be sought by injecting local anesthetic such as ropivacaine, bupivacaine, and lidocaine to the femoral area. As femoral veins are a routine sampling site for postmortem blood, this short report aimed to describe the levels of local anesthetics in ipsilateral (i.e., side of surgery) and contralateral (i.e., opposite side) femoral blood in ten medico-legal autopsy cases that had undergone a hip fracture surgery within 7 days before death. Postmortem blood samples were systematically collected from the ipsilateral and contralateral femoral veins, and toxicological analysis was performed in an accredited laboratory. The sample comprised six female and four male decedents who died at the age of 71-96 years. Median postoperative survival was 0 days and median postmortem interval 11 days. Strikingly, ropivacaine concentration was a median of 24.0 (range 1.4-28.4) times higher on the ipsilateral than contralateral side. The median ipsilateral concentration of ropivacaine clearly exceeded the 97.5th reference percentile measured in this laboratory for ropivacaine in postmortem cases representing all causes of death. The remaining drugs did not show high concentrations or notable differences between the sides. Our data clearly advise against performing postmortem toxicology on femoral blood from the operated side; the contralateral side may constitute a better sampling site. Toxicology reports that are based on blood collected from the operated area should be interpreted with caution. Larger studies are needed to confirm the findings, with accurate records of the dosage and administration route of local anesthetics.
... LC is the most commonly utilized anesthetic in DME surgical procedures, but in some of the earliest research TC was used instead. This may be due to the fact that TC has been utilized in the medical sector for a longer period of time than LC, however clinical investigations have demonstrated that LC is more effective than TC at reducing patient pain [28][29][30] . So, despite the fact that TC has been used by physicians for a longer period of time, LC is the anesthetic of choice among surgeons for the treatment of DME, as it has been demonstrated to be more effective. ...
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Diabetes-related macular edema is a fast-spreading condition that has damaged the lives of countless people throughout the globe. The current incorporation of subthreshold micropulse laser has indicated the precedence of laser therapy in the treatment of diabetic macular edema; nonetheless, vitreoretinal surgery in conjunction with anesthetics correlates with early mitigation of damage to the fovea. Surgery is a delicate procedure that necessitates careful consideration of the types and locations of anesthetics used. Depending on the individual being treated, various drugs and methods may be necessary. For example, some individuals may be allergic to conventional anesthetics, resulting in more severe consequences. In the surgical treatment of diabetic macular edema, the topical anesthetic was utilized more frequently than subconjunctival anesthesia, according to the review’s statistical analysis. The examined literature indicated that topical lidocaine was the most employed anesthetic for vitreoretinal surgery; however, alternatives to lidocaine exist, and their effects should be investigated. Consequently, we would want to highlight the impacts of each of the several surgical medications and anesthetics used to treat diabetic macular edema.
... Thus, we can postulate that the neuronal responses we recorded after application of 5-HT onto our cultured isolated myenteric neurons were mediated by the activation of this HT receptor subtype and were then blocked by acute cocaine perfusion. The fact that cocaine had a similar blocking effect on neuronal responses evoked by the three compounds tested could also indicate an Cells 2023, 12, 577 9 of 13 unspecific effect of the drug on neuronal voltage-gated Na + channels, considering it was used as a local anesthetic in the early 19th century [43]. However, the results of our organ bath experiments with comparable EFS-induced contractile responses before and after cocaine addition somehow rule out this hypothesis, pointing towards a specific effect of cocaine on the nicotinergic and/or serotoninergic systems. ...
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Cocaine is one of the most consumed illegal drugs among (young) adults in the European Union and it exerts various acute and chronic negative effects on psychical and physical health. The central mechanism through which cocaine initially leads to improved performance, followed by addictive behavior, has already been intensively studied and includes effects on the homeostasis of the neurotransmitters dopamine, partly mediated via nicotinic acetylcholine receptors, and serotonin. However, effects on the peripheral nervous system, including the enteric nervous system, are much less understood, though a correlation between cocaine consumption and gastrointestinal symptoms has been reported. The aim of the present study was to gain more information on the effects of cocaine on enteric neuronal functions and the underlying mechanisms. For this purpose, functional experiments using an organ bath, Ussing chamber and neuroimaging techniques were conducted on gastrointestinal tissues from guinea pigs. Key results obtained are that cocaine (1) exhibits a stimulating, non-neuronal effect on gastric antrum motility, (2) acutely (but not chronically) diminishes responses of primary cultured enteric neurons to nicotinic and serotonergic stimulation and (3) reversibly attenuates neuronal-mediated intestinal mucosal secretion. It can be concluded that cocaine, among its central effects, also alters enteric neuronal functions, providing potential explanations for the coexistence of cocaine abuse and gastrointestinal complaints.
... Discovery of plant-based antiglaucoma drugs and anaesthetizing agent for ocular tissue has led to the exponential growth in ocular pharmaceutics (Ruetsch, 2001). Despite technological advances in synthesizing drugs, the pharmaceutical industry still seeks new active compounds from natural sources as well as from revisiting already-established naturally derived compounds. ...
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Objective: Traditional herbal plants have been in use since ancient times to treat ophthalmic conditions; so, the aim of this study is to evaluate some potent Indian traditional medicinal plants used in ophthalmic diseases in order to summarize their potential effect in ophthalmology along with their mechanism of action. Materials and methods: Databases PubMed, Google Scholar, and Embase were extensively explored. Additionally, relevant textbooks and literatures were consulted to summarize most of the considerable scientific literature for the review. Search term included ophthalmology, glaucoma, cataract, trachoma, conjunctivitis, traditional medicines, Unani drugs, and ayurvedic drugs were used. Around 80 review articles were consulted from the year 1982 to 2021. Results: The traditional medicinal plants are easily available, cost-effective and have no associated side effects in comparison to current conventional treatments. Moreover, these drugs in oppose to modern medicine, have an inherent potential to accelerate the body's own immunity to fight against any infection. A large volume of scientific studies has reported the beneficial effects of traditional drugs in ophthalmology. Conclusion: This review, therefore, describes the potential benefits and uses of some traditional medicinal plants used in ophthalmic diseases.
... Cocaine is a very powerful stimulant drug that is obtained from the Erythroxylon coca plant. It has been used in South America as a mild stimulant akin to coffee for thousands of years in the form of chewed coca leaves [4]. Cocaine hydrochloride is a purified chemical that was isolated in the early 1900s and used as an analgesic prior to the development of anesthetics as a class [5]. ...
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We present the case of a 23-year-old male with no significant past medical history who experienced acute chest pain. A diagnostic workup revealed that the patient had a non-ST-segment elevation myocardial infarction. Although the patient was not forthcoming initially with his cocaine use, he did admit it later in his emergency department course. The timing of his rise and fall of troponin is presented. The pathophysiology of cocaine-related chest pain and infarction is discussed. The patient continued to make an uneventful recovery.
Article
Background: Spinal anesthesia remains the preferred technique for lower abdominal and orthopedic procedures. Objectives: This study compares the effects of an intrathecal injection of pethidine combined with dexamethasone versus intrathecal bupivacaine alone in patients undergoing lower extremity orthopedic surgeries. Methods: In this prospective, randomized, controlled, double-blinded study, 46 participants scheduled for elective lower extremity orthopedic surgeries were randomly allocated into two groups. Group PD (n = 23) received an intrathecal injection of 1 mg/kg preservative-free pethidine combined with 4 mg dexamethasone, diluted with 0.9% sodium chloride saline to a total volume of 3 mL. Group B (n = 23) received an intrathecal injection of 3 mL (15 mg) of 0.5% hyperbaric bupivacaine alone. The primary outcome measured was the time to the first need for rescue analgesia. Secondary outcomes included spinal anesthesia characteristics, intraoperative hemodynamic stability, and incidence of perioperative adverse events. Results: The time to first need for rescue analgesia was significantly longer in Group PD (7.76 ± 0.79 hours) compared to Group B (4.48 ± 0.63 hours). Differences in the onset of sensory and motor blocks between Group PD (6.39 ± 1.12 and 10.09 ± 2.23 minutes, respectively) and Group B (6.43 ± 1.99 and 9.96 ± 2.33 minutes, respectively) were statistically non-significant. However, the regression time for sensory and motor blocks was significantly shorter in Group PD compared to Group B (146.74 ± 15.35 and 119.56 ± 14.13 minutes vs. 188.44 ± 6.84 and 168.04 ± 5.25 minutes, respectively). Incidence of hypotension and shivering was also less frequent in Group PD than in Group B. Conclusions: Intrathecal administration of 1 mg/kg pethidine plus 4 mg dexamethasone provided improved spinal anesthesia, with extended postoperative analgesia, minimal intraoperative hemodynamic disturbances, and reduced incidence of shivering compared to bupivacaine alone in patients undergoing lower extremity orthopedic surgeries. This approach may be particularly beneficial for patients with hypersensitivity to ester or amide local anesthetics, offering a cost-effective alternative to standard local anesthetics.
Chapter
Anesthesia is an integral aspect of cataract surgery, providing patient comfort and safety during the procedure. The use of anesthesia has been a crucial component of cataract surgery since its inception and its evolution has had a significant impact on the progress and outcome of the procedure.
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The significant synthetic potential and reactivity of tetracyanoethylene (TCNE) have captured the interest of numerous chemical communities. One of the most promising, readily achievable, yet least explored pathways for the reactivity of TCNE involves its interaction with arylamines. Typically, the reaction proceeds via tricyanovinylation (TCV); however, deviations from the standard chemical process have been observed in some instances. These include the formation of heterocyclic structures through tricyanovinyl intermediates, aliphatic dicarbonitriles through the cleavage of the C–C bond of a tetracyanoethyl substituent, complexation, and various pericyclic reactions. Therefore, the objective of this study is to review the diverse modes of interaction of TCNE with aromatic nitrogen-containing compounds and to focus the attention of the chemical community on the synthetic capabilities of this reagent, as well as the various biological and optical activities of the structures synthesized based on TCNE.
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The present work has developed a straightforward, gentle, and effective approach for synthesizing arylamines and 5-substituted-1H-tetrazole derivatives, and among the two tested catalysts, molybdenum trioxide (MoO3) proved to be highly effective. The selective hydrogenation of nitroarenes to arylamines presents a significant challenge due to the complex reaction mechanism and the competitive hydrogenation of other reducible functional groups. It facilitated the transfer hydrogenation of nitrobenzene using hydrazine hydrate-produced amino compounds and enabled the [3 + 2] cycloaddition of sodium azide with aromatic nitriles to yield 5-substituted-1H-tetrazoles. The structure of compound 5-(4-bromophenyl)-1H-tetrazole (5k) was verified through single-crystal X-ray analysis, and the calculation of Green Chemistry Metrics showed the optimal range. Notably, the MoO3 catalyst can be reutilized for up to seven cycles with minimal loss of effectiveness. These attributes make molybdenum trioxide particularly attractive for industrial applications. This methodology offers several advantages over traditional synthetic methods.
Article
The aim of the study was to evaluate and compare the efficacy of extra-oral mandibular nerve block (infra-zygomatic approach/lateral approach) vs. intra-oral (Gow-Gates) mandibular nerve block in arch bar fixation for management of mandibular fractures. A total of 200 patients reported with maxillofacial fractures. Out of them, 50 patients who required arch bar fixation for management of mandibular fractures were divided into two groups: Group I: Extra-oral and Group II: Intra-oral mandibular nerve blocks. The intra-operative pain, time of onset of anaesthesia, volume of drug administered, depth of needle insertion, repetition of injections and postoperative complications were analysed. In Group I (Extra-oral nerve block), the time of onset of anaesthesia, volume of anaesthesia administered, needle depth, number of repetition of injections and postoperative complications were more as compared to Group II. No significant difference was observed in intra-operative pain score between two groups. Intra-oral approach with Gow-Gates technique seemed to be efficient and easy to operate as compared to extra-oral approach, for arch bar fixation of mandibular fractures in an output door setting, as extra-oral approach is more technique-sensitive and may lead to certain complications which require operation theatre setting with medical attention.
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The use of multimodal anaesthesia and analgesia is desirable as part of a complete analgesic plan. Analgesic strategies for perioperative pain treatment include combinations of drugs with different means of action to increase their efficacy and to reduce the required doses and adverse effects. Local anaesthetics prevent the transduction and transmission of painful stimuli through their action on neuronal cell membranes. They undergo minimal systemic absorption and are therefore ideal alternatives to drugs that could result in systemic toxicity. Numerous benefits have been recognised for the use of local anaesthesia, such as a decreased need for systemic analgesics and decreased hospitalisation periods. Local anaesthetics have been used in veterinary medicine in several ways. Anatomical landmarks can be used to identify the target nerves and the clinician can employ an electrical nerve stimulator or ultrasound guidance to perform a more accurate injection. Local anaesthetic techniques can implement other drugs, apart from or in combination with local anaesthetics, such as opioids, α2−adrenergic agonists or vasoconstricting agents. This review article presents and discusses the most common techniques of local anaesthetic use in small animals, with the aim of providing the clinician with further and comprehensive information regarding the analgesic options during the perioperative period.
Article
In this article, we will discuss the history, pharmacodynamics, and neurotoxicity of psychostimulants and hallucinogens. The drugs discussed are widely used and have characteristic toxidromes and potential for neurological injuries with which the practicing clinician should be familiar. Psychostimulants are a class of drugs that includes cocaine, methamphetamine/amphetamines, and cathinones, among others, which produce a crescendoing euphoric high. Seizures, ischemic and hemorrhagic strokes, rhabdomyolysis, and a variety of movement disorders are commonly encountered in this class. Hallucinogens encompass a broad class of drugs, in which the user experiences hallucinations, altered sensorium, distorted perception, and cognitive dysfunction. The experience can be unpredictable and dysphoric, creating a profound sense of anxiety and panic in some cases. Recognizing the associated neurotoxicities and understanding the appropriate management is critical in caring for these patient populations. Several of these agents are not detectable by standard clinical laboratory analysis, making identification and diagnosis an even greater challenge.
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Background: The relief of pain and suffering is, and always has been, one of the primary concerns of mankind and one of the prime factors that has influenced the course of history of medicine. Transversus abdominis plane (TAP) block is a regional anaesthetic technique which blocks the abdominal neural afferents by introducing local anaesthetic into the neuro-fascial plane between the internal oblique and the transversus abdominis muscle. Aim: To compare the efficacy of Dexmedetomidine and dexamethasone as an adjuvant to 0.2%ropivacaine in ultrasound guided transverses abdominis plane block in infra umbilical surgeries in terms of, 1. Time to initial postoperative pain. 2. Time to initial rescue analgesia. 3. Quality of block.. 4. Total postop analgesic consumption. 5. Patient satisfaction with regard to pain relief. 6. Post-operative nausea and vomiting. Materials And Methods: We included 80 patients of age between 18-60 years of American Society of Anesthesiologists status (ASA)I and II scheduled for elective infraumbilical surgeries in our study. We randomly allotted these patients into two groups namely Group A and Group B of each. Patients in Group APatients who received transversus abdominis plane block with - 18ml Ropivacaine 0.2%+ 2 ml Dexamethasone 8mg. Patients in Group B received transversus abdominis plane block with-18ml Ropivacaine 0.2%+ 2 ml Dexmedetomidine .This TAP block was given soon after the surgery is completed. The duration of block and regression of sensory block, time for rescue analgesia, degree of sedation, hemodynamic parameters, post operative analgesia and adverse effects were noted. Result: The two groups were comparable on the basis of duration of surgery, site of surgery, ASA and BMI. Heart rates and mean arterial pressure were compared and it was found to be significantly lower in group B compared to group A until initial 5 hours. In our study we found that the visual analogue score at rest and on coughing between groups A and B was statistically insignificant. However, the time to first rescue analgesia (330 mins vs 240 mins) and total analgsic consumption in the 24 hours period post operatively was significantly lesser for group A compared to group B. Ramsey sedation score was significantly higher in group B compared to group A until 8 hourspost operatively. Nausea and vomiting in 3 cases of group A , and 2 cases in group B. No other significant side effects were noted. Conclusion: USG-guided TAP block is an effective and safe adjunct for postoperative analgesia in infra umblical surgeries. Addition of dexamethasone as an adjuvant prolongs the duration and reduces post-operative analgesic requirement in patients significantly more than dexmedetomidine whereas dexamethasone provides better control of the heart rate and mean arterial pressure.
Chapter
Corticosteroids and local anesthetics are two medications that have significantly impacted the structure of the medical field and improved patient care. Both categories of drugs have distinct histories and applications. Corticosteroids are synthetic drugs that mimic the effects of natural steroid hormones produced by the adrenal glands. Corticosteroids possess potent anti-inflammatory properties and are widely used to manage autoimmune and anti-inflammatory conditions with a wide application in the trauma and orthopedics fields especially for the injectable corticosteroids. Local anesthetics block nerve impulses in a specific area of the body, thus preventing pain signals from being transmitted to the brain. Over the years, corticosteroids and local anesthetics have undergone significant advancements in terms of formulation, delivery methods, and safety profiles. They continue to play a crucial role in modern medicine, providing relief to patients and enabling various surgical and medical interventions with reduced pain and inflammation. Especially, injectable corticosteroids and local anesthetics can be effective in the management of a variety of musculoskeletal conditions including tendonitis, tenosynovitis, bursitis, and osteoarthritis. Multiple knee joint disorders are frequently addressed with corticosteroids with or without local anesthetics injection. The use of corticosteroids should be carefully considered and monitored by a healthcare professional. Patients should also be informed of the potential risks and benefits of these medications.
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Nα‐aroyl‐N‐aryl‐phenylalanine amides (AAPs) are RNA polymerase inhibitors with activity against Mycobacterium tuberculosis and non‐tuberculous mycobacteria. We observed that AAPs rapidly degrade in microsomal suspensions, suggesting that avoiding hepatic metabolism is critical for their effectiveness in vivo. As both amide bonds are potential metabolic weak points of the molecule, we synthesized 16 novel AAP analogs in which the amide bonds are shielded by methyl or fluoro substituents in close proximity. Some derivatives show improved microsomal stability, while being plasma‐stable and non‐cytotoxic. In parallel with the metabolic stability studies, the antimycobacterial activity of the AAPs against Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium avium and Mycobacterium intracellulare was determined. The stability data are discussed in relation to the antimycobacterial activity of the panel of compounds and reveal that the concept of steric shielding of the anilide groups by a fluoro substituent has the potential to improve the stability and bioavailability of AAPs.
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Australasian Anaesthesia (the Blue Book) is produced every two years, and contains a diverse range of topics of interest to anaesthetists, intensive care physicians and pain medicine specialists.
Article
Background: Local and regional anesthesia is associated with numerous clinical and institutional advantages relative to general anesthesia. As anesthesiologists and surgeons increasingly integrate local and regional anesthesia into their clinical practice, an understanding of the principles, evolution, and trends underpinning modern anesthetic techniques continues to be relevant. Methods: A review of the literature in databases Medline, PubMed, and EMBASE identified recent developments, ongoing trends, and historical milestones in upper-limb regional anesthesia. Results: Advances in regional anesthetic techniques in the last century have led to reduced postoperative pain, improved safety, and improved outcomes in upper-limb surgery. The development of ultrasound-guided techniques, as well as pharmacological advances in local anesthetic drugs and adjuncts, has further advanced the role of regional anesthesia. Wide-awake local anesthesia with no tourniquet has allowed certain procedures to be performed on select patients in outpatient and low-resource settings. Conclusions: This review provides an overview of local and regional anesthesia in the upper-limb from its historical origins to its contemporary applications in upper-limb surgery, particularly during the COVID-19 pandemic.
Article
AimTo compare the efficacy and onset of local anesthesia using buffered versus non-buffered 2% lidocaine with 1:100,000 adrenaline and 4% articaine with 1:100,000 adrenaline in dental extraction.MethodologyA prospective, clinical study was carried out in oral and maxillofacial surgery department. Twenty-eight patients were considered in the study and were divided into 4 groups. Each group randomly received either buffered 2% lidocaine with 1:100,000 adrenaline, non-buffered 2% lidocaine with 1:100,000 adrenaline, buffered 4% articaine with 1:100,000 adrenaline or non-buffered 4% articaine with 1:100,000 adrenaline. The outcome variable was onset of anesthesia and effectiveness of anesthesia in buffered and non-buffered group.ResultsResults showed that the mean onset of time and efficacy of local anesthesia was significantly better in buffered when compared with non-buffered local anesthetic solution with adrenaline.Conclusion In conclusion, the addition of sodium bicarbonate as a buffering agent decreases time of onset and increases the effectiveness of local anesthetics, thus providing comfort to the patient. The mean onset of time for first symptom as well as lip numbness was more for non-buffered lidocaine followed by non-buffered articaine, buffered lidocaine and buffered articaine. The mean onset of time for subjective and objective symptoms was more for non-buffered anesthetic solution as compared to buffered anesthetic solution. VAS readings were not statistically significant among the four groups.
Article
Cocaine is one of the oldest and most widely used illicit drugs in the world and is responsible for major worldwide medical and social problems. Drug addiction is a disease state where the body relies on a substance for normal functioning and develops a physical dependence leading to compulsive and repetitive use despite negative consequences to the user's health, mental state, or social life. The primary driver for the development of anti-cocaine vaccines has been the failure to develop effective pharmacological treatments to combat cocaine dependence. Despite several decades of research, no approved pharmacological treatments for cocaine dependence are available to assist addicts to overcome cocaine withdrawal or to prevent drug relapse. This Perspective highlights the challenges associated with anti-cocaine vaccines, including the current state of anti-cocaine vaccines and catalytic antibody research to aid in the fight against cocaine addiction.
Article
The topical route for local anaesthesia including ointments and creams can be easily washed off by wetting agents or with contact or movement. The goal and objective of the present study was to develop and formulate a transdermal patch for local anaesthesia. These patches were formulated by solvent casting method by the use of Hydroxypropyl Methylcellulose (HPMC) polymer, different enhancers, and vasoconstrictor which is the key ingredient for enhancing aesthetic activity. Formulated patches were evaluated for the physical and physicochemical parameters like moisture content, moisture uptake, folding endurance, water vapour permeability, drug content, and drug release, and in vivo study was done on rats. Amongst all the formulations, F7 was considered the ideal formulation which is the combination of HPMC polymer, polyoxyethylene 2-oleyl ether as an enhancer, and vasoconstrictor Tetrahydrozoline. For in vivo testing Tail flick method was applied and the effect of anaesthesia was maximum as compared to other formulations. In comparison to the control formulation, there was a 2.34-fold increase in aesthetic activity. When compared to the control formulation, the F7 formulation exhibited improved and longer efficacy. A transdermal bupivacaine patch incorporating a penetration enhancer and a vasoconstrictor could be created to improve the local cosmetic effects of bupivacaine.
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