Role of ß-Caryophyllene in the Antinociceptive and Anti-Inflammatory Effects of Tagetes lucida Cav. Essential Oil.

Tagetes lucida Cav. (Asteraceae) is an ancient medicinal plant commonly used to alleviate pain. Nevertheless, scientific studies validating this property are lacking in the literature. Animal models of pain were used to evaluate the antinociceptive and anti-inflammatory activities of T. lucida essential oil (TLEO) and a bioactive metabolite. The chemical constitution and possible toxicity of the extract and the mechanism of action of ß-caryophyllene were also explored. Temporal course curves and dose-response graphics were generated using TLEO (0.1-10 mg/kg or 3.16-31.62 mg/kg) and ß-caryophyllene (3.16-10 mg/kg). Metamizole (80 mg/kg) and indomethacin (20 mg/kg) were used as reference drugs in the formalin assay and writhing test in rats and mice, respectively. The ß-caryophyllene mechanism of action was explored in the presence of naloxone (1 mg/kg), flumazenil (10 mg/kg), WAY100635 (0.16 mg/kg), or nitro-l-arginine methyl ester (L-NAME) (20 mg/kg) in the formalin test in rats. GC/MS analysis demonstrated the presence of geranyl acetate (49.89%), geraniol (7.92%), and ß-caryophyllene (6.27%). Significant and dose-dependent antinociceptive response was produced by TLEO and ß-caryophyllene without the presence of gastric damage. In conclusion, ß-caryophyllene was confirmed as a bioactive compound in the T. lucida analgesic properties by involving the participation of receptors like opioids, benzodiazepines, and Serotonin 1A receptor (5-HT1A), as well as nitric oxide.

Metamizole for Postoperative Pain in Pediatric Patients Undergoing Subarachnoid Anesthesia.

BACKGROUND: Efficient postoperative pain management, which is aimed at decreasing the risk of complications and drug-induced side effects, without affecting the quality of analgesia, is part of today's concept of enhanced recovery after surgery, that is, fast-track surgery. STUDY QUESTION: The objective of this study was to determine whether effective management of acute postoperative pain was possible without opioids, while avoiding complications, drug-induced side effects, and suboptimal treatment. Introduction of metamizole, which has regained popularity, into a multimodal analgesia regimen was used, as opioids are not routinely administered. STUDY DESIGN: The study was prospective, observational, unrandomized, and without the control group. MEASURES AND OUTCOMES: This study was performed in a pediatric hospital with 300 beds and an average of 1700 annual surgical interventions. The study group comprised 378 patients aged 1-17 years, undergoing lower abdominal or limb surgery between June 2016 and June 2017. Children underwent subarachnoid anesthesia combined with intravenous sedation and received not routinely but on demand postoperative opioid analgesia. The pain was self-assessed by the pediatric patient or was assessed by the nurse using pain scores. RESULTS: Metamizole proved to be safe, efficient, and very well tolerated by children. Multimodal analgesia using acetaminophen, nonsteroidal anti-inflammatory drug with metamizole for the treatment of moderate to severe pain in children undergoing surgery, required a single opioid dose in 292 patients (77.24%) of the 378 in this study. CONCLUSIONS: In pediatric patients undergoing surgery, subarachnoid anesthesia combined with intravenous sedation, multimodal analgesia that includes metamizole, and nonpharmacological complementary therapies in pain management enable avoidance or reduction of opioids to a single dose, without undertreatment. There is also a minimum of anesthesia, accelerated children's recovery and a rapid return to presurgical levels of function.

Comparative Analgesia Between Acupuncture and Dipyrone in Odontalgia.

The aim of this study was to assess whether the effectiveness of acupuncture is similar to the use of analgesics in the management of toothache. The research included 56 volunteers who were divided into 4 groups: Real Acupuncture group, Placebo Acupuncture group, Real Dipyrone group, and Placebo Dipyrone group. The interventions of the study were performed before the dental care. Inclusion criteria were toothache of pulpal origin with pain scale (Visual Analogue Scale) above 4, absence of medication for the pain, and aged over 18 years. The Real Acupuncture volunteers received a session of acupuncture using piercing needles, while volunteers from the Placebo Acupuncture group received an acupuncture session using non-piercing sham needles. Volunteers from the Real Dipyrone group received a dipyrone tablet and the Placebo Acupuncture group received a tablet with no active ingredient. Before any therapeutic intervention, we collected samples from the volunteers' saliva to analyze the salivary cortisol, the volunteers rated the intensity of their pain using VAS, and we measured their energy level by the Ryodoraku method. After 20 minutes of treatment, all the volunteers' analysis parameters were collected again. The Real Acupuncture group presented a greater reduction of VAS than the reduction obtained by the Real Dipyrone group (p<0.05). There was no statistically significant difference between the groups for the salivary cortisol and energy level variables. It can be concluded that acupuncture was more effective in reducing odontalgia than the dipyrone and that it can be an alternative for odontalgia management.

Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer.

BACKGROUND: Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl2 ), an adjuvant that blocks the NMDA receptor channel. METHODS: Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl2 (200 mg/kg), or the combination DIP-MgCl2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests. RESULTS: DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone. CONCLUSIONS: These results suggest that DIP-MgCl2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required. SIGNIFICANCE: This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered.

Metamizol Relieves Pain Without Interfering With Cerulein-Induced Acute Pancreatitis in Mice.

OBJECTIVES: Animal models are essential to understand the pathogenesis of acute pancreatitis (AP) and to develop new therapeutic strategies. Although it has been shown that cerulein-induced AP is associated with pain in experimental animals, most experiments are carried out without any pain-relieving treatment because researchers are apprehensive of an interference of the analgetic agent with AP-associated inflammation. In light of the growing ethical concerns and the legal tightening regarding animal welfare during experiments, this attitude should be changed. METHODS: Acute pancreatitis was induced by cerulein in the C57BL/6J and FVB/N mouse inbred strains. One group received vehicle only, and the other was treated with metamizol as analgetic agent. Pain sensation and parameters of AP were analyzed as well as the effect of metamizol in the pancreas and its actions in the brain. RESULTS: We report that oral administration of metamizol protects cerulein-treated mice from abdominal pain without influencing the clinical and histopathological course of the disease. In addition, it could be shown that metamizol reduces the central pain response. CONCLUSIONS: This study reveals that oral administered metamizol has no influence on the cerulein-induced AP and can be given as an analgesic to increase animal welfare in experiments with induced AP.

Effects of intravenous metamizole on ongoing and evoked activity of dura-sensitive thalamic neurons in rats.

Migraine and tension-type headache (TTH) are the most common forms of primary headaches. A general key mechanism underlying development of both the diseases is the trigeminal system activation associated with the ascending nociceptive transmission via the trigemino-thalamo-cortical pathway. The ventroposteromedial (VPM) nucleus is a key thalamic structure, receiving afferent inflow from the craniofacial region; it holds the third-order neurons responsible for conveying sensory information from the extra- and intracranial nociceptors to the cortex. The VPM is currently seen as a therapeutic target for various antimigraine medications, which is shown to reduce the VPM neuronal excitability. A non-opioid analgesic metamizole is widely used in some countries for acute treatment of migraine or TTH. However, the precise mechanisms underlying anticephalgic action of metamizole remain unclear. The objective of our study performed in the rat model of trigemino-durovascular nociception was to evaluate the effects of intravenously administered metamizole on ongoing and evoked firing of the dura-sensitive VPM neurons. The experiments were carried out on rats under urethane-chloralose anesthesia. Cumulative administration of metamizole (thrice-repeated intravenous infusion of 150 mg/kg performed 30 min apart) in 56% of cases produced a suppression of both the ongoing activity of the thalamic VPM neurons and their responses to dural electrical stimulation. Although the inhibitory effect was prevailing, a number of VPM neurons were indifferent to the administration of metamizole. These data suggest that one of the main components of neural mechanism underlying anticephalgic action of metamizole is suppression of the thalamo-cortical nociceptive transmission associated with trigemino-vascular activation.

Treatment of neuropathic pain with the capsaicin 8% patch: is pretreatment with lidocaine necessary?

The capsaicin 8% patch can effectively treat neuropathic pain, but application can cause discomfort or a burning sensation. Until March 2013, it was recommended that patients be pretreated with a topical anesthetic, for example lidocaine, before capsaicin patch application. However, speculation existed over the need for pretreatment and its effectiveness in alleviating treatment-associated discomfort. This article compares tolerability to and efficacy of the capsaicin patch in pretreated and non-pretreated patients. All patients received a single capsaicin patch application. Pretreated patients received a lidocaine plaster before and intravenous lidocaine and metamizole infusions during capsaicin patch application. Pain levels, assessed using a Numeric Rating Scale (NRS), were used to determine tolerability and efficacy. All patients (pretreated n = 32; non-pretreated n = 26) completed 100% of the intended capsaicin patch application duration. At the time of capsaicin patch removal, 69% of pretreated and 88% of non-pretreated patients reported an NRS score increase, which returned to baseline by 6 hours post-treatment. There was no significant difference in mean NRS score between patient groups at any time during or after capsaicin patch treatment. Response was similar between patient groups; capsaicin patch treatment provided rapid and significant pain reductions that were sustained over 12 weeks. The same proportion of pretreated and non-pretreated patients reported willingness to receive retreatment with the capsaicin patch. This analysis shows that the capsaicin 8% patch is generally tolerable, and the small discomfort associated with patch application is short-lived. Lidocaine pretreatment does not have a significant effect on tolerability, efficacy, or patient willingness to receive retreatment.

Síndrome de Kounis secundario a reacción alérgica a metamizol / Kounis syndrome secondary to an allergic reaction to metamizole

Durante las reacciones anafilácticas pueden ocurrir eventos cardiovasculares graves como el vasoespasmo coronario o el infarto agudo de miocardio. Esta causa de cardiopatía isquémica es conocida aunque poco frecuente. Presentamos el caso de un paciente que sufrió un episodio anginoso tras una reacción anafiláctica por la administración de metamizol, objetivándose en la coronariografía ausencia de lesiones significativas(AU)

Severe cardiovascular events, such as coronary vasospasm or acute myocardial infarction can occur during anaphylactic reactions. Although rare, this cause of ischaemic heart disease is known. We present the case of a patient who suffered an angina episode after an anaphylactic reaction due tot administering metamizole, with no significant lesions observed in the coronary catheterisation(AU)

Standardized antipyretic treatment in stroke: a pilot study.

BACKGROUND: Fever after acute cerebral injury is associated with unfavorable functional outcome and increased mortality, but there is controversy about the optimal antipyretic treatment. This study investigated an institutional standard operating procedure (SOP) for fever treatment in stroke patients including a sequence of pharmacologic and physical interventions. METHODS: A 4-step antipyretic SOP was established for patients with acute cerebral ischemia or hemorrhage and a body temperature ≥37.5°C within the first 6 days after admission. Data on the course of body temperature, duration of fever and achievement of normothermia were recorded. Results were compared to a historic control group that underwent conventional treatment. RESULTS: A total of 77 patients (mean age 70.4 ± 14.2 years) received 331 antipyretic interventions. Sequential administration of paracetamol (n = 219), metamizole (n = 71) and calf packing (n = 24) resulted in a significant drop in body temperature after 60 min in each instance. In 5 of 9 cases which were refractory to previous attempts, normothermia followed the infusion of ice-cooled saline. In more than 90% of cases treated per protocol, normothermia was achieved within 120 min. Compared to conventional treatment, fever burden was significantly lower within the first 4 days after admission (p < 0.001). CONCLUSION: This SOP may help to optimize antipyretic treatment for stroke patients.

Postoperative and preincisional electrical nerve stimulation TENS reduce postoperative opioid requirement after major spinal surgery.

BACKGROUND AND OBJECTIVE: Preincisional and postoperative transcutaneous electrical nerve stimulation (TENS) administration reduces postoperative opioid demand in abdominal surgery. Aim of this study was to find out whether a comparable effect of TENS applies in major spinal surgery. METHODS: Thirty-eight patients of both sex scheduled for lumbar interbody fusion were enrolled and divided randomly into 3 groups. Group A received TENS preincisional and postoperative, group B received this treatment postoperative only, and group C was the sham controlled. The postoperative demand on piritramid to achieve a visual anlog scale pain score <3 was delivered either by nurse or by a patient-controlled analgesia pump, when the patients were alert. The setting of the patient-controlled analgesia pump, bolus of piritramid 2 mg intravenously (IV), lockout time of 20 minutes, and maximum dose of piritramid 15 mg within 4 hours, the coanalgesic therapy diclofenac 75 mg IV, and the rescue medication metamizol 1 g IV was identical for all patients. The total amount of piritramid administered over the first 24 hours after surgery and an optional rescue medication were recorded. RESULTS: All groups were compared by pairs. The postoperative demand on piritramid differed significantly A versus B (P<0.05), A versus C (P<0.05), and B versus C (P<0.05). Neither sex, body mass index, current, duration, and type of operation nor the occurrence of hypotensive phases showed any significant association with postoperative piritramid demand. The necessity of rescue medication was significantly higher in group C than in group A. CONCLUSIONS: Postoperative TENS as well as the combination of preincisional and postoperative TENS therapy reduce the postoperative demand of piritramid in major spinal surgery in a safe and simple way free of systemic side effects.

Potenciais interações medicamentosas em prescrições de um hospital-escola de Porto Alegre / Potential drug interactions among prescriptions of a teaching hospital in Porto Alegre

Introdução: Relatos das prevalências de interações medicamentosas em hospitais brasileiros são escassos. Objetivos: Descrever a prevalência de interações medicamentosas potenciais entre os fármacos prescritos nas enfermarias clínicas e cirúrgicas de um hospital-escola. secundariamente, descrever as características dessas interações e relacionar a sua ocorrência com o número de medicamentos prescritos e a idade dos pacientes. Pacientes e Métodos: Os dados foram coletados durante uma semana de out/2007, de 2a a 6a feira, a partir da última ficha de prescrição encontrada nos prontuários, envolvendo 128 fichas de prescrição com 10,5±4,1 fármacos. Os pacientes tinham 58,6±16,9 anos e 51,2% eram homens. A doença cardiovascular foi a enfermidade principal (23,4%) e a comorbidade (42,5%) mais frequentemente encontrada. A análise das interações foi feita através de consulta a um sistema interativo (Micromedex®). Resultados: 485 interações foram encontradas, estando presentes em 79,7% (IC95%: 72,6-86,8) das fichas de prescrição (média 3,8). A interação mais frequente foi captopril/dipirona (9,7%), seguida por dipirona/furosemida (4,5%), e os fármacos mais envolvidos foram dipirona (29,3%) e captopril (21,2%). A maioria das interações tinha mecanismo farmacodinâmico (65,5%), gravidade moderada (55,5%), começo tardio (61,3%) e bom embasamento científico (71,1%). A prevalência de interações esteve associada fortemente com o número de fármacos prescritos (r=0,65, p<0,001) e fracamente com a idade do paciente.

Introduction: Reports of the prevalence of drug interactions in Brazilian hospitals are scarce. Aims: To describe the prevalence of potential drug interactions among the medical drugs prescribed in the clinical and surgical units of a teaching hospital. Secondarily, to describe the characteristics of drug interactions and relate their occurrence to the number of prescribed medications and patient age. Patients and Methods: The data were collected from Monday to Friday of a week in Oct 2007, starting from the last prescription form found in the medical charts, and involved 128 prescription forms with 10.5±4.1 drugs. The patients’ mean age was 58.6±16.9 years and 51.2% were males. Cardiovascular disease was the main disease (23.4%) and the most frequently found comorbidity (42.5%). The analysis of interactions was done through consultation with an interactive system (Micromedex®). Results: 485 cases of drug interactions were found, being present in 79.7% (CI95%: 72.686.8) of the prescription forms (mean 3.8). The most frequent interaction was captopril/dipyrone (9.7%), followed by ipyrone/furosemide (4,5%), and the most frequently involved drugs were dipyrone (29.3%) and captopril (21.2%). Most of the interactions had a pharmacodynamic mechanism (65.5%), moderate severity (55.5%), late onset (61.3%), and a good scientific basis (71.1%). The prevalence of interactions was strongly associated with the number of drugs prescribed (r=0.65, p<0.001) and weakly associated with patient age.

A population-based case-control teratologic study of oral dipyrone treatment during pregnancy.

OBJECTIVE: To study the possible human teratogenic effect of oral dipyrone, an antipyretic and analgesic drug treatment during pregnancy. DESIGN AND SETTING: The analysis of cases with different congenital abnormalities and their matched population controls without congenital abnormalities, in addition to a comparison between cases and malformation controls (Down's syndrome) in the population-based, large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. STUDY PARTICIPANTS: 22 843 neonates or fetuses with congenital abnormalities (cases), 38 151 matched newborns without congenital abnormalities (population controls) and 834 neonates or fetuses with Down's syndrome (malformation controls). MAIN OUTCOME MEASURES: 25 congenital abnormality groups. RESULTS: 1382 (6%) cases, 1911 (5%) population controls and 74 (8.9%) malformation controls were born to mothers treated with dipyrone during pregnancy. The case-matched population control analysis showed a higher rate of diaphragmatic defect (adjusted prevalence odds ratio [POR] 2.7; 95% CI 1.0, 6.8), cardiovascular malformations (POR 1.3; 95% CI 1.0, 1.7) and other isolated congenital abnormalities (POR 1.8; 95% CI 1.1, 2.9) after oral dipyrone treatment during the second and third months of gestation, i.e. in the critical period for most major congenital abnormalities. However, the evaluation of only medically recorded dipyrone use did not confirm these possible associations. The comparison of dipyrone treatment between 25 congenital abnormalities groups and malformation controls as the referent group also did not show any difference in the dipyrone use during the second and third months of gestation. CONCLUSIONS: The higher occurrence of dipyrone treatment in the case mothers compared with population control mothers can be explained by recall bias and/or chance. However, the higher rate of diaphragmatic congenital abnormalities can be considered as a signal and merits further investigation.

[Postoperative pain therapy after tonsillectomy in children. An observational study for 7 days]. / Postoperative Schmerztherapie nach Tonsillektomie im Kindesalter. Eine Verlaufsbeobachtung über 7 Tage.

OBJECTIVE: We investigated the efficacy and side-effects of a concept for pain therapy after tonsillectomy in children. PATIENTS AND METHODS: A total of 100 children aged between 6 and 14 years were treated according to the following protocol for pain therapy after tonsillectomy: after induction of anaesthesia the children received 35-40 mg/kg acetaminophen rectally and 0.1 mg/kg piritramide i.v.. Additionally, boluses of 0.05 mg/kg pitritramide i.v. were allowed in the recovery room and 2 doses of 20 mg/kg acetaminophen were given rectally every 6 h on the day of surgery. On the following day the children received 30 mg/kg acetaminophen 3 times per day and from the second postoperative day onwards 1 mg/kg diclofenac was given 3 times a day. The rescue therapy was 5 mg/kg metamizol orally. The severity of the postoperative pain was evaluated by a visual pain scale (VAS) (0-100), side-effects such as vomiting and postoperative haemorrhage were documented. The Friedman test was used for testing the time course of pain intensity. RESULTS: The median of the VAS was 42 on the day of surgery, 35 on the first postoperative day and fell continuously to 10 by the 6th postoperative day. The decrease of pain severity was statistically significant (p <0.05). A rescue therapy was necessary in 6 patients on the day of surgery and in 9 patients on the first postoperative day. 7 patients suffered a postoperative haemorrhage, 4 out of the 7 needed a surgical revision and 2 out of 100 patients vomited. CONCLUSION: We conclude that this protocol for pain therapy after tonsillectomy was effective. The incidence of postoperative haemorrhage and vomiting was low.

Extrapleural regional versus systemic analgesia for relieving postthoracotomy pain: a clinical study of bupivacaine compared with metamizol.

BACKGROUND: The effects of a local anesthetic delivered through a catheter inserted in the extrapleural region by a surgeon and an analgesic agent given systemically on pain after thoracotomy were assessed. METHODS: The patients in group I (n = 25) had a catheter inserted between the parietal pleura and the endothoracic fascia by a surgeon, and 0.5% bupivacaine was given through this catheter. Another 25 patients (group II) had metamizol given intravenously. Respiratory function tests, arterial blood gases, range of shoulder motion, and postoperative pain were evaluated for each group. Bupivacaine and metamizol were given just before finishing the thoracotomy and then repeated every 4 hours for 3 days. RESULTS: There was no statistical difference in arterial blood gases between the groups (P >.05). There were statistically significant differences in the respiratory function tests, range of shoulder motion, and visual analogue scale (P <.05) between the groups. Group I had fewer complications than group II. There was no mortality in either group. CONCLUSIONS: Bupivacaine given through a catheter to the extrapleural region before finishing thoracotomy is substantially beneficial for the prevention of postoperative pain and reduction of postoperative complications.

[Combined premedication at adenectomy in children]. / Kombinirovannaia premedikatsiia pri adenotomii u detei.

Adenoid vegetation is a frequent pathology in children, and adenotomy (AT) is the only method of its treatment. The problem of anesthesia at AT has always remained an acute one: the risk of general anesthesia exceeds manifold the risk of intervention itself. At the same time, the local anesthesia is not always an method, therefore, the authors put the goal to improve it through potentiating. A total of 180 children, aged 3 to 14, were divided into several groups; anesthesia at AT was implemented according to the below described methods and with regard for the age-related doses of preparations: Group 1--a 2% lydocain solution administered endonasally (e/n); Group 2--lydocain plus diazepam solution administered e/n; Group 3--same preparations and 50% metamizol solution administered e/n; Group 4--lydocain, metamizol e/n, and diazepam administered transbuccally, i.e. chewing gum; Group 5--a 4% articain solution and metamizol e/n plus diazepam administered transbuccally; Group 6--the same technique after a preliminary administration of lydocain; Group 7--clonidine, administered transbuccally, was added. The adequacy of anesthesia was evaluated by using the parameters of the vegetative nervous system and hemodynamics. It was demonstrated that the administration of lydocain alone leads to a sharp activation of the sympathoadrenal system; metamizol and diazepam, especially when administered transbuccally, contribute to an enhanced efficiency of anesthesia, while the endonasal administration of articain and metamizol, after a preliminary introduction of lydocain, combined with the transbuccal administration of diazepam and clonidine is the most optimal variant, however, this method can not be acknowledged as an ideal one and needs further improvement.

Tratamiento del dolor postoperatorio con pca en cirugía del abdomen superior: estudio comparativo, tramadol versus metamizol y ketorolaco / Management of postoperative pain with PCA in upper abdominal surgery. Comparative study: trama dol versus metamizol and ketorolac

El objetivo de nuestro estudio fue realizar un análisis comparativo de la eficacia analgésica postoperatoria de tres fármacos: Tramadol, Ketorolaco y Metamizol, empleando la técnica de PCA más infusión contínua en pacientes sometidos a cirugía de abdomen superior. Para ello sometimos a 100 pacientes divididos en tres grupos: Tramadol (32); Ketorolaco (37) y Metamizol (31), a un estudio aleatorizado y a doble ciego donde analizamos distintas variables: valoración del dolor en la Escala Verbal Compuesta (EVC), y en la escala Analógica Visual (EAV), estado de Sedación, variables hemodinámicas, respiratorias y endocrino-metabólicas, así como los posibles efectos secundarios.Material y métodos: El dolor postoperatorio puede producir modificaciones a distintos niveles pudiendo éstas ayudarnos a valorar de una manera más objetiva el dolor. Nosotros hemos estudiado estos cambios a nivel respiratorio, hemodinámico y endocrinometabólico para, así, ayudarnos a determinar conjuntamente, con la Escala Verbal Compuesta (EVC), cual es el fármaco que presenta mejor comportamiento analgésico en el postoperatorio de estos pacientes.Resultados: Los resultados del estudio demuestran que la eficacia analgésica de Tramadol es superior a la de Ketorolaco y Metamizol tanto en la valoración del dolor en la Escala Ve r bal Compuesta (EVC) como en el número de abandonos por falta de analgesia.Conclusiones: No encontramos diferencias valorables en el resto de variables analizadas como sedación, parámetros de función respiratoria, hemodinámicos, endocrino-metabólicos ni tampoco en el apartado de los efectos secundarios (AU)

[Differential indications of non-opioid drugs for postoperative analgesia II. Quantification of the analgesic effect of a combination of metamizol plus diclofenac via patient-controlled analgesia]. / Untersuchungen zum differenzierten Einsatz von Nichtopioiden zur postoperativen Analgesie II. Quantifizierung des analgetischen Effektes der Kombination von Metamizol plus Diclofenac mittels der patientenkontrollierten Analgesie.

OBJECTIVE: In a previous study we investigated the analgesic efficacy of metamizol. After laparoscopic operations, in particular, the reduction of postoperative opioid requirements within the first 24 h after surgery attained clinical relevance (-67%). In the present study we investigated the analgesic efficacy of supplementary diclofenac. METHODS: 86 patients, scheduled for minor orthopaedic surgery, laparoscopic cholecystectomy or resection of the thyroid gland, participated in a doubleblind, randomised, placebo-controlled study. The setting was comparable to our previous study, apart from the supplementary administration of diclofenac. Before induction of anaesthesia, verum-treated patients received a diclofenac suppository (100 mg), in addition to metamizol (1 g/100 ml NaCl 0.9% intravenous over 15 min). These infusions were repeated at 6h and 12h. In addition to the third infusion, the patients received a further diclofenac suppository (100 mg). Cumulated doses of buprenorphine (PCA, patient-controlled analgesia), pain scores (0-10), blood pressure, pulse and side effects were recorded during the first 6 h and again at 24 h. RESULTS: All verum-treated patients had significantly less pain immediately after surgery and required lower cumulated doses of buprenorphine during the first 24 h after operation (laparoscopic cholecystectomy -33%, minor orthopaedic surgery -73%, resection of thyroid gland -60%). CONCLUSIONS: Combination of metamizol and diclofenac cause a clinically relevant reduction in opioid requirements, in particular after minor orthopaedic surgery and resection of the thyroid gland. There is no need for supplementary diclofenac following laparoscopic surgery.

Analgesic effect of Irvingia gabonensis stem bark extract.

Irvingia gabonensis is used medicinally in most parts of tropical Africa for the treatment of a number of ailments. In West Africa the Mende tribe of Sierra Leone uses the stem bark to relieve pain. In order to establish a pharmacological rationale for the traditional use of this plant as a remedy for pain, the water and ethanol extracts of the powdered stem bark were screened for analgesic activity and compared with standard analgesic drugs. The water extract and morphine protected the mice from heat-induced pain. In contrast, the ethanol extract and metamizole sodium showed very low level of analgesic activity in this test. However, using tail pressure as a source of pain, the water and ethanol extracts, metamizole sodium and morphine offered protection to the mice against pain stimuli. Morphine and the water extract were more potent as analgesic agents in heat than non-heat pain test. The analgesic effects of the water extract and morphine were blocked by a non-selective opioid receptor antagonist, naloxone in both tests, whereas the analgesic effects of the ethanol extract and metamizole sodium were not antagonized by the same dose of the opioid antagonist. The data presented in this study suggest that the active principle(s) in the water extract has analgesic profile similar to that of the narcotic analgesic and the ethanol extract might contain compound(s) that behave like non-narcotic analgesic agent. These findings provide for the first time the pharmacological basis for the folkloric use of Irvingia gabonensis in the relief of pain.

[Anthocyanins and analgesics or a possibility of a new analgetic combination]. / Antotsiani i analgetitsi ili edna vuzmozhnost za nova analgetichna kombinatsiia.

Studies were carried out on male white mice to investigate the influence of cantocyans on pain both singly and in combination with the classic analgetics. The following tests were used: the test for narcotic analgetics "hot plate" and the analgetic morphine, administered subcutaneously in sub- and nonanalgetic doses (10 and 5 mg/kg of body mass respectively); the test for nonnarcotic analgetics-chemical peritoneal stimulation with 3% of acetic acid and the analgetic analgin, administered subcutaneously in a nonanalgetic dose (100 mg/kg of body mass). The results from the experiments showed that antocyans did not possess its own analgetic effect in both of the experimental models. However their combination with morphine and analgin, administered in noneffective analgetic doses, caused manifested analgetic effect of the combinations in all used doses of antocyans (50, 100 and 200 mg/kg of body mass). The possibility for therapeutic usage of analgetic combinations of antocyans and narcotic and nonnarcotic analgetics is discussed.