Electrical Impulse Propagation Research Articles

Transformation of a plasma boundary curvature into electrical impulses moving along a plasma surface

The self-consistent propagation of electrical impulses and of the accompanying distortions of the electron surface in the framework of a cold plasma model with a sharp boundary has been described with help of a derived system of two equations. The method of ‘shallow water theory’ has been applied for the case of bounded plasma and deriving an equation with which to link the spatial and temporal structures and evolution of the boundary curvature and the surface charge. Under certain conditions, such perturbations can propagate along the boundary without changing their shape for a long distance. An approximate analytical solution has been found, and numerical calculations have been performed. Mutual connections between basic parameters of the considered perturbations (velocity components, electrostatic field, etc.) have been presented.

Transport and localization on dendrite-inspired flat band linear photonic lattices

The capacity of a physical system to transport and localize energy or information is usually linked to its spatial configuration. This is relevant for integration and transmission of signals as performed, for example, by the dendrites of neuronal cells. Inspired by recent works on the organization of spines on the surface of dendrites and how they promote localization or propagation of electrical impulses in neurons, here we propose a linear photonic lattice configuration to study how the geometric features of a dendrite-inspired lattice allows for the localization or propagation of light on a completely linear structure. We show that by increasing the compression of the photonic analogue of spines and thus, by increasing the coupling strength of the spines with the main chain (the “photonic dendrite”), flat band modes become prevalent in the system, allowing spatial localization in the linear – low energy – regime. Furthermore, we study the inclusion of disorder in the distribution of spines and show that the main features of ordered systems persist due to the robustness of the flat band states. Finally, we discuss if the photonic analog, having evanescent interactions, may provide insight into linear morphological mechanisms at work occurring in some biological systems, where interactions are of electric and biochemical origin.

Resistance of Embryonic Chick Atria to Inhibition of HCN-Channels and Components of the “Ca<sup>2+</sup>-Clock”

Despite its medical importance, the cellular mechanisms activity and the contribution of various ion channels of embryonic heart automatism are not yet fully understood. In this study we investigated the effects of specific ion-channel inhibitors on the generation of action potentials in pacemaker cells of the right atrium in chicken embryos (HH36). We used microelectrode technique and evaluated the sensitivity of pacemaker cells to ivabradine (inhibitor of HCN-channels, through which the hyperpolarization-activated current, If), ryanodine (agonist of ryanodine receptors) and SN6 (inhibitor of Na+/Ca2+-exchange). It was found that the right atrium cells have a phase of slow diastolic depolarization. However, these cells were not sensitive to ivabradine (3 μM). We did not register significant changes in the electrophysiological parameters of action potentials.When ryanodine (1 μM) and SN6 (10 μM) were added to the perfusion solution, we observed similar effects: spontaneous rate the generation of action potential increased by 15%. Disturbance of rhythmic activity or disruption of the generation of electrical impulses were not observed in right atrial samples of chicken embryos. The obtained results allow us to conclude that, at this of embryonic development stage, HCN4-channels, ryanodine receptors, and the Na+/Ca2+-exchange are not decisive for maintaining the automatism of the right atrial cells in the chick embryo. We assume that the ion currents flowing through these channels are important in electrophysiology in adult animals, but they have a modulating function in the embryonic myocardium.

Epidemiology and Outcomes Associated with PR Prolongation.

PR prolongation is defined primarily as delayed conduction through the AV node, but can also signify delayed electrical impulse propagation through any part of the conduction system. The prevalence of PR prolongation ranges from 1% to 5% in patients younger than 50 years, with increasing prevalence, after the sixth decade of life and in patients with organic heart disease. Contemporary studies have documented increased risk of atrial arrhythmias, heart failure, and mortality in patients with PR prolongation. Future studies are needed to more accurately risk stratify elderly patients with PR prolongation who may be at increased risk of adverse outcomes.

Novel analytical technique for mathematical model representing communication signals: A new travelling wave solutions

The Lonngren wave equation, which simulates electrical signals in the semiconductor material known as tunnel diode, is taken into account in this work. New rational, trigonometric, and hyperbolic type travelling wave solutions are obtained by solving the non-linear equation using the advanced exp -Ψ(η)-expansion function technique. Graphs and simulations are used to show the relationships between the coefficient of the non-linearity term and other variables, as well as how these terms affect the wave behaviour in the presented solutions. By assigning special values to the constants in the solutions, a physical analysis is also carried out to determine how the conductivity of the model affects the propagation and dispersion of electrical impulses. In order to demonstrate the originality of our findings, we also developed a table-based comparison of the obtained solutions with those found in the literature.

Overview of Cardiac Arrhythmias and Treatment Strategies.

Maintenance of normal cardiac rhythm requires coordinated activity of ion channels and transporters that allow well-ordered propagation of electrical impulses across the myocardium. Disruptions in this orderly process provoke cardiac arrhythmias that may be lethal in some patients. Risk of common acquired arrhythmias is increased markedly when structural heart disease caused by myocardial infarction (due to fibrotic scar formation) or left ventricular dysfunction is present. Genetic polymorphisms influence structure or excitability of the myocardial substrate, which increases vulnerability or risk of arrhythmias in patients. Similarly, genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups within the population that affect specific drug biotransformation reactions. Nonetheless, identification of triggers involved in initiation or maintenance of cardiac arrhythmias remains a major challenge. Herein, we provide an overview of knowledge regarding physiopathology of inherited and acquired cardiac arrhythmias along with a summary of treatments (pharmacologic or non-pharmacologic) used to limit their effect on morbidity and potential mortality. Improved understanding of molecular and cellular aspects of arrhythmogenesis and more epidemiologic studies (for a more accurate portrait of incidence and prevalence) are crucial for development of novel treatments and for management of cardiac arrhythmias and their consequences in patients, as their incidence is increasing worldwide.

An iterative approach using Sawi transform for fractional telegraph equation in diversified dimensions

Abstract In the present study, 1D, 2D, and 3D fractional hyperbolic telegraph equations in Caputo sense have been solved using an iterative method using Sawi transform. These equations serve as a model for signal analysis of electrical impulse transmission and propagation. Along with a table of Sawi transform of some popular functions, some helpful results on Sawi transform are provided. To demonstrate the effectiveness of the suggested method, five examples in 1D, one example in 2D, and one example in 3D are solved using the proposed scheme. Error analysis comparing approximate and exact solutions using graphs and tables has been provided. The proposed scheme is robust, effective, and easy to implement and can be implemented on variety of fractional partial differential equations to obtain precise series approximations.

Sinus node dysfunction and atrial fibrillation-Relationships, clinical phenotypes, new mechanisms, and treatment approaches.

Although the anatomical basis of the pathogenesis of sinus node dysfunction (SND) and atrial fibrillation (AF) is located primarily in the left and right atria, increasing evidence suggests a strong correlation between SND and AF, in terms of both clinical presentation and formation mechanisms. However, the exact mechanisms underlying this association are unclear. The relationship between SND and AF may not be causal, but is likely to involve common factors and mechanisms, including ion channel remodeling, gap junction abnormalities, structural remodeling, genetic mutations, neuromodulation abnormalities, the effects of adenosine on cardiomyocytes, oxidative stress, and viral infections. Ion channel remodeling manifests primarily as alterations in the "funny" current (If) and Ca2+ clock associated with cardiomyocyte autoregulation, and gap junction abnormalities are manifested primarily as decreased expression of connexins (Cxs) mediating electrical impulse propagation in cardiomyocytes. Structural remodeling refers primarily to fibrosis and cardiac amyloidosis (CA). Some genetic mutations can also cause arrhythmias, such as SCN5A, HCN4, EMD, and PITX2. The intrinsic cardiac autonomic nervous system (ICANS), a regulator of the heart's physiological functions, triggers arrhythmias.In addition, we discuss arrhythmias caused by viral infections, notably Coronavirus Disease 2019 (COVID-19). Similarly to upstream treatments for atrial cardiomyopathy such as alleviating CA, ganglionated plexus (GP) ablation acts on the common mechanisms between SND and AF, thus achieving a dual therapeutic effect.

Role of Connexin 43 phosphorylation on Serine-368 by PKC in cardiac function and disease.

Intercellular communication mediated by gap junction channels and hemichannels composed of Connexin 43 (Cx43) is vital for the propagation of electrical impulses through cardiomyocytes. The carboxyl terminal tail of Cx43 undergoes various post-translational modifications including phosphorylation of its Serine-368 (S368) residue. Protein Kinase C isozymes directly phosphorylate S368 to alter Cx43 function and stability through inducing conformational changes affecting channel permeability or promoting internalization and degradation to reduce intercellular communication between cardiomyocytes. Recent studies have implicated this PKC/Cx43-pS368 circuit in several cardiac-associated diseases. In this review, we describe the molecular and cellular basis of PKC-mediated Cx43 phosphorylation and discuss the implications of Cx43 S368 phosphorylation in the context of various cardiac diseases, such as cardiomyopathy, as well as the therapeutic potential of targeting this pathway.

214 THE IMPACT OF ARRHYTHMIA ON PROGNOSIS IN HOSPITALIZED COVID-19 PATIENTS. A CARDIAC TELEMETRIC MONITORING STUDY

Abstract Background Cardiovascular abnormalities have been largely reported in patients with COVID-19. Among these, myocardial injury and rhythm disorders represent one of the most important complications in patients affected by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Moreover, a poorer prognosis has been documented in COVID-19 patients when complicated by arrhythmias, independently by age and sex. Objectives The aims of the present study were to identify some of non-cardiac and cardiac comorbidities and some myocardial electrical features (including QT dispersion) associated with arrhythmia in hospitalized COVID-19 patients. Moreover, another objective was to contribute in analyzing the impact of arrhythmias on outcome in this setting of patients. Methods At admission, each patient underwent cardiac telemetry monitoring through entire hospitalization period. In all the subjects, laboratory analyses, standard 12-lead electrocardiogram (both at admission and on discharge), and lung imaging examination (by means of both ultrasound scans and computed tomography) were performed. Patients exhibiting arrhythmia during in-hospital period were divided into three groups: i, with brady-arrhythmias; ii, with tachy-arrhythmias; and, iii, with tachy- and brady-arrhythmias. Results Two-hundred patients completed the study (males, 123; mean age, 70.1 years); of these, 80 patients (40%) exhibited rhythm disorders on cardiac telemetry. Patients with arrhythmia resulted to be older (p<0.0001) than patients without arrhythmia. Moreover, patients with arrhythmia showed: i, greater number of comorbidities (p<0.0001); ii, higher values of creatinine (p=0.007), B-type natriuretic peptide (p<0.0001), troponin (p<0.0001), c-reactive protein (p=0.01), ferritin (p=0.001), d-dimer (p<0.0001), and procalcitonin (p=0.0008); iii, QT interval (p=0.002), QTc interval (p=0.04), and QTc dispersion (p=0.01); and, iiii, lower values of sodium (p=0.03), magnesium (p=0.04), glomerular filtration rate (p<0.0001), and hemoglobin (p=0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. Multivariate analysis showed that age (OR=1.14 [95% CI: 1.07-1.22]; p=0.0004), coronary artery disease (OR=12.7 [95% CI: 2.38-68.01]; p=0.005), and circulating troponin (OR=1.05 [95% CI: 1.003-1.10]; p=0.04) represented risk factors independently associated with arrhythmia. By analyzing all-cause in-hospital mortality, it resulted a ∼forty-fold higher among patients with arrhythmia (OR=39.66 [95% CI: 5.20-302.51]; p=0.0004) when compared to patients without rhythm disorders. Conclusion In the present study, arrhythmias have been to be associated with ageing, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and abnormalities in myocardial electrical impulse propagation in patients affected by SARS-CoV-2 infection. In alignment with previous reports, the presence of arrhythmia seems to be associated with a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetric monitoring should be encouraged in COVID wards.

Electrochemical and Electroconductive Behavior of Silk Fibroin Electrospun Membrane Coated with Gold or Silver Nanoparticles.

The surface modification of materials obtained from natural polymers, such as silk fibroin with metal nanoparticles that exhibit intrinsic electrical characteristics, allows the obtaining of biocomposite materials capable of favoring the propagation and conduction of electrical impulses, acting as communicating structures in electrically isolated areas. On that basis, this investigation determined the electrochemical and electroconductive behavior through electrochemical impedance spectroscopy of a silk fibroin electrospun membrane from silk fibrous waste functionalized with gold or silver nanoparticles synthetized by green chemical reduction methodologies. Based on the results obtained, we found that silk fibroin from silk fibrous waste (SFw) favored the formation of gold (AuNPs-SFw) and silver (AgNPs-SFw) nanoparticles, acting as a reducing agent and surfactant, forming a micellar structure around the individual nanoparticle. Moreover, different electrospinning conditions influenced the morphological properties of the fibers, in the presence or absence of beads and the amount of sample collected. Furthermore, treated SFw electrospun membranes, functionalized with AuNPs-SFw or AgNPS-SFw, allowed the conduction of electrical stimuli, acting as stimulators and modulators of electric current.

Benchmarking functional connectivity by the structure and geometry of the human brain.

The brain's structural connectivity supports the propagation of electrical impulses, manifesting as patterns of coactivation, termed functional connectivity. Functional connectivity emerges from the underlying sparse structural connections, particularly through polysynaptic communication. As a result, functional connections between brain regions without direct structural links are numerous, but their organization is not completely understood. Here we investigate the organization of functional connections without direct structural links. We develop a simple, data-driven method to benchmark functional connections with respect to their underlying structural and geometric embedding. We then use this method to reweigh and reexpress functional connectivity. We find evidence of unexpectedly strong functional connectivity among distal brain regions and within the default mode network. We also find unexpectedly strong functional connectivity at the apex of the unimodal-transmodal hierarchy. Our results suggest that both phenomena-functional modules and functional hierarchies-emerge from functional interactions that transcend the underlying structure and geometry. These findings also potentially explain recent reports that structural and functional connectivity gradually diverge in transmodal cortex. Collectively, we show how structural connectivity and geometry can be used as a natural frame of reference with which to study functional connectivity patterns in the brain.

COVID-19 and arrhythmia: The factors associated and the role of myocardial electrical impulse propagation. An observational study based on cardiac telemetric monitoring.

BackgroundThe heart is commonly involved in COVID-19, and rhythm disorders have been largely reported.ObjectiveTo evaluate the association of some non-cardiac and cardiac comorbidities and QT dispersion with arrhythmias and their impact on outcomes in hospitalized patients with COVID-19.MethodsEach patient underwent cardiac telemetry monitoring through the entire hospitalization period, laboratory analyses, 12-lead ECG, and lung imaging examination. Patients with arrhythmia were divided into three groups (bradyarrhythmias, tachyarrhythmias, and tachy- and bradyarrhythmias).ResultsTwo-hundred patients completed the study (males, 123; mean age, 70.1 years); of these, 80 patients (40%) exhibited rhythm disorders on telemetry. Patients with arrhythmia were older (p < 0.0001), had a greater number of comorbidities (p < 0.0001), higher values of creatinine (p = 0.007), B-type natriuretic peptide (p < 0.0001), troponin (p < 0.0001), C-reactive protein (p = 0.01), ferritin (p = 0.001), D-dimer (p < 0.0001), procalcitonin (p = 0.0008), QT interval (p = 0.002), QTc interval (p = 0.04), and QTc dispersion (p = 0.01), and lower values of sodium (p = 0.03), magnesium (p = 0.04), glomerular filtration rate (p < 0.0001), and hemoglobin (p = 0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. At multivariate analysis, age [odds ratio (OR) = 1.14 (95% CI: 1.07–1.22); p = 0.0004], coronary artery disease [OR = 12.7 (95% CI: 2.38–68.01); p = 0.005], and circulating troponin [OR = 1.05 (95% CI: 1.003–1.10); p = 0.04] represented risk factors independently associated with arrhythmia. All-cause in-hospital mortality was ∼40-fold higher among patients with arrhythmia [OR = 39.66 (95% CI: 5.20–302.51); p = 0.0004].ConclusionArrhythmias are associated with aging, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and prolonged QTc dispersion in patients with COVID-19, and confer a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetry should be encouraged in COVID wards.

A Large-scale Virtual Patient Cohort to Study ECG Features of Interatrial Conduction Block

Abstract Interatrial conduction block refers to a disturbance in the propagation of electrical impulses in the conduction pathways between the right and the left atrium. It is a risk factor for atrial fibrillation, stroke, and premature death. Clinical diagnostic criteria comprise an increased P wave duration and biphasic P waves in lead II, III and aVF due to retrograde activation of the left atrium. Machine learning algorithms could improve the diagnosis but require a large-scale, well-controlled and balanced dataset. In silico electrocardiogram (ECG) signals, optimally obtained from a statistical shape model to cover anatomical variability, carry the potential to produce an extensive database meeting the requirements for successful machine learning application. We generated the first in silico dataset including interatrial conduction block of 9,800 simulated ECG signals based on a bi-atrial statistical shape model. Automated feature analysis was performed to evaluate P wave morphology, duration and P wave terminal force in lead V1. Increased P wave duration and P wave terminal force in lead V1 were found for models with interatrial conduction block compared to healthy models. A wide variability of P wave morphology was detected for models with interatrial conduction block. Contrary to previous assumptions, our results suggest that a biphasic P wave morphology seems to be neither necessary nor sufficient for the diagnosis of interatrial conduction block. The presented dataset is ready for a classification with machine learning algorithms and can be easily extended.

Non-monotone cellular automata: Order prevails over chaos

We consider a model for the propagation of electrical impulses or activity in a neuronal network. The vertices of a square lattice represent neurons, and the edges of the lattice represent the synaptic connections. Each vertex v is assigned a type: inhibitory or excitatory. The dynamics of propagation of the initial activity captures features of the “integrate-and-fire” model.We study the spread of activation in a large network and describe possible spatio-temporal limiting patterns depending on the initial activation. The rich palette of the limits with qualitatively different properties, including expanding patterns, fixed patterns, and patterns moving across the network, allows us to argue that this is a versatile model for the study of associative memory.

Cardiac Electrophysiological Changes and Downregulated Connexin 43 Prompts Reperfusion Arrhythmias Induced by Hypothermic Ischemia-Reperfusion Injury in Isolated Rat Hearts.

The purpose of this study was to determine the utility of the monophasic action potential (MAP) changes as an arrhythmic biomarker in hypothermic ischemia-reperfusion. The hypothermic ischemia-reperfusion model was subjected to 60min of cardioplegic arrest while the isolated rat hearts were preserved with a multidose cold K-H solution at 4°C. During the reperfusion period, the heart's arrhythmia and monophasic action potential were also monitored. The myocardial damage was assessed using HE and TTC stains. Immunohistochemistry and Western blotting were used to assess the expression and distribution of Connexin 43 (Cx43) and Akt. Collectively, prolonged action potential durations, increased dispersion of repolarization, and downregulated and lateralized Cx43 all contribute to the derangement of electrical impulse propagation that may underlie arrhythmogenesis in the cold ischemic heart following cardioplegic arrest. MAP might be used as a biomarker for arrhythmias caused by hypothermic ischemia-reperfusion.

Engineering Models of the Heart Left Ventricle.

Despite capturing the imagination of scientists for decades, the goal of creating an artificial heart for transplantation proved to be significantly more challenging than initially anticipated. Toward this goal, recent ground-breaking studies demonstrate the development of functional left ventricular (LV) models. LV models are artificially constructed 3D chambers that are capable of containing liquid within the engineered cavity and exhibit the functionality of native LV including contraction, ejection of fluid, and electrical impulse propagation. Various hydrogels and polymers have been used in manufacturing of LV models, relying on techniques such as electrospinning, bioprinting, casting, and molding. Most studies scaled down the models based on the dimensions of the human or rat ventricle. Initially, neonatal rat cardiomyocytes were the cell type of choice for construction the LV models. Yet, as the stem cell biology field advanced, recent studies focused on the use of cardiomyocytes derived from human induced pluripotent stem cells. In this review, we first describe the physiological characteristics of the human heart, to establish the parameter space for modeling. We then elaborate on current advances in the field and compare recently developed LV models among themselves and with the native human left ventricle. Fabrication methods, cell types, biomaterials, functional properties, and disease modeling capability are some of the major parameters that have distinguished these models. We also highlight some of the current challenges in this field, such as vascularization, cell composition and fidelity, and discuss potential solutions to overcome them.

Adenovirus increases arrhythmia susceptibility during acute cardiac infection

Myocarditis is responsible for 42% of sudden cardiac death in young adults, yet mechanisms underlying virally induced arrhythmia remain elusive. Adenovirus is a leading etiological agent of myocarditis but species‐specificity has limited development of animal disease models. Normal electrical impulse propagation in the heart is achieved through intercellular coupling via gap junctions, composed primarily of connexin43 (Cx43). Changes in Cx43 expression, localization, and/or function underlie the arrhythmias of sudden cardiac death. Given that gap junctions also propagate innate and adaptive antiviral immune responses, we hypothesized that adenovirus would target Cx43 to facilitate replication. Our prior work has demonstrated that Cx43 expression and function are indeed reduced rapidly during adenoviral infection limiting gap junction communication in human epithelial and cardiac cells. We are now employing a recently described cardiotropic strain of mouse adenovirus, MAdV‐3, to develop our work into whole animal studies and investigate virally‐induced alterations in cardiac electrophysiology and the molecular mechanisms of the resulting arrhythmogenic substrate. Adult mice were inoculated with MAdV‐3 and sampled after 7 days to model acute cardiac infection. We find MAdV‐3 viral genomes are specifically enriched in heart tissue, confirming cardiotropism. No cardiomyopathy was apparent by echocardiography or histopathology, consistent with human acute myocarditis patients. We find reductions in cardiac ion channel and connexin mRNA transcript levels after infection, and at the protein level, Cx43 is phosphorylated at residues known to reduce function. Ex vivo optical mapping experiments illustrate decreased conduction velocity in infected hearts. Turning to primary adult mouse cardiomyocytes, we detect prolonged action potential duration and impaired K+ current in infected cells by patch clamping. Confocal and super‐resolution localization microscopy of infected cardiac tissue and isolated cardiomyocytes reveals remodeling of gap junctions with alterations in complexing with scaffolding proteins and other ion channels at the cell‐cell junction. Finally, employing human iPSC‐derived cardiomyocytes and human adenovirus type‐5, we find increased Cx43 phosphorylation and, using optical mapping, perturbation of intercellular coupling during infection, just as we see with MAdV‐3. Our data demonstrate that reduced cellular coupling and ion channel function during adenoviral infection generates an arrhythmogenic substrate prior to an appreciable immune response or cardiomyopathy development. MAdV‐3 infection therefore provides a novel model of cardiac infection and myocarditis and provides physiologically relevant insight into mechanisms of virally‐induced arrhythmias.

BS-514-04 ADENOVIRUS INCREASES ARRHYTHMIA SUSCEPTIBILITY DURING ACUTE CARDIAC INFECTION

Myocarditis underlies 42% of sudden cardiac death in young adults, yet viral arrhythmogenic mechanisms remain elusive. Adenovirus is a leading cause but species-specificity has limited disease modeling in mice. Gap junctions, composed primarily of connexin43 (Cx43), enable electrical impulse propagation in the heart. Changes in Cx43 expression, localization, and/or function cause arrhythmias. Gap junctions propagate innate and adaptive antiviral responses, and our prior work has demonstrated that Cx43 expression and function are reduced during human adenoviral infection.

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern.

Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or ‘crack’ cocaine, the free base. While the first is commonly administered by insufflation (‘snorting’) or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine’s prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.