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1.
Life Sci ; 260: 118430, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931800

RESUMO

AIMS: Previous investigations demonstrated that tramadol, as a painkiller, similar to morphine induces tolerance and dependence. Furthermore, the cannabinoid receptor 1 (CB1R) located in the nucleus accumbens (NAc) plays a critical role in morphine-induced conditioning. Therefore, the main objective of this study was to evaluate the role of NAc CB1R in tramadol induced conditioning and reinstatement. MAIN METHODS: In the present experiment, the effect of NAc CB1 receptors on tramadol induced conditioning was tested by microinjecting of arachidonylcyclopropylamide (ACPA, CB1R agonist) and AM 251 (CB1R inverse agonist) in the NAc during tramadol-induced conditioning in the adult male Wistar rats. In addition, the role of NAc CB1R in the reinstatement was also evaluated by injecting ACPA and AM 251 after a 10-days extinction period. KEY FINDINGS: The obtained data revealed that the administration of tramadol (1,2, and 4 mg/kg, ip) dose-dependently produced conditioned place preference (CPP). Moreover, intra-NAc administration of ACPA (0.25, 0.5, and 1 µg/rat) dose-dependently induced conditioning, while the administration of AM-251 (30, 60, and 120 ng/rat) induced a significant aversion. In addition, the administration of a non-effective dose of AM251 during tramadol conditioning inhibited conditioning induced by tramadol. On the other hand, the administration of ACPA after extinction induced a significant reinstatement. Notably, the locomotor activity did not change among groups. SIGNIFICANCE: Previous studies have shown that tramadol-induced CPP occurs through µ-opioid receptors. The data obtained in the current study indicated that CB1R located in the NAc is involved in mediating conditioning induced by tramadol. Besides, CB1R also plays a vital role in the reinstatement of tramadol-conditioned animals. It might be due to the effect of opioids on enhancing the level of CB1R.


Assuntos
Analgésicos Opioides/efeitos adversos , Condicionamento Psicológico/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Receptor CB1 de Canabinoide/fisiologia , Tramadol/efeitos adversos , Analgésicos Opioides/administração & dosagem , Animais , Condicionamento Clássico , Relação Dose-Resposta a Droga , Extinção Psicológica/efeitos dos fármacos , Masculino , Núcleo Accumbens/metabolismo , Piperidinas/administração & dosagem , Piperidinas/farmacologia , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Ratos Wistar , Receptor CB1 de Canabinoide/agonistas , Tramadol/administração & dosagem
2.
J Opioid Manag ; 16(4): 297-306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32885838

RESUMO

Tramadol is a centrally acting dual-mechanism (opioid and monoamine reuptake inhibition) analgesic that has been noted to have a lower risk of abuse compared to conventional opioids such as morphine. Oral tramadol has been ap-proved in the United States since 1995 and intravenous (IV) tramadol has been widely prescribed outside the United States (OUS); nevertheless, IV tramadol has not yet been approved for use in the United States. This paper provides a review of the pharmacokinetics (PK) of the IV tramadol dosing regimen being developed in the United States, its abuse potential as documented in the literature, and its safety record in clinical practice, and discusses how IV tramadol may become a useful option for patients in the United States with acute pain.


Assuntos
Dor Aguda , Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Tramadol , Dor Aguda/tratamento farmacológico , Administração Intravenosa , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacocinética , Humanos , Morfina , Tramadol/efeitos adversos , Tramadol/farmacocinética
3.
Biosci Rep ; 40(9)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32803252

RESUMO

OBJECTIVES: In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties. METHODS: A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention. RESULTS: In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not. CONCLUSION: Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints.


Assuntos
Osso e Ossos/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/fisiopatologia , Tramadol/efeitos adversos , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Animais , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/ultraestrutura , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Modelos Animais de Doenças , Módulo de Elasticidade/efeitos dos fármacos , Masculino , Meniscos Tibiais/fisiopatologia , Camundongos Endogâmicos C57BL , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Osteoartrite do Joelho/diagnóstico por imagem , Sinovite/induzido quimicamente , Sinovite/patologia , Tramadol/farmacologia , Microtomografia por Raio-X
4.
Int Marit Health ; 71(2): 109-113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32604453

RESUMO

The widespread use of opioids for the treatment of moderate or severe acute and chronic pain has become a public health problem due to the physical and psychological dependence and tolerance they produce. The increasingly higher doses that patients require may reach toxic levels or lead to accidents, including fatalities. We present the case of a welder who, while working for a shipping container company, fell from height without a safety harness and subsequently died as a result of a traumatic brain injury. Post-mortem examination revealed a cardiac blood tramadol concentration of 2.83 mg/L, which is 3-4 times higher than the maximum therapeutic dose. The combined use of synthetic opioids and antidepressants may heighten the adverse neurological and psychiatric effects. A review of the literature, identified studies, including previous reports of fatalities, supported our causal hypothesis of a serotonin syndrome. This syndrome can lead to a loss of cognitive and sensory capacity, interfere with decision-making ability, and produce mental confusion and dizziness, among other symptoms. In order to prevent harm to themselves and others, all persons who are currently taking these kinds of drugs should avoid dangerous tasks at work and must be advised by a physician regarding the type of activities that are safe for them to perform.


Assuntos
Acidentes por Quedas/mortalidade , Acidentes de Trabalho/mortalidade , Analgésicos Opioides/efeitos adversos , Tramadol/efeitos adversos , Adulto , Analgésicos Opioides/sangue , Antidepressivos/sangue , Lesões Encefálicas Traumáticas/mortalidade , Interações Medicamentosas , Humanos , Masculino , Espanha , Tramadol/sangue , Cloridrato de Venlafaxina/sangue , Soldagem
6.
Biomed Res Int ; 2020: 2732958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219129

RESUMO

Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.


Assuntos
Extratos Vegetais/farmacologia , Romã (Fruta)/química , Sementes/química , Doenças Testiculares/tratamento farmacológico , Testículo/efeitos dos fármacos , Tramadol/efeitos adversos , Analgésicos Opioides , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Espermátides/efeitos dos fármacos , Espermatozoides/metabolismo , Doenças Testiculares/patologia , Testículo/patologia
7.
Plast Reconstr Surg ; 145(3): 780-789, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32097326

RESUMO

BACKGROUND: Facial fractures are painful injuries routinely managed by opioids after surgical repair. Studies have identified patient risk factors and prescribing patterns associated with opioid use in medicine and general surgery; however, little is known about these entities in the facial trauma population. METHODS: A retrospective cohort study of opioid-naive patients undergoing surgical repair of facial fractures was conducted using the Truven Health MarketScan Commercial Claims and Encounters (2006 to 2015) and Medicaid Multi-State Databases (2011 to 2015). Eligible procedures included nasal, nasoorbitoethmoid, orbital, mandible, and Le Fort fracture repair. Opioid type, daily dosage, and prescription duration were analyzed. Multivariable logistic regression was performed to determine independent predictors of prescription refill. RESULTS: A total of 20,191 patients undergoing surgical repair of facial fractures were identified. Of these, 15,861 patients (78.6 percent) filled a perioperative opioid prescription. Refill (58.7 percent) and potentially inappropriate prescribing (39.4 percent) were common among this population. Patient factors including prior substance use (adjusted OR, 1.84; 95 percent CI, 1.63 to 2.07) and history of mental health disorder (adjusted OR, 1.43; 95 percent CI, 1.06 to 1.91) were independent predictors of refill. Increased odds of refill were seen in patients prescribed tramadol (OR, 1.98; 95 percent CI, 1.48 to 2.66) and those who underwent multiple surgical repairs (OR, 3.38; 95 percent CI, 2.54 to 4.50). CONCLUSIONS: Refill and potentially inappropriate prescribing occurred at high rates in facial trauma patients undergoing surgical repair. Additional studies are needed to develop guidelines for proper opioid prescribing in this population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Assuntos
Analgésicos Opioides/efeitos adversos , Ossos Faciais/lesões , Fixação de Fratura/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Fraturas Cranianas/cirurgia , Adolescente , Adulto , Prescrições de Medicamentos/normas , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Prescrição Inadequada/prevenção & controle , Prescrição Inadequada/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Epidemia de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/etiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Padrões de Prática Médica/normas , Estudos Retrospectivos , Fatores de Risco , Fraturas Cranianas/complicações , Tramadol/efeitos adversos , Estados Unidos , Adulto Jovem
9.
J Surg Res ; 247: 406-412, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31685252

RESUMO

BACKGROUND: Multimodal analgesic regimes are required to treat pain. Intraperitoneal (IP) agents, such as local anesthetics (LAs), have been shown to reduce pain after abdominal surgery. Other IP analgesics have been tested in several randomized control trials (RCTs), but no reviews or guidelines have evaluated their use. Tramadol is an effective oral and intravenous analgesia with recent evidence supporting the use of IP tramadol (IPT). We aimed to review the efficacy of IPT as an adjunct to intraperitoneal local anesthetics (IPLAs) for pain relief after abdominal surgery. MATERIALS AND METHODS: Relevant articles were identified by two independent reviewers from MEDLINE, EMBASE and PubMed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines up to January 2019. Only RCT comparing IPT + IPLA with IPLA alone were included. Outcomes recorded were the postoperative analgesic requirement, pain scores at 4 h and 24 h and adverse events. Data were analyzed with Review Manager, version 5.3. RESULTS: A total of five RCTs (4× laparoscopic cholecystectomy and 1× abdominal hysterectomy) were included in this review from 419 studies screened. All doses were given as a single bolus. Pain relief requirements over the first 24 h weres less in the IPT + IPLA groups when compared with those in IPLA alone. Pain scores were less for IPT + IPLA groups at 4 h and 24 h. There were no significant differences in adverse events between groups. CONCLUSIONS: In summary, IPT, in combination with IPLA, is effective in the management of acute postoperative pain and reduces the total amount of pain relief consumed in the first 24 h after surgery. Studies reporting the use of IPT + IPLA reported no toxicity or systemic adverse events. Further research into standardizing the dosing of IPT to optimize its effectiveness and further reduce the additional analgesic requirement is indicated.


Assuntos
Dor Aguda/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Tramadol/administração & dosagem , Abdome/cirurgia , Dor Aguda/diagnóstico , Dor Aguda/etiologia , Analgésicos Opioides/efeitos adversos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Injeções Intraperitoneais , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tramadol/efeitos adversos
10.
Ann Pharmacother ; 54(3): 247-253, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31648533

RESUMO

Background: Hypoglycemia is a rare adverse effect of tramadol that is described in the medical literature and package insert. Objective: The purpose of this study was to review reports of tramadol and hypoglycemia in the Food and Drug Administration Adverse Event Reporting System (FAERS) database to determine a potential association. Methods: Disproportionality analysis with Bayesian correction was used to compare tramadol and hypoglycemia with other medications in FAERS. The results were considered significant if the fifth percentile of the Empirical Bayesian geometric mean distribution (EB05) >2. Logistic regression odds ratios was used to determine if age, diabetes medications, and renal insufficiency masked the disproportionality of hypoglycemia, with the fifth percentile of the logistic regression odds ratio (LR05) >2 indicating a potential signal. The Interaction Signal Score (INTSS) was computed to determine the influence of predisposing risk factors on the signal. Results: A total of 605 cases of tramadol-associated hypoglycemia were reported, but our results were not significant (EB05: 1.590). Tramadol-associated hypoglycemia was significant in patients who did not take diabetes medications (EB05: 2.256; LR05: 2.2104). Renal insufficiency was not found to increase the risk of tramadol-associated hypoglycemia (INTSS: 0.865). There was a significant signal for tramadol-associated hypoglycemia in patients aged 0 to 1 year (LR05: 3.0240) and 2 to 4 years (LR05: 2.6853). Conclusion and Relevance: Results of our analysis suggest a potential signal between hypoglycemia and tramadol use in patients not taking diabetes medications. Our results do not support a predisposition for tramadol-associated hypoglycemia in patients with renal insufficiency, increasing age, and/or diabetes as noted in the tramadol package insert.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Analgésicos Opioides/efeitos adversos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Tramadol/efeitos adversos , Adulto , Idoso , Teorema de Bayes , Bases de Dados Factuais , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Insuficiência Renal/complicações , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/epidemiologia , Estados Unidos , United States Food and Drug Administration
11.
Eur J Pain ; 24(3): 639-648, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31782864

RESUMO

BACKGROUND: Opioids and non steroidal anti inflammatory drugs (NSAIDs) are commonly used for pain relief in acute pancreatitis (AP). Opioids carry risk of sphincter of oddi constriction. Although diclofenac prevents post endoscopic retrograde cholangio-pancreatography (ERCP) pancreatitis, few reports of diclofenac associated AP are also present. Although, both tramadol and diclofenac are commonly used for pain relief in AP, no study has evaluated their comparative efficacy and safety. MATERIALS AND METHODS: Forty-six eligible participants were randomized to either diclofenac or tramadol. Primary objectives of our study were improvement in pain intensity on visual analogue scale (VAS pain score after 1 hr of drug administration) and number of patients requiring supplementary analgesia. The secondary objectives were total number of times of supplementary analgesia requirement, time to significant decrease (33%) in VAS pain score from baseline, number of painful days (VAS pain score >5), VAS pain score on 7th day, side effects, all cause death and complications of pancreatitis between the two groups. RESULTS: Although 46 patients were randomized, the final analysis included 41 participants. Five patients were withdrawn from the study (intubation = 3, altered sensorium = 2). No significant difference was seen in terms of VAS score after 1 hr of drug administration, number of patients requiring supplementary analgesic and number of painful days. However, time taken to significant reduction of pain was lower in the diclofenac group (p = .028). Both the agents were comparable in terms of safety. Although complications were less in the diclofenac group, the difference was not statistically significant. CONCLUSION: Both diclofenac and tramadol are equally effective in controlling pain in AP with similar safety profile. SIGNIFICANCE: There are no studies that have compared the safety and efficacy of two commonly used analgesics for pain relief in patients with AP. We found that both diclofenac and tramadol are equally effective in decreasing the pain associated with AP. There is also no significant difference in the incidence of side effects between both the groups. Hence both diclofenac and tramadol can be used safely and effectively for pain control in AP. TRIAL REGISTRATION: The trial was registered with clinical trials registry India (Number- CTRI/2018/05/014309).


Assuntos
Pancreatite , Tramadol , Doença Aguda , Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/uso terapêutico , Método Duplo-Cego , Humanos , Dor/tratamento farmacológico , Dor/etiologia , Dor Pós-Operatória/tratamento farmacológico , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Tramadol/efeitos adversos
12.
Basic Clin Pharmacol Toxicol ; 126(3): 226-235, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31520564

RESUMO

Tramadol is a weak opioid that is commonly used for chronic low back pain (LBP). Despite its effectiveness, duplicated use of tramadol, which may indicate abuse or dependence, may exacerbate potential adverse reactions. This population-based, cross-sectional study aimed to investigate the prevalence of duplication of tramadol and its associated factors among patients with LBP. From a Korean nationwide claims database, non-hospitalized patients aged 40-99 years with LBP without malignancy were prescribed tramadol during 2014-2016. Duplication of tramadol was defined as overlapping of prescription days. Among them, we defined "extensive duplication (ED)" when days of tramadol duplication cover 10% or more of the days prescribed tramadol. Patient and healthcare utilization factors associated with ED were examined using a logistic regression model. The study population was 6 417 503 patients. Of these, 13.7% were ED users. The age- and sex-standardized prevalence of using tramadol twice or more a year was 14.06 per 100 people in 2014, 13.74 per 100 people in 2015 and 13.52 per 100 people in 2016. ED occurred more in those in the group aged 70-79 years (OR 1.12, 95% CI 1.11-1.13) than 40-49 years and in those with comorbidities, such as drug abuse (OR 2.99, 95% CI 2.05-4.36) or depression (OR 1.75, 95% CI 1.72-1.77). Based on the results of this study, a proper management system is needed to avoid tramadol duplication among older people and patients with drug abuse or depression.


Assuntos
Analgésicos Opioides/administração & dosagem , Dor Crônica/tratamento farmacológico , Dor Lombar/tratamento farmacológico , Tramadol/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Estudos Transversais , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , República da Coreia , Tramadol/efeitos adversos
13.
Andrologia ; 52(1): e13454, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31721272

RESUMO

Tramadol is widely abused in Nigeria and has been reported to cause fertility decline via testicular oxidative stress. This study investigated the effect of vitamin E, an antioxidant on some reproductive parameters in male Wistar rats administered tramadol. Twenty male Wistar rats (180-200 g) were randomly assigned into four groups (n = 5) thus: Control (0.2 ml vehicle: olive oil), tramadol-treated (20 mg/kg of tramadol), vitamin E-treated (100 mg/kg of vitamin E) and tramadol + vitamin E-treated (received tramadol and vitamin E) groups. Drugs were administered orally and daily for 28 days. Sperm count, Johnsen's score, germinal epithelial height and serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) concentrations were significantly (p < .05) decreased in tramadol-treated and tramadol + vitamin E compared with control and vitamin E-treated groups. Sperm motility, morphology, viability, seminiferous tubular diameter, Leydig cell count, Sertoli cell count and malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase concentrations were not significantly different among the groups. Histology of testis and epididymis in all groups showed no toxicity but decreased sperm population in tramadol-treated and tramadol + vitamin E-treated groups. Tramadol did not cause testicular oxidative stress but impaired testicular function by suppressing testosterone, FSH and LH secretion. Vitamin E administration could not attenuate this impairment in testicular function.


Assuntos
Infertilidade Masculina/tratamento farmacológico , Espermatozoides/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias/complicações , Tramadol/efeitos adversos , Vitamina E/administração & dosagem , Administração Oral , Animais , Modelos Animais de Doenças , Ejaculação/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Masculino , Nigéria , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia
14.
Biochem Med (Zagreb) ; 30(1): 010802, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839727

RESUMO

Introduction: Hypoglycaemia has been reported as an unusual complication of tramadol use and in a few cases of tramadol poisoning, but the exact mechanism is not known. Case description: An ambulance crew was dispatched to an unconscious 46-year old man. A glucometer point-of-care measurement revealed a profound hypoglycaemia (1.9 mmol/L). Treatment with intravenous glucose was started and the patient was transported to the hospital. The patient had several episodes of pulseless electrical activity requiring cardiopulmonary resuscitation in the ambulance and upon arrival in the hospital. Despite continuous glucose infusion the hypoglycaemia was difficult to correct during the next few hours and the patient developed hypokalaemia. Further investigation to identify the cause of hypoglycaemia revealed that insulin and C-peptide were inappropriately raised. A toxicological investigation revealed the presence of tramadol and its metabolites in lethal concentrations. Also acetaminophen, ibuprofen and lormetazepam were present. Ethanol screening was negative (< 0.1 g/L) and no sulfonylurea were detected. The patient developed multiple organ failure, but eventually recovered. What happened: The hypoglycaemia was caused by inappropriate stimulation of insulin secretion in a patient intoxicated with tramadol. The sudden hypokalaemia was caused by a massive intracellular shift of potassium in response to the hyperinsulinemia, triggered by the intravenous administration of glucose. Main lesson: To our knowledge, we are the first to document a significant rise in endogenous insulin production in a hypoglycaemic patient presenting with tramadol intoxication. Our observation suggests that hyperinsulinemia could be the cause of the hypoglycaemia associated with tramadol use.


Assuntos
Analgésicos Opioides/efeitos adversos , Hipoglicemia/diagnóstico , Tramadol/efeitos adversos , Analgésicos Opioides/uso terapêutico , Glicemia/análise , Peptídeo C/sangue , Glucose/administração & dosagem , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/etiologia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Tramadol/uso terapêutico
15.
Int Clin Psychopharmacol ; 35(1): 42-48, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31567513

RESUMO

Evidence suggests that opioids can modulate gonadal function, with consequent decreased release of sex hormones. We attempted to investigate the sexual function of males using tramadol hydrochloride (HCL) and its relationship to levels of free testosterone, luteinizing hormone, and follicle stimulating hormone, and to compare them with heroin use disorder patients and healthy controls. Our sample consisted of 60 opiate use disorder patients (assessed by Structured Clinical Interview for DSM-IV Axis I) (30 heroin and 30 tramadol) and 30 healthy controls. Sexual dysfunction was assessed using the International Index of Erectile Function. Free testosterone, follicle stimulating hormone, and luteinizing hormone levels were measured in morning blood samples using enzyme-linked immunosorbent assay (ELISA). Results showed that there was a decrease of luteinizing hormone and free testosterone levels in opiate use disorder patients compared with healthy controls, with heroin-dependent patients having significantly lower levels than those using tramadol. Opiates' effect on follicle stimulating hormone had mixed results. Opioid-dependent patients (both tramadol HCL and heroin using patients) developed sexual dysfunction more than healthy controls, which was generalized, with erectile dysfunction being the most affected domain. These findings are of ultimate importance, considering the fact that people use opioids to enhance their sexual performance in many countries.


Assuntos
Transtornos Relacionados ao Uso de Opioides/epidemiologia , Disfunções Sexuais Fisiológicas/epidemiologia , Tramadol/efeitos adversos , Adolescente , Adulto , Estudos de Casos e Controles , Estudos Transversais , Hormônio Foliculoestimulante/metabolismo , Dependência de Heroína/sangue , Dependência de Heroína/epidemiologia , Humanos , Hormônio Luteinizante/metabolismo , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/sangue , Fumar/epidemiologia , Testosterona/metabolismo , Adulto Jovem
17.
BMJ Case Rep ; 12(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31831513

RESUMO

An 18-year-old woman with a history of hollow visceral myopathy presented with a small-bowel obstruction. High-dose opioid analgesia was required subsequently during hospital admission. She suffered two episodes of documented fasting hypoglycaemia, despite adjustment of parenteral carbohydrate administration. Investigations for non-insulin-mediated hypoglycaemia revealed a low morning cortisol of 109 nmol/L and an inappropriately low Adrenocorticotropic hormone (ACTH) level of 2.2 pmol/L. A diagnosis of secondary adrenal insufficiency was confirmed on repeat cortisol and ACTH testing. The 250 µg short Synacthen test cortisol response was normal, suggestive of acute rather than chronic ACTH deficiency. This pattern was consistent after further opioid exposure. Adrenal recovery occurred shortly after opioid cessation. Opioid-induced hypoadrenalism is likely an under-recognised clinical entity with potentially serious adverse patient outcomes. There are reported cases involving commonly prescribed opioids including fentanyl and tramadol. However, we believe this is the first reported clinical case of acute transient opioid-induced secondary hypoadrenalism associated with fasting hypoglycaemia.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Analgésicos Opioides/efeitos adversos , Fentanila/efeitos adversos , Hipoglicemia/etiologia , Tramadol/efeitos adversos , Adolescente , Insuficiência Adrenal/complicações , Analgésicos Opioides/farmacologia , Feminino , Fentanila/farmacologia , Humanos , Tramadol/farmacologia
18.
Value Health ; 22(11): 1231-1239, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31708059

RESUMO

BACKGROUND: For patients undergoing percutaneous coronary intervention, gene-drug associations exist relevant to first-line treatment options-antiplatelet agent, clopidogrel, and pain medication, tramadol. Knowledge of genotype information may allow for avoidance of adverse drug events during critical clinical windows. OBJECTIVE: This evaluation estimated cost-effectiveness associated with a multi-gene panel pre-emptively testing two genes providing CYP2C19 genotype-guided strategy for antiplatelet therapy, with CYP2D6 genotype-guided pain management, compared to single gene test for CYP2C19 with random assignment for pain treatment, and to no testing (empiric clopidogrel with random assignment for pain treatment). METHODS: Decision analysis modeling was used to project costs from a payer perspective and patient quality-adjusted life years (QALYs) from the three strategies. The model captured composite risks of major adverse cardiovascular events and pain therapy-related adverse drug events and associated utility estimates. We conducted sensitivity analyses to assess influential input parameters. RESULTS: Over 15 months, multi-gene testing was least costly and yielded more QALYs compared to both single gene and no testing; total incremental costs were $1646 lower with incremental gains of 0.04 QALYs for multi-gene compared with single gene and $11 368 lower with 0.17 QALY gains compared to no test. Base case analyses revealed multi gene was dominant compared to both single gene and no test, as it demonstrated cost savings with increased QALYs. CONCLUSIONS: For these patients, a multi-gene-guided strategy yields a favorable incremental cost-effectiveness ratio compared to the other two treatment strategies. Pre-emptively ascertaining additional gene-drug pair information can inform clinical and economic decision-making at the point of care.


Assuntos
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Testes Genéticos/economia , Testes Genéticos/métodos , Intervenção Coronária Percutânea/métodos , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacocinética , Clopidogrel/efeitos adversos , Clopidogrel/farmacocinética , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Humanos , Modelos Econômicos , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/farmacocinética , Anos de Vida Ajustados por Qualidade de Vida , Tramadol/efeitos adversos , Tramadol/farmacocinética
19.
Drug Alcohol Depend ; 205: 107533, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704378

RESUMO

BACKGROUND: Although much is known about the correlates of heroin overdose, less is known about pharmaceutical opioid (PO) overdose. This study aimed to examine correlates of opioid overdose deaths by opioid and compare correlates between opioids. METHODS: Analysis of opioid overdose deaths in Australia between 2000-2015, extracted from the National Coronial Information System (NCIS). The NCIS is an online database of deaths reportable to the coroner, and contains coroner's findings, autopsy and toxicology reports. Deaths were categorized into mutually exclusive groups: 1) Heroin deaths; and 2) PO deaths (excluding heroin). PO deaths were examined by individual opioid. RESULTS: There were 10,795 opioid overdose deaths over the study period. Relative to deaths occurring in major cities, deaths in regional/remote areas had 15.2 (95 % CI: 11.5-20.2) times the risk of being attributed to pharmaceutical fentanyl than heroin. Relative to deaths among people without a recorded history of chronic pain, deaths among people with a recorded history of chronic pain had a 1.9-10.7-fold increased risk of the death being attributed to POs than heroin. Deaths among people with a recorded history of substance use problems where the opioid was injected prior to death had 7.2 and 1.7 times the risk of being attributed to methadone and pharmaceutical fentanyl (respectively) than heroin. CONCLUSIONS: Findings suggest the need to: educate PO consumers about the risks of overdose at the time of prescribing; increase coverage and engagement in opioid dependence treatment (particularly in regional/remote areas); and increase uptake of take-home naloxone to reduce opioid overdose mortality.


Assuntos
Analgésicos Opioides/efeitos adversos , Dor Crônica/mortalidade , Overdose de Drogas/mortalidade , Heroína/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/mortalidade , Adolescente , Adulto , Analgésicos Opioides/uso terapêutico , Austrália/epidemiologia , Dor Crônica/diagnóstico , Dor Crônica/tratamento farmacológico , Overdose de Drogas/dietoterapia , Overdose de Drogas/prevenção & controle , Prescrições de Medicamentos/normas , Feminino , Fentanila/efeitos adversos , Fentanila/uso terapêutico , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Morfina/efeitos adversos , Morfina/uso terapêutico , Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Tramadol/efeitos adversos , Tramadol/uso terapêutico , Adulto Jovem
20.
CNS Neurol Disord Drug Targets ; 18(10): 758-768, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721720

RESUMO

Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer's disease and Parkinson's disease. Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer's disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson's Disease (PD).


Assuntos
Doença de Parkinson Secundária/induzido quimicamente , Convulsões/induzido quimicamente , Síndrome da Serotonina/induzido quimicamente , Tramadol/efeitos adversos , Analgésicos Opioides/efeitos adversos , Animais , Humanos
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