Triptan and ergotamine overdoses in the United States: Analysis of the National Poison Data System.

OBJECTIVE: To examine the clinical outcomes of intentional overdoses involving triptans and ergotamines with a retrospective review of the National Poison Data System (NPDS). METHODS: This was a 5-year retrospective cross-sectional study (2014-2018) using the NPDS. Demographics, exposure characteristics, and outcomes were described. Univariate logistic regression was used to estimate the odds ratio (OR) for major effect or death. A multivariable logistic regression model with inclusion criteria of p < 0.1 in univariate analysis was implemented with backwards selection. RESULTS: In this population (n = 1,489), multiple exposure was most common (n = 1,145). The mean age was 31.2 years and 1,197 (80.4%) participants were female. Major effects from a single exposure were seen in <1% with no recorded deaths. Triptan ingestion (n = 328) resulted in hypertension (14%), tachycardia (10.7%), drowsiness (11%), nausea (6.4%), vomiting (4.6%), vertigo (4%), chest pain (3.7%), and diaphoresis (2.4%). Ergotamine ingestion (n = 16) resulted in abdominal pain (16%), vomiting (12.5%), numbness (12.5%), nausea (6.3%), diarrhea (6.3%), and vertigo (6.3%). No clinical effect was seen in 90 (26.2%). No cases met Hunter criteria for serotonin syndrome. There is risk of major event or death due to age (OR 1.02; 95% confidence interval [CI] 1.01-1.04; p = 0.004), multiple product exposure (OR 9.50; 95% CI 2.29-39.48; p = 0.002), and concomitant overdose with benzodiazepines (OR 1.71; 95% CI 1.05-2.78; p = 0.032) or tricyclic antidepressants (OR 3.16; 95% CI 1.88-5.31; p < 0.001). CONCLUSION: The risk of major effect or death was low and predicted by age, multiple product exposure, and concomitant benzodiazepine or tricyclic antidepressant. The triptan toxidrome consists of hypertension, tachycardia, and drowsiness. The toxic effects of ergotamine are acute gastrointestinal syndrome with vertigo and numbness. No cases of serotonin syndrome were seen.

Novel psychoactive substances. / Nye psykoaktive stoffer.

There has been a significant increase in the number of new intoxicants on the illegal drugs market globally, also in Norway. The substances are given the name NPS: Novel Psychoactive Substances, and are mainly sold over the Internet. Uncertain dosage of potent substances entails a risk of accidental overdose, and therefore serious intoxication and death. In this article we provide an overview of current knowledge with regard to these substances.

[The development from drug to designer drug].

Synthetic "designer drugs" with hallucinogenic properties have become increasingly popular among recreational drug users in recent years. Some of the designer drugs are chemically modified drugs previously used in treatment of depression and chronic fatigue. The drugs are available from a large number of internet distributers. There is very little knowledge of the clinical symptoms and how intoxicated people should be treated. We present a review of published literature (including 284 intoxicated patients) and experiences from the Danish poison centre concerning two chemical derivatives of earlier registered drugs.

Creatin-kinase elevation after accidental ingestion of almotriptan in an 18-month-old girl.

Few studies have been published to demonstrate tolerability and efficacy of almotriptan in adolescents and children with migraine, particularly in the first years of life, though preliminary results are favorable. We report the case of an 18-month-old infant with elevation of serum levels of creatin-kinase after the accidental ingestion of almotriptan. A previously healthy 18-month-old girl (weight: 13 kg) was admitted to our Department four hours after the accidental ingestion of 6.25 mg of almotriptan (0.48 mg/kg), without any specific symptom. The performed investigations showed high serum levels of creatin-kinase (CK) (527 IU/L; normal values: 24-170 IU/L). Transaminase, creatinine, aldolase, myoglobin and troponin T serum levels were normal. The electrocardiogram proved negative. Initial management consisted of parenteral rehydration with saline solution. CK levels lowered significantly at 12 hours (455 IU/L) and at 65 hours (188 IU/L) after the ingestion. No symptoms were observed before discharge and on follow-up.

A report of an outbreak of toxicity from a novel drug of abuse: ERIC-3.

BACKGROUND: Novel drugs of abuse are becoming more common in the UK, and they represent particular difficulties in management. We present a case series of toxicity due to a novel substance Eric-3. METHODS: This was a retrospective case note review over a 6-month period. Patients were included if their presentation was due to ingestion of Eric-3. Physiological data, symptoms, outcome and destination of the patient from the ED were collected. Postmortem toxicological analysis was obtained for one of the patients who died. RESULTS: 41 attendances were identified from 18 patients. Two patients died and five were admitted to ITU. Heart rate and temperature on arrival tended to be above normal (mean heart rate was 112 bpm, with an SD of 18; mean temperature was 37.45° with an SD of 0.95°). 63.4% of attendances included agitation and 34.1% choreiform movements. α-Methyltryptamine and 3-/4-flouroephedrine were found in the blood of one of the patients who died. CONCLUSIONS: In this outbreak, Eric-3 gave symptoms similar to other stimulants. It may have been a novel substance 3-/4-flouroephedrine. It underlines the need for prospective data collection and information sharing.

Poisoning with illicit substances: toxicology for the anaesthetist.

The consumption of illicit substances represents a considerable threat to the health and wellbeing of particular sectors of our communities. Hospitalisation is sometimes required for the treatment of the direct toxic effects of the drugs as well as for injuries sustained while under their influence. Although poisoning with 'traditional' substances of abuse such as opioids, cocaine and cannabis still predominate in terms of numbers, the availability and use of new psychoactive substances are on the rise. These latter agents, some of which began life as failed pharmaceutical products, have enjoyed renewed status as recreational stimulants, entactogens or hallucinogens, properties that originally precluded them from legitimate use. These drugs may act by enhancing endogenous release of neurotransmitters, inhibiting their reuptake back into neurons or having direct effects on receptors, and may involve adrenergic, dopaminergic or serotonergic systems. The use of intravenous lipid emulsion for the symptomatic treatment of drug overdose has become a fertile ground for research and may hold promise as a non-specific treatment for poisoning with illicit substances. Dexmedetomidine, an α(2)-receptor agonist with a central sympatholytic effect, may be able to counteract the cardiovascular and central nervous system overstimulation that may accompany stimulant toxicity.

[Pediatric poisoning with triptans: review of cases in the Lille poison center between 2000 and 2010]. / Intoxications pédiatriques par les triptans : revue des cas recensés au centre antipoison de Lille (2000-2010).

BACKGROUND AND OBJECTIVE: Triptans are recommended to treat acute migraine. Pediatric data remain insufficient for making decisions in cases of triptan poisoning. Consequently, hospitalization is often warranted as a precautionary measure. This study aims to more accurately estimate the risks incurred when a young child ingests triptan tablets. MAIN OUTCOME MEASURES: This study reviewed all cases of acute triptan poisoning listed by the Lille poison center between January 2000 and December 2009 in children younger than 6 years. Cases with certain ingestion, no drug interactions, and no other known etiology were selected. The gravity of each case was estimated by the poisoning severity score and follow-up was conducted by phone. RESULTS: A cohort of 84 patients was collected: 6% were lost to follow-up. The mean intake was 1.22 tablets (range, 0.25-6), for the most part zolmitriptan (64.2%), eletriptan (14.3%) and naratriptan (14.3%). Fifty-nine children (74.5%) were admitted to the hospital and 20 children monitored at home. The majority received evacuation or adsorbing treatment. Symptoms were not frequent (13%) and were well tolerated, in particular on the hemodynamic level (ten cases of PSS1). The adverse events observed were tachycardia (4 cases), arterial hypertension (1 case), dyspnea (2 cases), drowsiness (2 cases), marbling of the extremities (1 case), vomiting (3 cases), and digestive pain (1 case). The 2 cases of dyspnea, induced by 2.5mg and 7.5mg of zolmitriptan, respectively, were associated with cardiovascular symptoms and were left untreated. According to its pharmacological action, the potential risk of a serotoninergic syndrome is a concern with triptan intake. No severe complication was recorded, so based on this study, our guidelines were updated. The response should be less alarmist, but a watchful attitude should be retained. Hospitalization should not be systematic, but focused on the patient's cardiac history, the dose, and the symptomatology. If the child remains at home, specific action should be managed: an adsorbing treatment and close monitoring by phone remain essential.

Combined intoxication with methylone and 5-MeO-MIPT.

Although preclinical studies suggest that methylone (2-methylamino-1-[3,4-methylenedioxyphenyl]propan-1-one) and 5-MeO-MIPT (5-methoxy-N-methyl,N-isopropyl tryptamine) may have psychostimulant properties, the scientific reports about the clinical effects of these agents are scant. We describe a 27-year-old male patient with substance intoxication after a single ingestion of the mixture of methylone and 5-MeO-MIPT. Though he bought the drug as pure methylone powder via an internet order, our chemical analyses indicated that the drug was composed of about 60% methylone (120 mg) and 38% 5-MeO-MIPT (76 mg). This case report suggests that clinicians should be alert to the possibility of the emergence of methylone or 5-MeO-MIPT intoxication, and substance-related mental disorder may be complicated by combined use of other psychoactive drugs.

Emerging drugs of abuse.

Several new and emerging substances are being diverted for abuse. Most of these emerging abused substances do not cause traditional drug screens to turn positive. The health effects of these substances have not yet been fully elucidated. Health care providers should be aware of the existence of these new abused substances.

Fatality due to acute alpha-methyltryptamine intoxication.

In February 2003, the Miami-Dade County Medical Examiner Department reported the first known death in the country related to alpha-methyltryptamine (AMT). AMT is an indole analogue of amphetamine investigated in the 1960s as an antidepressant, stimulant, and monoamine oxidase inhibitor. Today, AMT is recognized as a powerful psychedelic drug among high school and college-aged men and women. Its popularity is partly due to the multitude of anecdotal websites discussing AMT as well as its legality and availability for purchase via the Internet prior to April 2003. Emergency designation of AMT as a Schedule 1 controlled substance by the Drug Enforcement Administration occurred shortly after the death in Miami-Dade County. The case in Miami involved a young college student who, prior to death, advised his roommate that he was "taking hallucinating drugs" and as a result had "discovered the secret of the universe". Approximately 12 h later, the roommate discovered the deceased lying in bed unresponsive. An empty 1-g vial of AMT was recovered from the scene and sent to the toxicology laboratory. Initial screening of urine by enzyme-multiplied immunoassay technique was positive for amphetamines, and the basic drug blood screen detected a small peak later identified by mass spectrometry as AMT. For quantitation, AMT was isolated using solid-phase extraction, derivatized with pentafluoropropionic anhydride, and analyzed using gas chromatography-mass spectrometry. Quantitative analysis was based upon m/z 276, 303, and 466 for AMT and m/z 306, 333, and 496 for the internal standard, 5-methoxy-alpha-methyltryptamine. A linear calibration curve from 50 to 500 ng/mL was used to calculate the concentration of AMT in the samples and controls. Blood, tissue, and gastric specimens were diluted to bring the observed concentration within the limits of the standard curve. Matrix matched controls were extracted and analyzed with each run. Postmortem iliac vein blood revealed 2.0 mg/L, gastric contents (48 g collected at autopsy) contained 9.6 mg total of AMT, liver contained 24.7 mg/kg, and the brain contained 7.8 mg/kg. An additional Medical Examiner case from another jurisdiction revealed 1.5 mg/L in antemortem serum.

Endogenous toxins and mycotoxins in forage grasses and their effects on livestock.

Plant toxins are the chemical defenses of plants against herbivory. Grasses have relatively few intrinsic toxins, relying more on growth habit to survive defoliation and endophytic fungal toxins as chemical defenses. Forage grasses that contain intrinsic toxins include Phalaris spp. (tryptamine and carboline alkaloids), sorghums (cyanogenic glycosides), and tropical grasses containing oxalates and saponins. Toxic effects of these grasses include neurological damage (Phalaris staggers), hypoxia (sudangrass), saponin-induced photosensitization (Brachiaria and Panicum spp.), and bone demineralization (oxalate-containing grasses). Endophytic toxins in grasses include ergot alkaloids in tall fescue and tremorgens (e.g., lolitrem B) in perennial ryegrass. Lolitrems cause neurological effects, producing the ryegrass staggers syndrome. Annual ryegrass toxicosis is caused by corynetoxins, which are chemically similar to tunicamycin antibiotics. Corynetoxins are produced by Clavibacter bacteria that parasitize a nematode, Anguina agrostis, that may infect annual ryegrass. Corynetoxins inhibit glycoprotein synthesis, causing defective formation of various blood components of the reticulo-endothelial system. Another mycotoxin in ryegrass is sporidesmin, which causes liver damage and secondary photosensitization (facial eczema). Fusarium toxins such as zearalenone and trichothecenes also occur in forage grasses. Kikuyugrass poisoning results in severe damage to the ruminal epithelium and omasal mucosa, and neurological signs. The causative agent, which may be associated with army worm predation of the grass, has not been identified. The properties and significance of these toxins are reviewed.

Fatal intoxication involving etryptamine.

A case of fatal intoxication due to the ingestion of Etryptamine (ethyltryptamine) is reported. Toxicological findings included the following tissue distribution: blood (heart) 5.6 mg/L; urine 80.4 mg/L; vitreous 2.4 mg/L; bile 22.0 mg/L; stomach contents 52.9 mg, brain 16.2 mg/g; liver 18.3 mg/g and kidney 24.0 mg/g. Anatomic pathology showed pulmonary edema and generalized visceral congestion with some epicardial petechiae.

Tryptamine alkaloid toxicosis in feedlot sheep.

Tryptamine alkaloid toxicosis (Phalaris staggers) was diagnosed in feedlot sheep. Clinical signs of toxicosis, which were exacerbated by excitement, included gait abnormalities, muscular tremors, nystagmus, and convulsions. An estimated 8% of the most severely affected lambs had clinical signs of toxicosis. Gross lesions detected in the brain of affected lambs consisted of focal gray-green discoloration in the brain stem and thalamus; these areas had microscopic evidence of intraneuronal pigment accumulation. Brain specimens obtained at slaughter indicated that 60% of the lambs had lesions consistent with tryptamine alkaloid toxicosis. Tryptamine alkaloids were found in low concentrations in the feed. Lambs exposed to these feeds had higher death losses than those that were not exposed to the feeds. Cobalt concentration in the feed was higher than that previously reported to be associated with Phalaris staggers.

[Etryptamine, a new designer drug with a fatal effect]. / Etryptamin, eine neue Designer-Droge mit fataler Wirkung.

Capsules with etryptamine have been commonly available on the market since the middle of 1985. Up to 1962 this CNS-stimulating, monoamine-oxidase-inhibiting drug was sold as an antidepressant (Monase). A case of fatal intoxication is reported. The exact amount of etryptamine taken several hours before death are not known, but it could have been in the range of 700 mg. This drug was detected in tissue by means of common analytical techniques (GLC, GC-MS, HPLC, TLC). Etryptamine cross-reacts with the Emit-st amphetamine assay and can also be detected in urine using these techniques. The level in postmortem blood was 1.1 mg/l. The effects the young man showed were like those known from intoxication with amphetamines, MAO inhibitors, and thymoleptics. Malignant hyperthermia is discussed as a possible cause of death. It is suggested that trade in etryptamine should be controlled.