Loperamide toxicity: a case report of turning bowels and twisting points

Introduction: Loperamide is a synthetic mu-receptor agonist used for the treatment of diarrhea however it has recently been illicitly used for a euphoric high or to diminish opiate withdrawal symptoms. In case reports, loperamide abuse has been associated with varied cardiac arrhythmias, most notably ventricular tachycardia and torsades de pointes, presumably related to prolongation of the QTc. Clinical Findings: A 32-year-old male with known prior opioid use disorder presented unresponsive, found to have polymorphic ventricular tachycardia, torsades de pointes, prolonged QTc and QRS, and transient left ventricular (LV) dysfunction. Diagnosis, interventions, and outcomes: When his mental status cleared, the patient reported taking up to 40 pills of loperamide daily with the intent of alleviating opiate withdrawal symptoms. This was felt to be the cause of his QTc prolongation, leading to cardiac toxicity and subsequent dysrhythmia. Patient initially required temporary pacing wire, which was removed hospital day three. He was discharged with suboxone and duloxetine and connected with substance use disorder specialists. Conclusions: We describe a patient with cardiac toxicity associated with loperamide misuse. In the wake of the current opioid epidemic, it is possible that occurrences of loperamide toxicity will increase. It is important for physicians to understand and identify the life-threatening effects of loperamide toxicity in order for proper diagnosis and management

Serotonin Syndrome Associated With Vilazodone Overdose in a 22-Month-Old Treated With Dexmedetomidine.

BACKGROUND: Vilazodone was approved by the U.S. Food and Drug Administration in 2011 as a treatment for major depression disorder. Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A agonist used in the treatment of depression in adults. Vilazodone increases the availability and activity of serotonin and its neural pathways. Vilazodone blocks the serotonin reuptake pump and desensitizes serotonin receptors (especially 5HT1A autoreceptors), therefore increasing serotonergic neurotransmission. Its partial agonist actions at presynaptic somatodendritic 5HT1A autoreceptors theoretically enhance serotonergic activity, contributing to antidepressant actions. There are limited reports exploring its effects in children after unintentional ingestion. Typical adult dosing is titrated from an initial dose of 10 mg up to a maximum dose of 40 mg daily. Serotonin syndrome classically manifests with restlessness, hyperthermia, tachycardia, mydriasis, and increased tone, and is typically treated with benzodiazepines, cyproheptadine, and supportive care. Dexmedetomidine has also been used in case reports to treat serotonin syndrome. CASE REPORT: We report the case of a toddler with a laboratory-confirmed vilazodone overdose exhibiting symptoms of serotonin syndrome, including restlessness, hyperthermia, mydriasis, dystonia, agitation, seizure-like activity, roving eye movement, tachycardia, and elevated creatine kinase. The patient was admitted and initially treated with supportive care and lorazepam per recommendations of the poison center, which did not recommend cyproheptadine use. On decompensation with suspected serotonin syndrome, the patient was treated with dexmedetomidine. In addition, urine toxicology screening (Amphetamines II assay; Roche, Indianapolis, IN) was positive for amphetamines; however, confirmatory testing (gas chromatography-mass spectrometry) was negative. The patient improved and was discharged after returning to her baseline status at 74 h post ingestion. Importantly, this patient did not require intubation and mechanical intubation, in spite of the large amount of vilazodone ingested. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: With increasing prescription of vilazodone, emergency physicians should have a high level of suspicion so as not to miss this toxidrome. The possibility of false-positive amphetamine screenings when an overdose of vilazodone is suspected should be investigated. Finally, systematic evaluation of the use of dexmedetomidine as treatment for serotonin syndrome or vilazodone ingestion should be done to confirm efficacy

Crotaline Fab antivenom appears to be effective in cases of severe North American pit viper envenomation: An integrative review

Abstract Background In 2000, the United States Food and Drug Administration approved Crotalidae Polyvalent Immune Fab (Ovine) (hereafter, FabAV), "for the management of patients with minimal to moderate North American Crotalid envenomation." Because whole-IgG pit viper antivenom is no longer available in the United States, FabAV is currently the only specific treatment option available to United States clinicians treating snakebite victims of any severity. No clinical trial data are available concerning the effectiveness of FabAV for treatment of severe snakebite, but several published articles describe its use in this setting. Methods We performed a comprehensive review of the English-language medical literature to identify all publications (1996 to July, 2008) containing data about the administration of FabAV. Two trained reviewers separately extracted case-level data concerning the administration of FabAV to patients with severe envenomation by North American crotaline snakes to a standardized form. Descriptive statistics were used. In addition, we hand-searched the US National Poison Data System reports for the years 2000–2006 to identify and describe any reports of death that occurred after FabAV administration. Results The literature review found 147 unique publications regarding FabAV. Twenty-four evaluable cases of severe human envenomation treated with FabAV were identified in 19 publications. Seven cases were described in five cohort studies, and 17 cases were described in 14 single patient case reports or non-cohort case series. Sixty-five specific severe venom effects were reported in these 24 patients, of which 50 effects (77%) improved or resolved after FabAV therapy. Initial control of all severe venom effects was achieved in 12 patients (50%). The rate at which initial control was achieved was significantly higher among patients reported in the cohort series than in the case series and non-cohort reports (100% vs. 29%, P = 0.005). The median dose of FabAV used to obtain initial control was 6 vials (range: 4 – 18 vials). Nine patients had severe venom effects that persisted despite FabAV therapy. Recurrent and/or delayed-onset severe defibrination syndrome occurred in 12 patients, most of whom did not receive recommended maintenance FabAV dosing. No patient developed systemic bleeding. Conclusion In this structured literature review, FabAV appears to be effective in the management of severe crotaline snake envenomation. Incomplete response to therapy, recurrence of venom effects, and delayed-onset venom effects were reported in case reports, but not reported in cohort studies.</p

Hyaluronan Constitutively Regulates Activation of COX-2-mediated Cell Survival Activity in Intestinal Epithelial and Colon Carcinoma Cells*

Hyaluronan is a major component of the pericellular matrix surrounding tumor cells, including colon carcinomas. Elevated cycooxygenase-2 levels have been implicated in several malignant properties of colon cancer. We now show for the first time a strong link between hyaluronan-CD44 interaction and cyclooxygenase-2 in colon cancer cells. First, we have shown that increased expression of hyaluronan synthase-2 induces malignant cell properties, including increased proliferation, anchorage-independent growth, and epithelial-mesenchymal transition in HIEC6 cells. Second, constitutive hyaluronan-CD44 interaction stimulates a signaling pathway involving ErbB2, phosphoinositide 3-kinase/AKT, β-catenin, and cyclooxygenase-2/prostaglandin E2 in HCA7 colon carcinoma cells. Third, the HA/CD44-activated ErbB2 → phosphoinositide 3-kinase/AKT → β-catenin pathway stimulates cell survival/cell proliferation through COX-2 induction in hyaluronan-overexpressing HIEC6 cells and in HCA7 cells. Fourth, perturbation of hyaluronan-CD44 interaction by hyaluronan oligomers or CD44-silencing RNA decreases cyclooxygenase-2 expression and enzyme activity, and inhibition of cyclooxygenase-2 decreases hyaluronan production suggesting the possibility of an amplifying positive feedback loop between hyaluronan and cyclooxygenase-2. We conclude that hyaluronan is an important endogenous regulator of colon cancer cell survival properties and that cyclooxygenase-2 is a major mediator of these hyaluronan-induced effects. Defining hyaluronan-dependent cyclooxygenase-2/prostaglandin E2-associated signaling pathways will provide a platform for developing novel therapeutic approaches for colon cancer