Pharmacobezoar After Venlafaxine and Oxazepam Overdose: How Pharmacokinetics Could Help?-A Grand Round.

ABSTRACT: The authors present here a case of a pharmacobezoar after drug overdose, diagnosed using multiple blood samples for TDM. This grand round highlights the importance of a dialog between a clinician and a TDM consultant for the optimal care of a patient.

Methylene blue used in the treatment of refractory shock resulting from drug poisoning.

BACKGROUND: Methylene blue inhibits the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, decreasing vasodilation and increasing responsiveness to vasopressors. It is reported to improve haemodynamics in distributive shock from various causes including septicaemia and post-cardiac surgery. Reports of use in overdose are limited. We describe the use of methylene blue to treat a case of refractory distributive shock following a mixed drug poisoning. CASE DETAILS: A 41-year-old male presented following reported ingestion of 18 g extended-release quetiapine, 10 g controlled-release carbamazepine, 240 mg fluoxetine, 35 g enteric-coated sodium valproate and 375 mg oxazepam. He was comatose and intubated on presentation. Progressive hypotension developed. Echocardiogram revealed a hyperdynamic left ventricle, suggesting distributive shock. The patient remained hypotensive despite intravenous fluid boluses, escalating vasopressor infusions. Arterial blood gas revealed metabolic acidaemia and high lactate. Methylene blue was administered as loading-dose of 1.5 mg/kg and continuous infusion (1.5 mg/kg/h for 12 h, then 0.75 mg/kg/h for 12 h) resulting in rapid improvement in haemodynamic parameters and weaning of vasopressors. Serum quetiapine concentration was 18600 ng/mL (30-160 ng/mL), collected at the time of peak toxicity. CONCLUSION: Severe quetiapine poisoning produces hypotension primarily from alpha-adrenoreceptor antagonism. Methylene blue may have utility in the treatment of distributive shock resulting from poisoning refractory to standard vasopressor therapy.

Toxicokinetics of a dipyridamole (Persantin) intoxication: case report.

We report a case of a 51-year-old woman who was admitted to the hospital after ingestion of large doses of dipyridamole (12 g), temazepam (1 g) and oxazepam (0.2 g) with suicidal intent. The highest dipyridamole concentration that was measured in serum was 9.2 mg/L, which was paralleled by impaired platelet activation. For temazepam and oxazepam, peak serum concentrations were 8.5 and 1.3 mg/L, respectively. The patient was treated with activated charcoal, magnesium sulfate and aminophylline and could be discharged in good physical condition within 17 hours. This is the first report that provides toxicokinetic data and a corresponding pharmacodynamic effect after an intoxication with dipyridamole.

[Time limits for gastrointestinal decontamination in poisoning]. / Tidsgraenser for gastrointestinal dekontaminering ved forgiftning.

A 70-year-old man was admitted to hospital within 5 hours after an intended overdose of benzodiazepines and morphine. He was treated with flumazenil and naloxone but GID was considered unsafe. 24 hours after admission the patient had a GCS at 5 and significant respiratory insufficiency. After intubation, large amounts of tablets were aspirated and activated charcoal instilled. Respirator treatment was required for 24 hours and the course was complicated by aspiration pneumonia. The case challenges strict time limits and a restricted attitude towards gastric emptying in massive overdose.

Idiopathic recurrent stupor: a warning.

A proposal that an endogenous benzodiazepine-like agent named endozepine-4 might be responsible for presentations of recurrent stupor has gained wide acceptance. A case of recurrent stupor over two decades is presented with many similarities to previous cases of "endozepine stupor". This case, however, was caused by exogenous benzodiazepine administration and serves as a warning to clinicians to beware of this diagnosis.

Relative toxicity of benzodiazepines in overdose.

OBJECTIVE: To assess the sedative effects in overdose of temazepam and oxazepam compared with other benzodiazepines to determine if this explains reported differences in fatal toxicity. DESIGN: Cohort study of patients admitted with benzodiazepine poisoning. SETTING: Newcastle, Australia. SUBJECTS: 303 patients who had ingested benzodiazepine alone or in combination with alcohol and presented to a general hospital which served a well defined geographical area. MAIN OUTCOME MEASURES: Degree of sedation: Glasgow coma score, McCarron Score, and whether patients were stuporose or comatose. RESULTS: Oxazepam produced less and temazepam more sedation than other benzodiazepines. Unadjusted odds ratios for coma with oxazepam and temazepam compared with other benzodiazepines were 0.0 (95% confidence interval 0.0 to 0.85) and 1.86 (0.68 to 4.77) respectively, chi 2 = 7.08, 2df, P = 0.03. After adjustment for potentially confounding effects of age, dose ingested, and coingestion of alcohol, the odds ratios were 0.22 (0.0 to 1.43) for oxazepam and 1.94 (0.57 to 6.23) for temazepam. Similar results were obtained for other measures of sedation. CONCLUSIONS: These results were in accordance with fatal toxicity indices derived from coroners' data on mortality and rates of prescription. The relative safety of benzodiazepines in overdose should be a consideration when they are prescribed.

Fatal intoxication with amlodipine.

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition of continuous calcium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of severe hypercalcemia and hyperglycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.

Skin blisters as a manifestation of oxazepam toxicity.

A 75 year-old comatous patient was admitted after ingestion of 200 mg oxazepam. Skin blisters, attributed to oxazepam toxicity, appeared on the left forearm the following day and regressed spontaneously nine days later.

[A drowsy child: benzodiazepine poisoning?]. / Een suf kind: benzodiazepine-intoxicatie?

In The Netherlands accidental intoxications in children due to benzodiazepines are regularly encountered. In 1987 of 1630 requests for information at the National Poison Control Centre about probable benzodiazepine intoxications 144 (8.8%) concerned children 0-12 years of age. The symptoms of this type of intoxication are non-specific and if the physician does not think of benzodiazepine intoxication extensive diagnostic procedures may be performed. If children show symptoms e.g. unconsciousness, ataxia and hypotonia, the physician should always think of benzodiazepine intoxication and try to confirm or to exclude this possibility by toxicological analysis. We discuss ways and means of the diagnosis and how to avoid pitfalls on the way.