piperidines and Drug-Overdose

Synthetic opioids are compounds that were created to act on the opioid receptors. Novel synthetic opioids include various analogs of fentanyl (e.g., acetylfentanyl, acryloylfentanyl, carfentanil, furanylfentanyl, 4-fluorobutyrylfentanyl or ocfentanil) and newly emerging non-fentanyl compounds with different chemical structures, such as AH-7921, MT-45, and U-47700. In the last years, these drugs have rapidly emerged on the recreational drug market, and their abuse has been increasing worldwide. Due to the high potency and the low dose required to produce desired effects, the risk of overdose for these compounds including severe health implications, is quite high. Several fatal intoxication cases related to the abuse of synthetic opioids have recently been reported in the literature.. As a consequence, the detection of these compounds in biological samples is crucial in order to get a better understanding of their concentration and distribution in body fluids. We overviewed the analytical approaches for the investigation of synthetic opioids in postmortem samples reported in the literature, with special emphasis given to cases of lethal intoxication.

Topics: Analgesics, Opioid; Benzamides; Drug Overdose; Fentanyl; Humans; Illicit Drugs; Piperidines

The importance of glucose control in reducing the complications of diabetes mellitus has been clearly demonstrated. The emergency physician routinely is expected to treat a wide range of problems related to this disease, including making the initial diagnosis of type 2 and occasionally type 1 diabetes. Also common are patients with poorly controlled diabetes. The recent introduction of new classes of agents to lower blood glucose, especially in type 2 diabetes, should improve the control in this category of patient and reduce the complication rate. Some of these agents, such as troglitazone, have potentially fatal complications and require careful monitoring. Emergency physicians should be aware of the common complications of these drugs because patients can present to the ED with them. Hypoglycemia, a common cause of 911 calls and emergency visits, is not a side effect of either metformin or acarbose. Insulin lispro has improved postprandial glycemic control for type 1 and some insulin-requiring type 2 diabetics. Hypoglycemia is less of a risk with insulin lispro, and quality of life is better with this rapidly acting insulin. Newer methods of insulin delivery, such as continuous subcutaneous infusion, have greatly improved glucose control, given greater freedom to patients, and reduced the risks of hypoglycemia.

Topics: Acarbose; Administration, Oral; Carbamates; Chromans; Diabetes Mellitus; Drug Overdose; Emergencies; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Metformin; Piperidines; Sulfonylurea Compounds; Thiazoles; Thiazolidinediones; Troglitazone

The drugs used to treat diabetes mellitus are diverse and involve several classes. However, these drugs can be roughly separated into hypoglycaemic agents, such as insulin and the sulphonylureas, and antihyperglycaemic agents, such as the biguanides, the alpha-glucosidase inhibitors and troglitazone. Reports of insulin overdose are rare. The major effects of insulin overdose are secondary to the insult to the CNS produced by hypoglycaemia. The mainstay of insulin overdose management is glucose replacement therapy. Sulphonylureas are the most commonly used oral antihyperglycaemic agents in the management of type 2 (non-insulin-dependent; NIDDM) diabetes mellitus. Sulphonylureas primarily cause serum glucose reduction by stimulating the release of preformed insulin from the pancreatic islets. The mainstay of sulphonylurea overdose management is glucose replacement therapy, and in severe cases, reduction of insulin release. In the large majority of patients intravenous glucose supplementation will be sufficient to maintain euglycaemia. Repaglinide, a meglitinide analogue, is a new nonsulphonylurea oral hypoglycaemic agent. In overdose, this drug may produce prolonged hypoglycaemia similar to the sulphonylureas. The primary problem with biguanide overdose is the potential for lactic acidosis. The management of biguanide overdose is largely supportive and directed at correcting the metabolic acidosis along with associated complications. The alpha-glucosidase inhibitors, acarbose, voglibose and miglitol competitively and reversibly inhibit the alpha-glucosidase enzymes (glucoamylase, sucrase, maltase and isomaltase) in the brush border in the small intestine, which delays the hydrolysis of complex carbohydrates. They appear unlikely to produce hypoglycaemia in overdose, but abdominal discomfort and diarrhoea may occur. Troglitazone is the first thiazolidinedione antidiabetic drug available. There are no data on overdose, probably because of its very recent introduction. Overdoses with antidiabetic drugs produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare when treatment is initiated early. The management of the hypoglycaemic drugs (insulin and sulphonylureas) is based primarily on restoring and maintaining euglycaemia via intravenous dextrose supplementation. In the case of the sulphonylureas, reduction of insulin secretion via pharmacological intervention may also be necessary. Wi

Topics: Carbamates; Drug Overdose; Glucose; Humans; Hypoglycemic Agents; Insulin; Piperidines; Sulfonylurea Compounds

A MEDLINE search from 1966-1996 revealed no reports of cisapride poisoning. An 8-mo-old, 8.9 kg girl received 8 mL of cisapride (Propulsid Suspension, 1 mg/mL, Janssen Pharmaceutica, Titusville, NJ) rather than the usual dose of 0.8 mL, resulting in an inadvertent, 10-fold, iatrogenic, dosing error. She developed emesis, hyperactive bowel sounds, abnormal behavior, mild hyperthermia, tachycardia, hypertension, and thrombocytosis. This is the first published report of poisoning with cisapride.

Topics: Administration, Oral; Cisapride; Drug Labeling; Drug Overdose; Female; Humans; Infant; Parasympathomimetics; Piperidines; Poisoning

Cisapride is an oral prokinetic agent used to facilitate or restore motility in the gastrointestinal tract. The National Animal Control Center has received 17 reports of accidental overexposure of dogs to cisapride since 1994. Doses of 640 mg/kg in dogs were reported to be lethal, but severe clinical signs have been noted at acute exposures as low as 18 mg/kg. The most common signs include diarrhea, muscle tremors and fasciculations, ataxia and incoordination, and hyperthermia. Available treatment is symptomatic and supportive. Activated charcoal is effective in reducing plasma cisapride levels.

Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Cisapride; Dog Diseases; Dogs; Drug Interactions; Drug Overdose; Gastrointestinal Motility; Half-Life; Intestinal Absorption; Male; Piperidines; Poison Control Centers

To determine the dose of naltrexone necessary to fully antagonize a high dose of remifentanil in cats.. Prospective experimental study.. Six healthy adult cats weighing 4.9 ± 0.7 kg.. In a first phase, remifentanil (200 μg kg(-1) followed by 60 μg kg(-1) minute(-1) ) was administered intravenously to two cats, causing an increase in locomotor activity. Naltrexone (100 μg kg(-1) ) was then administered intravenously every minute until the increase in locomotor activity had been reversed. In a second phase, six cats were used. Baseline thermal threshold was determined, naltrexone (600 μg kg(-1) ) was administered intravenously and 30 minutes later thermal threshold determination repeated. Remifentanil (200 μg kg(-1) followed by 60 μg kg(-1) minute(-1) ) was administered intravenously and thermal threshold determination repeated at 60, 120, 180, and/or 240 minutes after naltrexone administration. Thermal threshold determinations were started shortly after the start of the continuous rate infusion (CRI) of remifentanil and this CRI was discontinued immediately after thermal threshold determination. If an increase in thermal threshold was found, naltrexone administration was repeated at decreasing intervals in the next experiment (all cats were not used for all dosing intervals). Experiments were repeated until a naltrexone dosing interval was found that prevented increases in thermal threshold for 4 hours in all six cats.. In the first phase, both cats became severely dysphoric following remifentanil administration. A cumulative naltrexone dose of 300 μg kg(-1) was necessary to restore normal behavior in both cats. In the second phase, hourly administration of naltrexone (600 μg kg(-1) ) prevented increases in thermal threshold associated with hourly administration of remifentanil for 4 hours. Less frequent administration did not prevent increases in thermal threshold consistently.. Hourly administration of naltrexone (600 μg kg(-1) ) antagonizes the behavioral and antinociceptive effects of a high dose of remifentanil in cats.. Naltrexone may be useful for the treatment of opioid overdose in cats.

Topics: Analgesics, Opioid; Animals; Cat Diseases; Cats; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Overdose; Female; Hyperkinesis; Naltrexone; Narcotic Antagonists; Piperidines; Prospective Studies; Remifentanil

Topics: Cholinesterase Inhibitors; Donepezil; Drug Overdose; Follow-Up Studies; Humans; Piperidines

Topics: Cholinesterase Inhibitors; Donepezil; Drug Overdose; Humans; Medication Adherence; Piperidines

New generations of novel synthetic opioids (NSOs) have emerged to fill a void in the illicit drug markets left by the decline in popularity of fentanyl analogs subsequent to core-structure scheduling of fentanyl-related substances in the United States and China. These new opioids include members of the 2-benzyl benzimidazole (eg, isotonitazene, metonitazene, N -pyrrolidino etonitazene, protonitazene, etodesnitazene), benzimidazolone (eg, brorphine), and cinnamylpiperazine (eg, AP-238, 2-methyl AP-237) subclasses. Novel synthetic opioids continue to be detected in opioid-related fatal overdoses, demonstrating the harms associated with exposure to these drugs. Between January 2020 and December 2021, 384 casework blood samples were reported by our laboratory to contain 1 or more of the prior listed 8 NSOs. Isotonitazene (n = 144), metonitazene (n = 122), and brorphine (n = 91) were the 3 most prevalent substances, with positivity for isotonitazene and brorphine peaking just before the announcement of emergency scheduling. These NSOs have been documented as significant drivers of drug mortality, and this case series described here highlights the challenges medical examiners and coroners face in staying current with emerging drugs. Challenges include regional differences, rapid turnover, short lifecycles, variable toxicology testing, and difficulty in assessing individual drug toxicity in polydrug cases.

Topics: Analgesics, Opioid; Cell Proliferation; Drug Overdose; Fentanyl; Humans; Piperidines; United States

Topics: Analgesics, Opioid; Cause of Death; Drug Overdose; Fatal Outcome; Female; Fentanyl; Humans; Imidazoles; Michigan; Middle Aged; Opioid-Related Disorders; Piperidines; Population Surveillance; Synthetic Drugs

Donepezil is the most commonly prescribed acetylcholinesterase inhibitor for the treatment of Alzheimer's disease, an ailment that affects millions of older adult patients. By inhibiting the breakdown of acetylcholine in the central nervous system, donepezil has been shown to slow cognitive decline and improve patients' functional status. While donepezil is well-tolerated and generally considered safe at therapeutic doses, taking more than the prescribed dose could result in adverse cholinergic effects that range from mild gastrointestinal distress to serious cardiac dysrhythmias. We present a case of an 84-year-old man who developed gastrointestinal and cardiac disturbances after ingesting seven-times his daily dose of donepezil. As no specific antidote is available for donepezil overdose, this case highlights the importance of supportive care with particular attention to the management of cardiac dysrhythmias in patients displaying signs of toxicity.

Topics: Aged, 80 and over; Alzheimer Disease; Arrhythmias, Cardiac; Cholinesterase Inhibitors; Donepezil; Drug Overdose; Electrocardiography; Humans; Indans; Male; Piperidines

Repaglinide is a short-acting insulin secretagogue with high interindividual variability in pharmacokinetics due to genetic polymorphisms. Little is known about repaglinide overdoses, both with respect to pharmacokinetics and appropriate management. Given its short serum half-life of less than 1 h, hypoglycemic effects of repaglinide are expected to cease within a few hours post-ingestion.. A 15-year-old girl ingested 10.5 mg of repaglinide in a suicide attempt. Few hours later, she developed a strong food craving, nausea, abdominal pain, and a headache. The lowest recorded serum glucose was 44 mg/dl (2.4 mmol/l) 14 h post-ingestion. Using liquid chromatography-mass spectrometry, we detected repaglinide serum levels of 5.3, 2.6, and 1.0 ng/ml at 14, 20, and 26 h post-ingestion, respectively.. This case illustrates that in the context of overdose, repaglinide can lead to prolonged hypoglycemia. We therefore recommend glucose monitoring and observation for 24 h in all patients who remain hypoglycemic or show symptoms of hypoglycemia for an unusually long period of time.

Topics: Adolescent; Blood Glucose; Carbamates; Chromatography, Liquid; Drug Overdose; Female; Half-Life; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Piperidines; Tandem Mass Spectrometry

1,2-Diarylethylamines including lanicemine, lefetamine, and remacemide have clinical relevance in a range of therapeutic areas including pain management, epilepsy, neurodegenerative disease and depression. More recently 1,2-diarylethylamines have been sold as 'legal highs' in a number of different forms including powders and tablets. These compounds are sold to circumvent governmental legislation regulating psychoactive drugs. Examples include the opioid MT-45 and the dissociative agents diphenidine (DPH) and 2-methoxy-diphenidine (2-MXP). A number of fatal and non-fatal overdoses have been linked to abuse of these compounds. As with many 'legal highs', little is known about their pharmacology. To obtain a better understanding, the effects of DPH, 2-MXP and its 3- and 4-MeO- isomers, and 2-Cl-diphenidine (2-Cl-DPH) were investigated using binding studies at 46 central nervous system receptors including the N-methyl-D-aspartate receptor (NMDAR), serotonin, dopamine, norepinephrine, histamine, and sigma receptors as well as the reuptake transporters for serotonin, dopamine and norepinephrine. Reuptake inhibition potencies were measured at serotonin, norepinephrine and dopamine transporters. NMDAR antagonism was established in vitro using NMDAR-induced field excitatory postsynaptic potential (fEPSP) experiments. Finally, DPH and 2-MXP were investigated using tests of pre-pulse inhibition of startle (PPI) in rats to determine whether they reduce sensorimotor gating, an effect observed with known dissociative drugs such as phencyclidine (PCP) and ketamine. The results suggest that these 1,2-diarylethylamines are relatively selective NMDAR antagonists with weak off-target inhibitory effects on dopamine and norepinephrine reuptake. DPH and 2-MXP significantly inhibited PPI. DPH showed greater potency than 2-MXP, acting with a median effective dose (ED50) of 9.5 mg/kg, which is less potent than values reported for other commonly abused dissociative drugs such as PCP and ketamine.

Topics: Acetamides; Analgesics, Opioid; Animals; Drug Overdose; Humans; Ketamine; Phencyclidine; Phenethylamines; Piperidines; Psychotropic Drugs; Pyridines; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Serotonin

This paper describes the first reported death involving ocfentanil, a potent synthetic opioid and structure analogue of fentanyl abused as a new psychoactive substance in the recreational drug scene. A 17-year-old man with a history of illegal substance abuse was found dead in his home after snorting a brown powder purchased over the internet with bitcoins. Acetaminophen, caffeine and ocfentanil were identified in the powder by gas chromatography mass spectrometry and reversed-phase liquid chromatography with diode array detector. Quantitation of ocfentanil in biological samples was performed using a target analysis based on liquid-liquid extraction and ultra performance liquid chromatography tandem mass spectrometry. In the femoral blood taken at the external body examination, the following concentrations were measured: ocfentanil 15.3μg/L, acetaminophen 45mg/L and caffeine 0.23mg/L. Tissues sampled at autopsy were analyzed to study the distribution of ocfentanil. The comprehensive systematic toxicological analysis on the post-mortem blood and tissue samples was negative for other compounds. Based on circumstantial evidence, autopsy findings and the results of the toxicological analysis, the medical examiner concluded that the cause of death was an acute intoxication with ocfentanil. The manner of death was assumed to be accidental after snorting the powder.

Topics: Acetaminophen; Adolescent; Caffeine; Chromatography, Liquid; Drug Overdose; Fatal Outcome; Humans; Illicit Drugs; Male; Mass Spectrometry; Piperidines; Postmortem Changes

Diphenidine (1-(1,2-diphenylethyl)piperidine) and its 2-methoxylated derivative methoxphenidine (MXP, 2-MeO-diphenidine) are substances with dissociative effects that were recently introduced for "recreational" purpose through the online-based sale of new psychoactive substances (NPS). A number of analytically confirmed non-fatal intoxications associated with diphenidine or MXP have occurred in Sweden and were included in the STRIDA project.. Observational case series of consecutive patients with admitted or suspected intake of NPS and requiring intensive treatment in an emergency room and hospitalization in Sweden.. Blood and urine samples were collected from intoxicated patients presenting at emergency departments all over the country. NPS analysis was performed by multi-component liquid chromatography-mass spectrometry methods. Data on clinical features were collected during telephone consultations with the Poisons Information Centre and retrieved from medical records. Information was also obtained from online drug discussion forums.. Over a 12-month period from January to December 2014, 750 cases of suspected NPS intoxication originating from emergency departments were enrolled in the STRIDA project of which 14 (1.9%) tested positive for diphenidine and 3 (0.4%) tested positive for MXP. Co-exposure to several other NPS (e.g., 5-/6-(2-aminopropyl)benzofuran, 2-4-bromomethcathinone, butylone, 3,4-dichloromethylphenidate, 5-methoxy-N-isopropyltryptamine, methiopropamine, and α-pyrrolidinopentiothiophenone), also including other dissociative substances (3-/4-methoxyphencyclidine), and classical drugs of abuse (e.g., cannabis and ethanol) was documented in 87% of these cases. The 17 patients were aged 20-48 (median: 32) years, and 13 (76%) were men. They commonly presented with hypertension (76%), tachycardia (47%), anxiety (65%), and altered mental status (65%) including confusion, disorientation, dissociation, and/or hallucinations. Eight patients (47%) displayed severe intoxication (Poisoning Severity Score 3). The diphenidine- or MXP-positive patients required hospitalization for 1-3 (median: 2) days. In addition to standard supportive therapy, half of the cases were treated with benzodiazepines and/or propofol.. The adverse effects noted in analytically confirmed cases of NPS intoxication involving diphenidine or MXP were similar to those reported for other dissociative substances such as ketamine and methoxetamine. However, the high proportion of polysubstance use might have played a role in the intoxication and clinical features in some cases.

Topics: Adult; Chromatography, Liquid; Drug Overdose; Emergency Medical Services; Female; Hospital Costs; Hospitalization; Humans; Illicit Drugs; Male; Mass Spectrometry; Middle Aged; Piperidines; Poison Control Centers; Poisoning; Predictive Value of Tests; Psychotropic Drugs; Severity of Illness Index; Substance Abuse Detection; Sweden; Time Factors; Treatment Outcome; Young Adult

We report the case of a patient who underwent surgical aortic valve replacement. During general anaesthesia maintenance, the patient received a remifentanyl infusion via a target controlled infusion (TCI) system. The infusion pump that was prepared to deliver the infusion showed malfunction at the beginning of the surgery, so it was quickly replaced with a second pump. After a few minutes into the surgery, the patient presented with hypotension refractory to treatment. The remifentanyl syringe also emptied faster than expected. On reviewing the TCI pump, it was found that it was erroneously programmed for propofol instead of remifentanyl, thus the patient had received a very high dose of remifentanyl that was probably the cause of the haemodynamic disturbances. The incident was an error in equipment use, facilitated by hurry, lack of checking of the equipment prior to its use, and the complex and unclear design of the devices' screens. After analysis of this incident, all TCI pumps were reviewed, and all the programs for infrequently used drugs were deleted. Furthermore, 2 pumps were selected for exclusive use in the cardiac surgery theatre, one with propofol-only programming, and the other with remifentanyl-only programming, both clearly marked and situated in fixed places in that theatre.

Topics: Anesthetics, General; Aortic Valve; Drug Overdose; Equipment Failure; Equipment Failure Analysis; Heart Valve Prosthesis Implantation; Humans; Hypotension; Infusion Pumps; Intraoperative Complications; Male; Medication Errors; Piperidines; Propofol; Remifentanil; Risk Management

Topics: Anesthesia, General; Anesthetics, Intravenous; Bronchoscopy; Drug Overdose; Equipment Failure; Humans; Infant; Infusion Pumps; Medication Errors; Piperidines; Propofol; Remifentanil

We report the case of a 13 year old patient who received 3.0 mg of remifentanil during a 50-minute surgical procedure as a result of a dosage miscalculation. The patient failed to awaken at the conclusion of the procedure and showed signs of opioid overdose. She recovered spontaneously two hours later.

Topics: Adolescent; Analgesics, Opioid; Anesthesia Recovery Period; Anesthetics, Intravenous; Drug Overdose; Female; Humans; Infusions, Intravenous; Medication Errors; Piperidines; Remifentanil; Time Factors

Topics: Anesthesia, General; Anesthetics, Intravenous; Drug Overdose; Equipment Failure; Humans; Infusion Pumps; Male; Medical Errors; Middle Aged; Piperidines; Remifentanil; Urologic Surgical Procedures, Male

Topics: Antitussive Agents; Child, Preschool; Delirium; Drug Overdose; Humans; Male; Piperidines

Topics: Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Opioid; Drug Overdose; Equipment Failure; Female; Humans; Piperidines; Remifentanil; Syringes; Young Adult

Topics: Anesthesia, Intravenous; Anesthetics, Intravenous; Blood Gas Analysis; Blood Pressure; Drug Overdose; Female; Heart Rate; Humans; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Medical Errors; Piperidines; Propofol; Remifentanil

A fatal suicidal ingestion of drugs, together with activated charcoal, is reported. The death occurred 31 hours after the self-administration. The autopsy revealed a large amount of gastric content that appeared to be a compact mass of black color. Toxicologic analyses showed the presence of toxic levels of desalkylflurazepam and trazodone; metamizole and pridinol were also detected. The obtained results supported the hypothesis of a death due to acute intoxication delayed by the self-administration of activated charcoal, which elimination was probably hindered by the action of pridinol.

Topics: Aged; Anti-Anxiety Agents; Anti-Inflammatory Agents, Non-Steroidal; Antidotes; Charcoal; Dipyrone; Drug Overdose; Female; Flurazepam; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Gastrointestinal Contents; Humans; Methods; Piperidines; Suicide; Trazodone

Fluoxetine (Prozac) is a widely prescribed drug in adults and children, and it has an active metabolite, norfluoxetine, with a prolonged elimination time. Although uncommon, Prozac causes QT interval prolongation and arrhythmias; a patient who took an overdose of Prozac exhibited a prolonged QT interval (QTc 625 msec). We looked for possible mechanisms underlying this clinical finding by analysing the effects of fluoxetine and norfluoxetine on ion channels in vitro.. We studied the effects of fluoxetine and norfluoxetine on the electrophysiology and cellular trafficking of hERG K+ and SCN5A Na+ channels heterologously expressed in HEK293 cells.. Voltage clamp analyses employing square pulse or ventricular action potential waveform protocols showed that fluoxetine and norfluoxetine caused direct, concentration-dependent, block of hERG current (IhERG). Biochemical studies showed that both compounds also caused concentration-dependent reductions in the trafficking of hERG channel protein into the cell surface membrane. Fluoxetine had no effect on SCN5A channel or HEK293 cell endogenous current. Mutations in the hERG channel drug binding domain reduced fluoxetine block of IhERG but did not alter fluoxetine's effect on hERG channel protein trafficking.. Our findings show that both fluoxetine and norfluoxetine at similar concentrations selectively reduce IhERG by two mechanisms, (1) direct channel block, and (2) indirectly by disrupting channel protein trafficking. These two effects are not mediated by a single drug binding site. Our findings add complexity to understanding the mechanisms that cause drug-induced long QT syndrome.

Topics: Adult; Antidepressive Agents, Second-Generation; Blotting, Western; Cell Line; Cell Membrane; Cisapride; Dose-Response Relationship, Drug; Drug Overdose; Ether-A-Go-Go Potassium Channels; Female; Fluoxetine; Humans; Long QT Syndrome; Membrane Potentials; Muscle Proteins; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Patch-Clamp Techniques; Piperidines; Protein Transport; Pyridines; Sodium Channels; Time Factors; Transfection

A critically ill septic patient on haemofiltration for acute renal failure suffered sudden circulatory and respiratory collapse. The cause of the collapse was traced to an interaction between mechanical devices (syringe driver infusion pumps and haemofiltration equipment) connected to two central venous catheters.

Topics: Acute Kidney Injury; Adolescent; Analgesics, Opioid; Critical Illness; Drug Overdose; Equipment Failure; Female; Hemofiltration; Humans; Hypnotics and Sedatives; Infusion Pumps; Piperidines; Propofol; Remifentanil

We present a case of delirium due to amitriptyline overdose, which resolved rapidly following initiation of the cholinesterase inhibitor donepezil. The authors discuss the possibility of cholinesterase inhibitors being an effective choice in the management of anticholinergic drug induced delirium.

Topics: Amitriptyline; Cholinergic Antagonists; Delirium; Donepezil; Drug Overdose; Humans; Indans; Male; Middle Aged; Piperidines

A 79-year-old woman with Alzheimer's disease was admitted due to acute cholinergic symptoms induced by overdose (45 mg) of donepezil (DPZ). Physical examination showed bradycardia, sinus arrhythmia, vomiting and respiratory insufficiency. She was treated with atropine intravenously and her cholinergic symptoms subsided in the next evening. After 5 days she was discharged from the hospital and DPZ was withholded for about 4 weeks. The plasma concentration of DPZ was 54.6 ng/ml on admission and gradually decreased to the normal limits in about 90 hours. The calculative half-life of DPZ was about 55 hours. Since the half-life of DPZ is long and differs between individuals, hospitalization and treatment with atropine is recommended for cholinergic side effects induced by overdose of DPZ. It is important to prevent dosing errors in cooperation with medical providers, patients and families.

Topics: Aged; Alzheimer Disease; Arrhythmia, Sinus; Bradycardia; Cholinesterase Inhibitors; Donepezil; Drug Overdose; Electrocardiography; Female; Humans; Indans; Piperidines; Vomiting

Topics: Aged; Brain Stem Infarctions; Cholinesterase Inhibitors; Diagnosis, Differential; Donepezil; Drug Overdose; Humans; Indans; Insecticides; Male; Nootropic Agents; Organophosphorus Compounds; Piperidines

Topics: Aged; Cholinesterase Inhibitors; Cognition Disorders; Dementia, Multi-Infarct; Donepezil; Drug Overdose; Female; Humans; Indans; Piperidines; Poison Control Centers

Diphenidol (Cephadol, Vontrol), an antiemetic agent used in the treatment of vomiting and vertigo, has been reported to cause various adverse effects including drowsiness, hypotension, confusion, hallucination, restlessness, and other antimuscarinic effects. Serious toxic effects might be anticipated after intentional or accidental ingestion.. Retrospective analysis of all case records of the PCC-Taiwan defining diphenidol overdose during 1985-1996.. The data of 21 patients with diphenidol overdose were analyzed; 17 were < 3 years old and unintentionally poisoned, in contrast to the suicide attempts by four adults. The average amount of ingestion was 222.5 mg with a range of 25-800 mg. Most patients manifested only transient CNS, cardiovascular, or oculo-facial effects, but four children suffered from severe toxicity after an ingestion of 11.7-80 mg/kg diphenidol. Commonly reported toxicity in diphenidol overdose included facial flush (10), tachycardia, restlessness (6), seizures (4), dyspnea, drowsiness, mydriasis, coma, and fever (3). With supportive therapy, a good recovery was the rule except for one fatality of a 2 1/2-year-old boy who ingested 15 mg/kg diphenidol and presented with recurrent seizures, hypotension, respiratory failure, and coma.. Although not previously reported, accidental diphenidol overdose may result in serious anticholinergic toxicity in children. Treatment is supportive and the therapeutic role of physostigmine in diphenidol poisoning is still unclear.

Topics: Adult; Aged; Antiemetics; Child, Preschool; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Infant; Male; Middle Aged; Piperidines; Poison Control Centers; Poisoning; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Topics: Cisapride; Drug Overdose; Female; Gastroesophageal Reflux; Humans; Infant; Long QT Syndrome; Piperidines

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Drug Overdose; Narcotics; Piperidines