Clinical outcomes associated with orphenadrine deliberate self-poisoning: a retrospective poisons centre study.

INTRODUCTION: Orphenadrine overdoses can cause antimuscarinic toxicity, respiratory failure, refractory seizures and cardiotoxicity. The dose-toxicity relationship is poorly defined. Orphenadrine is marketed as immediate and sustained release formulations, and it is not known how the formulation impacts on toxicity. We determined the clinical toxicity of orphenadrine in patients referred to a regional poisons centre. METHODS: Retrospective case series of patients in New South Wales with orphenadrine deliberate self-poisoning from January 2016 to April 2022 referred to the New South Wales Poisons Information Centre. Demographics, history of exposure, treatment and outcomes were extracted from clinical databases. Receiver-operating characteristic curves were constructed to determine thresholds predicting toxicity. RESULTS: Forty-eight patients were identified, with information on clinical outcomes in 46 patients and doses in 41 patients. All patients were older than 12 years. The median orphenadrine dose was 770 mg (range 210-10,000 mg), 59 per cent as the immediate release formulation, and 67 per cent reported coingestants. Doses of sustained release formulations were significantly greater than immediate release formulations, median 2,750 mg versus 595 mg. Common clinical features were drowsiness (59 per cent), sinus tachycardia (37 per cent) and confusion (33 per cent). Three patients had mild hypotension, three were intubated for coma, and two had seizures; no patients suffered ventricular dysrhythmias. All patients survived, with 75 per cent being medically cleared within 24 hours of presentation. A dose-toxicity relationship was observed, but conclusions are limited by the small number of cases with moderate or severe toxicity. DISCUSSION: All patients survived, and severe cardiac and neurological toxicity were not observed. This contrasts to published case reports noting severe poisoning at similar or lower doses. Formulation may have an impact on outcomes, with lesser toxicity from sustained release products. CONCLUSIONS: Orphenadrine doses up to 10 g were associated with antimuscarinic toxicity and sedation, but not severe cardiotoxicity. More research exploring the effect of dose and formulation on outcomes is required.

Clinical and patient characteristics associated with severe outcome in diphenhydramine toxicity.

BACKGROUND: Diphenhydramine is frequently misused and ingested recreationally for its antihistaminergic and antimuscarinic effects and is often involved in both serious and fatal poisonings, either in isolation or in combination with other xenobiotics. OBJECTIVE: This analysis sought to determine which patient and encounter characteristics were associated with severe outcome after diphenhydramine overdose. METHODS: This is an analysis of the multi-center ToxIC registry (2010-2016). Descriptive analysis of all cases with diphenhydramine listed as the "primary agent" contributing to toxicity were included. Analysis sought to determine which patient and encounter characteristics were associated with severe outcome, defined as occurrence of seizure, ventricular dysrhythmia, or intubation. To determine which patient and encounter characteristics were individually associated with severe outcome, we performed chi-square tests. Fisher's exact tests were used in the case of sparse data. We also performed multivariable logistic regression to further determine independent risk factors for severe outcome in diphenhydramine overdose. RESULTS: Eight hundred and sixty-three cases remained after exclusion with 15.6% (n = 135) of all patients having one or more severe outcome. The most common severe outcome was seizures which occurred in 98 (11.6%) of all ingestions. Females comprised 59.1% (n = 510) of all ingestions. Most ingestions were intentional (86.0%, n = 742) with the most common known reason for an intentional ingestion being self-harm, accounting for 37.5% (n = 324) of all ingestions. Self-harm ingestions and ingestions in males were more commonly associated with intubation. When examining outcomes by age, there were no significant differences overall or in any individual outcome except intubation in which children 0-12 were less likely to be intubated as compared to teens and adults. Signs and symptoms most strongly associated with a severe outcome included acidemia (pH < 7.2), QRS prolongation (QRS > 120 ms), and elevated anion gap (AG > 20). DISCUSSION: Acidemia, QRS prolongation, and elevated anion gap are associated with severe outcomes in diphenhydramine toxicity. Further research is warranted to determine their predictive characteristics.

Unintentional overdose of hyoscine hydrobromide in a young child.

A 4-year-old girl presented with confusion, ataxia and hallucinations 3 hours after an accidental overdose of 108 µg per kg of hyoscine hydrobromide (Kwells Kids). She was hypotensive and tachycardic at presentation. Investigations revealed QTc prolongation on ECG. The girl was admitted for observation overnight and was noted to have persistent visual and auditory hallucinations, which resolved without treatment. To our knowledge, this is the first reported case of an overdose of hyoscine hydrobromide at such a young age. Clinicians should be aware that unintentional ingestions in this age group may present with psychiatric manifestations. Hyoscine hydrobromide is easily accessible and available over the counter. It has serious consequences in overdose. Its packaging and appearance are attractive to young children making it susceptible to unintentional ingestions. We argue that its container should be altered to be more childproof.

Atropine toxicity caused by erroneous intranasal administration in a pediatric patient: case report.

A 28-month-old boy mistakenly received intranasal atropine sulfate instead of Otrivin (xylometazoline hydrochloride) for the treatment of adenoid hypertrophy. Later on, he came to the emergency department with anticholinergic manifestations after the administration of multiple drops. The child presented with a tonic-clonic seizure lasting for a few minutes, followed by a brief loss of consciousness, vomiting, agitation, and irritability, all of which were stabilized by a dose of intravenous lorazepam. Subsequently, he was admitted to the pediatric intensive care unit for observation. Afterwards, he developed agitation and unsteady gait, both of which resolved after receiving neostigmine. Eventually, the child became asymptomatic and was discharged home. To the best of our knowledge, only one similar case has been reported in the literature. SIMILAR CASES PUBLISHED: 1.

Physostigmine is superior to non-antidote therapy in the management of antimuscarinic delirium: a prospective study from a regional poison center.

CONTEXT: Poison centers (PCs) frequently manage patients with antimuscarinic delirium. However, controversy surrounds the antidotal use of physostigmine for its treatment. The aim of this study was to prospectively investigate physostigmine versus non-antidote therapy for the management of antimuscarinic delirium in a single regional PC. METHODS: This was a prospective observational analysis of patients diagnosed with antimuscarinic delirium and treated in consultation with a regional PC. Certified Specialists in Poison Information (CSPIs) use a clinical guideline to recommend the use of physostigmine. Using a previously derived altered mental status score, we quantified the rate of delirium improvement with physostigmine compared to non-antidote therapy two hours after initial patient identification. We also recorded adverse events (defined a priori as bradycardia, vomiting, seizures) and resource utilization (intubation and physical restraint). RESULTS: We identified 245 patients and included 154 in the analysis. The most common exposure classes were antihistamines (68%), analgesics (19%), and antipsychotics (19%). CSPIs recommended physostigmine in 81% (125) of cases and the treatment team administered it in 37% (57) of these. We observed delirium control in 79% of patients who received physostigmine versus 36% of those who did not. The odds of delirium control were six times greater for patients receiving physostigmine than for patients treated with non-antidote therapy (OR 6.6). Adverse events were rare and did not differ significantly between the groups. Physostigmine was not associated with changes in the incidence of intubation or restraint. CONCLUSIONS: This study provides further evidence of both the safety and efficacy of physostigmine in the treatment of antimuscarinic delirium.

Use of a physostigmine continuous infusion for the treatment of severe and recurrent antimuscarinic toxicity in a mixed drug overdose.

INTRODUCTION: Physostigmine was once a widely used antidote for the treatment of antimuscarinic toxicity. However, reports describing the association of physostigmine with asystole and seizures in severe tricyclic antidepressant poisoning resulted in a decrease in use. Recent literature has demonstrated that physostigmine is a safe and effective antidote for the treatment of antimuscarinic toxicity. There are only two previously published articles regarding the use of physostigmine administered as a continuous intravenous infusion for persistent antimuscarinic toxicity. We present a case of physostigmine continuous infusion for the treatment of antimuscarinic symptoms in a polydrug overdose due to the ingestion of diphenhydramine along with bupropion, citalopram, acetaminophen, and naproxen. CASE PRESENTATION: A 13-year-old female presented with hyperthermia, myoclonus and rigidity, hallucinations, severe agitation, and antimuscarinic toxicity including inability to sweat after a polydrug overdose. Several doses of lorazepam were administered followed by physostigmine which produced resolution of hallucinations and attenuation of the antimuscarinic symptoms including perspiration, temperature improvement, and decreased agitation. After periods of improvement and recurrence of antimuscarinic effects, a continuous infusion of physostigmine was administered at 2 mg/h and continued for almost 8 h to maintain attenuation of symptoms. GABAergic agents including lorazepam and phenobarbital were used later in the hospital course for presumed symptoms of serotonergic and adrenergic toxicity after resolution of antimuscarinic effects. The patient did not experience any adverse effects of physostigmine administration. DISCUSSION: Physostigmine administered as a continuous infusion may be a reasonable treatment option for severe and recurrent symptoms related to antimuscarinic toxicity.

Atropine eye drops: an unusual homicidal poisoning.

In March 2009, the body of a 51-year-old man was found in the boot of his car. The body had been frozen before being dismembered at the abdomen. The autopsy failed to determine the cause of death. Systematic toxicological analyses of the victim's peripheral blood and urine showed the presence of atropine, a powerful anticholinergic. Atropine was therefore specifically detected and quantified throughout the victim's biologic samples by HPLC-MS² in the biologic fluids and UHPLC-MS² in the hair. The atropine concentrations were 887 ng/mL in the cardiac blood, 489 ng/mL in the peripheral blood, 6693 ng/mL in the gastric contents (1.1 µg), 6753 ng/mL in the urine, and 2290 pg/mg in the hair. The blood concentrations measured in the decedent were consistent with an overdose of atropine, which was determined as the cause of death. The manner of death was a homicide with criminal intent.

Intoxication with a tropenol ester.

BACKGROUND: While the effects of medicinal products are investigated in depth before approval, often very little is known about the intermediates occurring during synthesis. The pharmacological properties of these intermediates can differ substantially from those of the end product. AIMS: To describe a work accident involving intoxication with such an intermediate, tropenol ester. CASE REPORT: A healthy 40-year-old chemical-technical operative erroneously used a scrubbing brush that had just been used to clear up tropenol ester, contaminating his work clothes. Presumably, contact was made with his skin when removing his work clothes later. Shortly thereafter, he developed signs of anticholinergic intoxication with mydriasis, dry mouth, abnormal coordination and later sleepiness and seizures. The patient received intensive medical treatment. Two weeks later, the anticholinergic symptoms had subsided. Qualitative analysis of a urine sample showed traces of tropenol ester. The substance is a muscarinic acetylcholine receptor antagonist. CONCLUSIONS: The clinical symptoms and biomonitoring suggest that intoxication with tropenol ester had occurred, which, as a tertiary amine, readily passes through the blood-brain barrier. The protracted course suggests high affinity for the receptor. Appropriate safety precautions must be taken when handling research substances and intermediates of unknown toxicity.

[Severe atropine poisoning mimicking acute stroke]. / Intoxication grave à l'atropine mimant une urgence neurovasculaire.

INTRODUCTION: Atropine is a strong antagonist of muscarinic receptors widely used in various diseases because of its anticholinergic action. CASE-REPORT: We report here a case of accidental poisoning due to ingestion of atropine eyes drops that caused severe neurologic disorders mimicking an acute stroke. Correct diagnosis was finally made by detecting atropine in the cerebrospinal fluid of the patient. CONCLUSIONS: Atropinic poisoning can induce misleading neuropsychiatric disorders mimicking stroke. Therefore, this diagnosis should be considered in patients presenting an unexplained encephalopathy with anticholinergic manifestations, especially when bilateral mydriasis occurs.

Review of the epidemiology and characteristics of intentional cyproheptadine overdose in Hong Kong.

OBJECTIVES: To identify the epidemiological characteristics and clinical outcome in patients who intentionally ingested cyproheptadine or cyproheptadine-containing sleeping pills, and to investigate any association between dose ingested and reported adverse effects. METHOD: A retrospective study was performed based on data from the Hong Kong Poison Information Centre from July 2005 to December 2009. Fifty-seven eligible patients were recruited. Patients' epidemiological data, type and dose of cyproheptadine or cyproheptadine-containing sleeping pills ingested, symptoms, clinical outcome, and length of stay in hospital were reviewed. RESULTS: The majority of patient with intentional overdose had no (42.1%) or mild (40.4%) sedative symptoms. Some 17% of patients developed anticholinergic symptoms, such as delirium, agitation, disorientation, and hallucination. The mean dose ingested was found to be significantly higher in patients who presented with delirium (188.6 mg) than those who were asymptomatic (49.8 mg) (p < 0.001). The time of symptom onset in all symptomatic patients was less than 6 h. CONCLUSIONS: The majority of patients with intentional cyproheptadine overdose had no or mild symptoms only. Patients who have ingested a significant amount of cyproheptadine are more prone to develop delirium. Patients who remain asymptomatic 6 h after exposure are unlikely to develop serious symptoms.

Fatal intoxication because of trihexyphenidyl.

Trihexyphenidyl (THP) is an anticholinergic agent with forensic toxicological interest. We present a case of a 59-year-old woman with a history of paranoid disorder, who was found dead in the house where she lived alone. The autopsy findings revealed no marked pathological changes. Toxicological analysis based on gas chromatography-mass spectrometry (GC-MS) analysis revealed THP and its major metabolite (hydroxy-THP) in blood and urine, with THP concentrations of 0.053 and 0.560 mg/L, respectively. The blood and urine ethanol concentrations were low 0.096 and 0.100 g/L, respectively. Based on these results, we determined the cause of death to be THP poisoning. It is suggested that rare case of death associated with THP overdosage should be taken in conjunction with central nervous system depressants (benzodiazepines, ethanol) and/or with other pathological disorders. Thus, our case could not be supportive for this allegation.

Epidemic of poisoning caused by scopolamine disguised as Rohypnol tablets.

OBJECTIVE: An epidemic of scopolamine poisonings occurred in Oslo in 2008 among users of illicit drugs, caused by fake Rohypnol pills. The clinical features, diagnostic process, and handling of the epidemic are presented. METHODS: Suspected cases of scopolamine poisoning were extracted by reviewing registration forms from an ongoing prospective clinical study of acute poisonings in Oslo. Medical records of extracted contacts were examined and cases included according to specified clinical criteria. RESULTS: Forty-four cases of probable scopolamine poisoning were registered. Main clinical features were mydriasis, visual hallucinations, plucking behavior, agitation, and coma. No clinical diagnosis of anticholinergic syndrome was made prior to forensic analysis of the tablets, the most frequent diagnosis up to this point being unspecified drug-induced psychosis. Later in the epidemic, scopolamine poisoning became the dominating diagnosis. Ten patients were admitted to psychiatric hospitals, the rest recovered in medical units, or left health care against medical advice. DISCUSSION: Scopolamine poisonings are rare, but the resulting anticholinergic syndrome is well described. The syndrome was not recognized until the forensic analysis result strikingly changed how the patients were diagnosed and handled. A unique aspect of this epidemic was the intoxicating agent being scopolamine-containing tablets looking like Rohypnol, sold and used under the impression of being the latter. CONCLUSION: Recognizing the anticholinergic syndrome is important to provide proper treatment. Forensic analysis was the key to correct diagnosis in this outbreak, demonstrating its importance in verifying an epidemic of poisoning by fake drugs.

Determination of orphenadrine plasma levels using HPLC with diode array detection and a novel solid-phase extraction procedure in psychiatric patients.

Orphenadrine is an antimuscarinic agent mainly used for the treatment of parkinsonism and to alleviate the neuroleptic syndrome induced by antipsychotic drugs. A new, rapid analytical method, based on liquid chromatography with diode array detection (DAD), has been developed and applied to the determination of orphenadrine in plasma of schizophrenic patients for therapeutic drug monitoring and toxicological purposes. The chromatographic separation was performed on a pentafluorophenyl reversed phase column with a mobile phase composed of acetonitrile-phosphate buffer mixture. DAD detection was carried out at 220 nm. A careful and rapid solid-phase extraction procedure on cyanopropyl cartridges was chosen for plasma sample purification and pre-concentration obtaining good extraction yield values for the analyte (>96.0%). The assays showed a linear response for orphenadrine (30-1000 ng mL(-1)). The method is also precise and selective. Thus, the method developed seems to be suitable for routine analysis of orphenadrine in psychiatric patients. Moreover, it was applied to plasma samples from a psychotic patient who had tried to poison himself with 1000 mg of orphenadrine and was undergoing polypharmacy.

Acute anticholinergic syndrome from Atropa belladonna mistaken for blueberries.

PURPOSE: To report the first case in the ophthalmic literature of acute anticholinergic syndrome after ingestion of Atropa belladonna mistaken for blueberries. METHODS: A 36-year-old woman presented to our ophthalmic emergency department with complaints of blurry vision, lightning flashes, disorientation, loss of balance, agitation, and anxiety for 24 hours. Ophthalmic examination revealed bilateral pupillary dilatation and paresis of accommodation. Additional symptoms of the anticholinergic syndrome were elicited on further questioning. RESULTS: Anticholinergic intoxication was suspected and the patient admitted to have eaten six "blueberries" found in the forest the previous day. The patient identified Atropa belladonna as the source of the berries she had eaten when shown photographs of the plant and its fruit. The recommendations of the Swiss Toxicological Information Centre were followed and physostigmine, the antidote for severe poisoning when 10 or more berries are ingested, was not administered. CONCLUSIONS: Accidental ingestion of Atropa belladonna berries may cause patients to first consult an ophthalmologist. It is important to recognize the anticholinergic syndrome caused by such intoxication in order to make a proper diagnosis, avoid unnecessary testing, and provide expedient appropriate treatment when required.

The early toxicology of physostigmine: a tale of beans, great men and egos.

Mid-19th century European visitors to Old Calabar, an eastern province of Nigeria, could not avoid becoming aware of native belief in the power of the seeds of a local plant to determine whether individuals were innocent or guilty of some serious misdemeanour. The seeds were those of a previously unknown legume and soon referred to as the ordeal bean of Old Calabar. Their administration was known locally as 'chop nut'. Missionaries who arrived in Calabar in 1846 estimated that chop nut caused some 120 deaths annually and documented the course of poisoning. The latter information and samples of the beans rapidly found their way to Scotland, the home of the missionaries' parent church, explaining why the early toxicology of physostigmine, quantitatively the most important of three active alkaloids in the beans, has such strong Scottish, predominantly Edinburgh, associations. However, it was 1855 before the first of many medical scientists, Robert Christison, a toxicologist of repute, investigated the effects of the beans to the extent of eating part of one himself and documenting the moderate, if not severe, consequences. A further 6 years were to pass before Balfour's comprehensive botanical description of the bean plant appeared. It was he who named it Physostigma venenosum. It was not so long until the next event, one that sparked more intensive and international interest in the beans. In 1863 a young Edinburgh ophthalmologist, Argyll Robertson, published a paper announcing the arrival of the first agent that constricted the pupil of the eye. The drug was an extract of Calabar beans and Argyll Robertson openly admitted that he had been alerted to its unusual property by his physician friend, Thomas Fraser. A minor flood of contributions on the ophthalmic uses of bean extracts followed in the medical press in the next few months; those on their systemic toxicity were fewer. Fraser's MD thesis, submitted to the University of Edinburgh in 1862 and clearly pre-dating Argyll Robertson's involvement with the beans, became generally available a few weeks after the appearance of Argyll Robertson's paper and was the first to address in detail the features of systemic administration of extracts of the beans. A major problem facing all early researchers of the beans was that of deciding how best to extract their active principle, a task made all the more difficult because bioassays were the only means of determining if the toxin was being tracked. The stability of extracts was an inevitable issue and the active principle finally became known as physostigma or physostigmine, after the botanical name of the parent plant. The features of physostigmine toxicity were soon exhaustively documented, both in animals and humans. How they were mediated was another matter altogether. Fraser maintained that muscular paralysis, the cardinal feature, was the result of depression of the spinal cord and was generally, but far from unanimously, supported. Of those who had reservations, Harley was the most prominent. He concluded that paralysis was secondary to effects on the motor nerve endings and, in so doing, came nearest to present-day knowledge at a time when acetylcholine, cholinesterases and cholinesterase inhibitors were not even imagined. Differences of opinion on the mode of action of the beans were to be expected and it is hardly surprising that they were not resolved. No standard formulation of physostigmine was available so the potency of those used would have varied from one investigator to another, the range of animals experimented upon was large while the number used by any researcher was commonly in single figures, more readily available cold-blooded creatures seemed less sensitive to physostigmine toxicity than warm-blooded ones and only Fraser determinedly pursued an answer; in general, the others made one foray into bean research then turned their attentions elsewhere. The same problems would beset other aspects of bean research. While Fraser did not get as close to the mode of action of physostigmine as Harley, he reigns supreme when it comes to antagonism between physostigmine and atropine. By this time, the 1870s had dawned and although the concept of antagonism between therapeutic agents was not new, it had little, if any, reliable scientific foundation. This was about to change; antagonism was becoming exciting and rational. Fraser's firm belief that physostigmine and atropine were mutually antagonistic at a physiological level was contrary to the conventional wisdom of his contemporaries. This alone would earn him a place in history but his contribution goes much, much further. Unlike any other at the time, he investigated it with scientific rigour, experimenting on only one species, ensuring as best he could the animals were the same weight, adjusting the doses of drugs he gave them for bodyweight, determining the minimum lethal dose of each drug before assessing their antagonistic effects, adopting a single, incontrovertible endpoint for efficacy and carrying out sufficient numbers of experiments to appear convincing in a later era where the statistical power of studies is all-important. To crown it all, he presented his results graphically. Fraser never claimed to have discovered the antagonism between physostigmine and atropine. Bartholow in 1873 did, based on work done in 1869. But his data hardly justify it. If anyone can reasonably claim this particular scientific crown it is an ophthalmologist, Niemetschek, working in Prague in 1864. His colleague in the same discipline, Kleinwächter, was faced with treating a young man with atropine intoxication. Knowing of the contrary actions of the two drugs on the pupil, Niemetschek suggested that Calabar bean extract might be useful. Kleinwächter had the courage to take the advice and his patient improved dramatically. Clearly, this evidence is nothing more than anecdotal, but the ophthalmologists were correct and, to the present day, physostigmine has had an intermittent role in the management of anticholinergic poisoning. The converse, giving atropine to treat poisoning with cholinesterase inhibitors, of which physostigmine was the first, has endured more consistently and remains standard practice today. It is salutary to realise that the doses and dosage frequency of atropine together with the endpoints that define they are adequate were formulated by Fraser and others a century and a half ago.

Pediatric poisoning from trimedoxime (TMB4) and atropine automatic injectors.

OBJECTIVE: To describe the effects of combined trimedoxime (TMB4) and atropine poisoning from automatic injectors (AI) in children. STUDY DESIGN: Data was collected from two sources: calls to the Israel Poison Information Center (IPIC) during a 1-year period and a cohort of children who presented to pediatric emergency departments (EDs) after unintentional injection of an AI. Demographic data and data regarding the type of AI, site and time of injection, and the clinical manifestations were abstracted. RESULTS: Data were available for 142 patients. The median age was 8.5 years (range 1.25-18 years). The dose of atropine and TMB4 was higher than the recommended dose for age in 22 (15.5%) cases. There were few side effects attributable to atropine: dilated pupils (26.7%), dryness of mucous membranes (24.6%), and tachycardia (22.5%). Compared with children injected with an age-appropriate dose, children injected with an AI that contained a dose that exceeds the recommended one were more likely to be symptomatic ( P = .029). There were no side effects characteristic to oximes, and no specific medical intervention was required. CONCLUSIONS: Unintentional pediatric atropine and TMB4 injection, even an adult dose in a small child, does not cause significant side effects.

[The influence of aminostigmine on the parameters of nonspecific resistance and immune system of the organism upon acute poisoning of benzyl 3-quinuclidylate].

The results of experiments on outbred rats weighing 180 -240 g showed that the acute poisoning with benzyl 3-quinuclidylate decreases the parameters of nonspecific resistance of the organism, reduces the antibody production mainly to T-dependent antigens (sheep red blood cells), decreases the activity of natural killers and the antibody-dependent cell-mediated cytotoxicity, and suppresses the formation of delayed-type hypersensitivity. Aminostigmine partly inhibits the immunotoxicity benzyl 3-quinuclidylate.

Three cases of substitution errors leading to hyoscine hydrobromide overdose.

We report three patients with anticholinergic poisoning caused by the substitution of hyoscine hydrobromide for hyoscine butylbromide in preparations compounded by two different pharmacists. The patients took the preparations for gastrointes tinal discomfort and presented with altered mental status tachycardia, facial flushing, dilated pupils, and dry skin shortly after the ingestion. In one patient the intoxication was initially not recognized and he was treated as suffering from an acute cerebrovascular accident. Two patients experienced long-lasting effects such as decreased ability to concentrate, memory dis turbances, tremor, and photo- and phonophobia. It was obviously impossible to elucidate the exact nature of the relationship between the intoxication and these long-lasting complaints. Information from the Belgian poison control center revealed that cases of substitution error with hyoscine hydrobromide are not unique The Belgian authorities issued a warning to all pharmacists.