• 약학회지
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• 제36권3호
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• pp.230-240
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• 1992

The metabolic profile of doxylamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy] ethanamine, was determined in the human urine. The free fractions of extracts were obtained without hydrolysis, and the conjugated fractions of extracts were obtained with enzyme hydrolysis using ${\beta}-glucuronidase/arylsulfatase$ from Helix pomatia. The mixture of acetic anhydride/pyridine (10 : 1, v : v) was used to derivatize the urinary extracts and then analyzed by gas chromatography and mass selective detector. N-desmethyldoxylamine, doxylamine carboxylic acid, desaminohydroxydoxylamine, N, N-didesmethyldoxylamine, N-acetyl conjugates of N-desmethyl and N, N-didesmethyldoxylamine, quarternary ammonium N-glucuronide of doxylamine, N-desmethyldoxylamine N-glucuronide and unchanged doxylamine were detected in the human urine obtained after oral treatment with doxylamine succinate. $N-methyl-{\alpha}-hydroxy-2-[1-phenyl-1-(2-pyridinyl)$ ethoxy] ethanamine, which can be a key intermediate of this metabolism, was tentatively identified by the interpretation of its mass spectrum. In this study, we proposed the metabolic pathway of doxylamine in the human on the basis of our data of the identified metabolites of doxylamine.

• 대한임상독성학회지
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• 제8권2호
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• pp.88-96
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• 2010

Purpose: Doxylamine is antihistamine drug that is used as a hypnotic. It is also used for suicidal attempts because it can be easily purchased at the pharmacy without a prescription. There were many articles about the complications after doxylamine intoxication such as a rhabdomyolysis, but only a few articles have reported on seizure. We reviewed the cases of doxylamine intoxication with seizure that were treated in the emergency department. Methods: We reviewed the medical records of the patients who were over 15 years old and who were intoxicated by doxylamine at 3 emergency medical centers from January 2006 to June 2010. We reviewed the patients' age, gender, the dose of doxylamine ingested, if gastrointestinal decontamination was done, the time from intoxication to hospital arrival, the seizure history, treatment of seizure, the electroencephalography (EEG) results, the brain computed tomography (CT) results and the blood test results. Results: There were 168 patients who were intoxicated by doxylamine during the study period. Twelve patients had a seizure episode. The differences between the patients who developed seizure and the patients who did not were the dose and the serum levels of sodium and creatinine. The only clinically meaningful difference was the amount of doxylamine. The amount of doxylamine ingested (>29 mg/kg) predicted the development of seizure with a sensitivity of 75% and a specificity of 92% on the ROC curve. One patient among the seizure patients expired in the emergency department. Conclusion: In case of doxylamine intoxicated patients, there is close relationship between seizure and ingested amount, so close observation needs to be done for the patients who ingest too much because doxylamine can cause death. Further prospective studies are needed for doxylamine intoxicated patients with a seizure episode.

• Clinical and Experimental Pediatrics
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• 제45권8호
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• pp.1033-1037
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• 2002

Doxylamine is an antihistamine of the ethanolamine class. It is used primarily as a sleep-inducing agent. Clinicians should be aware of the complications in rhabdomyolysis patients who ingest doxylamine succinate and over-the-counter antihistamines. The easy availability of these substances increases the potential not only of intentional overdose by adults but also of inadvertent ingestion by children. Prompt intervention and careful assessment of renal function, urinary output, and serum creatine kinase levels may represent the difference between an uncomplicated and acute renal failure. Recognition of the potential for rhabdomyolysis and institution of vigorous treatment may prevent acute renal failure in patients who have taken an overdose of the drug. A 14-year-old male was found to have hematuria and oliguria. Evaluation of the patient revealed myoglobinuria, and a creatine kinase(CK) level of 117,563 IU/L. He was recovered by massive fluid administration, urine alkalization and mannitol infusion. We report a case of a suicide attempt in a child where ingestion of the doxylamine complicated by non-traumatic rhabdomyolysis with brief review related literatures.

• 대한임상독성학회지
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• 제2권1호
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• pp.15-19
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• 2004

Doxylamine succinate is an antihistamine used primarily as a sleep-induction. It can be gotten without a doctor's prescription in Korea, so it' s overdoses were frequently encountered. There were several reports that the overdoses of doxylamine might cause rhabdomyolysis, but few cases have been reported that it is related to acute renal failure (ARF). In cases that ARF occur, most of them are not severe enough to require hemodialysis. We experienced two cases of severe rhabdomyolysis complicating ARF after doxylamine overdose and treated with hemodialysis. Clinicians should be aware of the potentially lethal complications of rhabdomyolysis in patients who ingest doxylamine succinate and the needs for prompt intervention and careful assessment of renal function.

• 대한임상독성학회지
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• 제1권1호
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• pp.27-33
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• 2003

Purpose: According as the accessibility about drugs becomes various, the occurrence of drug intoxication is increasing. Since report that doxylamine causes rhabdomyolysis often, drug-induced rhabdomyolysis is one of the most important complications in patients with drug intoxication. Acute renal failure (ARF)'s availability is important to the management in rhabdomyolysis, but report about rhabdomyolysis or ARF occurrence for whole intoxicated drugs is lacking up to now. Methods: This research did to 61 patient who had rhabdomyolysis of drug intoxication. First, object patients were divided into two gruops: doxylamine-ingested (Group I) vs non-doxylamine ingested (Group II). And then we analyzed on the early patient's clinical events and laboratory data. We used ROC curve to recognize'the early clinical factors that could forecast ARF appearance among these patients in addition. Results: Almost rhabdomyolysis was happened by doxylamine in drug intoxication ($55.7\%$). However, as compared to group II, group I showed better clinical course, lesser ARF occurrence and hemodialysis requirement. In group II, time was longer in hospital reaching from intoxication, the ARF occurrence rate was higher ($52.6\%$). Analyzing the ROC curve to useful initial factors, they were creatinine, uric acid and interval time from ingestion to hospital. These cut-off values were 1.44 mg/dL, 6.8 mg/dL and 5 hrs. Sensitivity for ARF estimate was $100\%$, specificity $69-98\%$. Conclusion: Compared to group II, Doxylamine-ingested group showed good clinical course. Creatinine, uric acid, interval time from ingestion to hospital aided in ARF estimate in drug-induced rhabdomyolysis.

• 대한임상독성학회지
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• 제8권2호
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• pp.79-87
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• 2010

Purpose: The previous studies on $H_1$ antihistamine overdose have generally been limited to cases of acute doxylamine succinate (DS) poisoning, yet there have been some studies on diphenhydramine (DPH) overdosing. But many clinicians consider the two drugs to be very similar and to have similar ingredients. The purpose of this study was to clarify the toxicologic characteristics and clinical outcomes between DS and DPH poisoning/overdose. Methods: We reviewed the medical and intensive care records of the patients with acute DS or DPH poisoning and who admitted to our emergency department from January 2008 and April 2010. We collected patient information regarding the features of the poisoning and the clinical and demographic characteristics. The patients were assessed for the clinical outcomes, the GCS, the PSS (Poisoning Severity Score) and the SOFA (Sequential Organ Failure Assessment). Results: Fifty seven patients (45 cases of DS poisoning and 12 cases of DPH poisoning) were enrolled. Compared with the DS group, the DPH group had higher incidences of intubation, serious mental change, QTc prolongation and ECG conduction abnormality (p=0.041, <0.001, 0.014 and 0.044, respectively). The DPH group had a higher PSS and a longer ICU stay. The peak CPK time and the CPK normalization time were longer for the patients with rhabdomyolysis due to DS poisoning. Conclusion: Two common $H_1$ antihistamines, doxylamine and diphenhydramine, are in the same ethanolamine-structural class, but the toxico-clinical outcomes are different according to many aspects. Therefore, clinicians could take a careful approach for the differential diagnosis and management between DS and DPH poisoning.

• 대한임상독성학회지
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• 제20권1호
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• pp.8-14
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• 2022

Purpose: This study was undertaken to investigate how sedative-hypnotics affect the occurrence and severity of the patient's symptoms. In addition, we conducted a study to determine the type of patients who reacted severely and required hospitalization; patients were accordingly classified as hospitalized patients and patients discharged from the emergency room. Methods: From January 2017 to December 2019, we investigated the demographics, drug information, history, laboratory tests, and severity of patients who visited our emergency department and were diagnosed with benzodiazepine, zolpidem, and doxylamine succinate overdose. We further compared details of hospitalized patients and discharged patients. Results: Subjects who had overdosed and visited the ED included 120 for benzodiazepine, 147 for zolpidem, and 27 for doxylamine succinate. Comparisons between the three groups revealed differences in their early diagnosis, psychiatric history, and sleep disturbance. Differences between groups were also determined for mental state, poisoning history, treatment received in the intensive care unit, and intubation and ventilator support. In cases of benzodiazepine overdose, we obtained a high hospitalization rate (40.0%), admission to the intensive care unit (24.2%), and intubation rate (18.3%). Comparisons between hospitalized patients and discharged groups showed differences in transferred patients, early diagnosis, and mental state. Conclusion: Patients poisoned by sedative-hypnotics are increasing every year. In cases of benzodiazepine and zolpidem, the hospitalization rates were high, and benzodiazepine overdose resulted in hospitalization, intensive care unit admission, and pneumonia in a majority of cases. Therefore, active treatment and quick decisions in the emergency room are greatly required.

• 대한임상독성학회지
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• 제7권2호
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• pp.156-163
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• 2009

Purpose: Doxylamine succinate (DS) is frequently used to treat insomnia and it may induce rhabdomyolysis in the overdose cases. The purpose of this study is to evaluate the factors that can predict the serum creatine kinase (CK) level normalization time for patients with rhabdomyolysis due to DS ingestion. Methods: This study was conducted on 71 patients who were admitted with rhabdomyolysis after DS ingestion during the period from January 2000 to July 2009. Rhabdomyolysis was defined as a serum CK level over 1,000 U/L. The collected data included the general characteristics, the anticholinergic symptoms, the ingested dose, the peak serum CK level, the time interval (TI) from the event to the peak CK level and the TI from the event to a CK level below 1,000 U/L. We evaluated the correlation between the patients' variables and the TI from the event to the peak CK level time and the time for a CK level below 1,000 U/L. Results: The mean ingested dose per body weight (BW) was $30.86{\pm}18.63\;mg/kg$ and the mean TI from the event to treatment was $4.04{\pm}3.67$ hours. The TI from the event to the peak CK level was longer for the patients with a larger ingestion dose per BW (r=0.587, p<0.05). The CK normalization time was longer for the patients with a larger ingested dose per BW (r=0.446, p<0.05) and a higher peak CK level (r=0.634, p<0.05). Conclusion: The ingested dose per BW was correlated with the TI from the event to the peak CK level, and the ingested dose per BW and the peak CK level have significant correlations with the CK normalization time. These factors may be used to determine the discharge period of patients who had rhabdomyolysis following a OS overdose.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.117.2-118
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• 2000

• 대한의생명과학회지
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• 제10권3호
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• pp.299-303
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• 2004

The number of acute drug intoxication who visiting to emergency department which is located near urban and rural area concomitantly is inclined to increase slightly, The purpose of this study was the investigation of methods and strategies of management of acute drug intoxication in emergency department Clinical trials were done on 92 cases of acute drug intoxication visiting to Emergency Department of Chungnam National University Hospital during 4 months from April to July 2003. 1. The total number of acute drug intoxication during this period was 92 patients, which presented 0.95％ of all the emergency department visiting patients during the study. The intentional ingestions were observed in 84 cases (91.3％). 2. The maximal point of age distribution was 4th decade. The number of that was 21 cases (22.8％). 3. The number of patients who had ingested benzodiazepines and doxylamine succinates was 26 cases (28.2％), organophosphorus was 20 (21.7％), paraquat was 10 (10.8％), others were 36 (39.3％). 4. Five kinds of po1ydrug ingestion was observed in 3 cases, four kinds was observed in 3, three kinds was observed in 5 and co-ingestion of alcohol was observed in 28 cases (30.4％). 5. The mortality was occurred in 4 cases, 2 of them were caused by paraquat, 1 of them was caused by organophosphorus (OP), 1 of them was caused by acetic acid. 6. The gastric larvage as a mean of treatment modality was done in 57 cases (61.9％). The use of activated charcoal was done in 8 (8.69％). The maintenance of tracheal intubation was done in 6 (6.52％). 7. The mean observational period in emergency department was 8 hours 42 minutes in benzodiazepine and doxylamine succinate group, 21 hours 46 minutes in OP, 20 hours 39 minutes in other germicidal except OP, 23 hours 9 minutes in paraquat group. Without a drug information and intoxication center in Korea, We should minimize the exhaustion of medical resources by establishment of determinant criteria which can be seen in relatively less-complicated cases of acute drug intoxication. Thus, we should consider the introduction of simple toxicology treatment protocol and toxicologic observation unit in emergency department as possible means to reduce economical and social burdens.