Association of the OPRM1 variant rs1799971 (A118G) and clinical manifestations in tramadol poisoned patients: a cross-sectional study.

INTRODUCTION: The opioid receptor mu1 is a protein coding gene that can have different codes for a protein and may have variations (polymorphisms) affecting how opioids work. The aim of this study was to investigate the prevalence of the most common opioid receptor mu1 polymorphism (A118G) and any relationship between this polymorphism and features following tramadol overdose. MATERIALS AND METHODS: This was a cross-sectional study of patients admitted with tramadol poisoning to an Iranian hospital. These patients were not taking any other drugs or medications and had no history of seizures. RESULTS: The results showed that among the 83 patients included in the study, 57 (69 per cent) had the AA genotype, 25 (30 per cent) had the AG genotype, and one (1 per cent) had the GG genotype for the opioid receptor mu1 A118G polymorphism. Nausea and/or vomiting occurred in nine (11 per cent) patients and dizziness in 38 (46 per cent) patients. Serious adverse events included seizures in 51 (60 per cent) patients and respiratory failure requiring mechanical ventilation in 21 (25 per cent) patients. However, there was no significant association between the opioid receptor mu1 A118G polymorphism and these adverse events. DISCUSSION: In our study, the frequency of the A allele was greater than the G allele, and the AA genotype was more prevalent than AG. The GG genotype was the least common among the polymorphisms of opioid receptor mu1 rs1799971. There was no significant association between the opioid receptor mu1 A118G polymorphism and symptoms in tramadol-poisoned patients. Although these allele proportions are similar to the results reported in other Caucasian populations, they are dissimilar to the findings in Chinese and Singaporean populations. In these Asian studies, the predominant allele was the G allele. It has been suggested that a mutated G allele will decrease the production of opioid receptor mu1-related messenger ribonucleic acid and related proteins, leading to fewer mu-opioid receptors in the brain. CONCLUSIONS: This study found no significant association between the opioid receptor mu1 A118G polymorphism and adverse outcomes in tramadol-poisoned patients. However, more research is needed to draw more definitive conclusions due to the limited evidence and variability of opioid receptor mu1 polymorphisms in different populations.

Marked and prolonged serotonin toxicity in a tramadol-poisoned patient with a pharmacokinetic study.

BACKGROUND: Tramadol poisoning rarely causes serotonin toxicity, which mechanisms remain poorly understood. We investigated alterations in tramadol pharmacokinetics in a tramadol-poisoned patient who presented with marked and prolonged serotonin toxicity. CASE REPORT: A 21-year-old male self-ingested 750 mg-tramadol, 200 mg-sotalol, 400 mg-propranolol and 6 mg-lorazepam. He was a kidney transplant patient treated with mycophenolate, tacrolimus, prednisone, and paroxetine. He developed transitory cardiovascular failure and prolonged serotonin toxicity requiring sedation, muscle paralysis, and cyproheptadine, with a favorable outcome. METHODS: We measured plasma concentrations of tramadol, M1, M2, and M5 using liquid-chromatography-tandem mass spectrometry, calculated elimination half-lives and metabolic ratios of the compounds, and genotyped cytochromes involved in tramadol metabolism. RESULTS: Elimination half-lives of tramadol (6.1 h) and M1 (7.1 h) were normal while those of M2 (26.5 h) and M5 (16.7 h) prolonged. M1 metabolic ratio (0.12) was 2-fold reduced, M2 metabolic ratio (197) 1000-fold increased and M5 metabolic ratio (0.12) normal. This metabolic profile in a patient with normal CYP2D6-metabolizer status based on genotyping supports CYP2D6 inhibition by paroxetine and propranolol, two strong mechanism-based inhibitors. Only M2 present in sufficient concentrations up to 48 h could explain the prolonged serotonin toxicity. CONCLUSION: Marked and prolonged serotonin toxicity was attributed to increased M2 production due to paroxetine- and propranolol-related CYP2D6 inhibition of tramadol metabolism.

Machine learning algorithms to predict seizure due to acute tramadol poisoning.

INTRODUCTION: This study was designed to develop and evaluate machine learning algorithms for predicting seizure due to acute tramadol poisoning, identifying high-risk patients and facilitating appropriate clinical decision-making. METHODS: Several characteristics of acute tramadol poisoning cases were collected in the Emergency Department (ED) (2013-2019). After selecting important variables in random forest method, prediction models were developed using the Support Vector Machine (SVM), Naïve Bayes (NB), Artificial Neural Network (ANN) and K-Nearest Neighbor (K-NN) algorithms. Area Under the Curve (AUC) and other diagnostic criteria were used to assess performance of models. RESULTS: In 909 patients, 544 (59.8%) experienced seizures. The important predictors of seizure were sex, pulse rate, arterial blood oxygen pressure, blood bicarbonate level and pH. SVM (AUC = 0.68), NB (AUC = 0.71) and ANN (AUC = 0.70) models outperformed k-NN model (AUC = 0.58). NB model had a higher sensitivity and negative predictive value and k-NN model had higher specificity and positive predictive values than other models. CONCLUSION: A perfect prediction model may help improve clinicians' decision-making and clinical care at EDs in hospitals and medical settings. SVM, ANN and NB models had no significant differences in the performance and accuracy; however, validated logistic regression (LR) was the superior model for predicting seizure due to acute tramadol poisoning.

Trends in hydrocodone combination product exposures reported to California Poison Control System (CPCS) following DEA rescheduling.

CONTEXT: On October 6, 2014, the United States Drug Enforcement Administration (DEA) implemented a regulatory change for hydrocodone combination products (HCPs), moving them from Schedule III to II, in an effort to decrease drug overdoses. Existing research suggests this regulatory action reduced HCP prescribing and dispensing; however, there is limited research assessing its possible effects on overdoses and accidental exposures. OBJECTIVE: To analyze the changes in opioid exposures reported to the California Poison Control System (CPCS) before and after DEA rescheduling of HCPs. METHODS: We collected monthly exposure data reported to CPCS from 2012 to 2019 and conducted interrupted time series analyses to assess changes in exposures after rescheduling for HCPs, tramadol, oxycodone, morphine, codeine, fentanyl, and heroin. Additional analyses were done to assess any changes in exposures resulting in severe outcomes (moderate or major health effects). For HCPs, we also conducted logistic regressions to identify characteristics of exposures resulting in severe outcomes before and after rescheduling. RESULTS: Overall monthly opioid exposures reported to CPCS decreased after DEA rescheduling of HCPs. These decreases were significant for HCP, tramadol, and morphine (p < 0.001). Exposures significantly increased for heroin and fentanyl (p < 0.001). There were no significant changes in the share of severe outcomes attributed to HCP exposures after rescheduling. DISCUSSION: The DEA rescheduling of HCPs was associated with a significant decrease in HCP exposures and prescription opioid exposures overall, but was associated with increased fentanyl and heroin exposures. While other initiatives may have contributed to this decrease, our findings suggest that rescheduling may be a useful regulatory strategy to reduce drug exposures. CONCLUSION: DEA rescheduling of HCPs was associated with a significant reduction in prescription opioid exposures, suggesting that rescheduling high-risk drugs may be an effective strategy to improve public health.

Rhabdomyolysis: a case-based critical reflection on its causes and diagnosis.

Rhabdomyolysis is a rare and complex condition that involves injury of the skeletal muscle fibres, resulting in the release of substances such as creatine kinase and myoglobin. It is associated with acute kidney injury and mortality. This article describes the case of a 40-year-old man who presented to the emergency department after an overdose of tramadol hydrochloride. It uses critical reflection to explore traumatic and non-traumatic causes of rhabdomyolysis and reviews the literature relating to the diagnosis of rhabdomyolysis through laboratory and point-of-care testing. To ensure the timely identification of patients at risk of deterioration, emergency nurses need to be aware of the potential causes and the clinical signs and symptoms of rhabdomyolysis.

Tramadol use and public health consequences in Iran: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Misuse of tramadol, an opioid prescription analgesic, is known as a public health challenge globally. We aimed to systematically review studies on the prevalence of non-prescribed use, regular tramadol use and dependence, tramadol-induced poisoning and mortality in Iran. METHODS: Consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, international (Medline, Scopus, Web of Science) and Persian (SID) databases were systematically searched up to June 2019. Other relevant data were collected through personal contacts and review of reference lists. Pooled estimates of prevalence of tramadol use in subgroups of males and females, percentage of tramadol poisoning among admitted poisoning cases, tramadol-associated seizures and mortality among tramadol poisonings and percentage of tramadol as a cause of death among fatal drug-poisoning records were estimated through a random-effects model. RESULTS: A total of 84 records were included. Pooled estimates of last 12-month use of tramadol in the Iranian general population were 4.9% [95% confidence interval (CI) = 4.1-5.9] and 0.8% (95% CI = 0.2-1.8) among males and females, respectively. The estimates for last 12-month use among Iranian male and female university students were 4.8% (95% CI = 1.9-8.9) and 0.7% (95% CI = 0.3-1.1), respectively. Six heterogeneous reports indicated the existence of regular use of tramadol and dependence in Iran. Sixty-two studies provided data on tramadol-induced poisoning, seizures and mortality. The pooled estimate of the percentage of tramadol poisoning among all drug-poisoning patients was 13.1% (95% CI = 5.7-22.9). The overall estimates of seizures and mortality among tramadol-poisoning patients were 34.6% (95% CI = 29.6-39.8) and 0.7% (95% CI = 0.0-1.9), respectively. The pooled percentage of tramadol-related fatalities among drug-poisoned cases was 5.7% (95% CI = 0.5-15.4). CONCLUSION: Despite control policies, tramadol use is as prevalent as the use of illicit opioids in Iran. Numerous cases of tramadol abuse, dependence, poisonings, seizures and hundreds of tramadol-related deaths have been reported in recent years.

Associations Between Opioid Prescribing Patterns and Overdose Among Privately Insured Adolescents.

OBJECTIVES: Little is known about the risk for overdose after opioid prescription. We assessed associations between the type of opioid, quantity dispensed, daily dose, and risk for overdose among adolescents who were previously opioid naive. METHODS: Retrospective analysis of 1 146 412 privately insured adolescents ages 11 to 17 years in the United States captured in the Truven MarketScan commercial claims data set from January 2007 to September 2015. Opioid overdose was defined as any emergency department visit, inpatient hospitalization, or outpatient health care visit during which opioid overdose was diagnosed. RESULTS: Among our cohort, 725 participants (0.06%) experienced an opioid overdose, and the overall rate of overdose events was 28 events per 100 000 observed patient-years. Receiving ≥30 opioid tablets was associated with a 35% increased risk for overdose compared to receiving ≤18 tablets (hazard ratio [HR] = 1.35; 95% confidence interval: 1.05-1.73; P = .02). Daily prescribed opioid dose was not independently associated with an increased risk for overdose. Tramadol exposure was associated with a 2.67-fold increased risk for opioid overdose compared to receiving oxycodone (adjusted HR = 2.67; 95% confidence interval: 1.90-3.75; P < .0001). Adolescents with preexisting mental health conditions demonstrated increased risk for overdose, with HRs ranging from 1.65 (anxiety) to 3.09 (substance use disorders). CONCLUSIONS: One of 1600 (0.06%) previously opioid-naive adolescents who received a prescription for opioids experienced an opioid overdose a median of 1.75 years later that resulted in medical care. Preexisting mental health conditions, use of tramadol, and higher number of dispensed tablets (>30 vs <18) were associated with an increased risk of opioid overdose.

Acute bone marrow suppression and gastrointestinal toxicity following acute oral methotrexate overdose.

OBJECTIVE: Acute methotrexate overdose rarely causes systemic toxicity due to saturable absorption and rapid renal elimination. We present a case of methotrexate toxicity following acute overdose. CASE REPORT: A 56-year-old female presented soon after an overdose of 1250 mg of methotrexate, zopiclone and tramadol. The methotrexate was initially under-reported (500 mg) and folinic acid was not provided. Despite normal renal function, the patient developed toxicity. She represented 5 days following the overdose with mucositis, bone marrow suppression and prolonged febrile neutropenia. Treatment included folinic acid, broad-spectrum antibiotics, filgrastim, red cell and platelet transfusion. Her bone marrow began to recover 12 days following the overdose. She was discharged home on Day 17. DISCUSSION: Severe toxicity following an acute ingestion of a large amount of methotrexate is rarely reported. The development of toxicity was unexpected in this case given methotrexate's pharmacokinetics and the patient's normal renal function. The serum methotrexate concentrations were below the treatment threshold of the folinic acid rescue therapy nomogram suggesting that the nomogram should not be relied on in acute ingestions. Large acute oral methotrexate poisoning can result in systemic toxicity and folinic acid therapy should be provided in ingestions >1000 mg.

Correlation between plasma concentrations of tramadol and its metabolites and the incidence of seizure in tramadol-intoxicated patients.

BACKGROUND: Seizure is one of the important symptoms of tramadol poisoning, but its causes are still unknown. The aim of this study is to find a relationship between tramadol and the concentrations of its metabolites versus the incidence of seizures following the consumption of high doses of tramadol. METHODS: For this purpose, the blood samples of 120 tramadol-intoxicated patients were collected. The patients were divided in two groups (seizure and non-seizure). The concentrations of tramadol and its metabolites (M1, M2 and M5) were measured by using a high-performance liquid chromatography method. The relationship between tramadol and the levels of its metabolites and seizure incidences was also investigated. RESULTS: In 72% of the patients, seizures occurred in the first 3 h after the ingestion of tramadol. The seizure incidences were significantly correlated with the patients' gender, concentrations of tramadol, M1 and M2 and the history of previous seizures (p<0.001). The average concentration of M2 was significantly higher in males (p=0.003). A previous history of the use of sedative-hypnotics and the co-ingestion of benzodiazepines and other opioids were shown to significantly decrease the rate of seizure. The rate of seizure was directly related to the concentrations of tramadol and its metabolites. Higher M2 concentration in males can be considered a reason for increased incidences of seizures in males. The plasma concentration of M1 affected the onset of seizure. CONCLUSIONS: Therefore, it can be concluded that differences in the levels of the metabolites can affect the threshold of seizure in tramadol-intoxicated patients.

Observational study of dermatological manifestations in patients admitted to a tertiary poison center in Iran

Background/aim: Acute unintentional and deliberate poisoning by medications and chemicals is a frequent emergency, especially in Iran. This study aimed to evaluate the frequency and character of skin findings occurring in patients with acute intentional and aunintentional poisoning. Materials and methods: This prospective observational study was performed at the Loghman Hakim Hospital Poison Center over a period of 6 months from April 2016 to September 2016. Data including patient demographics, cause of poisoning, and level of consciousness were collected. Pediatric patients (under the age of 13) and patients who died in the first hours of admission were excluded from the study. Results: The most common cause of toxicity-related admission in our patients was methadone overdose. The most common skin finding in these patients was xerosis. According to our results, there was an association between tramadol poisoning and self-induced lesions. Shin hyperpigmentation was found to be significantly more frequent in patients with lead poisoning. Conclusion: Further study is recommended to shed light on the possible association of drug poisoning and skin lesions.

Opioid drug poisonings in Ohio adolescents and young adults, 2002-2014.

CONTEXT: Opioids represent a drug class that adolescents and young adults intentionally misuse and abuse. When taken on their own or with other substances in this manner, opioids pose an increased risk of overdose and potential death. OBJECTIVE: To determine trends of opioid drug poisonings among adolescents and young adults in Ohio from 2002 to 2014 using Poison Control Center (PCC) data. METHODS: Data were obtained from Ohio PCCs from 2002 to 2014 for opioid drug poisonings amongst 10-29 year olds. Trends were evaluated with Poisson regression. Ohio counties with higher opioid drug poisoning rates were identified using age-adjusted resident population estimates. Chi-square tests were conducted to compare these county rates to the Ohio rate. RESULTS: Both unintentional and intentional Ohio PCC opioid drug poisonings peaked in 2009, and there were significant declines through 2014. Almost 40% of intentional opioid drug poisonings were for young adults aged 18-24 years. Suspected suicide poisonings were 64.9% female, misuse poisonings were 54.5% male, and abuse poisonings were 60.1% male. Commonly reported substances included tramadol, heroin, and acetaminophen combinations with hydrocodone or oxycodone. Benzodiazepines and ethanol were the most common substances reported in conjunction with opioids. The top four Ohio counties with significantly higher opioid drug poisoning rates than the state average in 2014 were Hamilton, Mahoning, Butler, and Fairfield. CONCLUSION: This study enhances the understanding of Ohio's opioid epidemic so that future prevention efforts and legislation can better target needed resources. Both males and females would benefit from opioid education early in their lives.

Is naloxone the best antidote to reverse tramadol-induced neuro-respiratory toxicity in overdose? An experimental investigation in the rat.

CONTEXT: Since the banning of dextropropoxyphene from the market, overdoses, and fatalities attributed to tramadol, a WHO step-2 opioid analgesic, have increased markedly. Tramadol overdose results not only in central nervous system (CNS) depression attributed to its opioid properties but also in seizures, possibly related to non-opioidergic pathways, thus questioning the efficiency of naloxone to reverse tramadol-induced CNS toxicity. OBJECTIVE: To investigate the most efficient antidote to reverse tramadol-induced seizures and respiratory depression in overdose. MATERIALS AND METHODS: Sprague-Dawley rats overdosed with 75 mg/kg intraperitoneal (IP) tramadol were randomized into four groups to receive solvent (control group), diazepam (1.77 mg/kg IP), naloxone (2 mg/kg intravenous bolus followed by 4 mg/kg/h infusion), and diazepam/naloxone combination. Sedation depth, temperature, number of seizures, and intensity, whole-body plethysmography parameters and electroencephalography activity were measured. RESULTS: Naloxone reversed tramadol-induced respiratory depression (p < .05) but significantly increased seizures (p < .01) and prolonged their occurrence time. Diazepam abolished seizures but significantly deepened rat sedation (p < .05) without improving ventilation. Diazepam/naloxone combination completely abolished seizures, significantly improved rat ventilation by reducing inspiratory time (p < .05) but did not worsen sedation. None of these treatments significantly modified rat temperature. CONCLUSIONS: Diazepam/naloxone combination is the most efficient antidote to reverse tramadol-induced CNS toxicity in the rat.

Forensic Toxicology Perspectives of Methadone-associated Deaths in Tehran, Iran, a 7-year Overview.

Methadone has a long history of pain relief and successful substitute for maintenance treatment in heroin and narcotic addiction. The aim of the study was to assess the trends of methadone-associated deaths in Tehran, Iran, in 2009-2015, from a forensic toxicology point of view. All methadone-associated deaths during this 7-year study period were evaluated according to demographic parameters and forensic toxicology analysis results. Results showed that 1274 cases of methadone-associated deaths were investigated during the study period. The incidence rate of methadone-associated deaths had risen 7.7 times in 2015 in comparison with 2009 (p < 0.05). The majority of cases were men (90.35%), aged from 20 to 40 years. About 80% of cases had shown positive results for other drugs and poisons in combination with methadone. Methamphetamine and tramadol were the most drugs detected in post-mortem samples. Death rates among methadone users in Tehran, Iran, increased year by year during 2009-2015. These findings raise the attention to the concomitant use of drugs with the need for changes in regulation and regulatory policy to restrict access and use of controlled drugs.

Two Fatal Intoxications Due to Tramadol Alone: Autopsy Case Reports and Review of the Literature.

Since tramadol was marketed, it has been widely prescribed as a pain killer because of its relatively safe profile among opioids.Nevertheless, intoxication can occur: overdose can lead to fatal outcomes mostly in association with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased central nervous system (CNS) depression.Fatal outcomes only attributable to tramadol are a rare entity. In this case report, 2 fatal cases are described due to tramadol stand-alone intoxication with peculiar characteristics.In case 1, gas chromatography - mass spectrometry analysis detected tramadol in all specimens (32 µg/mL in the heart blood, 23.9 µg/mL in the femoral blood, 3.3 µg/mL in the bile, and 1.4 µg/mL in the urine). No other CNS depressants were detected by toxicological analysis.In case 2, gas chromatography - mass spectrometry analysis detected tramadol in all specimens (7.5 µg/mL in the heart blood, 5.8 µg/mL in the femoral blood, and 18 µg/mL in the urine). No other CNS depressants were detected by toxicological analysis.Review of the literature was performed to clarify the actual knowledge on this topic.

Refractory Cardiogenic Shock During Tramadol Poisoning: A Case Report.

Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. Tramadol intoxication can be lethal, and this drug is frequently involved in voluntary overdose. Classically, tramadol intoxication is associated with neurological and respiratory side effects. In contrast, cardiac effects are poorly documented in the literature. We report a case of severe tramadol intoxication, with plasma concentration 20 times the toxic threshold, complicated by refractory cardiogenic shock, successfully treated by extra corporeal life support (ECLS) with a favorable cardiac outcome and ECLS weaning at day 10. Seizure, clonus, and nonreactive mydriasis were present during 4 days, and complete awakening was delayed to day 15. Poisoning caused by high doses of tramadol can lead to refractory cardiogenic shock, and ECLS can be considered as effective rescue therapy in this context.

[A Case of Acetaminophen Poisoning Associated with Tramcet Overdose].

Tramcet is a mixture of tramadol and acetaminophen. Acetaminophen poisoning may be caused by excessive intake of Tramcet. A 17-year-old female took excessive quantity of Tramcet before noon. She reported it herself in the emergency room. Her main complaint was nausea and dizziness. Acetaminophen may cause liver damage with dose-dependent manner. Because there was a possibility of acetaminophen poisoning, we started oral acetylcysteine. She was discharged from hospital 5 days later without side effects of acetylecysteine and liver damage.

Sequencing CYP2D6 for the detection of poor-metabolizers in post-mortem blood samples with tramadol.

Tramadol concentrations and analgesic effect are dependent on the CYP2D6 enzymatic activity. It is well known that some genetic polymorphisms are responsible for the variability in the expression of this enzyme and in the individual drug response. The detection of allelic variants described as non-functional can be useful to explain some circumstances of death in the study of post-mortem cases with tramadol. A Sanger sequencing methodology was developed for the detection of genetic variants that cause absent or reduced CYP2D6 activity, such as *3, *4, *6, *8, *10 and *12 alleles. This methodology, as well as the GC/MS method for the detection and quantification of tramadol and its main metabolites in blood samples was fully validated in accordance with international guidelines. Both methodologies were successfully applied to 100 post-mortem blood samples and the relation between toxicological and genetic results evaluated. Tramadol metabolism, expressed as its metabolites concentration ratio (N-desmethyltramadol/O-desmethyltramadol), has been shown to be correlated with the poor-metabolizer phenotype based on genetic characterization. It was also demonstrated the importance of enzyme inhibitors identification in toxicological analysis. According to our knowledge, this is the first study where a CYP2D6 sequencing methodology is validated and applied to post-mortem samples, in Portugal. The developed methodology allows the data collection of post-mortem cases, which is of primordial importance to enhance the application of these genetic tools to forensic toxicology and pathology.

Trends in analgesic exposures reported to Texas Poison Centers following increased regulation of hydrocodone.

CONTEXT: In October 2014, the Drug Enforcement Administration reclassified hydrocodone to schedule II, increasing regulations on use. The impact of rescheduling hydrocodone on opioid exposures is unclear, especially in states with special restrictions required for prescribing schedule II agents. OBJECTIVE: To assess whether changes in exposures to prescription opioid analgesics and heroin as reported to poison centers occurred in the 6 months after hydrocodone rescheduling. We hypothesized that hydrocodone exposures would decrease, while less tightly regulated opioids, such as codeine and tramadol, would increase. MATERIALS AND METHODS: This study compares opioid analgesic exposures reported to Texas Poison Centers before and after this change in a state that requires special prescription pads for Schedule II agents. Cases included all opioid analgesic exposures reported to a statewide poison center network, comparing exposures from 6 months before to 6 months after heightened regulations. Specific opioids with large changes in reported exposures were further characterized by patient age and exposure intent. RESULTS: Hydrocodone exposures decreased from 1567 to 1135 (28%, p = 0.00017), decreasing for all ages. Codeine exposures increased significantly from 189 to 522 (176%, p = 0.00014), including a 263% increase for age >20 years. Codeine misuse increased 443% and adverse drug events 327%. Oxycodone exposures increased from 134 to 189 (39%, p = 0.0143), increasing only among patients age >20 years. Reported heroin exposures increased from 156 to 179 (15%, p = 0.2286) and tramadol from 666 to 708 (6%, p = 0.0193). Other opioid exposures changed little or had limited reports. DISCUSSION: The increased regulation of hydrocodone was followed temporally by a decrease in reported hydrocodone exposures, but also increases in codeine, oxycodone and tramadol exposures. This may reflect a shift in prescribing practices, changes in street availability of hydrocodone or decreased drug diversion. CONCLUSION: The increased regulation was temporally associated with decreased hydrocodone exposures reported to Texas Poison Centers.

Hypo and hyperglycemia among tramadol overdose patients in Loghman Hakim Hospital, Tehran, Iran.

Tramadol is a synthetic and centrally active analgesic. Hypoglycemia as another possible major side effect among abusers has not been known well. Our objective is evaluation of the Blood Glucose Level (BGL) among tramadol-overdosed patients. This prospective cross-sectional study was performed from Feb to June 2013; BGL was measured at the time of admission, 8 and 12 hours later. All patients with hypoglycemia received infusion of 0.5-1 gr/kg of hypertonic dextrose and their BGL was checked every hour until normal BGL. Patients' demographic, clinical and paraclinical data were collected. Totally, 128 patients with a mean (SD) age of 24.5 (6.9) years were recruited; 127 (99.2%) were male. Seizure occurred in 59.4% cases. Mean ± SD admission BGL was 94.88 ± 21.5mg/dL. Fourteen patients experienced hypoglycemia within 12 hours period. Hyperglycemia was experienced in 8 patients (6.25%) on admission day. There was no significant relation between the dose of tramadol and BGL. In conclusion, hypoglycemia must be considered as an important side effect of tramadol-overdose. It is suggested that serial BGL monitoring in cases of Tramadol-overdose should be done for early recognition of hypoglycemia and its timely management. Also hyperglycemia may be revealed.