Propofol Infusion Syndrome: A Retrospective Analysis at a Level 1 Trauma Center

Objectives. The propofol infusion syndrome (PRIS), a rare, often fatal, condition of unknown etiology, is defined by development of lipemic serum, metabolic acidosis, rhabdomyolysis, hepatomegaly, cardiac arrhythmias, and acute renal failure. Methods. To identify risk factors for and biomarkers of PRIS, a retrospective chart review of all possible PRIS cases during a 1-year period was conducted at a level 1 trauma hospital in ICU patients over 18 years of age receiving continuous propofol infusions for ≥3 days. Additional study inclusion criteria included vasopressor support and monitoring of serum triglycerides and creatinine. Results. Seventy-two patients, 61 males (84.7%) and 11 females (15.3%), satisfied study inclusion criteria; and of these, 3 males met the study definition for PRIS, with 1 case fatality. PRIS incidence was 4.1% with a case-fatality rate of 33%. The mean duration of propofol infusion was 6.96 days. A positive linear correlation was observed between increasing triglyceride levels and infusion duration, but no correlation was observed between increasing creatinine levels and infusion duration. Conclusions. Risk factors for PRIS were confirmed as high dose infusions over prolonged periods. Increasing triglyceride levels may serve as reliable biomarkers of impending PRIS, if confirmed in future investigations with larger sample sizes

pitolisant, a novel histamine-3 receptor competitive antagonist, and inverse agonist, in the treatment of excessive daytime sleepiness in adult patients with narcolepsy

Narcolepsy is a debilitating sleep disorder that presents with excessive daytime sleepiness (EDS) and cataplexy, which is a sudden paralysis of muscle tone triggered by strong emotions such as laughing. It is also associated with many other disorders, including psychiatric disorders, neurologic illnesses, and medication side effects. Common causes of delayed and incorrect diagnoses of these conditions include lack of physician familiarity with narcolepsy symptoms and comorbidities which mask narcolepsy signs and symptoms. Current pharmacologic therapies include Modafinil and Armodafinil for EDS and sodium oxybate for cataplexy. This review discusses the epidemiology, pathophysiology, risk factors, presentation, treatment of narcolepsy, and the role of a novel drug, Pitolisant, in the treatment of EDS in adults with narcolepsy. Pitolisant is a histamine-3 receptor (H3R), competitive antagonist, and inverse agonist, acting through the histamine system to regulate wakefulness. It is a novel drug approved in August 2019 by the FDA, is not classified as a controlled substance, and is approved for use in Europe and the United States to treat EDS and cataplexy in narcolepsy. Recent phase II and III trials have shown that Pitolisant helps reduce the ESS score and cataplexy. In summary, based on comparative studies, recent evidence has shown that Pitolisant is non-inferior to Modafinil in the treatment of EDS but superior to Modafinil in reducing cataplexy

Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimer\u27s Disease: A comprehensive review.

Alzheimer\u27s disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in the treatment of AD. Currently, Adulhelm is the only Food and Drug Administration (FDA) approved drug that acts to slow the progression of this disease. Adulhelm is an anti-amyloid drug that functions by selectively binding amyloid aggregates in both the oligomeric and fibrillar states. Studies show Adulhelm may help to restore neurological function in patients with AD by reducing beta-amyloid plaques and reestablishing neuronal calcium permeability. At present, there is concern the magnitude of this drug\u27s benefit may only be statistically significant, although not clinically significant. Despite skepticism, Adulhelm has proven to significantly decrease amyloid in all cortical brain regions examined. With such high stakes and potential, further research into Adulhelm\u27s clinical efficacy is warranted in the treatment of AD

Viloxazine, a Non-stimulant Norepinephrine Reuptake Inhibitor, for the Treatment of Attention Deficit Hyperactivity Disorder: A 3 Year Update.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Current treatment options for ADHD include pharmacological treatment (stimulants, non-stimulants, anti-depressants, anti-psychotics), psychological treatment (behavioral therapy with or without parent training, cognitive training, neurofeedback), and complementary and alternative therapies (vitamin supplementation, exercise). Central nervous system (CNS) stimulants are the primary pharmacological therapy used in treatment; however, these stimulant drugs carry a high potential for abuse and severe psychological/physical dependence. Viloxazine, a non-stimulant medication without evidence of drug dependence, is a selective norepinephrine reuptake inhibitor that has historically been prescribed as an anti-depressant medication. The extended-release (ER) form was approved by the US Food and Drug Administration (FDA) in April 2021 for the treatment of ADHD in pediatric patients aged 6-17 years. Phase 2 and 3 randomized control trials have demonstrated significant efficacy of viloxazine in improving ADHD symptoms versus placebo. Related to its long-standing use as an antidepressant, the safety profile and pharmacokinetics of viloxazine are well understood. Viloxazine appears to be a suitable alternative to current standard-of-care pharmacotherapy for ADHD, but the further investigation remains to be done in comparing its efficacy to that of current treatments

Midazolam nasal spray to treat intermittent, stereotypic episodes of frequent seizure activity: pharmacology and clinical role, a comprehensive review.

An intranasal formulation of midazolam, Nayzilam, has been FDA-approved to treat intermittent, stereotypic episodes of frequent seizure activity. Nayzilam is easy to administer and can quickly treat seizures that occur outside of the hospital. The intra-nasal route of administration allows non-medical personal to administer the drug which makes it more accessible and user-friendly in the event of a seizure. Many studies have indicated quick cessation of seizures with Nayzilam compared to rectal diazepam, which has been the standard of care treatment. Nayzilam has been proven to be safe and effective for acute seizures in children, deeming it a revolutionary alternative in times where intravenous administration is not possible

Phenothiazines and their Evolving Roles in Clinical Practice: A Narrative Review.

Phenothiazines, a diverse class of drugs, can be used to treat multiple mental health and physical conditions. Phenothiazines have been used for decades to treat mental illnesses, including schizophrenia, mania in bipolar disorder, and psychosis. Additionally, these drugs offer relief for physical illnesses, including migraines, hiccups, nausea, and vomiting in both adults and children. Further research is needed to prove the efficacy of phenothiazines in treating physical symptoms. Phenothiazines are dopaminergic antagonists that inhibit D2 receptors with varying potency. High potency phenothiazines such as perphenazine are used to treat various psychiatric conditions such as the positive symptoms of schizophrenia, the symptoms of psychosis, and mania that can occur with bipolar disorder. Low/mid potency phenothiazines such as chlorpromazine antipsychotic drugs that have been used to treat schizophrenia and schizophrenia-like disorders since the 1950s and are utilized in numerous disease states. The present investigation aims to elucidate the effects of phenothiazines in clinical practice

Selective Serotonin Reuptake Inhibitors and Associated Bleeding Risks: A Narrative and Clinical Review.

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects of SSRIs include increased suicidality of patients under the age of 25, sexual dysfunction, anxiety, dizziness, weight gain, gastrointestinal distress, and headache. Other side effects include prolonging the QT interval, coagulopathy, and the risk of serotonin syndrome, as well as SSRI discontinuation syndrome. Sites of increased bleeding related to SSRI use have been reported to occur in the upper gastrointestinal tract, as well as intracranially. Based on the current literature, three studies have found that SSRIs are not associated with increased bleeding and/or increased perioperative risk, while others have demonstrated that SSRIs are associated with an increased risk in perioperative use. The inhibition of serotonin reuptake can affect platelet aggregation since platelets also express the serotonin transporter. SSRIs can result in decreased storage of serotonin in platelet dense granules. Increased serotonin can also increase gastric acid secretion, which increases the risk for ulceration. SSRIs in combination with NSAIDs also show a significantly increased risk of upper GI bleeding. Some studies show an increased bleeding risk from 30% to 70% when taking a combination of vitamin K antagonists and SSRIs in hospitalized patients. Related to the high prevalence of conditions that are treated with SSRIs, the bleeding risk associated with this class of medication merits further study

Buprenorphine and its formulations: a comprehensive review.

Buprenorphine, a novel long-acting analgesic, was developed with the intention of two purposes: analgesia and opioid use disorder. Regarding its pharmacodynamics, it is a partial agonist at mu receptors, an inverse agonist at kappa receptors, and an antagonist at delta receptors. For the purpose of analgesia, three formulations of buprenorphine were developed: IV/IM injectable formulation (Buprenex®), transdermal patch formulation (Butrans®), and buccal film formulation (Belbuca®). Related to opioid dependence, the formulations developed were subcutaneous extended release (Sublocade®), subdermal implant (Probuphine®), and sublingual tablets (Subutex®). Lastly, in order to avoid misuse of buprenorphine for opioid dependence, two combination formulations paired with naloxone were developed: film formulation (Suboxone®) and tablet formulation (Zubsolv®). In this review, we present details of each formulation along with their similarities and differences between each other and clinical considerations

Methamphetamine Use: A Narrative Review of Adverse Effects and Related Toxicities.

Methamphetamine has been labeled America\u27s most dangerous drug and has received significant public health attention. Stimulant addiction and tolerance are heavily documented in the literature; increasingly larger doses maintain euphoria in short time periods to withstand stimulant tolerance. Stimulant deaths are high in the United States and abroad. Between 2013 and 2019, deaths related to methamphetamine use quadrupled from 3,616 to 16,127. Methamphetamine use increased four-fold from 2015 to 2016. Due to this increase in methamphetamine use and its associated medical complications, the mortality rate associated with methamphetamine use has doubled over the past ten years. Cardiopulmonary symptoms include chest pain, palpitations, and shortness of breath. Methamphetamine-related myocardial infarction can also occur. Central nervous system symptoms include agitation, anxiety, delusions, hallucinations, and seizures. Methamphetamine-induced psychosis may unmask underlying psychiatric disorders. It can also cause cerebral vasculitis, which elicits cortical blindness and ischemic strokes. Methamphetamine-induced neurotoxicity in serotonergic systems is more diffuse, involving the striatum, hippocampus, septum, amygdala, and hypothalamus leading to mood changes, psychosis, and memory impairment. This narrative review will aim to highlight the adverse effects as well as the toxicity that can occur with methamphetamine use