Anticoagulation in Atrial Fibrillation Patients

Atrial fibrillation (AF) is the most common arrhythmia and may cause thromboembolic events, typically stroke. Advances in pharmacological approaches to anticoagulation and groundbreaking large randomized controlled trials of non-vitamin K antagonist oral anticoagulants (NOACs) have changed the paradigm of anticoagulation therapy. Furthermore, observational studies support the efficacy and safety of NOAC. Few studies address the differences among NOACs, but prescriptions should be based on a thorough understanding of their pharmacological differences, including interactions, side effects, reversibility, and practical approach. In a subset of patients with AF, warfarin may still be the preferable option. Consequently, an individualized approach to oral anticoagulation is crucial

A closer look at opioid-induced adrenal insufficiency. A narrative review

Among several opioid-associated endocrinopathies, opioid-associated adrenal insufficiency (OIAI) is both common and not well understood by most clinicians, particularly those outside of endocrine specialization. OIAI is secondary to long-term opioid use and differs from primary adrenal insufficiency. Beyond chronic opioid use, risk factors for OIAI are not well known. OIAI can be diagnosed by a variety of tests, such as the morning cortisol test, but cutoff values are not well established and it is estimated that only about 10% of patients with OIAI will ever be properly diagnosed. This may be dangerous, as OIAI can lead to a potentially life-threatening adrenal crisis. OIAI can be treated and for patients who must continue opioid therapy, it can be clinically managed. OIAI resolves with opioid cessation. Better guidance for diagnosis and treatment is urgently needed, particularly in light of the fact that 5% of the United States population has a prescription for chronic opioid therapy

Illicitly Manufactured Fentanyl Entering the United States

The 'third wave' of the ongoing opioid overdose crisis in the United States (US) is driven in large measure by illicitly manufactured fentanyl (IMF), a highly potent synthetic opioid or an analog developed in clandestine laboratories primarily in China and Mexico. It is smuggled into this country either as IMF or as precursors. The southern border of the US is a frequent point of entry for smuggled IMF and the amounts are increasing year over year. IMF is also sometimes mixed in with other substances to produce counterfeit drugs and dealers as well as end-users may not be aware of IMF in their products. IMF is inexpensive to produce and when mixed with filler materials can be used to cut heroin, vastly expanding profitability. It is an attractive product for smuggling as very tiny amounts can be extremely potent and highly profitable. Drug trafficking over the border also involves the tandem epidemic of money laundering as drugs enter the country and cash payments exit. While drug smuggling in and out of the US (and other nations) has been going on for decades, the patterns are changing. Highly potent and potentially lethal IMF is a dangerous new addition to the illicit drug landscape and one with disastrous consequences

Cocaethylene : When Cocaine and Alcohol Are Taken Together

Cocaine is taken frequently together with ethanol and this combination produces a psychoactive metabolite called cocaethylene which has similar properties to the parent drug and may be more cardiotoxic. Cocaethylene has a longer half-life than cocaine, so that people who combine cocaine and ethanol may experience a longer-lasting, as well as more intense, psychoactive effect. Cocaethylene is the only known instance where a new psychoactive substance is formed entirely within the body. Although known to science for decades, cocaethylene has not been extensively studied and even its metabolic pathways are not entirely elucidated. Like its parent drug, cocaethylene blocks the reuptake of dopamine and increases post-synaptic neuronal activity; the parent drug may also block reuptake of serotonin as well. Cocaethylene has been studied in animal models in terms of its pharmacology and its potential neurological effects. Since the combination of cocaine and alcohol is commonly used, it is important for clinicians to be aware of cocaethylene, its role in prolonging or intensifying cocaine intoxication, and how it may exacerbate cocaine induced cardiovascular disorders. Most cardiac-related risk assessment tools do not ask about cocaine use, which can prevent clinicians from making optimal therapeutic choices. Greater awareness of cocaethylene is needed for clinicians, and those who use cocaine should also be aware of the potential for polysubstance use of cocaine and ethanol to produce a potentially potent and long-lasting psychoactive metabolite

Cocaine and Cardiotoxicity : A Literature Review

Long-term cocaine use, as well as acute cocaine use, is associated with adverse cardiovascular consequences, including arrhythmias, angina, myocardial infarction, heart failure, and other conditions. Over the long term, cocaine can result in structural changes to the heart such as increased left-ventricular mass and decreased left-ventricular end-diastolic volume. Patients arriving with cocaine-associated cardiovascular complaints may not be forthcoming about their cocaine or polysubstance abuse or may be unresponsive. The role of beta-blockers, a first-line treatment for many forms of heart disease, is controversial in this population. Cocaine is a powerful sympathomimetic agent, and it was thought that beta-blockade would result in unopposed alpha-adrenergic stimulation and adverse consequences. A number of small, singlecenter, retrospective and observational studies suggest that beta-blockers may be safe, effective, and beneficial in this population. Further study is needed to clarify the role of beta-blockers in this population

Suicide by Opioid : Exploring the Intentionality of the Act

Opioid toxicity can result in life-threatening respiratory depression. Opioid-overdose mortality in the United States is high and increasing, but it is difficult to determine what proportion of those deaths might actually be suicides. The exact number of Americans who died of an opioid overdose but whose deaths might be classified as suicide remains unknown. It is important to differentiate between those who take opioids with the deliberate and unequivocal objective of committing suicide, that is, those with active intent, from those with passive intent. The passive-intent group understands the risks of opioid consumption and takes dangerous amounts, but with a more ambiguous attitude toward suicide. Thus, among decedents of opioid overdose, a large population dies by accident, whereas a small population dies intending to commit suicide; but between them exists a sub-population with equivocal intentions, waxing and waning between their desire to live and the carelessness about death. There may be a passive as well as active intent to commit suicide, but less is known about the passive motivation. It is important for public health efforts aimed at reducing both suicides and opioid-use disorder to better understand the range of motivations behind opioid-related suicides and how to combat them

Multimechanistic Single-Entity Combinations for Chronic Pain Control : A Narrative Review

Atypical opioids such as tramadol, tapentadol, and cebranopadol combine two complementary mechanisms of action into a single molecule, creating novel analgesic agents. These are synthetic small molecules: cebranopadol is not yet market released; tramadol and tapentadol are commercially available and have immediate-release (IR) and extended-release (ER) formulations. Tramadol has been widely used in the United States in recent years and works as a prodrug in that its metabolites are active in inhibiting serotonin and norepinephrine reuptake. Tapentadol is a direct-acting agent with a faster onset of action and is a muopioid-receptor agonist and also inhibits noradrenaline reuptake. Cebranopadol is the newest of these drugs, a first-in-class atypical analgesic that combines mu-opioid receptor (MOR) agonism with activity at the nociception/orphanin (NOP) FQ petide receptors. Cebranopadol may be considered a partial kappaopioid receptor agonist as well. The pharmacology of these unique single-entity agents allows them to offer analgesic benefit with fewer side effects and risks. Clinical studies have demonstrated the safety and efficacy of tramadol and tapentadol, and promising but limited studies for cebranopadol show good analgesic effect and safety. Serotonin toxicity or 'serotonin syndrome' may occur with accumulation of serotonin with tramadol. While the misuse of these agents is limited in the United States, tramadol misuse is prevalent in Iran and parts of Africa. Patients have been successfully rotated from one of these agents to another. All three agents show promise in the treatment of cancer and non-cancer pain and their unique formulation in a single molecule reduces the pill burden

The Basic Pharmacology of Opioids Informs the Opioid Discourse about Misuse and Abuse: A Review

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Treating Apnea of Prematurity

Premature babies often suffer apnea of prematurity as a physiological consequence of an immature respiratory system. Hypercapnia may develop, and neonates with apnea of prematurity are at an increased risk of morbidity and mortality. The long-term effects of apnea of prematurity or their treatments are less clear. While a number of treatment options exist for apnea of prematurity, there is no clear-cut "first-line" approach or gold standard of care. Effective treatments, such as caffeine citrate, carbon dioxide inhalation, nasal continuous positive airway pressure, nasal intermittent positive pressure ventilation, and others, may be associated with safety concerns. More conservative treatments are available, such as kangaroo care, postural changes, and sensory stimulation, but they may not be effective. While apnea of prematurity resolves spontaneously as the respiratory system matures, it can complicate neonatal care and may have both short-term and long-term consequences. The role, if any, that apnea of prematurity may play in mortality of preterm neonates is not clear