Asia Pacific Journal of Medical Toxicology
Year:2014 | Volume:3 | Issue:2|Papers Count:12

Non-medical use of prescription drugs (also known as medication diversion) is a common problem in middle and low income countries where monitoring capacities and law enforcement mechanisms are not efficiently developed.Prescribed central nervous system (CNS) stimulants, sedative hypnotics and long-lasting opioids are the most important drugs diverted throughout the world (1-4). Non-medical use of stimulant medications used for attention deficit hyperactivity disorder (ADHD) including methylphenidate mostly occurs among younger population at school ages (1,4). On the other hand, diversion of sedative hypnotics such as benzodiazepines and opioids such as tramadol, methadone and buprenorphine is commonly done by opioid dependent adults (2,3-5). In this issue of the journal, clinical effects of non-medical use of modafinil -a CNS stimulant- in the United States and tramadol in opioid dependents in Iran have been addressed.

Background: Modafinil, a non-amphetamine central nervous system stimulant, is a wakefulness-promoting agent indicated for use in shift work sleep disorder, narcolepsy, and obstructive sleep apnea. The trend in modafinil overexposure over a ten-year period and the population likely to experience a resulting clinical effect is evaluated.Methods: Using data from the American Association of Poison Control Center (AAPCC) National Poison Data System (NPDS), a retrospective review of all reported modafinil overexposures over a ten-year period (2001-2010) was conducted. In order to determine whether age, reason and acuity had a role in predicting medical outcome, odds ratios (OR) were calculated using binomial logistic regression analysis.Results: There were 1,100 modafinil overexposures reported with known outcomes, of which 600 cases (54%) were women and 367 (33%) were £ 5 years old. Seventy-seven percent of the exposures were acute ingestions and the majority was unintentional. The number of reported modafinil exposures increased with time until 2007. Adults were more likely to have an adverse effect than children £ 5 years of age. Patients with an intentional overexposure were more likely to have an effect than those with an unintentional overexposure (OR = 5.2; 95% CI 3.9-7.1; P < 0.001).Conclusion: The frequency of reported modafinil exposures increased with time until 2007. The majority of exposures resulted in no adverse clinical effect. Older patients and those with intentional exposure were more likely to experience a clinical effect.

Background: Bungarus caeruleus (common krait) bite during monsoon season is common in northwest India. Respiratory failure is responsible for high mortality in the victims. In this study we report our experience with manual ventilation using bag valve mask (BVM) in patients with neuroparalysis due to common krait bite.Methods: This prospective study was conducted between June 2009 and December 2009. All consecutive patients with diagnosis of common krait bite who were manually ventilated by BVM were studied. The duration of ventilation and complications associated with ventilation were noted. Polyvalent anti snake venom was administered as per the "national snake bite protocol" and patients were followed up until final outcome.Results: Thirty-four patients (70.6% men) were studied. All patients except two came from rural areas and they were hospitalized between June and September. Majority of patients were bitten during the night while sleeping on the floor. The mean time interval between bite and arrival to hospital was 4.4 hours. Ptosis (100%) was he most common clinical finding followed by ophtalmoplegia (80%) and limb muscle weakness (74%). Twenty-four patients (70%) developed respiratory symptoms and 20 (59%) were intubated and manually ventilated by BVM. Mean duration of assisted ventilation was 34.6±12.8 hours. Hoarseness of voice and throat pain were noted in all intubated patients following extubation, which responded to conservative therapeutic measures. The mean duration of hospitalization was 6 ± 1.6 days. All patients except one survived.Conclusion: Manual ventilation with BVM in patients with neuroparalysis due to common krait bite is a safe and effective modality in resource constraint settings.

Background: Tramadol overdose is relatively common in Iran. A series of tramadol poisoned patients with paresthesia and decreased muscle strength are described.Methods: In this prospective cross-sectional study, all referred cases to Mashhad Medical Toxicology Center with suspected tramadol poisoning between 1st July 2010 and 1st September 2012 were included. Patients with mixed overdose, history of neurologic and musculoskeletal disorders including primary seizure, and history of addiction were excluded. Patients were visited on admission, 6 and 12 hours later. All cases underwent complete neurologic examination. Muscle strength was assessed with manual muscle testing.Results: Tramadol overdose accounted for 1026 cases during the study period. Eight hundred eighty nine cases were excluded and finally 137 cases were tramadol only overdose. Most patients (92%) were men. Mean (SD, min-max) age was 24.5 (6.9, 10-42) years. The strength of upper and lower limbs symmetrically declined in the first visit and increased gradually in 6 and 12 hours post-admission, but the strength of lower limbs was more significantly affected on admission and after 6 hours (P < 0.001) compared to upper limbs. Paresthesia happened in 64%, 9% and 0% in upper limbs and 86%, 35% and 3% in lower limbs on admission, and after 6 and 12 hours. No spasticity and flaccidity were observed. On admission, pupils were symmetrically reactive and 6.7 (2.3, 1-11) mm wide. Pupil size significantly declined to 5.6 (2.1, 1.3-9.0) mm 6 hours later (P < 0.001).Conclusion: Transient paresthesia and transient symmetrical decline in muscle strength of upper and lower limbs are potential neurologic complications following tramadol abuse and overdose. Further studies are needed to fully clarify the pathogenesis and mechanism of these complications following tramadol overdose.

Background: Cardiovascular effects of acute organophosphate (OP) poisoning are common. This study was aimed to assess the cardiovascular effects of OP poisoned patients in Nepal.Methods: This was a prospective hospital-based cross-sectional study of 115 acute OP poisoned patients presenting in emergency department of a tertiary care teaching hospital of central Nepal during November 2008 to October 2011. Cardiovascular manifestations were assessed by physical examination and electrocardiogram (ECG). All data including demographic features, clinical findings and outcomes were entered into a pre-structured proforma.Results: A total of 115 OP poisoned patients were studied. Mean age of the patients was 29.8±13.9 years. Fifty-seven patients (49.6%) developed cardiac effects that all had sinus tachycardia. Sinus bradycardia was observed in 3 patients (2.61%). Hypertension was detected in 23 patients (20%) and pulmonary edema developed in 24 patients (20.9%). The most common ECG abnormalities recorded were prolonged QTc in 21 patients (18.26%) and ventricular extra systole in 14 patients (12.2%). Five patients developed polymorphic ventricular tachycardia (VT) and 3 patients developed ventricular fibrillation (VF) which could not be reverted back despite adequate treatments and led to death (mortality rate: 6.9%).Conclusion: Cardiac effects of OP poisoning can be life-threatening. Prompt diagnosis, early supportive and definitive therapies with atropine and oximes along with vigilant monitoring of the patients for prominent cardiac effects such as QT prolongation, VT or VF during hospital stay can definitely save lives of the victims.

Background: It is becoming apparent that although inhibition of cholinesterase plays a key role in organophosphate (OP) toxicity, other factors are also important. One of the contributing factors for severity of OP poisoning is electrolyte imbalances such as hypokalemia. This study was aimed at evaluating the value of hypokalemia in association with plasma cholinesterase (PChE) levels in predicting morbidity and mortality of acute OP poisoning.Methods: In this cross sectional study patients with definitive diagnosis of OP poisoning were enrolled. Pre-interventional clinical features were observed and noted with severity assessment as per Proudfoot classification, along with measurement of serum potassium ion ([K+]) concentration and PChE level.Results: Fifty OP poisoned patients (33 men, 17 women) were enrolled with median age of 27.1 years. The most common clinical manifestation was congested conjunctiva (82%) followed by miosis (78%) and bronchorrhea (78%). A total of 21 cases presented with one or more severe clinical features according to Proudfoot classification. Among them, 61.9% of cases (13 out of 21) developed hypokalemia. Muscle weakness or fasciculation developed with mean serum [K+] of 3.31 ± 0.11. Ventilatory support was required at the mean serum [K+] of 3.27 ± 0.10 mmol/L. Fatality was noted when the mean serum [K+] reduced to 2.90 ± 0.06 mmol/L. Correlation of the clinical effects and serum [K+] was significant (P < 0.001). In addition, muscle weakness, fasciculation, convulsion and respiratory distress were associated with marked suppression of PChE (>75%). Death was mostly observed among patients who had respiratory distress associated with hypokalemia and grossly reduced PChE.Conclusion: For severe clinical features of OP poisoning, serum [K+] and PChE level are greatly reduced. Hence, these biochemical findings can be proposed as OP poisoning predictive markers. Clinicians and medical toxicologists should consider hypokalemia associated with reduced PChE level as alarming signs of poor prognosis in OP poisoned patients.

Background: There is much debate about effects of medicinal plants such as saffron (Crocus sativus) on human health. Women are highly involved in farming and processing of this plant. This study is aimed at evaluating the saffron impacts on miscarriage rate of female farmers working in saffron fields.Methods: This was a prospective case-control study on pregnant female farmers during harvesting season of saffron in December 2005 to evaluate miscarriage rate among them. All pregnant women who were between the first and twentieth week of gestation and were participated in saffron harvesting and processing in previous years were studied. The subjects were divided into two age and gestational age-matched groups of cases and controls. The cases were prohibited from working in saffron fields and in return they were paid same as the average amount of their monthly income. They were trained not have any exposure to saffron and a team supervised them on their adherence during the study period. Nevertheless, they were free for working in other careers. On the other hand, the controls were allowed for working in the fields and processing saffron.Results: Forty-one subjects were included in case group and 38 subjects in control group. Median age of all subjects was 25 years. The groups were not significantly different from each other according to history of miscarriage and 2nd occupation. Four subjects experienced miscarriage that all of them belonged to control group having contact to saffron. None of cases had miscarriage. Using Fisher’s exact test, it was found that miscarriage rate was significantly higher (10.6% vs. 0%, P = 0.03) among female farmers who had saffron exposure.Conclusion: Exposure to saffron may increase the risk of miscarriage. Hence, it is suggested that pregnant women avoid contact with considerable amounts of saffron especially for female farmers working in saffron fields.

Background: Pesticide poisoning is a common method of suicide attempt and less commonly accidental poisoning in Bangladesh. This review for the first time estimated the extent and characteristics of pesticide poisoning in Bangladesh and explored existing limitations in methodologies of studies done on poisoning in the country.Methods: A narrative search in electronic medical databases including MEDLINE, Google Scholar and Banglajol was carried out. Search terms used were “Bangladesh”, “pesticide”, “poisoning” and “organophosphate”. Relevant studies were collected and assessed for their originality. Organization reports were also collected. Studies after the year 2000 were only selected. Methodologies of the studies were carefully scrutinized.Results: Estimated case load of poisoning in hospitals of Bangladesh was 7.1% (CI 6.9-7.2) of total admissions. Pesticide poisoning accounted for 39.1% (CI 37.6-40.6%) of total poisoning cases admitted in different levels of hospitals in Bangladesh. Majority of them were due to WHO class-II pesticides (moderately hazardous). Reported frequency of different pesticides includes organophosphate compounds (OPCs) in 89.8%, rodenticides in 4.3%, carbamates in 4.0%, unknown compounds in 1.6% and pyrethroids in 0.3% of cases. Pesticide poisoning was responsible for 72.6% (CI 68.0-76.8) of total poisoning related deaths. Approximately 0.7 deaths per 100,000 population was due to pesticide poisoning. Reporting the frequency of chemical nature of pesticides varied significantly with methodology used for case identification (P < 0.001). In studies that toxidromic assessment was used, most cases were treated as OPC poisoning. In studies that applied sample identification by evaluation of container/pack and reading its label, over 30% of cases were due to carbamates. Presence of only one toxicological analysis center in the country has made routine chemical identification practically impossible.Conclusion: Pesticide poisoning is responsible for great number of admissions and deaths in Bangladesh. Creating a register of commercially available pesticides in each region for rapid identification of nature of the pesticide is recommended.

Background: Diazoxide is the main therapeutic agent for congenital hyperinsulinism. The drug is generally well tolerated; however, in this report severe adverse effects including heart failure (HF) and pulmonary hypertension (PH) in an infant are reported.Case report: A sixteen-day male infant with persistent hypoglycemia and with diagnosis of congenital hyperinsulinism underwent near total pancreatectomy. Despite surgery, hypoglycemia persisted, and thus oral dizoxide 5 mg/kg/dose three times per day was administered. At four months of age, the patient was again admitted to the hospital because of respiratory distress and poor feeding from a week earlier. On physical examination, he was tachypneic and mild intercostal retraction was present. Tachycardia existed without definitive murmur. Moderate hepatomegaly was detected. Chest X-ray revealed cardiomegaly. Echocardiography showed right atrial and ventricular dilatation, and pulmonary pressure of 70 mmHg. In the next day, respiratory failure developed and so the patient was intubated and mechanically ventilated. Diazoxide was discontinued and 10% dextrose water (DW) was initiated. Four days later, the patient was extubated. Blood glucose remained in normal limit. Gradually the concentration of DW was decreased. The patient was discharged and followed up without any medication. Echocardiogram in one month later showed normal heart dimension and reduction of pulmonary pressure to 20 mmHg, and resolution of right atrial and ventricular enlargement.Discussion: Diazoxide reduces peripheral vascular resistance and blood pressure as the result of direct vasodilatory effect on smooth muscles in peripheral arterioles. It causes sodium and water retention and decrease of urinary output which can result in expansion of plasma and extracellular fluid volume, and consequently edema and congestive cardiac failure.Conclusion: Diazoxide therapy for infants with congenital hyperinsulinism is associated with the threat of PH and HF. Periodic echocardiography may be helpful for the infants under long term diazoxide therapy.

Background: Cocaine poisoning is known for causing severe clinical effects such as tachycardia, hypertension, agitation and confusion. Absence of clinical manifestations in cocaine poisoning is unusual.Case report: A 26-year old man, known to be a cocaine addict, declared that he was forced by cocaine dealers to swallow many tablets of cocaine, six hours prior to admission to emergency department. Clinical examination, cardiac, hematological and biochemical checkups were unremarkable. The patient was clinically stable and left the hospital seven hours after admission by self-discharge. Blood and urine toxicological screening tests for benzodiazepines, barbiturates, tricyclic antidepressants and ethanol were negative. Patient’s blood sample was not sufficient for analysis of cocaine and its metabolites. Using high-performance liquid chromatography, urine and gastric lavage samples were positive for cocaine. Quantification of cocaine and its metabolites including benzoylecgonine (BZE) and ecgonine methyl ester (EME) in urine was done using gas chromatography-mass spectrometry. Results revealed high levels of cocaine and its metabolites (cocaine: 360 mg/L, BZE: 1350 mg/L, EME: 780 mg/L).Discussion: Cocaine poisoning is generally accompanied by various clinical effects. In our case, despite the confirmed poisoning, no clinical sign was noticed. Fatal poisonings were reported with cocaine urinary concentrations of lower than that found in our patient.Conclusion: Asymptomatic cocaine poisoning with high cocaine levels in urine is of note.

To the Editor;Tramadol, a synthetic opioid is mainly used to treat acute and chronic pain. Although this drug is not an over-the-counter medication, it has been illicitly accessible to and abused by opium addicts. Studies showed excessive and widespread use of tramadol in Iran. Tramadol may cause constipation, drowsiness, tachycardia and respiratory distress, while the most severe complications of tramadol overdose include refractory seizures, rhabdomyolysis and renal failure. These serious complications may occur in sequence in tramadol overdose, as seizure can induce rhabdomyolysis, and renal failure mostly results from rhabdomyolysis (2,3). It has been reported that seizure develops in approximately one-third of cases with tramadol overdose (1,3,4).

Dear Editor;I wish to thank the authors for their careful comment (1), on our short report entitled “Aluminum Phosphide Poisoning: A Case Series in North Iran” (2).Unfortunately, as we were excited to display the findings of our series, some facts were missed from the methods of the article. The results presented in our series was collected from eight patients with definitive aluminum phosphide (AlP) poisoning diagnosed by taking history from the patients (or relatives) and clinical presentations (nausea and vomiting, metabolic acidosis, liver damage, etc.). Also, for some cases, the container of the rice tablet was brought by the patient or relatives.