盐酸替扎尼定的合成

4-氯-2-硝基苯胺依次经还原、缩合成环、硝化、还原制倒丶屑涮?-氯-4-氨基-2,1,3-苯并噻二唑,再与1-乙酰基咪唑烷-2-酮缩合、水解、成盐制得盐酸替扎尼定,总收率46%.     

Clonidine overdose: a review.

The pharmacology and pharmacokinetics of clonidine and the symptoms and treatment of acute clinidine overdosage are reviewed. Clonidine, a relatively safe and effective antihypertensive agent when used at therapeutic dosages, reduces blood pressure through a centrally mediated reduction in vasomotor tone. The primary symptoms of clonidine overdosage are central nervous system depression, bradycardia, hypotension, miosis, hypotonia, respiratory depression and possibly seizures. Gastric lavage followed by administration of activated charcoal is used to decrease absorption following acute oral ingestion. Intravenous fluid therapy and dopamine infusion are recommended for severe hypotension, and atropine sulfate is used to manage persistent bradycardia. Treatment of hypotension with alpha-adrenergic blocking agents (e.g., tolazoline) is not recommended unless patients fail to respond to dopamine infusion and administration of i.v. fluids.     

A fatal case of bupropion (Zyban) overdose

A sensitive and reproducible method for the identification and the quantitative determination of bupropion (BUP) and its major metabolites, hydroxybupropion (OH-BUP) and threohydrobupropion (T-BUP), was developed in blood and urine. The three compounds were extracted with a solid-phase extraction procedure followed by LC-ESI-MS-MS separation and quantification using decadeuterated lidocaine as internal standard. BUP and its metabolites were satisfactorily identified by multiple reactions monitoring detection. The limits of detection and quantification were determined at 5 and 10 microg/L, respectively, for each analyte. The intraday and interday coefficients of variability were lower than 11.9% for BUP and its metabolites. This method was applied to the forensic case of a 35-year-old male who died after a suspected ingestion of 30 slow-release tablets of Zyban. As samplings were performed at least 72 h after the drug intake, BUP had disappeared from blood, but OH-BUP and T-BUP were present at the concentrations of 5.8 and 30.4 mg/L, respectively. In urine, concentrations ranged from 42.9 mg/L for BUP to 617 mg/L for T-BUP. These results agree with the hypothesis of a successful suicide attempt.     

Tizanidine in the treatment of spasticity

Summary A double-blind crossover trial compared tizanidine with baclofen in 36 patients with spasticity. Tizanidine appeared to reduce lower limb spasticity more effectively and to have fewer side effects, but no statistically significant differences emerged when the two drugs were compared. An additional open study of tizanidine confirmed the beneficial action in a selected minority of patients with spasticity. This drug may have an important role in the management of spasticity, but further studies are required.     

Acute cyclosporin overdose. A review of present clinical experience

Although cyclosporin is widely used in transplant patients, experience regarding the consequences of an overdose is limited. This article summarises the data available on 27 patients with oral (n = 20) or parenteral (n = 7) overdosage of cyclosporin. The available clinical data are consistent with predictions derived from animal toxicological studies, suggesting a low acute toxicity of the drug in humans. Acute oral overdoses result in minimal clinical manifestations and/or mild degrees of renal dysfunction, primarily in patients with previously impaired kidney function. Acute parenteral overdoses may have more serious consequences, premature neonates being at particular risk of developing life-threatening reactions. Determinations of blood concentrations of cyclosporin are of limited use in the management of patients with acute overdose. Guidelines are suggested for the management of such patients.     

Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have increasingly replaced tricyclic antidepressants (TCAs) in the treatment of depression. They appear to be safer in overdose, but there is little information on their spectrum of toxicity in overdose, or relative toxicity of each agent. Objective: To determine the effect of SSRIs in overdose, as a group, and the relative toxicity of five different SSRIs. METHODS: A review of consecutive SSRI poisoning admissions to a single toxicology unit. Outcomes examined were length of stay [LOS], intensive care [ICU] admission rate, coma, seizures, electrocardiographic [ECG] abnormalities, and presence of serotonin syndrome [SS]. Logistic regression was used to model the outcome QTc >440 msec. RESULTS: There were 469 SSRI poisoning admissions analyzed after exclusions. The median LOS for all SSRI overdose admissions was 15.3 h (IQR: 10.5-21.3) and 30 of 469 (6.4%; 95% CI 4.3-9.0%) cases were admitted to ICU. The incidence of seizures was 1.9% and coma was 2.4%. Serotonin syndrome occurred in 14% of overdoses. Comparison of median QTc intervals of the five SSRIs was significantly different (p=0.0002); citalopram (450 IQR: 436-484) was individually different to fluoxetine (p=0.045), fluvoxamine (p=0.022), paroxetine (p=0.0002), and sertraline (p=0.001). The proportion of citalopram overdoses with a QTc >440 msec was 68%, differing significantly from sertraline (adjusted OR: 5.11 95% CI 2.32-11.27). Comparison of median QT intervals of the five SSRIs was statistically different (p=0.026); citalopram (400 IQR: 380-440) was individually different from sertraline (p=0.023). CONCLUSIONS: This study shows SSRIs are relatively safe in overdose despite serotonin syndrome being common. The exception was citalopram, which was significantly associated with QTc prolongation. We believe that cardiac monitoring should be considered in citalopram overdose, particularly with large ingestions and patients with associated cardiac disease.     

Metaraminol (Aramine) in the management of a significant amlodipine overdose

OBJECTIVE: To report a patient with a significant amlodipine self-poisoning who failed to clinically respond to conventional treatment and was managed with metaraminol (Aramine). PATIENT: A 43-year old male presenting after ingestion of 560 mg amlodipine, who failed to respond clinically to treatment with fluid resuscitation, calcium salts, glucagon and norepinephrine/epinephrine inotropic support. MAIN RESULTS: Following a loading bolus of 2 mg and intravenous infusion (83 microg/min) of metaraminol (Aramine) there was improvement in his blood pressure, cardiac output and urine output. CONCLUSIONS: This is the first case report of the beneficial use of metaraminol (aramine) in the management of significant amlodipine poisoning unresponsive to conventional therapy.     

Lack of toxic effects following acute overdose of cellcept (mycophenolate mofetil)

Mycophenolate mofetil is an immunosuppressive drug used for prevention of graft rejection following solid organ transplant and for treatment of autoimmune disorders. We report a case of a 24-year-old female with lupus nephritis that presented following ingestion of 10 grams of mycophenolate in a suicide gesture. Serum levels confirmed ingestion. The patient was treated with decontamination and supportive care and recovered with no adverse effect.     

替托尼定与双氯芬酸治疗急性痉挛性肌痛的比较

目的：临床观察和评估替托尼定治疗急性痉挛性肌痛的有效性和安全性。方法：急性痉挛性肌痛６０例，男性３９例，女性２１例，年龄３９±ｓ９ａ。随机均分为３组，分别服用替托尼定１ｍｇ，ｔｉｄ，替托尼定１ｍｇ加双氯芬酸２５ｍｇ，ｔｉｄ，双氯芬酸２５ｍｇ，ｔｉｄ，共１４ｄ，观察在接触时、运动时、休息时及夜间在服药前后疼痛程度的变化；并记录不良反应。结果：３组服药ｄ４的总有效率分别为８１％，８３％和６５％。前２组的不良反应为轻微的嗜睡（１０％）。结论：替托尼定较双氯芬酸更快、更有效地解除痉挛性肌痛（Ｐ＜０．０５），合适剂量为３ｍｇ／ｄ。     

Life-threatening ventricular arrhythmia (torsades de pointes) after haloperidol overdose.

A 48-year-old woman developed QT prolongation and episodes of life-threatening ventricular tachycardia (torsades de pointes) after intentional overdose of haloperidol and orphenadrine. The arrhythmia did not respond to conventional anti-arrhythmic therapy but was suppressed by atrial overdrive pacing. A literature review identified haloperidol as the most likely cause of the torsades de pointes.     

Hepatoxicity evaluation in rats given a single overdose of Acetaminophen (Paracetamol)

Of the various parameters measured in the Serum of rats given a single overdose of acetaminophen (APAP), methaemoglobin (M-Hb) free and conjugated bilirubin seem to be better diagnostic indicators of APAP poisoning than alkaline phosphatase (ALP).     

Effectiveness of delayed activated charcoal administration in simulated paracetamol (acetaminophen) overdose

AIMS: Oral activated charcoal is used to treat drug overdose and is effective at reducing drug absorption when administered within 1 h of drug ingestion. There are fewer data on efficacy when the delay is longer, as is the case in most drug overdoses. This study investigated the efficacy of activated charcoal at preventing paracetamol (acetaminophen) absorption after simulated overdose when administration was delayed between 1 and 4 h. METHODS: An open randomized-order four-way crossover study was performed in healthy volunteers comparing the effect of activated charcoal 50 g on the absorption of 3 g paracetamol tablets when administered after an interval of 1, 2 or 4 h or not at all. Plasma paracetamol concentrations were measured over 9 h after paracetamol ingestion using h.p.l.c. and areas under the curve between 4 and 9 h (AUC(4,9 h)) calculated as a measure of paracetamol absorption. RESULTS: Activated charcoal significantly reduced paracetamol AUC(4,9 h) when administered after 1 h (mean reduction 56%; 95% Confidence intervals 34, 78; P<0.002) or 2 h (22%; 6, 39; P<0.03) but not after 4 h (8%; -8, 24). When administered after 1 h activated charcoal reduced individual plasma paracetamol concentrations significantly at all times between 4 and 9 h after paracetamol administration. Administration at 2 or 4 h had no significant effect. CONCLUSIONS: These results in healthy volunteers cannot be extrapolated directly to poisoned patients. However, they provide no evidence of efficacy for activated charcoal when administered after an interval of more than 2 h.     

Computer-Assisted Retrospective Clinical Activities Statistics (CARCAS) Program

Clinical pharmacy services have been demonstrated to have a positive impact on patient care in the hospital setting. Accurate and complete documentation of interventions aimed at improving drug use is essential to assess workload characteristics, determine the impact of pharmacist activities, justify current programs and predict future clinical staffing requirements. The need for an improved system of collecting and analyzing clinical workload statistics led to the development of a Computer-Assisted Retrospective Clinical Activities Statistics (CARCAS) Program in our department. Using a pre-defined clinical activity coding system, pharmacist activities were efficiently documented on a daily basis using an existing distributional computer system. Training requirements and data entry time were minimal. The CARCAS Program appeared to capture more clinical pharmacist activities than the earlier manual system. The flexibility of the CARCAS Program should permit adaptation to other hospitals with similar computer systems regardless of the nature of their clinical programs.