Case reportSuicidal overdose with relapsing clomipramine concentrations due to a large gastric pharmacobezoar
Introduction
Pharmacobezoars are concretions of pharmaceutical products that form and persist in the gastrointestinal tract [1]. Pharmacobezoars may form from various oral forms of drugs, both as a result of acute overdose and during chronic use of therapeutic doses [1], [2], [3], [4], [5], [6], [7], [8], [9]. Formation of pharmacobezoars is possible especially following massive abuse of sustained release tablets or capsules [5], [9], [10], [11], [12]. In those cases an active substance may be released from pharmacobezoars causing persistent or recurrent intoxication [9], [10], [13], [14], [15], [16].
Diagnosis of pharmacobezoars trapped in gastrointestinal tract is highly difficult. Pharmacobezoars have solid form and standard gastric lavage may reveal no pills in returning fluids. X-ray or computed tomography is not routinely performed in intoxicated patients. Moreover, most pharmaceutical products are not radio-opaque and plain X-ray may reveal no pathological shadows. The presence of pharmacobezoar in gastrointestinal tract should be suspected in cases of prolonged or recurrent intoxication.
Clomipramine is a dibenzazepine tricyclic antidepressants widely used in the treatment of depression, obsessive-compulsive disorders and phobias.
The paper presents a case of acute intoxication after massive doxepin and sustained-release clomipramine overdosage with relapsed toxic serum concentration of tricyclic antidepressants (TCAs) related to a large gastric pharmacobezoar. The intoxication was fatal despite surgical removal of the pharmacobezoar.
Section snippets
Case report
A 42-year-old female, with a 2-year history of depression, was admitted to the toxicological unit because of TCAs abuse with a suicidal intent. A letter found by ambulance staff in the patient pocket indicated that 14 h earlier she had ingested 60 tablets of Anafranil SR (75 mg clomipramine per tablet) and 30 capsules of doxepin (25 mg doxepin per capsule). At admission the patient was deeply unconscious with a Glasgow Coma Scale score (GCS) of 5. Arterial blood pressure (BP) was 90/50 mmHg and
Materials
Ethyl acetate (Sigma, Taufkirchen, Germany) was HPLC grade. Doxepin, clomipramine and N-desmethylclomipramine were purchased from Lipomed AG (Arlesheim, Switzerland). Biological samples of blood collected from femoral vein, eye vitreous, myocardium, brain and liver were obtained during autopsy and stored in −20 °C.
Sample preparation
Tissue sample (0.2 g) were homogenized and digested using 5 mL 0.1 N NaOH solution in 37 °C overnight. Aliquots of biological samples (1 mL each), were brought to pH 9 using 1 N HCl and 1 mL
Results
Post mortem examination revealed cerebral and pulmonary edema, passive hyperaemia of internal organs and shock kidneys. Post-mortem concentrations of doxepin, clomipramine and its main metabolite – norclomipramine in blood and internal organs was determined with gas chromatography with mass spectrometry (Table 1).
Discussion
In presented case the patient was admitted to Toxicology Unit 14 h after a suicidal abuse of TCAs. However, considering the information that there is a sustained-release preparation among the taken drugs, gastric lavage was performed. Moreover, repeated doses of activated charcoal and polyethylene glycols were used for decontamination of the gastrointestinal tract. Unfortunately, the applied methods of the gastrointestinal decontamination proved completely unsuccessful and failed to prevent
Funding
This research received no specific grant from any funding agency in the public, commercial, or not for-profit sectors.
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