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The swine industry is often forced to euthanize pigs in the first few weeks of life due to injuries, hernias, or unthriftiness. The majority of pigs are euthanized using carbon dioxide (CO2) gas asphyxiation but concerns as to the humaneness of CO2 are increasing. This study compared the euthanasia of weaned pigs using N2O (N2O, n = 9) or CO2 (n = 9), at 50% and 25% min&minus, 1 exchange rate, respectively. In addition, we administered an analgesic prior to euthanasia with CO2 (CO2B) exposure as a third treatment (n = 9) to elucidate behaviors indicative of pain. Pigs in the CO2 and N2O treatments lost posture at similar times (latency of 145.0 &plusmn, 17.3 and 162.6 &plusmn, 7.0 s respectively, p &gt, 0.10), while the CO2B treatment pigs lost posture the soonest (101.2 &plusmn, 4.7 s, p &lt, 0.01). The pigs in the CO2B treatment made more escape attempts than the CO2 or N2O pigs (16.4 &plusmn, 4.2, 4.7 &plusmn, 1.6, 0.3 &plusmn, 0.2, respectively, p &lt, 0.0004). However, pigs in N2O squealed more often than either the CO2 or CO2B pigs (9.0 &plusmn, 1.6, 2.8 &plusmn, 1.2, 1.3 &plusmn, 0.6, respectively, p &lt, 0.001). Given the similar time to loss of posture and shorter time displaying open mouth breathing, N2O may cause less stress to pigs, however, the greater number of squeals performed by these pigs suggests the opposite. It was not apparent that any behavior measured was indicative of pain. In conclusion, N2O applied at a 50% min&minus, 1 flow rate can be an alternative to CO2 for pig euthanasia.

Objective: Change Pain Latin America (CPLA) was created to enhance chronic pain understanding and develop pain management improving strategies in this region. During its seventh meeting (August 2016), the main objective was to discuss tramadol’s role in treating pain in Latin America. Furthermore, potential pain management consequences were considered, if tramadol was to become more stringently controlled. Methods: Key topics discussed were: main indications for prescribing tramadol, its pharmacological characteristics, safety and tolerability, effects of restrictions on its availability and use, and consequent impact on pain care quality. Results: The experts agreed that tramadol is used to treat a wide spectrum of non-oncological pain conditions (e.g. post-surgical, musculoskeletal, post-traumatic, neuropathic, fibromyalgia), as well as cancer pain. Its relevance when treating special patient groups (e.g. the elderly) is recognized. The main reasons for tramadol’s high significance as a treatment option are: its broad efficacy, an inconspicuous safety profile and its availability, considering that access to strong analgesics–mainly controlled drugs (classical opioids)–is highly restricted in some countries. The CPLA also agreed that tramadol is well tolerated, without the safety issues associated with long-term nonsteroidal anti-inflammatory drug (NSAID) use, with fewer opioid-like side effects than classical opioids and lower abuse risk. Conclusions: In Latin America, tramadol is a valuable and frequently used medication for treating moderate to severe pain. More stringent regulations would have significant impact on its availability, especially for outpatients. This could cause regression to older and frequently inadequate pain management methods, resulting in unnecessary suffering for many Latin American patients. © 2017 Informa UK Limited, trading as Taylor and Francis Group.

Aims: This study aimed to determine the occurrence of adverse drug reactions (ADRs) that caused admission to the intensive care unit (ICU) of a university hospital. Methods: Clinical records were reviewed for patients meeting the inclusion criteria who were admitted to the ICU between September and December 2012. Suspected cases of ADRs were documented. Nine researchers later evaluated causality using the Naranjo Algorithm, preventability using the Schumock and Thornton criteria, and clinical classification based on the dose–time–susceptibility system. Results: In total, 96 patients presented 108 cases of ADR (13.8%, 95% confidence interval 11.2–16.4%) as the cause of admission. The most frequent ADRs were bradyarrhythmias and upper gastrointestinal bleeding (12%). Therapeutic failure accounted for 20%. The most commonly associated medications were acetylsalicylic acid (16%) and losartan (10%). Forty-six cases were categorized as possible, and only one as definite. According to the dose–time–susceptibility classification, in 82% of the cases, the dosage was collateral (within the therapeutic range), and 90% were independent of time; the factors most associated with susceptibility to ADRs were comorbidities (42%) and age (49%). Forty-four percent of the ADRs were considered possibly preventable. Conclusions: ADRs contribute significantly to ICU admissions, and a significant number of ADRs are preventable. National studies are needed to assess their incidence and to establish classification standards to reduce their clinical impact. © 2016 The British Pharmacological Society

JUSTIFICATIVA E OBJETIVOS: O tratamento da dor envolve a utilização de analgésicos opioides, analgésicos comuns, anti-inflamatórios não hormonais (AINH's) e analgésicos adjuvantes. Tradicionalmente, estes fármacos são administrados por via sistêmica ou no neuroeixo. Entretanto, quando aplicados por estas vias, estão associados a efeitos colaterais importantes, os quais podem inviabilizar o seu uso. A administração tópica de analgésicos é uma alternativa. O objetivo deste trabalho é discutir os analgésicos tópicos, seus mecanismos de ação e eficácia clínica. CONTEÚDO: Trata-se de um trabalho de revisão que aborda a utilização tópica de anestésicos locais, capsaicina, clonidina, antidepressivos tricíclicos, cetamina, opioides e canabinoides, discutindo o seu mecanismo de ação e a sua eficácia. CONCLUSÕES: Os analgésicos tópicos são promissores como estratégia para o tratamento da dor, já que estão associados à menor incidência de efeitos colaterais. O benefício dos anestésicos locais, dos AINH's e da capsaicina está bem estabelecido, entretanto, a eficácia de clonidina, antidepressivos tricíclicos, cetamina, opioides e canabinoides ainda é questionável. Trabalhos demonstram que a abordagem multimodal é uma alternativa, porém estudos são necessários para confirmar esta hipótese. BACKGROUND AND OBJECTIVES: Pain treatment involves the usage of common and opioid analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and adjuvant analgesics. Traditionally, these drugs are administered systemically or into the neuraxis. However, when analgesics are applied through these pathways, they are associated with significant side effects, which can hinder its use. Topical administration of analgesics is an alternative. The objective of this paper is to discuss topical analgesics, the mechanisms of action and clinical efficacy. CONTENT: This is a review paper addressing the usage of the topical local anesthetics: capsaicin, clonidine, tricyclic antidepressants, ketamine, opioids and cannabinoids, discussing mechanism of action and effectiveness. CONCLUSIONS: Topical analgesics are promising as a strategy for pain treatment, as they are associated with lower incidence of side effects. The benefit of local anesthetics, NSAID's and capsaicin is well established. However, the efficacy of clonidine, tricyclic antidepressants, ketamine, opioids and cannabinoids is still questionable. Studies have shown that the multimodal approach is an alternative, but studies are needed to confirm this hypothesis. JUSTIFICATIVA Y OBJETIVOS: El tratamiento del dolor involucra la utilización de analgésicos opioides, analgésicos comunes, antiinflamatorios no hormonales (AINH's) y analgésicos adyuvantes. Tradicionalmente, esos fármacos son administrados por vía sistémica o en el neuro eje. Sin embargo, cuando se aplican por esas vías, están asociados a los efectos colaterales importantes, los cuales pueden impedir su uso. La administración tópica de analgésicos es una alternativa. El objetivo de este trabajo es discutir los analgésicos tópicos, sus mecanismos de acción y la eficacia clínica. CONTENIDO: Se trata de un trabajo de revisión que aborda la utilización tópica de anestésicos locales, capsaicina, clonidina, antidepresivos tricíclicos, cetamina, opioides y canabinoides, discutiendo su mecanismo de acción y su eficacia. CONCLUSIONES: Los analgésicos tópicos son promisorios como una estrategia para el tratamiento del dolor, ya que están asociados con una menor incidencia de efectos colaterales. El beneficio de los anestésicos locales, de los AINH's y de la capsaicina está muy bien establecido, sin embargo, la eficacia de la clonidina, los antidepresivos tricíclicos, cetamina, opioides y canabinoides, todavía es cuestionable. Algunos trabajos demuestran que el abordaje multimodal es una alternativa, pero más estudios son necesarios para poder confirmar esa hipótesis.

Item does not contain fulltext Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).

Alcohol intoxication is extremely rare in the neonatal period. Clinical presentation may be occurred by lethargy, tremor, mild fever, hypoglycemia, hypotonia, respiratory depression and coma. Intoxication usually appears as giving the baby alcohol with neglect of family or accident. The basic principle of therapy is support therapy and provision of clinical stabilization of the baby the elimination of alcohol from the body until it does. When the drops of 70% ethyl alcohol that her mother thought the gas drops unintentional was dripped to baby's mouth, lid of drug cover was opened and poured abundantly. Afterward, a 25 days old female case was presented to our hospital emergency service. Her physical examination was normal, serum ethyl alcohol level was 3.12 mg/dl (0.12 per mil). This case, that was provided clinical stabilization and applied only supportive therapy, was discharged four days later. In this report, we wanted to emphasize that family and/or caregivers should be well-trained drug administration in neonates. © The Journal of Current Pediatrics, published by Galenos Publishing.

The role of nitric oxide (NO) as a signalling molecule involved in many pathophysiological processes (e.g., smooth muscle relaxation, inflammation, neurotransmission, apoptosis) has been elaborated during the last decade. Since NO has also been found to inhibit cellular respiration, we review here the available information on the interactions of NO with cytochrome c oxidase (COX), the terminal enzyme of the respiratory chain. The effect of NO on cellular respiration is first summarized to present essential evidence for the fact that NO is a potent reversible inhibitor of in vivo O2 consumption. This information is then correlated with available experimental evidence on the reactions of NO with purified COX. Finally, since COX has been proposed to catalyze the degradation of NO into either nitrous oxide (N2O) or nitrite, we consider the putative role of this enzyme in the catabolism of NO in vivo.

Objective: The rate of polypharmacy is increasing in patients with psychotic disorders. Polypharmacy is defined as the concomitant use of two or more drugs at a time. As most psychotropic medications are metabolized via the cytochrome enzyme system, it is easy to predict that polypharmacy will increase the risk of drug-drug interactions. This study was planned to evaluate the interaction risks of medications used by patients with a diagnosis of schizophrenia and schizoaffective disorder., Method: This study enrolled inpatients and outpatients of 18-65 years of age, diagnosed with schizophrenia or schizoaffective disorder according to the DSM-IV classification, who had been receiving antipsychotics for at least 12 weeks. Co-administration of antipsychotic and other psychotropic drugs for at least 4 weeks was recorded as polypharmacy. The risk of interaction was determined as follows: all medications one patient was using were sent to the internet site https://drugs.com as individual treatment regimens, and interaction information for healthcare specialists was used., Results: The study sample consisted of 240 patients (141 males; 58.8%; 99 females; 41.2%) in total, with the schizophrenia spectrum of diseases (schizophrenia, schizoaffective disorder). One hundred and thirty six (56.6%) patients used only one antipsychotic and 104 (43.4%) patients used 2 or more antipsychotics. The mean number of medications was 2.58±1.22 (min 1-max 6), the mean number of interactions was 1.90±2.04 (min 1-max 10). One hundred and seventy two (71.7%) patients were taking medications with a risk of interaction, with 417 total drug interaction risks. Of the interaction risks, 87.8% (total number 366) were at a moderate level. Approximately one quarter of the patients (n=42, 24.4%) were using medications with a major risk, and two patients (1.2%) were taking drugs with a minor risk of interaction. Among probable outcomes of drug interactions, the first 3 places were occupied by a risk of anticholinergic side effects, a risk of CNS or respiratory depression and a risk of QT prolongation., Conclusion: The present study reports that an important percentage of patients are exposed to drug-drug interactions with ever-increasing use of multiple medications in the schizophrenia spectrum of diseases, and among these interactions, most major risks were cardiovascular risks, especially QT prolongation. Prospective studies with larger numbers of patients are needed in this area. © 2014, Cukurova Univ Tip Fakultesi Psikiyatri Anabilim Dali. All rights reserved.

Objective To determine the analgesic efficacy and safety of intravenous single-dose paracetamol versus morphine in patients presenting to the emergency department with renal colic. Methods A randomised double-blind study was performed to compare the efficacy of intravenous paracetamol (1 g) and 0.1 mg/kg morphine in patients with renal colic. The efficacy of the study drugs was measured by a visual analogue scale and a verbal rating scale at baseline and after 15 and 30 min. The adverse effects and need for rescue medication (1 μg/kg intravenous fentanyl) were also recorded at the end of the study. Results 133 patients were eligible for enrolment in the study, with 73 patients included in the final analysis (38 in the paracetamol group and 35 in the morphine group). The mean±SD age of the subjects was 30.2±8.6 years and 51 (70%) were men. The mean reduction in scores at 30 min after study drug administration was 63.7 mm (95% CI 57 to 71) for paracetamol and 56.6 mm (95% CI 48 to 65) for morphine. The difference between pain reduction scores for the two groups at 30 min was 7.1 mm (95% CI -18 to 4), demonstrating no statistical or clinical significance. Two adverse events (5.3%) were recorded in the paracetamol group and five (14.3%) in the morphine group (difference 9%, 95% CI -7% to 26%). Conclusion Intravenous paracetamol is effective in treating patients presenting with renal colic to the emergency department. Clinical trials registration no ClinicalTrials.gov ID number NCT01318187.

This article reviews the pharmacology, therapeutic efficacy and tolerability profile of the 7-day lower-dose (5, 10 and 20?gh) buprenorphine transdermal patch (BuTrans®, Norspan®) in the management of chronic non-malignant pain, with a focus on European labelling for the drug. Buprenorphine is a semi-synthetic opioid analgesic that acts primarily as a partial agonist at the mu opioid receptor. The transdermal formulation provides continuous delivery of buprenorphine, resulting in relatively consistent plasma drug concentrations throughout the 7-day dosing interval.The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip andor knee has been demonstrated in several randomized controlled trials, which have shown the formulation to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol tablets, noninferior to codeine plus paracetamol (acetaminophen) combination tablets (when transdermal buprenorphine was used together with regularly scheduled oral paracetamol) and generally superior to a matching transdermal placebo patch. Transdermal buprenorphine was significantly more effective than placebo in reducing chronic low back pain of at least moderate severity in two randomized, double-blind, crossover trials. Other clinical trials, including a randomized, double-blind, maintenance-of-analgesia study, have also demonstrated the analgesic efficacy of transdermal buprenorphine in patients with chronic non-malignant pain of various causes.In general, serious adverse events with transdermal buprenorphine are similar to those for other opioid analgesics. Transdermal buprenorphine has a ceiling effect for respiratory depression, and the main risk is when it is combined with other CNS depressants. The most frequently reported adverse events with transdermal buprenorphine are headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus, erythema, application site pruritus and application site reactions. Transdermal buprenorphine was better tolerated than sublingual buprenorphine in a 7-week, randomized, double-blind trial in patients with osteoarthritis pain. Nevertheless, as with other opioids, persistence with transdermal buprenorphine therapy is difficult for many patients because of adverse events or other reasons.Thus, transdermal buprenorphine has generally demonstrated good efficacy and tolerability in clinical trials in chronic non-malignant pain, providing effective background analgesia as part of pain management strategies for patients with osteoarthritis, low back pain and other persistent pain syndromes of at least moderate severity. It also has favourable pharmacodynamic and pharmacokinetic properties, which have beneficial clinical implications, most notably the convenience of once-weekly administration and no need for dosage adjustments in the elderly or those with compromised renal function, making it an opioid of choice in these patients, and a useful therapeutic option overall in the management of chronic non-malignant pain. © 2011 Adis Data Information BV. All rights reserved.

Midazolam has only sedative properties. However, dexmedetomidine has both analgesic and sedative properties that may prolong the duration of sensory and motor block obtained with spinal anesthesia. This study was designed to compare intravenous dexmedetomidine with midazolam and placebo on spinal block duration, analgesia, and sedation in patients undergoing transurethral resection of the prostate. In this double-blind randomized placebo-controlled trial, 75 American Society of Anesthesiologists' I and II patients received dexmedetomidine 0.5 mu g center dot A kg(-1), midazolam 0.05 mg center dot A kg(-1), or saline intravenously before spinal anesthesia with bupivacaine 0.5% 15 mg (n = 25 per group). The maximum upper level of sensory block and sensory and motor regression times were recorded. Postoperative analgesic requirements and sedation were also recorded. Sensory block was higher with dexmedetomidine (T 4.6 +/- A 0.6) than with midazolam (T 6.4 +/- A 0.9; P < 0.001) or saline (T 6.4 +/- A 0.8; P < 0.001). Time for sensory regression of two dermatomes was 145 +/- A 26 min in the dexmedetomidine group, longer (P < 0.001) than in the midazolam (106 +/- A 39 min) or the saline (97 +/- A 27 min) groups. Duration of motor block was similar in all groups. Dexmedetomidine also increased the time to first request for postoperative analgesia (P < 0.01 compared with midazolam and saline) and decreased analgesic requirements (P < 0.05). The maximum Ramsay sedation score was greater in the dexmedetomidine and midazolam groups than in the saline group (P < 0.001). Intravenous dexmedetomidine, but not midazolam, prolonged spinal bupivacaine sensory blockade. It also provided sedation and additional analgesia.

Background We aimed to investigate effects of low dose ketamine before induction on propofol anesthesia for children undergoing magnetic resonance imaging (MRI). Methods Forty-three children aged 9 days to 7 years, undergoing elective MRI were randomly assigned to receive intravenously either a 2.5 mg x kg(-1) bolus of propofol followed by an infusion of 100 microg x g(-1) x min(-1) or a 1.5 mg x kg(-1) bolus of propofol immediately after a 0.5 mg x kg(-1) bolus of ketamine followed by an infusion of 75 microg x kg(-1) x min(-1). If a child moved during the imaging sequence, a 0.5-1 mg x kg(-1) bolus of propofol was given. Systolic and diastolic blood pressures, heart rate, peripheral oxygen saturation and respiratory rates were monitored. Apnea, the requirement for airway opening maneuvers, secretions, nausea, vomiting and movement during the imaging sequence were noted. Recovery times were also recorded. Results Systolic blood pressure and heart rate decreased significantly in the propofol group, while blood pressure did not change and heart rate decreased less in the propofol-ketamine group. Apnea associated with desaturation was observed in three patients of the propofol group. The two groups were similar with respect to requirements for airway opening maneuvers, secretions, nausea-vomiting, movement during the imaging sequence and recovery time. Conclusions Intravenous administration of low dose ketamine before induction and maintenance with propofol preserves hemodynamic stability without changing the duration and the quality of recovery compared with propofol alone.