Protective effect of three developed gel formulations: Chitosan, Chitosan with Taurine and Chitosan with Dexpanthenol, on the acute overdose of Diclofenac sodium in preclinical studies

Objectives: To investigate the tissue-protective effects of three gel formulations (chitosan, chitosan with taurine or chitosan with dexpanthenol) as active substances against an acute overdose of diclofenac sodium. Methods: White outbred conventional male rats were allocated to five experimental groups: the first is an intact group that did not receive any drug, the second group is a control group that received 50mg/kg of diclofenac sodium once orally, the third, fourth and fifth groups are an experimental group that received our studied drugs at a dose of 0.16ml/100mg b.w. once orally 1 hr. before diclofenac sodium, the third group received chitosan-based gel 1%, the fourth group received chitosan-based gel 1% with 4% taurine and the fifth group chitosan-based gel 1% with 0.43% dexpanthenol. Blood samples were taken for biochemical, hematological and blood coagulation system tests on day 7th after administration of diclofenac sodium. Results: An acute overdose of diclofenac sodium caused marked extensive tissue necrosis in the liver, bleeding in the gastrointestinal tract and inflammatory process, these marks were evidenced by different changes in the test of the blood samples. Significantly 73.6% of the blood indicators were improved by the administration of chitosan-based gel 1% with 0.43% dexpanthenol, while 57.8% were improved by chitosan-based gel 1% with 4% taurine and 68.4% by chitosan-based gel 1%. Conclusion: Chitosan-based gel 1% with dexpanthenol 0.43% can help in mitigating hepatic injury, gastrointestinal bleeding, and systemic and local intestinal inflammation caused by an acute overdose of diclofenac sodium.

A description of the clinical course of severe benzonatate poisonings reported in the literature and to NPDS: A systematic review supplemented with NPDS cases

Background: Benzonatate is a commonly prescribed medication that can be lethal in acute overdose of a small number of capsules. Objective: This was a systematic review to describe the course of severe poisoning and deaths from benzonatate supplemented with the National Poison Data System (NPDS) fatalities module. Methods: The NPDS was queried from 2000 to 2018 for benzonatate fatalities. Pubmed, Cochrane, Embase, and Google Scholar were searched for combinations of benzonatate and “poisoning,” “overdose,” and “toxicity.” References of relevant articles were searched for additional publications. Articles were included if they described the clinical course of at least one patient suffering from benzonatate poisoning and available in English. Dual independent review and extraction were performed. Results: Seventeen cases from NPDS and 19 published reports met the inclusion criteria resulting in 36 cases, mostly (28/36) self-harm ingestions. Most patients were young [17 (11–29), median (IQR)] and female (22). Onset of toxicity was rapid at <5 min (9). Most common symptoms included cardiac arrest (29), seizures (24), and dysrhythmias (24). Treatments included intubation (26), cardiopulmonary resuscitation (28), vasopressors (20) and others. Return of spontaneous circulation was achieved in 23/28 patients, but most had significant neurologic deficits or other end organ damage and 5 survived with a good neurologic outcome. Conclusion and relevance: Overdose ingestions of benzonatate can cause significant toxicity with a rapid onset. Interventions performed were generally supportive in nature. Duration of directly toxic effects is short, but dramatic with neurologic devastation and resuscitated patients often still have a poor outcome.

Pharmacokinetic Disposition of Amiodarone When Given with an Intralipid Rescue Strategy

While the antiarrhythmic drug amiodarone is commonly used in clinical practice, it has a narrow therapeutic index that can lead to acute overdose. One proposed method to deal with this toxicity is lipid emulsion therapy, which may potentially quench the free amiodarone in blood and prevent its further distribution to target organs and tissues. In this study, we utilize an established swine model to examine the effects of Intralipid™ (IL) administration for acute amiodarone toxicity. A total of 14 pigs received an overdose of intravenous amiodarone. After twenty minutes, half of the pigs (n = 7) received IL while the control group (n = 7) received normal saline. Serum concentrations of amiodarone were then analyzed using a validated high-performance liquid chromatography (HPLC) method. Noncompartmental pharmacokinetic analyses were performed on the observed concentrations. There were no statistical differences in the area under the concentration time curve (6 h) or clearance, but there was a difference in the half-life between the two groups (3.12 vs. 0.85 h, p = 0.01). The administration of IL did not statistically change the overall exposure of amiodarone in the blood in the first 6 h; however, trends toward prolonged blood retention in the IL group were seen.

A Case Report of Hypoglycemia Following a Tramadol Overdose in a Non-Diabetic Patient

Introduction: Tramadol is an opioid analgesic that binds to mu-opioid receptors and inhibits the uptake of norepinephrine and serotonin. Through its activation of these receptors, it has potential to increase the utilization of glucose and/or decrease hepatic gluconeogenesis. Case Report: A 55-year-old male presents to the Emergency Department (ED) via Emergency Medical Services (EMS) following a self-reported overdose of alprazolam, lorazepam, acetaminophen with codeine, and tramadol. During EMS transport, the patient was found to be hypoglycemic with a glucose of 30 mg/dL and was administered 25 grams of intravenous (IV) dextrose 50% in water. The patient had no past medical history of diabetes mellitus, hypoglycemia, or hyperglycemia and was normoglycemic on his prior presentations to our facility 3 months and 2 years prior. Subsequent analysis found that the patient was negative for acetaminophen, ethanol, salicylates, tricyclics, and lithium. His urinalysis was positive for opiates and benzodiazepines. Upon arrival to the ED, the patient’s blood glucose was 131 mg/dL but subsequently dropped to 73 mg/dL, necessitating the initiation of continuous IV fluids containing dextrose. These fluids were discontinued 3.5 hrs later and the patient was discharged 16 days later. Discussion: This case illustrates that hypoglycemia can be a presenting symptom in patients with an acute overdose of tramadol with no previous history of glycemic dysregulation. Upon presentation it is important to closely monitor serum glucose concentrations to identify hypoglycemia early in order to initiate necessary hypoglycemia protocols.

Cardiac Complications Attributed to Hydroxychloroquine: A systematic review of the Literature Pre-COVID-19

Introduction: Hydroxychloroquine has been used for rheumatological diseases for many decades and is considered a safe medication. With the COVID-19 outbreak, there has been an increase in reports associating cardiotoxicity with hydroxychloroquine. It is unclear if cardiotoxic profile of hydroxychloroquine is previously underreported in the literature, or a new manifestation of COVID-19 and therapeutic interventions. This manuscript evaluates the incidence of cardiotoxicity associated with hydroxychloroquine prior to onset of COVID-19. Methods: PubMED, EMBASE, and Cochrane databases were searched for keywords derived from MeSH terms, prior to 4/9/2020. Inclusion eligibility was based on appropriate reporting of cardiac conditions and study design. Results: Sixty-nine articles were identified (58 case reports, 11 case series). Majority (84%) of patients were female, with a median age of 49.2(range 16-92) years. Fifteen of 185 patients with cardiotoxic events were in the setting of acute intentional overdose. In acute overdose, the median ingestion was 17,857  14,873 mg. Two of 15 patients died after acute intoxication. In patients with long-term hydroxychloroquine use (10.5 ± 8.9 years), new onset systolic heart failure occurred in 54 of 155 patients (35%) with median cumulative ingestion of 1,493,800 ± 995,517 mg. The majority of patients improved with withdrawal of hydroxychloroquine and standard therapy. Conclusions: Millions of hydroxychloroquine doses are prescribed annually. Prior to COVID-19 pandemic, cardiac complications attributed to hydroxychloroquine were uncommon. Further studies are needed to understand the impact of COVID-19 on the cardiovascular system to understand presence or absence of potential medication interactions with hydroxychloroquine in this new pathophysiological state.