A Survey on QT Correction for Methadone Administration

We investigated the impact of Bazett (B) and Fridericia (F) correction formulas on the evaluation of QT prolongation in patients during methadone administration and to explore the relationship between heart rate and corrected QT interval (QTc) according to both correction formulas. This study was conducted as a single-center, retrospective observational study. Subjects were cancer patients who underwent electrocardiographic evaluation for methadone therapy at our institute from April 1, 2013, to August 31, 2023. The study assessed the incidence of QT prolongation and analyzed the correlation between heart rate and QTc derived from the B and F formulas. The mean QTc of 430.3±25.8 msec for the B formula and 409.2±20.8 msec for the F formula. The incidence of QT prolongation was significantly lower with the F formula (8.4%) compared to the B formula (27.7%), indicating a 19.3% reduction in QT prolongation cases (p<0.001). Additionally, the difference in QTc between the two formulas increased with an increase in heart rate (p<0.001). These results suggest that the F formula for QT interval correction in methadone therapy potentially expands the eligible patients for this therapy.

Methadone use for acute opioid withdrawal in Tshwane shelters during the COVID-19 lockdown

Background: Temporary shelters were established for street-based people during the national level 5 coronavirus disease 2019 (COVID-19) lockdown. However, street-based substance users' need to access substances was not addressed, resulting in large numbers of people experiencing withdrawal. The Community Oriented Substance Use Programme (COSUP) in Tshwane provided methadone to manage opioid withdrawal. Methods: A cross-sectional, descriptive study was conducted using the daily methadone dosing records from shelters in Tshwane between March 2020 and September 2020. Results: The final analysis included 495 participants, of which 64 (12.9%) were initiated on 20 mg ­ 30 mg of methadone, 397 (80.2%) on 40 mg ­ 50 mg, and 34 (6.9%) on 60 mg ­ 70 mg. A total of 194 (39.2%) participants continued their initiation dose for 1­2 months, after which 126 (64.9%) had their doses increased, and 68 (35.1%) had their doses decreased. Approximately 12 (2.4%) participants were weaned off methadone after 1­3 months and 46 (9.3%) after 4­6 months. In all, 100 (20.2%) participants left the shelter prematurely and did not continue with methadone. A total of 126 (25.5%) participants continued to stay in the shelters and received methadone for 6 months, with 125 (25.3%) participants leaving the shelter with continued follow-up at a COSUP site. Conclusion: This study demonstrates variability in methadone dosing regimens among shelter residents. As the lockdown measures eased, many chose to leave the shelters, while others remained to receive methadone and other services. The COSUP appears to be effective during periods of increased vulnerability, since a large number of participants were successfully followed up. Contribution: Opioid dependence is a persistent, lifelong disease. It is multifaceted with complex environmental and individual determinants. This study highlighted the use of opioid substitution therapy during a period of increased vulnerability.

Methadone Reduced Nevirapine Pharmacokinetic Parameters in People Living With HIV in Malaysia

@#Introduction: The HIV epidemic in Malaysia predominantly affects males (90% of total HIV cases) mostly intravenous drugs users. Nevirapine-based of highly active antiretroviral therapy (HAART) once- or twice-daily dosage improve accessibility and effectiveness of antiretroviral treatment for HIV positive intravenous drug users (IDUs) receiving methadone maintenance treatment. Studies reported that concomitant administration of nevirapine with methadone reduced methadone plasma concentration. Since methadone and nevirapine were both known to be the substrate for cytochrome 2B6 (CYP 2B6), concomitant use of both drugs may affect nevirapine concentration too. However, methadone effect on nevirapine concentration is still unclear. This is a cross sectional study which reports how methadone co-administration affects the pharmacokinetic parameters of nevirapine in people living with HIV (PLHIV). Methods: 112 patients receiving nevirapine-based antiretroviral drugs were recruited. Seventeen were maintained with methadone without withdrawal symptoms. High-performance liquid chromatography was used to measure plasma nevirapine concentrations. Nevirapine population pharmacokinetics was modelled with a non-parametric approach using Pmetrics software. Result: According to univariate analysis, concurrent methadone administration increased the clearance of nevirapine by 25.3% (p = 0.046). Multivariate analysis showed that methadone medication was independently linked with lower nevirapine concentrations and area-under-curve (Cmin was reduced by 15.2%, p = 0.011, Cmax 19.5%; p = 0.003, AUC12 16.2%; p = 0.021 respectively). Conclusion: This study provides in-vivo evidence of methadone co-administration reducing nevirapine exposure. Since a low concentration of nevirapine will lead to treatment failure, monitoring is essential for PLHIV using both medications at the same time.

A Case of Withdrawal Syndrome after Opioid Discontinuation Following Pain Relief of Bone Metastases

Introduction: In patients receiving opioids, relief of cancer pain by palliative radiation therapy or other means can lead to opioid discontinuation and subsequent withdrawal symptoms, such as agitation, insomnia, and diarrhea, due to opioid-related physical dependence. Appropriate steps should be taken to prevent these symptoms. Case: A 72-year-old man underwent surgery for esophageal cancer. He developed low back pain and right lower limb pain, and was diagnosed with sacral and right iliac bone metastases. His pain was resistant to oxycodone (OXC), so he was simultaneously treated with methadone (MDN) and palliative radiotherapy. His pain gradually decreased, and MDN was tapered and switched to OXC, which was in turn discontinued at 20 mg/day at the patient's strong request. After OXC discontinuation, akathisia, anxiety, and diarrhea appeared as withdrawal symptoms. These were treated with immediate-release OXC, transdermal fentanyl, and suvorexant. Discussion: When discontinuing opioids, dose reduction below 10% per week is recommended, de-escalation to the lowest possible dose should be followed by cessation. In case of withdrawal symptoms, immediate-release opioids may be used, and opioid tapering should be attempted in parallel with symptom control.

Nylon 6-cellulose composite hosted in a hypodermic needle:Biofluid extraction and analysis by ambient mass spectrometry in a single device / 药物分析学报

This study proposes a hypodermic needle(HN)as a sorbent holder and an electrospray(ESI)emitter,thus combining extraction and analysis in a single device.A novel nylon 6-cellulose(N6-Cel)composite sorbent is proposed to extract methadone from oral fluid samples.The cellulosic substrate provides the composite with high porosity,permitting the flow-through of the sample,while the polyamide con-tributes to the extraction of the analyte.The low price of the devices(considering the holder and the sorbent)contributes to the affordability of the method,and their small size allows easy transportation,opening the door to on-site extractions.Under the optimum conditions,the analyte can be determined by high-resolution ambient ionization mass spectrometry at a limit of detection(LOD)as low as 0.3 μg/L and precision(expressed as relative standard deviation,RSD)better than 9.3％.The trueness,expressed as relative recovery(RR),ranged from 90％to 109％.As high-resolution mass spectrometers are not available in many laboratories,the method was also adapted to low-resolution spectrometers.In this sense,the direct infusion of the eluates in a triple quadrupole-mass spectrometry provided an LOD of 2.2 μg/L.The RSD was better than 5.3％,and the RR ranged from 96％to 121％.

Influencing factors of dropping-out from methadone maintenance treatment in Hangzhou City / 预防医学

Objective@#To analyze the factors affecting the dropping-out from methadone maintenance treatment (MMT) in Hangzhou City, so as to provide the evidence for improving the compliance to MMT.@*Methods@#One MMT clinic was sampled from each of the eight districts in Hangzhou City using a cluster random sampling method, and patients that received MMT and were at ages of 18 years and older and registered during the period from December 2020 through June 2021 were recruited. Participants' basic characteristics, illegality and crime within 6 months prior to MMT and family and social relationships were collected through questionnaire surveys, and factors affecting the dropping-out from MMT were identified using a multivariable logistic regression model. @*Results@#A total of 315 outpatients were included from MMT clinics. The participants had a mean age of (45.33±7.63) years, and included 245 men (77.78%) and 70 women (22.22%), with a dropping-out rate of 65.71%. Multivariable logistic regression analysis showed a low likelihood of dropping-out from MMT among patients at ages of 60 years and older (OR=0.080, 95%CI: 0.018-0.350), employees (OR=0.415, 95%CI: 0.236-0.727), patients without drug-related infectious diseases (OR=0.411, 95%CI: 0.231-0.731), patients with per dossing of 60 mL and higher (OR=0.431, 95%CI: 0.236-0.787) and patients without contact with drug-using friends (OR=0.328, 95%CI: 0.185-0.582), and a high possibility of dropping-out from MMT among patients with poor relationship with family members (OR=2.905, 95%CI: 1.127-7.488). @*Conclusion@#Age, working status, drug-related infectious diseases, dosing, relationship with family members and contact with drug-using friends affected the dropping-out from MTT in Hangzhou City.

Prediction of Relapse Among Individuals Undergoing Methadone Maintenance Therapy in Johor Bahru Health District

@#Introduction: Increase in the number of opioids seized in the recent year may indicate increased opioid use in Malaysia. In counteracting opioid abuse, Methadone Maintenance Therapy (MMT) was introduced in Malaysia but relapse following MMT has become an important issue. This study aimed to determine the prevalence and patient factors that served as predictors of opioid relapse among MMT patients. Method: A cross-sectional study involving 159 MMT patients who have reached dose stabilization (eight weeks at a constant dose of methadone) was conducted in Johor Bahru Health District. The dependent variable was opioid relapse, while the independent variables include socio-demographic characteristics, MMT history, crime history, cognitive and interpersonal factors, and social-environment influence. Face-to-face interviews using structured questionnaires and secondary data collection using data collection sheets were done. Multiple logistic regression was used to determine the predictors. Significant level set at alpha less than 5%. Result: The response rate was 86.9% with majority of them were Malay, male, and Muslim. The prevalence of opioid relapse was 11.9%. Those who were non-polydrug users (AOR=3.701, 95%CI=1.182, 11.587, p=0.025), classified as having moderate (AOR=5.869, 95%CI=1.524, 22.595, p=0.010) and high (AOR=5.952, 95%CI=1.000, 35.445, p=0.050) relapse risk response after given hypothetical situation whether respondent been offered drug or not, were more likely to have relapsed. Respondents with higher cognitive and behavioral problem-solving response scores were less likely to have relapsed (AOR=0.949, 95%CI=0.909, 0.991, p=0.008). Conclusion: About 1 in 5 MMT clients had relapsed after they reach dose stabilization. The predictors of opioid relapse were non-polydrug users, having moderate to high relapse risk, and cognitive and behavioral problem-solving responses.

The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion

ABSTRACT: The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.

RESUMO: O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.

Revisión de metadona intraoperatoria para el manejo de dolor posquirúrgico / Intraoperative methadone for the management of postsurgical pain a review

Pain management associated with surgery is a constant concern of the health team as well as the patient. Multiple proposals for analgesia have been made in the perioperative context. The use of opioids with rapid effect and easy titration in the intraoperative period are currently frequent; to then perform a postoperative analgesic control with drugs with a longer half-life, usually achieving adequate pain management. However, sometimes the standard analgesic scheme is not enough. The problems associated with this situation have led to the need for high doses of opioids in the postoperative period, with the requirement for monitoring, health personnel, and the adverse effects that these involve. Methadone is a long-acting, rapid-onset opioid, the latter secondary to its long elimination half-life. It is presumed that these characteristics have led patients to report adequate pain management, which has been related to a decrease in the need and dose of rescue opioids, in addition to delaying the requirement of these if necessary during the postoperative. These properties allow methadone to be a potential solution to perioperative pain management.

El manejo del dolor asociado a la cirugía es una preocupación constante del equipo de salud al igual que del paciente. Se han planteado múltiples propuestas de analgesia en el contexto perioperatorio, siendo actualmente frecuente el uso de opioides de rápido efecto y fácil titulación en el intraoperatorio; para luego realizar un control analgésico postoperatorio con fármacos de mayor vida media, logrando habitualmente un manejo adecuado del dolor. Sin embargo, a veces el esquema analgésico estándar no es suficiente. La problemática asociada a esta situación ha llevado a la necesidad de altas dosis de opioides en el posoperatorio, con el requerimiento de monitorización, personal de salud y efectos adversos que estos involucran. La metadona es un opioide de inicio de acción rápido y larga duración, este último secundario a su vida media de eliminación prolongada. Se presume que estas características han logrado que los pacientes reporten un adecuado manejo de su dolor, lo que se ha relacionado a una disminución en la necesidad y dosis de opioides de rescate, además de retrasar el requerimiento de éstos en el caso de ser necesarios durante el postoperatorio. Estas propiedades permiten que la metadona pueda ser una potencial solución al manejo del dolor perioperatorio.

Remarkable Response to Adjunctive Use of Methadone 5 mg Once Daily in a Patient with Refractory Cancer Pain

Introduction: Although stop-and-go method is recommended for the introduction of methadone by the Japanese guidelines, it may temporarily result in inadequate pain control and/or serious side effects. We report our experience that alleviation of symptoms was achieved by introducing low-dose methadone at an early stage on top of preceding opioids for a patient with refractory cancer pain. Case: Tapentadol and an analgesic adjuvant were given to a 70-year-old man to treat the patient’s old anal pain due to recurrence of rectal cancer at the rectal anastomosis. However, since the pain was poorly controlled, methadone 5 mg was given adjunctively once daily. After methadone medication, remarkable alleviation of pain and improvement in QOL were observed. Discussion: To achieve a safe pain management, adding a small amount of methadone at an early stage, as in this case, may possibly considered.

A Retrospective Survey of 28 Cases with Opioid Switching by Adding Methadone to the Preceding Opioid

The guide to proper use of methadone in Japan describes the SAG method (a method of stopping all leading opioids and starting methadone). Based on strict evaluation, our palliative care department introduces methadone by adding to the preceding opioid, and then tapering or discontinuation the preceding opioid. This time, we considered the clinical significance of 28 patients who received this method. In 20 of 28 cases (71.4%), methadone reached the maximum dose, and methadone titration could be safely performed without exacerbation of pain or serious adverse events. However, in order for this method to be performed safely, it is necessary to pay attention to the pharmacological properties of methadone, which has a long half-life, and to make a detailed evaluation and drug adjustment of the analgesic effect and adverse events after the introduction of methadone.

Measurement of Blood Methadone Concentration and Investigation of the Possibility of Early Effect Assessment in Japanese Patients with Cancer Pain

Methadone is a difficult medicine to assess the efficacy at an initial stage because the blood concentration of it varies greatly among individuals and it takes days to reach a steady state and cannot be increased for 7 days. Nevertheless, there are few reports of blood concentration together with effects after administration of methadone about Japanese cancer patients. In this study, we investigated changes in blood concentration and pain score (NRS), and factors that affect blood concentration. Dose per body weight was only correlated with blood concentration of methadone. In the effective cases, NRS decreased chronologically until the 7th day after treatment initiation, and significantly decreased from the 1st day compared to before treatment initiation, but in the ineffective cases, it tended to decrease until the 3rd day, but there was no change thereafter. The blood concentration increased to 110 ng/ml on the 7th day in the effective cases, and in the ineffective cases, it reached the concentration on the 3rd day. Thus there was no correlation between the blood concentration and the drug efficacy. The individual blood concentrations tended to increase slightly or decrease after the 3rd day, but in only one case, it continued to increase. From the above-mentioned, it was shown that the effect could be judged at an early stage, however, since there was a case in which the blood concentration continued to rise until the 7th day, it was considered that the early dose increase within 7 days after initiation should be performed carefully.

Prevalence Of Major Depressive Disorder And Its Association With Erectile Dysfunction Among Clients On Methadone Maintenance Therapy

@#Major Depressive Disorder (MDD) is substantially higher in people seeking Methadone Maintenance Therapy (MMT) as compared to the normal population. Erectile Dysfunction (ED) is one of the side effects of Methadone Maintenance Therapy (MMT) which is rarely explored as it is regarded as a sensitive topic. This study aims to determine the prevalence of MDD and its association with ED among MMT clients. A cross-sectional study was conducted involving 160 subjects who attended the Methadone outpatient clinic. The clients were given Patient Health Questionnaire-9 to screen for depressive symptoms and MINI International Neuropsychiatric Interview to diagnose MDD. ED was diagnosed using the 5-item International Index of Erectile Function. The results showed the prevalence of depression in clients on MMT was 30.6% and the prevalence of ED was 72.5%. On multivariate analyses, there were significant associations between ED with depression (P<0.05). Smoking also was found to be contributed to depression. Sociodemographic factors, comorbid medical illnesses, and illicit substance use were found to have no associations with depression. Therefore, given the prevalence of MDD and ED in MMT clients was high, routine assessment of depressive symptoms and sexual function in clients on methadone should be done to minimize their negative impact on the clients

The Proportion of Non-retention and Its Associated Factors Among Clients Receiving Methadone Maintenance Therapy in Kelantan, Malaysia

@#Introduction: Methadone maintenance therapy (MMT) requires a client to take a daily dose of methadone to reduce cravings for opioid and suppress withdrawal syndrome. Non-retention in the MMT will seriously expose more risk rather than the benefits of the program. Hence, determining the factors associated with non-retention to the MMT is essential. Thus, the present study was conducted to determine the proportion of non-retention and its associated factors among clients receiving MMT in Kelantan, Malaysia. Methods: By using a retrospective record review analysis, the required information of the clients was obtained from fourteen MMT clinics in Kelantan, Malaysia. A total of 155 clients were selected in this study using systematic random sampling. Multiple logistic regression analysis was performed to determine the factors associated with non-retention among clients receiving MMT. Results: It was found that the proportion of non-retention to the MMT in Kelantan, Malaysia was 21.9%. Clients with advanced age, taking daily direct observed therapy, and no underlying HIV were the predictors of non-retention among clients receiving MMT in Kelantan, Malaysia. Conclusion: The findings highlight a relatively high proportion of non-retention among the MMT clients. There is a need for an integrated, culturally relevant approach towards tackling the factors associated with non-retention in the future to keep this program sustainable and effective.

The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion / A necessidade de opioide na analgesia pós-operatória de cães submetidos à hemilaminectomia devido à extrusão do disco intervertebral

The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.(AU)

O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.(AU)

Serotonin syndrome associated with methadone and milk thistle seeds: a case report

Abstract Background Serotonin syndrome is rarely, potentially life threatening condition, associated with use of serotonin acting medications and psychoactive drugs. In the majority of cases the symptoms occur soon after the initiation of a new drug or a change in the dose. Objective To present a case report and to describe the possible mechanism of development of serotonin syndrome during the interactions between milk thistle seeds and methadone on hepatic cytochrome enzyme system P450. Methods A case report of a young man on regular therapy with methadone, who develop a serotonin syndrome after ingestion a high dose of milk thistle seeds. Results Commercial preparations of milk thistle include the extract silibinin, which exhibits no beneficial or harmful drug interactions at normal doses, but at higher concentrations it can lead to dose-dependent effects on methadone metabolism, through inhibition of CYP3A4 and P-glycoprotein. As a result, it may lead to enhanced serotonin re-uptake inhibition and increased serotonin activity. Discussion Milk thistle is widely used and recommended for detoxification, but it may have serious and life threatening interactions with psychotropic drugs and psychoactive substances when used in high doses.

A Case of Refractory Cancer Pain Successfully Treated with Opioid Switching by Adding Methadone

We report a case of refractory cancer pain that was successfully treated with opioid switching by adding methadone to the preceding opioid. A 38-year-old man had severe epigastric pain and back pain because of paraaortic lymph node metastasis of a gastroesophageal junctional carcinoma. His pain was treated with continuous intravenous morphine administration and the frequent use of a rescue dose. When the morphine dose was increased, respiratory depression developed; thus, his pain was considered refractory to the morphine, and methadone was added on. The pain was relieved after initiating methadone, and the frequency of the rescue dose was markedly decreased. The methadone dose was gradually increased in parallel, and the morphine dose was reduced and finally discontinued. No methadone-induced side effects were noted, and the patient was discharged with good analgesia. In our case, adding methadone without decreasing the preceding opioid dose under strict monitoring made it possible to stably switch the opioid without increasing pain.

Erectile Dysfunction and Methadone Maintenance Therapy

@#Erectile dysfunction is one of the most common side effects of methadone affecting more than half of methadone patient population. The problem is associated with prominent reduced quality of life. Erectile dysfunction may perpetuate greater problem if left untreated as patients may opt to use harmful self-treatment such as abusing methamphetamine. This illicit drug use to overcome the side-effects of methadone may lead to polysubstance use disorder that further compromise addiction therapy. To overcome this issue, both practitioners and patients play a major role in the management of erectile dysfunction. Patient awareness regarding erectile dysfunction and its impact as well as doctor’s active intervention to detect erectile dysfunction, are essential to improve the detection rate and management of erectile dysfunction. Frequent screening of erectile dysfunction and its risk factors will help with the identification of patients suffering from erectile dysfunction. Multiple treatments options such as bupropion, trazodone and many more are available to treat erectile dysfunction which will be further explored in this review.

Hematological and biochemical parameters in Spotted Paca (Cuniculus paca) undergoing pharmacological restraint and general anesthesia / Parâmetros hematológicos e bioquímicos em Cuniculus paca sob contenção química e anesthesia geral

The aim of this study was to assess the effects of chemical restraint, general anesthesia and opioid treatment on hematological components in Cuniculus paca. Eight healthy, adult, captivity female animals , underwent three laparoscopic procedures with a 15-day interval were evaluated. After physical restraint, an association of ketamine (25mg/kg) and midazolam (0.5mg/kg) was administered intramuscularly for chemical restraint. Posteriorly, anesthesia was induced and maintained with isoflurane; and randomly administered methadone (0.5mg/kg), tramadol (5mg/kg) or saline-placebo (0,1mL/kg) intramuscularly. After pharmacological restraint and in the final laparoscopy stage, venous blood samples were obtained for complete blood count, total plasma protein (TP), creatinine, alanine aminotransferase (ALT), sodium, potassium, chloride and ionized calcium analysis. During general anesthesia, hemoglobin, TP concentration and lymphocytes decreased (P=0.029; <0.001; 0.022 respectively), whereas the potassium levels increased (P=0.034). In conclusion, chemical restraint with ketamine/midazolam association causes a slight decrease in blood cellular components. Isoflurane anesthesia for laparoscopic procedure lead to decrease in hemoglobin, lymphocytes and protein concentrations, while potassium increased, without any influence from the tramadol or methadone treatment. However, these alterations were transient, and its hematologic values can collaborate in carrying out epidemiological, pathophysiological or case studies in the Cuniculus paca.(AU)

O objetivo do presente estudo foi avaliar os efeitos de contenção química, anestesia geral e tratamento com opiáceos nos parâmetros hematológicos em Cuniculus paca. Foram avaliados oito animais saudáveis, fêmeas, adultas, de cativeiro, que foram submetidas a três procedimentos laparoscópicos, com intervalo de 15 dias. Após a contenção física, uma associação de cetamina (25mg/kg) e midazolam (0,5mg/kg) foi administrada por via intramuscular para contenção química. Posteriormente, a anestesia foi induzida e mantida com isoflurano, e administrou-se aleatoriamente metadona (0,5mg/kg), tramadol (5mg/kg) ou placebo salina por via intramuscular. Após a contenção farmacológica e em estágio final da laparoscopia, foram obtidas amostras de sangue venoso para contagem sanguínea completa, proteína de plasma total (TP), creatinina, alanina aminotransferase (ALT), cálcio, sódio, potássio e cloreto ionizado. Durante a anestesia geral, a concentração de hemoglobina, TP e linfócitos diminuiu (P= 0,029;< 0,001; 0,022, respectivamente), enquanto os níveis de potássio aumentaram (P= 0,034). Em conclusão, a contenção química com associação de cetamina/midazolam promove uma ligeira diminuição dos componentes celulares do sangue. A anestesia com isoflavano para o procedimento laparoscópico levou a uma diminuição das concentrações de hemoglobina, linfócitos e proteínas, enquanto o potássio aumentou, sem qualquer influência do tratamento com tramadol ou metadona. No entanto, essas alterações foram transitórias, e os seus valores hematológicos obtidos podem colaborar na realização de estudos epidemiológicos, fisiopatológicos ou casuísticas para Cuniculus paca.(AU)