Acute pulmonary thromboembolism (PTE) is a major medical problem in many hospitalized patients with medical and surgical conditions, and venous thromboembolism is responsible for up to 15% of all in-hospital deaths. However, PTE complicating acute intoxication has been reported only rarely, and prophylaxis for venous thromboembolism is not routinely incorporated into the management of acute poisoning in emergency departments or general wards. We describe here a case of pulmonary thromboembolism that developed within 48 h of acute benzodiazepine overdose. A 47-year-old female patient was brought to the emergency department by ambulance. She had been found unconscious, and empty packages of medications prescribed by her psychiatrist and an empty bottle of liquor were found. The estimated drugs and amounts were alprazolam 22.5 mg, diazepam 150 mg, flunitrazepam 7.5 mg, fluoxetine 150 mg, and propranolol 600 mg. Approximately 40 hours after initial presentation, she complained of dyspnea and pulse oxymetry indicated 84%. Her arterial pH was 7.41, pCO2 41.6 mmHg, pO2 46.8 mmHg, and oxyhemoglobin saturation was 83.4%. The serum D-dimer concentration was 2.78 mcg/dL, and computed tomography of the chest showed acute PTE in the right upper lobar and segmental pulmonary arteries and both lower segmental pulmonary arteries. When caring for patients with sedative drug overdose, a high level of suspicion of PTE is required, and appropriate diagnostic and therapeutic measures might be undertaken when PTE is suspected. In addition, appropriate prophylaxis for venous thrombosis should be considered.
Alprazolam ; Ambulances ; Benzodiazepines* ; Diazepam ; Drug Overdose ; Dyspnea ; Emergency Service, Hospital ; Female ; Flunitrazepam ; Fluoxetine ; Humans ; Hydrogen-Ion Concentration ; Middle Aged ; Oxyhemoglobins ; Patients' Rooms ; Poisoning ; Propranolol ; Psychiatry ; Pulmonary Artery ; Pulmonary Embolism* ; Thorax ; Venous Thromboembolism ; Venous Thrombosis

15 patients with mild to moderate chronic renal failure treated in the medical examination of friendship hospital during 1996-1998. Benazepril was administrated at dose of 1 tablet every morning. The study found that after 6 months of treatment the blood creatinine concentration and glomerular filtration level were not different from these at the beginning of treatment which prove the capacity of delaying the progress of chronic renal failure. 12/15 patients had a significant reduction of 24 hours urinary protein. 3/15 patients had a negative urinary protein after 6 months of the treatment.
Kidney Failure, Chronic ; Benzazepines

OBJECTIVE: The purpose of this study is to evaluate the usefulness of administration of benzodiazepines in patients with major depression being treated with the antidepressant mirtazapine. METHODS: The subjects of this study included 503 patients between 18 and 65 years of age. They were diagnosed with major depression according to the ICD-10 and scored over 18 at baseline on the 17-item HAM-D scale. They were among the 925 patients who have participated in the Remeron (mirtazapine) post-marketing surveillance carried out between September 1999 and December 2000 at 33 institutes in Korea. The patients were initially started on 15 mg/day or 30 mg/day of mirtazapine orally and the dosages could be changed according to clinical judgment during the trial. Benzodiazepines could also be administrated according to clinical judgment. The clinical effects were evaluated before and 1, 2 and 6 weeks after treatment initiation. The therapeutic action of mirtazapine was evaluated using the 17-item HAM-D and CGI. The adverse effects were rated according to patient reports. RESULTS: Their mean age was 45 years old and 61.6% were women. 391 subjects (77.3%) from a total of 503 patients completed the trials. 313 (62.2%) patients were administrated benzodiazepines during the trial. These were alprazolam 37.0%, lorazepam 12.5%, clonazepam 9.1% and diazepam 7.0%. The reasons for prescribing benzodiazepines were: anxiety 43.1%, insomnia 18.3% and somatic symptoms 3.8%. The HAM-D scores of total patients were reduced from 26.1 to 10.9, and CGI scores from 4.5 to 3.0 after 6 weeks with significant changes beginning after 1 week of treatment. No significant differences were found in terms of each interval changes on the HAM-D and CGI scores between the groups with and without benzodiazepines. There were no significant differences of each interval changes of anxiety/agitation factors and sleep disturbance factors between the two groups. The occurrence of side effects was not significantly different between the two groups. CONCLUSION: Administration of benzodiazepines in patients with major depression being treated with mirtazapine may not be useful in reducing depressive symptoms, even for anxiety/agitation and sleep disturbance symptoms.
Academies and Institutes ; Alprazolam ; Anxiety ; Benzodiazepines* ; Clonazepam ; Depression* ; Diazepam ; Female ; Humans ; International Classification of Diseases ; Judgment ; Korea ; Lorazepam ; Middle Aged ; Sleep Initiation and Maintenance Disorders

OBJECTIVE: The purpose of this study is to evaluate the usefulness of administration of benzodiazepines in patients with major depression being treated with the antidepressant mirtazapine. METHODS: The subjects of this study included 503 patients between 18 and 65 years of age. They were diagnosed with major depression according to the ICD-10 and scored over 18 at baseline on the 17-item HAM-D scale. They were among the 925 patients who have participated in the Remeron (mirtazapine) post-marketing surveillance carried out between September 1999 and December 2000 at 33 institutes in Korea. The patients were initially started on 15 mg/day or 30 mg/day of mirtazapine orally and the dosages could be changed according to clinical judgment during the trial. Benzodiazepines could also be administrated according to clinical judgment. The clinical effects were evaluated before and 1, 2 and 6 weeks after treatment initiation. The therapeutic action of mirtazapine was evaluated using the 17-item HAM-D and CGI. The adverse effects were rated according to patient reports. RESULTS: Their mean age was 45 years old and 61.6% were women. 391 subjects (77.3%) from a total of 503 patients completed the trials. 313 (62.2%) patients were administrated benzodiazepines during the trial. These were alprazolam 37.0%, lorazepam 12.5%, clonazepam 9.1% and diazepam 7.0%. The reasons for prescribing benzodiazepines were: anxiety 43.1%, insomnia 18.3% and somatic symptoms 3.8%. The HAM-D scores of total patients were reduced from 26.1 to 10.9, and CGI scores from 4.5 to 3.0 after 6 weeks with significant changes beginning after 1 week of treatment. No significant differences were found in terms of each interval changes on the HAM-D and CGI scores between the groups with and without benzodiazepines. There were no significant differences of each interval changes of anxiety/agitation factors and sleep disturbance factors between the two groups. The occurrence of side effects was not significantly different between the two groups. CONCLUSION: Administration of benzodiazepines in patients with major depression being treated with mirtazapine may not be useful in reducing depressive symptoms, even for anxiety/agitation and sleep disturbance symptoms.
Academies and Institutes ; Alprazolam ; Anxiety ; Benzodiazepines* ; Clonazepam ; Depression* ; Diazepam ; Female ; Humans ; International Classification of Diseases ; Judgment ; Korea ; Lorazepam ; Middle Aged ; Sleep Initiation and Maintenance Disorders

BACKGROUND: Varenicline is recently known as smoking cessation medicine has no results of researches conducted in the actual practice settings except for incipient clinical trials. This research attempted to analyze the factors for smoking cessation by using Varenicline prescribed in the family clinic, and the efficacy of Varenicline. METHODS: Brief smoking cessation education was conducted on 140 people who visited the Department of Family Medicine at Dankook University and Varenicline was prescribed for them. This research checked whether smoking was stopped or not after six months and analyzed the factors for succeeding in smoking cessation. RESULTS: Varenicline was prescribed for the 140 people. After six months, 46 smokers were successful in smoking cessation, representing the rate of success of 35.4%, and after 12 months, 31 people of 83 people were successful in smoking cessation, representing the rate of success of 37.3%. The group less smoke than 24.3 cigarettes/day (the average daily smoking amount) has higher quit rate than the group more smoke than 24.3 by 4.9 times. The group takes Varenicline longer than 26.7 days (the average Varenicline dosage period) has higher quit rate than the group takes Varenicline shorter than 26.7 by 4 times. Smoking-cessation rate was 4.5 times when trying to stop smoking by the doctor's recommendation. It was higher than when trying to stop smoking by self-determination. In the multivariate analysis, there were significant relationships in daily smoking amount, dosage and period of Varenicline, and motivation of visits. CONCLUSION: Varenicline is one of the useful medication for quitting smoking in family practice setting. Better compliance of medicine shows better quitting rate.
Benzazepines ; Compliance ; Family Practice ; Humans ; Motivation ; Multivariate Analysis ; Quinoxalines ; Smoke ; Smoking ; Smoking Cessation ; Varenicline

Craving has been well known to be the most important clinical phenomenon in smoking cessation treatment and one that physicians always encounter. For successful and prolonged abstinence, understanding, evaluation, and management of craving are essential. The concept and definition of craving is still under debate, although its importance, relevance, and role in smoking relapse is evident. There are two types of craving, 'abstinence-induced craving' and 'cue-induced craving' according to time dynamic and causes. The evaluation of craving mainly depends on self-reported measures in the clinical field. Pharmacological treatments such as the nicotine patch, bupropion, and varenicline are effective for abstinence-induced craving. Psychosocial treatment and a few pharmacological agents such as nicotine gum and lozenges are useful for reducing cue-induced craving. This review was aimed at conveying up-to-date information on the characteristics, evaluation, and treatment of craving. Development of objective measurement tool for evaluation of craving is needed. The effects of pharmacological treatments on 'cue-induced craving' remain to be discovered. An active effort to alleviate each type of craving is necessary to enhance and prolong a patient's abstinence.
Benzazepines ; Bupropion ; Gingiva ; Nicotine ; Quinoxalines ; Recurrence ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Use Cessation Products ; Tobacco Use Disorder ; Varenicline

BACKGROUND: Varenicline is an effective smoking cessation aid. However, smokers prescribed with varenicline do not always receive varenicline for 12 weeks, as recommended. This study analyzed the subjects who received varenicline and investigated the effect of varenicline treatment duration on the success rate of 6-month smoking cessation. METHODS: This study retrospectively analyzed 78 subjects, who received varenicline, out of the 105 smokers that had visited the smoking cessation clinic after medical examination from September 2007 to December 2009. RESULTS: The subjects were all males. Twenty-two subjects (28.2%) had varenicline treatment for 12 weeks or longer; 18 subjects (23.1%) for 8~12 weeks; 22 subjects (28.2%) for 4~8 weeks; and 16 subjects (20.5%) for less than 4 weeks. The total success rate of the 6-month smoking cessation was 47.4%. The success rate of the 6-month smoking cessation was 63.6% in the group that received varenicline for 12 weeks or longer, which was higher than 41.1% of the group that early terminated the varenicline treatment (p=0.074). The period of varenicline treatment was extended for one more week, the odds ratio of the 6-month smoking cessation success increased to 1.172-folds (p=0.004; 95% confidence interval, 1.052~1.305). Adverse events occurred in 30.8% of the subjects who received varenicline, but no serious adverse events were found. CONCLUSION: If varenicline treatment period is extended, the odds ratio of the success rate for the 6-month smoking cessation increases. Therefore, an effort to improve drug compliance for varenicline in clinical practices could be helpful for the long-term success of smoking cessation.
Benzazepines ; Compliance ; Health Promotion ; Humans ; Male ; Medication Adherence ; Odds Ratio ; Quinoxalines ; Retrospective Studies ; Smoke ; Smoking ; Smoking Cessation ; Varenicline

Benzodiazepine derivatives, chlordiazepoxide(Librium), diazepam(Valium), nitrazepam(Mogadon) and oxazepam(Serenid-D) are mainly used as hypnotics at present. Diazepam has been used mainly for premedication in anesthesia and as an intravenous anesthetic agent. The pharmacological actions of these drugs are tranquilizing effects for central nervous system, slight depression on the cardiovascular and respiratory system, anticonvulsant, anxiolytic and antidepressant effects. A new benzodiazepine derivative, Flunitrazepam(Ro 5-4200) has strong hypnotic action, is anticonvulsant and antidepressant in spite of slight depression of the cardiovascular and respiratory systems. Furthermore the onset and duration of this drug are shorter than the others. In our clinical study, flunitrazepam in the dosage of 0.005mg/kg was administered intravenously, as an intravenous anesthetic induction agent, for 22 surgical adult patients. In each patient, the blood pressure, pulse rate, respiratory rate, minutes volume and arterial gas study were done, before and after administration of the Ro 5-4200. The results are as follows; 1. Dosage of this flunitrazepam is not constant as other benzodiazepines. 2. The effects of flunitrazepam on the cardiovascular system showed slight depression but no effect by one hour post-operation. 3. In respiratory system, the minute volume was depressed slightly and the respiratory rate was increased but negligibly. 4. Undesirable side effects attributed to this drug were not found, except the developing of cough (one case).
Adult ; Anesthesia ; Benzodiazepines ; Blood Pressure ; Cardiovascular System ; Central Nervous System ; Clinical Study* ; Cough ; Depression ; Diazepam ; Flunitrazepam ; Heart Rate ; Humans ; Hypnotics and Sedatives ; Premedication ; Respiratory Rate ; Respiratory System ; Tranquilizing Agents

OBJECTIVETo prepare Form A and Form B of benazepril hydrochloride and to compare the differences in spectrums, thermodynamics and crystal structure between two polymorphic forms.

METHODSForm A and Form B of benazepril hydrochloride were characterized by Fourier transform infrared spectroscopy (IR), thermal gravimetric analysis (TG), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and single crystal x-ray diffraction (SCXRD).

RESULTSPreparation method, crystal structure and polymorphic stability of Form A and Form B of benazepril hydrochloride were obtained. Based on the analysis of crystal structure of both polymorphs, Form A belonged to monoclone space group P2(1) with a=7.8655(4)Å, b= 11.7700(6)Å, c= 13.5560(7)Å, β= 102.9470(10)°, V=1223.07 (11)Å(3) and Z=2, while Form B belonged to orthorhombic space group P212121, with a=7.9353(8)Å, b=11.6654(11)Å, c=26.6453(16)Å, V=2466.5(4)Å(3) and Z=4. From the DSC and XRD results, Form B of benazepril hydrochloride could be transformed into Form A after heating treatment.

CONCLUSIONForm A and Form B of benazepril hydrochloride are both anhydrous and displayed different polymorphs due to different molecular configuration. Furthermore, Form A exhibits more stable than Form B at high temperatures.

BACKGROUND: Benzodiazepines have a hypnotic/sedative effect through the inhibitory action of gamma-aminobutyric acid type A receptor. Flumazenil antagonizes these effects via competitive inhibition, so it has been used to reverse the effect of benzodiazepines. Recently, flumazenil has been reported to expedite recovery from propofol/remifentanil and sevoflurane/remifentanil anesthesia without benzodiazepines. Endogenous benzodiazepine ligands (endozepines) were isolated in several tissues of individuals who had not received benzodiazepines. METHODS: Forty-five healthy unpremedicated patients were randomly allocated to either flumazenil or a control groups. Each patient received either a single dose of 0.3 mg of flumazenil (n = 24) or placebo (n = 21). After drug administration, various recovery parameters and bispectral index (BIS) values in the flumazenil and control groups were compared. RESULTS: Mean time to spontaneous respiration, eye opening on verbal command, hand squeezing on verbal command, extubation and time to date of birth recollection were significantly shorter in the flumazenil group than in the control group (P = 0.004, 0.007, 0.005, 0.042, and 0.016, respectively). The BIS value was significantly higher in flumazenil group than in the control group beginning 6 min after flumazenil administration. CONCLUSIONS: Administration of a single dose of 0.3 mg of flumazenil to healthy, unpremedicated patients at the end of sevoflurane/fentanyl anesthesia without benzodiazepines resulted in earlier emergence from anesthesia and an increase in the BIS value. This may indicate that flumazenil could have an antagonistic effect on sevoflurane or an analeptic effect through endozepine-dependent mechanisms.
Anesthesia ; Anesthesia, General ; Benzodiazepines ; Diazepam Binding Inhibitor ; Eye ; Fentanyl ; Flumazenil ; gamma-Aminobutyric Acid ; Hand ; Humans ; Ligands ; Methyl Ethers ; Parturition ; Respiration