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Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.
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Cannabinoides , Cannabis , Enfermedades Gastrointestinales , Alucinógenos , Humanos , Endocannabinoides , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Agonistas de Receptores de Cannabinoides , Enfermedades Gastrointestinales/tratamiento farmacológico , Desarrollo de Medicamentos , Dronabinol/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the influence of atipamezole on postoperative pain scores in cats. STUDY DESIGN: Controlled, randomized, masked clinical trial. ANIMALS: Twelve healthy female domestic cats. METHODS: Cats admitted for ovariohysterectomy (OVH) surgery were randomly allocated to group atipamezole (n = 6) or group saline (n = 6) and were premedicated with buprenorphine 20 µg kg(-1) intramuscularly (IM) and alfaxalone 3.0 mg kg(-1) subcutaneously (SC). Anaesthesia was induced with alfaxalone intravenously (IV) to effect and maintained with isoflurane in oxygen. Ten minutes after extubation, cats from group atipamezole received IM atipamezole (0.0375 mg kg(-1) ) whereas group saline received an equivalent volume [0.0075 mL kg(-1) (0.003 mL kg(-1) IM)] of 0.9% saline. A validated multidimensional composite scale was used to assess pain prior to premedication and postoperatively (20 minutes after extubation). If postoperative pain scores dictated, rescue analgesia consisting of buprenorphine and meloxicam were administered. Pain score comparisons were made between the two groups using a Mann-Whitney exact test. Results are reported as the median and range. RESULTS: Preoperatively, all cats scored 0. At the postoperative pain evaluation, the pain scores from group atipamezole [16 (range, 12-20)] were not significantly different from group saline [18 (range, 15-23)] (p = 0.28). All cats required rescue analgesia post-operatively. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole (0.0375 mg kg(-1) IM) administration did not significantly affect the postoperative pain scores in cats after OVH. Preoperative administration of buprenorphine (20 µg kg(-1) IM) did not provide adequate postoperative analgesia for feline OVH.
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Analgésicos Opioides/uso terapéutico , Buprenorfina/uso terapéutico , Histerectomía/veterinaria , Imidazoles/uso terapéutico , Ovariectomía/veterinaria , Dimensión del Dolor/veterinaria , Dolor Postoperatorio/veterinaria , Medicación Preanestésica/veterinaria , Analgesia Obstétrica/métodos , Analgesia Obstétrica/veterinaria , Animales , Gatos , Interacciones Farmacológicas , Femenino , Histerectomía/efectos adversos , Ovariectomía/efectos adversos , Dimensión del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Pregnanodionas/administración & dosificaciónRESUMEN
A 7-year-old castrated border collie dog was anesthetised for surgical resection of a hippocampal mass. Anesthesia was maintained using a previously unreported TIVA protocol for craniectomy consisting of alfaxalone and remifentanil. Recovery was uneventful, and the patient was discharged from hospital. We describe the anesthetic management of this case.
Protocol anesthésique associant alfaxalone et rémifentanil lors d'une résection d'une masse intracrânienne chez un border collie. Ce rapport de cas décrit la prise en charge anesthésique ainsi que le protocole d'anesthésie par perfusion intraveineuse utilisé lors d'une résection chirurgicale d'une masse hippocampale sur un border collie de 7 ans. La combinaison alfaxalone et rémifentanil, en tant qu'agents anesthésiques principaux, fut utilisée et le patient récupéra sans complication.(Traduit par Sébastien Bauquier).
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Anestésicos Intravenosos/administración & dosificación , Neoplasias Encefálicas/diagnóstico , Enfermedades de los Perros/cirugía , Perros/fisiología , Hipocampo , Animales , Neoplasias Encefálicas/cirugía , Craniectomía Descompresiva/veterinaria , Masculino , Piperidinas/administración & dosificación , Pregnanodionas/administración & dosificación , RemifentaniloRESUMEN
'Globesity' is a foremost challenge to the healthcare system. The limited efficacy and adverse effects of available oral pharmacotherapies pose a significant obstacle in the fight against obesity. The biology of the leading incretin hormone glucagon-like-peptide-1 (GLP-1) has been highly captivated during the last decade owing to its multisystemic pleiotropic clinical outcomes beyond inherent glucoregulatory action. That fostered a pharmaceutical interest in synthetic GLP-1 analogues to tackle type-2 diabetes (T2D), obesity and related complications. Besides, mechanistic insights on metabolic surgeries allude to an incretin-based hormonal combination strategy for weight loss that emerged as a forerunner for the discovery of injectable 'unimolecular poly-incretin-agonist' therapies. Physiologically, intestinal enteroendocrine L-cells (EECs) are the prominent endogenous source of GLP-1 peptide. Despite comprehending the potential of various G protein-coupled receptors (GPCRs) to stimulate endogenous GLP-1 secretion, decades of translational GPCR research have failed to yield regulatory-approved endogenous GLP-1 secretagogue oral therapy. Lately, a dual/poly-GPCR agonism strategy has emerged as an alternative approach to the traditional mono-GPCR concept. This review aims to gain a comprehensive understanding by revisiting the pharmacology of a few potential GPCR-based complementary avenues that have drawn attention to the design of orally active poly-GPCR agonist therapy. The merits, challenges and recent developments that may aid future poly-GPCR drug discovery are critically discussed. Subsequently, we project the mechanism-based therapeutic potential and limitations of oral poly-GPCR agonism strategy to augment intestinal GLP-1 for weight loss. We further extend our discussion to compare the poly-GPCR agonism approach over invasive surgical and injectable GLP-1-based regimens currently in clinical practice for obesity.
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Péptido 1 Similar al Glucagón , Incretinas , Humanos , Obesidad/tratamiento farmacológico , Receptores Acoplados a Proteínas G , Pérdida de Peso , PéptidosRESUMEN
The escalating global prevalence of type-2 diabetes (T2D) and obesity necessitates the development of novel oral medications. Agonism at G-protein coupled receptor-119 (GPR119) has been recognized for modulation of metabolic homeostasis in T2D, obesity, and fatty liver disease. However, off-target effects have impeded the advancement of synthetic GPR119 agonist drug candidates. Non-systemic, gut-restricted GPR119 agonism is suggested as an alternative strategy that may locally stimulate intestinal enteroendocrine cells (EEC) for incretin secretion, without the need for systemic drug availability, consequently alleviating conventional class-related side effects. Herein, we report the preclinical acute safety, efficacy, and pharmacokinetics (PK) of novel GPR119 agonist compounds ps297 and ps318 that potentially target gut EEC for incretin secretion. In a proof-of-efficacy study, both compounds demonstrated glucagon-like peptide-1 (GLP-1) secretion capability during glucose and mixed-meal tolerance tests in healthy mice. Furthermore, co-administration of sitagliptin with investigational compounds in diabetic db/db mice resulted in synergism, with GLP-1 concentrations rising by three-fold. Both ps297 and ps318 exhibited low gut permeability assessed in the in-vitro Caco-2 cell model. A single oral dose PK study conducted on healthy mice demonstrated poor systemic bioavailability of both agents. PK measures (mean ± SD) for compound ps297 (Cmax 23 ± 19â¯ng/mL, Tmax range 0.5 - 1â¯h, AUC0-24â¯h 19.6 ± 21â¯h*ng/mL) and ps318 (Cmax 75 ± 22â¯ng/mL, Tmax range 0.25 - 0.5â¯h, AUC0-24â¯h 35 ± 23â¯h*ng/mL) suggest poor oral absorption. Additionally, examinations of drug excretion patterns in mice revealed that around 25â¯% (ps297) and 4â¯% (ps318) of the drugs were excreted through faeces as an unchanged form, while negligible drug concentrations (<0.005â¯%) were excreted in the urine. These acute PK/PD assessments suggest the gut is a primary site of action for both agents. Toxicity assessments conducted in the zebrafish and healthy mice models confirmed the safety and tolerability of both compounds. Future chronic in-vivo studies in relevant disease models will be essential to confirm the long-term safety and efficacy of these novel compounds.
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Diabetes Mellitus Tipo 2 , Obesidad , Receptores Acoplados a Proteínas G , Animales , Humanos , Masculino , Ratones , Células CACO-2 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Células Enteroendocrinas/efectos de los fármacos , Células Enteroendocrinas/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/farmacología , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
AIMS: Patients with chronic health conditions not responding to conventional treatment can access medicinal cannabis (MC) prescriptions from clinicians in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, and depression in a large real-world sample of patients accessing prescribed medicinal cannabis. We hypothesized that all patient-reported outcomes (PROs) would improve from baseline to 3-months. METHODS: The QUEST Initiative is a large prospective multicenter study of patients with any chronic health condition newly prescribed medicinal cannabis between November 2020 and December 2021. Eligible patients were identified by 120 clinicians at medical centers across six Australian states. Consenting participants completed the EuroQol Group EQ-5D-5L health status questionnaire; European Organization for Research & Treatment of Cancer Quality of Life questionnaire (QLQ-C30); Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms in Fatigue and Sleep Disturbance, and the Depression Anxiety Stress Scale (DASS-21) before starting therapy, at 2-weeks titration, then monthly for 3-months. RESULTS: Of the 2762 consenting participants, 2327 completed baseline and at least one follow-up questionnaire. Ages ranged between 18-97 years (mean 51y; SD = 15.4), 62.8% were female. The most commonly treated conditions were chronic pain (n = 1598/2327; 68.7%), insomnia (n = 534/2327; 22.9%), generalized anxiety (n = 508/2327; 21.5%), and mixed anxiety and depression (n = 259/2327; 11%). Across the whole cohort both EQ-5D-5L utility scores and QLQ-C30 summary scores showed clinically meaningful improvement in HRQL from baseline to mean follow-up with d = 0.54 (95%CI:0.47 to 0.59) and d = 0.64 (95%CI:0.58 to 0.70) respectively; and clinically meaningful improvement in fatigue (d = 0.54; 95%CI:0.48 to 0.59). There was clinically meaningful reduction of pain for those with chronic pain (d = 0.65; 95%CI:0.57 to 0.72); significant improvements for those with moderate to extremely severe anxiety (X2 = 383; df = 4; p<0.001) and depression (X2 = 395; df = 4; p<0.001); and no changes in sleep disturbance. CONCLUSIONS: We observed statistically significant, clinically meaningful improvements in overall HRQL and fatigue over the first 3-months in patients with chronic health conditions accessing prescribed medical cannabis. Anxiety, depression, and pain also improved over time, particularly for those with corresponding health conditions. The study continues to follow-up patients until 12-months to determine whether improvements in PROs are maintained long-term. TRAIL REGISTRATION: Study registration - Australian New Zealand Clinical Trials Registry: ACTRN12621000063819. https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12621000063819.
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Dolor Crónico , Marihuana Medicinal , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Calidad de Vida , Australia/epidemiología , Dolor Crónico/tratamiento farmacológico , Marihuana Medicinal/uso terapéutico , Estudios de Seguimiento , Estudios Prospectivos , Fatiga/tratamiento farmacológicoRESUMEN
Fungi that are edible or fermentative were domesticated through selective cultivation of their desired traits. Domestication is often associated with inbreeding or selfing, which may fix traits other than those under selection, and causes an overall decrease in heterozygosity. A hallucinogenic mushroom, Psilocybe cubensis, was domesticated from its niche in livestock dung for production of psilocybin. It has caused accidental poisonings since the 1940s in Australia, which is a population hypothesized to be introduced from an unknown center of origin. We sequenced genomes of 38 isolates from Australia and compared them with 86 genomes of commercially available cultivars to determine (1) whether P. cubensis was introduced to Australia, and (2) how domestication has impacted commercial cultivars. Our analyses of genome-wide SNPs and single-copy orthologs showed that the Australian population is naturalized, having recovered its effective population size after a bottleneck when it was introduced, and it has maintained relatively high genetic diversity based on measures of nucleotide and allelic diversity. In contrast, domesticated cultivars generally have low effective population sizes and hallmarks of selfing and clonal propagation, including low genetic diversity, low heterozygosity, high linkage disequilibrium, and low allelic diversity of mating-compatibility genes. Analyses of kinship show that most cultivars are founded from related populations. Alleles in the psilocybin gene cluster are identical across most cultivars of P. cubensis with low diversity across coding sequence; however, unique allelic diversity in Australia and some cultivars may translate to differences in biosynthesis of psilocybin and its analogs.
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Alucinógenos , Psilocibina , Domesticación , Australia , Polimorfismo de Nucleótido Simple , Variación GenéticaRESUMEN
The endocannabinoid system (ECS) is an essential endogenous signaling system that may be involved in the pathophysiology of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS). Further research is required to understand the role of ECS in the development and maintenance of CWP and FMS. We provided the first systematic review and meta-analysis exploring the clinical relevance of ECS alterations in patients with CWP and FMS by comparing plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients and healthy controls. A systematic search was conducted to identify studies that measured plasma and/or interstitial levels of endocannabinoids and N-acylethanolamines in patients with CWP or FMS and healthy controls. A total of 8 studies were included for qualitative review, and 7 studies were included for meta-analysis. The findings identified increased plasma levels of oleoylethanolamide and stearoylethanolamide in patients with FMS compared with those in controls (P = 0.005 and P < 0.0001, respectively) and increased plasma levels of palmitoylethanolamide and interstitial levels of stearoylethanolamide in patients with CWP compared with those in controls (P = 0.05 and P = 0.001, respectively). There were no significant differences in other ECS parameters. Most studies did not account for variables that may influence ECS function, including cannabis use, concomitant medication, comorbidities, physical activity, stress levels, circadian rhythm, sleep quality, and dietary factors, suggesting that future studies should explore the correlation between these variables and endocannabinoid activity. We highlight the importance of investigating endocannabinoid activity in CWP and FMS because it will underpin future translational research in the area.
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PRACTICAL RELEVANCE: Increases in cat ownership worldwide mean more cats are requiring veterinary care. Illness, trauma and surgery can result in acute pain, and effective management of pain is required for optimal feline welfare (ie, physical health and mental wellbeing). Validated pain assessment tools are available and pain management plans for the individual patient should incorporate pharmacological and non-pharmacological therapy. Preventive and multimodal analgesia, including local anaesthesia, are important principles of pain management, and the choice of analgesic drugs should take into account the type, severity and duration of pain, presence of comorbidities and avoidance of adverse effects. Nursing care, environmental modifications and cat friendly handling are likewise pivotal to the pain management plan, as is a team approach, involving the cat carer. CLINICAL CHALLENGES: Pain has traditionally been under-recognised in cats. Pain assessment tools are not widely implemented, and signs of pain in this species may be subtle. The unique challenges of feline metabolism and comorbidities may lead to undertreatment of pain and the development of peripheral and central sensitisation. Lack of availability or experience with various analgesic drugs may compromise effective pain management. EVIDENCE BASE: These Guidelines have been created by a panel of experts and the International Society of Feline Medicine (ISFM) based on the available literature and the authors' experience. They are aimed at general practitioners to assist in the assessment, prevention and management of acute pain in feline patients, and to provide a practical guide to selection and dosing of effective analgesic agents.
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Dolor Agudo , Dolor Agudo/terapia , Dolor Agudo/veterinaria , Animales , Gatos , Manejo del Dolor/veterinariaRESUMEN
Introduction: Medicinal cannabis is prescribed in Australia for patients with chronic refractory pain conditions. However, measures of safety and effectiveness of different cannabinoids are lacking. We designed an observational study to capture effectiveness, adverse events (AEs), and health-related quality of life (HRQoL) measures in patients prescribed an oral medicinal cannabis formulation at Cannabis Access Clinics through the Cannabis Access Clinics Observational study (CACOS). Objectives: We aimed to evaluate effectiveness, reported AEs, and change in patient-reported outcomes in individuals prescribed a cannabinoid oil formulation for management of chronic pain. Methods: A cross-sectional analysis was conducted on patients prescribed an oil formulation of Δ9-tetrahydrocannabinol and cannabidiol for pain symptoms of at least 3-month duration. Clinician-reported AEs were organized by system, organ, class, and frequency. Analysis of patient-reported responses to a questionnaire was conducted using published minimal clinically important differences to determine meaningful change in HRQoL over time. Results: More than half (n = 91/151, 60.3%) of the participants experienced at least one AE during the observation period (mean 133 ± 116 days). No serious AEs were reported. Patient-reported pain impact scores were significantly reduced across the cohort (p = 0.034), and pain intensity scores verged on significance (p = 0.053). The majority of patients saw meaningful improvements in sleep (49.3%) and fatigue (35.6%). Conclusion: This analysis presents real-world data collected as part of standard of care. More than one-third of patients benefited from oral medicinal cannabis, which is impactful given the refractory nature of their pain. Amelioration of the impact of pain confirms continued prescribing of this formulation and validates our observational methodology as a tool to determine the therapeutic potency of medicinal cannabinoids.
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INTRODUCTION: This article reports the content validation of a Critical Appraisal Tool designed to Review the quality of Analgesia Studies (CATRAS) involving subjects incapable of self-reporting pain and provide guidance as to the strengths and weakness of findings. The CATRAS quality items encompass 3 domains: level of evidence, methodological soundness, and grading of the pain assessment tool. OBJECTIVES: To validate a critical appraisal tool for reviewing analgesia studies involving subjects incapable of self-reporting pain. METHODS: Content validation was achieved using Delphi methodology through panel consensus. A panel of 6 experts reviewed the CATRAS in 3 rounds and quantitatively rated the relevance of the instrument and each of its quality items to their respective domains. RESULTS: Content validation was achieved for each item of the CATRAS and the tool as a whole. Item-level content validity index and kappa coefficient were at least greater than 0.83 and 0.81, respectively, for all items except for one item in domain 2 that was later removed. Scale-level content validity index was 97% (excellent content validity). CONCLUSIONS: This 67-item critical appraisal tool may enable critical and quantitative assessment of the quality of individual analgesia trials involving subjects incapable of self-reporting pain for use in systematic reviews and meta-analysis studies.
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Objectives The aim of the study was to evaluate, in a controlled, randomised, masked clinical trial, the influence of administration rate of alfaxalone at induction on its relative potency in cats and to report the incidence of cardiorespiratory adverse effects. Methods Twelve healthy female domestic cats admitted for ovariohysterectomy were premedicated with buprenorphine 20 µg/kg intramuscularly and alfaxalone 3.0 mg/kg subcutaneously. Sedation scores were established (using a published scale ranging from 1 [no sedation] to 5 [profound sedation]) prior to anaesthesia induction with alfaxalone intravenously at 2 mg/kg/min (group A2; n = 6) or 0.5 mg/kg/min (group A0.5; n = 6) to effect until orotracheal intubation was achieved. Sedation scores and alfaxalone induction doses were compared between the groups, using a Mann-Whitney exact test. Results are reported as median and range. Presence of apnoea (no breathing for more than 30 s) or hypotension (mean arterial blood pressure <60 mmHg) within 5 mins postintubation was also reported. Results Although sedation scores (1.5 [range 1.0-3.0] and 2.5 [range 1.0-3.0] for A2 and A0.5, respectively) were not significantly different ( P = 0.32), cats in group A2 required significantly more alfaxalone (4.3 mg/kg [range 3.4-7.0 mg/kg]) than group A0.5 (2.1 mg/kg [range 1.5-2.5 mg/kg]) ( P = 0.002). Two cats in each group presented postinduction apnoea, and two cats in group A2 and three cats in group A0.5 presented postinduction hypotension. Conclusions and relevance The use of a slower induction infusion rate resulted in an increase in the alfaxalone relative potency without obvious cardiorespiratory benefit.
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Periodo de Recuperación de la Anestesia , Anestesia/veterinaria , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/cirugía , Pregnanodionas/administración & dosificación , Animales , Gatos , Femenino , Histerectomía/veterinaria , Ovariectomía/veterinaria , Proyectos Piloto , Respiración/efectos de los fármacos , Resultado del TratamientoRESUMEN
Objectives This was a randomised, blinded trial to investigate the influence of administration rate on the dose of propofol required for the orotracheal intubation of cats. Methods Twenty-four female domestic cats undergoing ovariohysterectomy were premedicated with oral tramadol (6 mg/kg) or intramuscular tramadol (4 mg/kg), and intramuscular dexmedetomidine (0.007 mg/kg). Oral or intramuscular (IM) tramadol was administered 60 or 30 mins prior to induction of anaesthesia, respectively. Dexmedetomidine was administered 30 mins prior to anaesthetic induction. Sedation scores were established prior to anaesthesia induction with propofol intravenously at 4 mg/kg/min (fast) or 1 mg/kg/min (slow) to effect until orotracheal intubation was achieved without coughing. If coughing occurred, the intubation process was paused for 15 s. Four groups were determined: IM tramadol/propofol fast (GIMF, n = 6); IM tramadol/propofol slow (GIMS, n = 6); oral tramadol/propofol fast (GOF, n = 6); oral tramadol/propofol slow (GOS, n = 6). The Shapiro-Wilk test was used to evaluate for normality of residuals. Sedation scores and propofol anaesthetic induction doses were compared between GIMF and GIMS groups, and between GOF and GOS groups using the Mann-Whitney test and the t-test, respectively ( P = 0.05). The presence of hypotension (mean arterial blood pressure <60 mmHg) or apnoea (no breathing for 30 s or more) within the first 15 mins postintubation was recorded. Results The median sedation scores for GIMF and GOF were not significantly different compared with those for GIMS ( P = 0.94) and GOS ( P = 0.70). However, the mean ± SD propofol anaesthetic induction doses were higher in GIMF (9.1 ± 1.8 mg/kg) and GOF (7.9 ± 1.7 mg/kg) than in GIMS (5.1 ± 1.5 mg/kg; P <0.01) and GOS (5.4 ± 0.3 mg/kg; P <0.01). No hypotension or apnoea were detected. Conclusions and relevance Using the slower anaesthetic induction rate resulted in an increase in propofol relative potency.
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Anestésicos Intravenosos/administración & dosificación , Gatos/fisiología , Propofol/administración & dosificación , Anestesia/veterinaria , Animales , Sedación Consciente/veterinaria , Femenino , Histerectomía/veterinaria , Masculino , Proyectos Piloto , Premedicación/veterinariaRESUMEN
Case summary This case report describes the clinical signs and treatment of an alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI. The cat was discharged from hospital following a prolonged recovery including obtunded mentation and cardiorespiratory depression for several hours following cessation of anaesthesia. The cat received supportive therapy that included supplemental oxygen via a face mask, intravenous crystalloid fluids and active rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its pharmacokinetics and previously reported lethal doses are discussed. Strategies for reducing the incidence of medication errors are presented. Relevance and novel information An unintentional overdose of alfaxalone by continuous rate infusion has not been reported previously in a cat. Treatment is supportive and directed towards maintenance of the cardiorespiratory systems. Whenever possible, smart pumps that have been designed to reduce human error should be used to help prevent medication errors associated with continuous rate infusions.
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Alfaxalone-2-hydroxpropyl-ß-cyclodextrin (alfaxalone-HPCD) was first marketed for veterinary use in Australia in 2001 and has since progressively became available throughout the world, including the USA, where in 2012 Food and Drug Administration (FDA) registration was granted. Despite the growing body of published works and increasing global availability of alfaxalone-HPCD, the accumulating evidence for its use in cats has not been thoroughly reviewed. The purpose of this review is: (1) to detail the pharmacokinetic properties of alfaxalone-HPCD in cats; (2) to assess the pharmacodynamic properties of alfaxalone-HPCD, including its cardiovascular, respiratory, central nervous system, neuromuscular, hepatic, renal, haematological, blood-biochemical, analgesic and endocrine effects; and (3) to consider the clinical application of alfaxalone-HPCD for sedation, induction and maintenance of anaesthesia in cats. Based on the published literature, alfaxalone-HPCD provides a good alternative to the existing intravenous anaesthetic options for healthy cats.
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Anestésicos Intravenosos/farmacología , Gatos/metabolismo , Oligosacáridos/farmacología , Pregnanodionas/farmacología , alfa-Ciclodextrinas/farmacología , Anestésicos Intravenosos/farmacocinética , Anestésicos Intravenosos/uso terapéutico , Animales , Oligosacáridos/farmacocinética , Oligosacáridos/uso terapéutico , Pregnanodionas/farmacocinética , Pregnanodionas/uso terapéutico , alfa-Ciclodextrinas/farmacocinética , alfa-Ciclodextrinas/uso terapéuticoRESUMEN
OBJECTIVE: To compare the analgesic effects of buprenorphine and butorphanol in domestic cats. DESIGN: 2-phase positive-controlled randomized masked clinical trial. ANIMALS: 39 healthy female cats (10 in phase 1 and 29 in phase 2). PROCEDURES: Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively. RESULTS: Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.
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Analgésicos Opioides/uso terapéutico , Buprenorfina/uso terapéutico , Butorfanol/uso terapéutico , Histerectomía/veterinaria , Ovariectomía/veterinaria , Periodo Perioperatorio/veterinaria , Analgésicos Opioides/administración & dosificación , Animales , Buprenorfina/administración & dosificación , Butorfanol/administración & dosificación , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Femenino , Histerectomía/efectos adversos , Ovariectomía/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/veterinariaRESUMEN
OBJECTIVE: To compare the perioperative analgesic effect between methadone and butorphanol in cats. DESIGN: Randomized controlled clinical trial. ANIMALS: 22 healthy female domestic cats. PROCEDURES: Cats admitted for ovariohysterectomy were allocated to a butorphanol group (n = 10) or methadone group (12) and premedicated with butorphanol (0.4 mg/kg [0.18 mg/lb], SC) or methadone (0.6 mg/kg [0.27 mg/lb], SC), respectively, in combination with acepromazine (0.02 mg/kg [0.01 mg/lb], SC). Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. A multidimensional composite scale was used to conduct pain assessments prior to premedication and 5, 20, 60, 120, 180, 240, 300, and 360 minutes after extubation or until rescue analgesia was given. Groups were compared to evaluate isoflurane requirement, propofol requirement, pain scores, and requirement for rescue analgesia. RESULTS: Propofol and isoflurane requirements and preoperative pain scores were not different between groups. During recovery, dysphoria prevented pain evaluation at 5 minutes. Pain scores at 20 minutes were significantly lower in the methadone group, and 6 of 10 cats in the butorphanol group received rescue analgesia, making subsequent pain score comparisons inapplicable. After 6 hours, only 3 of 12 cats in the methadone group had received rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: In the present study, methadone appeared to be a better postoperative analgesic than butorphanol and provided effective analgesia for 6 hours following ovariohysterectomy in most cats.