Materiały źródłowe

• #1 Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies | Communications Biology

  https://www.nature.com/articles/s42003-024-06019-6

  Snakebite envenoming is an important public health issue responsible for mortality and severe morbidity. Where mortality is mainly caused by venom toxins that induce cardiovascular disturbances, neurotoxicity, and acute kidney injury, morbidity is caused by toxins that directly or indirectly destroy cells and degrade the extracellular matrix. These are referred to as tissue-damaging toxins and have previously been classified in various ways, most of which are based on the tissues being affected (e.g., cardiotoxins, myotoxins). This categorisation, however, is primarily phenomenological and not mechanistic. […] The mechanisms of toxin-induced tissue damage and their clinical implications are discussed. […] Tissue-damaging effects are the leading cause of snakebite morbidity, including life-long disabilities such as permanent muscle tissue loss, contractures, hypertrophic scars, chronic ulceration, chronic renal disease, ocular damage and other debilitating pathologies.

• #1 Snakebite: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/168828-overview

  Pit viper venom is produced and stored in paired glands below the eyes. Pit vipers have hollow, mobile, relatively long fangs located in the front of the upper jaw and are capable of delivering venom quite efficiently. Fewer than 10% of pit viper bites are dry (meaning that no venom is deposited). A number of factors determine how much venom is delivered, including the species, age, size, and overall health of the snake, as well as its diet and the last time it had fed or released venom. […] Snake venom has been described as a „soup of antigens” and comprises a variety of protein and nonprotein substances. Most pit viper venom contains a mixture of metalloproteinases, collagenase, phospholipase, and hyaluronidase that can cause myonecrosis and dermatonecrosis. Multiple venom components, such as serine proteases, disintegrins, metalloproteinases, and C-type lectinlike proteins, produce a variety of hematologic effects, resulting in coagulopathy, platelet aggregation, platelet activation or inhibition, or increased coagulation, leading to thrombotic complications.

• #1 Snakebite – Wikipedia

  https://en.wikipedia.org/wiki/Snakebite

  The venom itself evolved through the process of natural selection; it retained and emphasized the qualities that made it useful in killing or subduing prey. […] Venom in many snakes, such as pit vipers, affects virtually every organ system in the human body and can be a combination of many toxins, including cytotoxins, hemotoxins, neurotoxins, and myotoxins, allowing for an enormous variety of symptoms. Snake venom may cause cytotoxicity as various enzymes including hyaluronidases, collagenases, proteinases and phospholipases lead to breakdown (dermonecrosis) and injury of local tissue and inflammation which leads to pain, edema and blister formation. […] In venom-induced consumption coagulopathy, toxins in snake venom promote hemorrhage via activation, consumption, and subsequent depletion of clotting factors in the blood. […] Snake venom is known to cause neuromuscular paralysis, usually as a flaccid paralysis that is descending; starting at the facial muscles, causing ptosis or drooping eyelids and dysarthria or poor articulation of speech, and descending to the respiratory muscles causing respiratory compromise.

• #1 Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies | Communications Biology

  https://www.nature.com/articles/s42003-024-06019-6

  Toxins with tissue-damaging capabilities can be broadly divided into two main groups based on the way they affect cells (and thus tissues). These include (a) cytotoxins, defined as toxins that are truly cytotoxic by directly affecting the viability of cells and (b) extracellular matrix (ECM) degrading enzymes, which, in addition to this action, may be indirectly cytotoxic, meaning that cell death occurs as a secondary effect and not by directly damaging the cells. […] The classification based on affected tissue type likely originates from the cell type on which the effect was initially tested. […] This led to many alternative names to describe these toxins, such as cytotoxin, direct lytic factor, membrane toxin, and others. […] However, studies on purified myotoxic PLA2s on other cell types have proven that the activity spectrum of these toxins is actually much broader than previously thought.

• #1 Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies | Communications Biology

  https://www.nature.com/articles/s42003-024-06019-6

  The destabilisation of the lipid bilayer makes the membrane more permeable to ions, thereby losing its membrane potential (becoming depolarised) and allowing a large influx of Ca2+ from the extracellular medium. […] The uncontrolled influx of calcium causes calcium overload in affected cell types (i.e., myocytes, nerve terminals) and induces more stress on the weakened cellular membrane and mitochondrial dysfunction, resulting in decreases in ATP production, which in turn may result in necrosis. […] The extracellular matrix (ECM) is a macromolecular structure made up of the interstitial matrix and the basement membrane. […] The basement membrane has multiple functions, such as providing structural support to capillary endothelial cells and many other cell types, acting as a filtration barrier, storing growth factors, preventing cells and larger molecules from passing through, and organising the tissue architecture.

• #1 Snake Envenomation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9854269/

  Snake envenomation can result in myocardial infarction, stroke, or other thrombotic effects. […] In severe cases of envenomation from Crotalinae (New World pit vipers), thrombocytopenia is common. […] Neuromuscular paralysis is one of the leading clinical disorders due to envenomation from elapids (snakes in the Elapidae family) such as naja, bungarus, and micrurus species. […] Myotoxicity may develop as a result of the direct effect of venom on muscle through myotoxic phospholipase A2, which disrupts the integrity of the plasma membrane and provokes calcium influx. […] Snake envenomation can result in acute kidney injury, which may progress to chronic kidney disease or renal failure. […] Other systemic effects of venom can include nausea, vomiting, diarrhea, and diaphoresis.

• #1

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/01000/neurological_and_neuro_ophthalmological.61.aspx

  Snakebites, a major health concern in developing countries, affect rural farming communities. Venom, primarily neurotoxin, injected during a snake bite disrupts the nervous system, causing symptoms like muscle weakness, paralysis, altered sensation, and coordination issues. This review focuses on evaluating neurological and neuro-ophthalmological manifestations associated with snakebites. […] Neurological and neuro-ophthalmological symptoms were common in both neurotoxic and hemotoxic snake bites, especially in neurotoxic cases. Ptosis was a prevalent manifestation across various snake bites, along with respiratory paralysis, limb weakness, dysphasia, and visual disturbances in some instances. However, most patients improved without residual neurological symptoms after treatment. […] Understanding patterns of neurological manifestations contributes valuable insights for the comprehensive management of snakebite.

• #1 Snakebites – Injuries; Poisoning – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/injuries-poisoning/bites-and-stings/snakebites

  Weakness of the bitten extremity may become evident within several hours. Systemic neuromuscular manifestations may be delayed for 12 hours and include weakness and lethargy; altered sensorium (eg, euphoria, drowsiness); cranial nerve palsies causing ptosis, diplopia, blurred vision, dysarthria, and dysphagia; increased salivation; muscle flaccidity; and respiratory distress or failure. Once the neurotoxic venom effects manifest, they are difficult to reverse and may last 3 to 6 days. Untreated, respiratory muscle paralysis may be fatal. […] For pit viper envenomation, the mainstay of treatment in the United States is an ovine-derived Crotalidae polyvalent immune FAb antivenom (purified FAb fragments of IgG harvested from pit viper venomimmunized sheep). The effectiveness of this antivenom is time and dose related; it is most effective in preventing venom-induced tissue damage when given as soon as possible. It is less effective if delayed but can reverse coagulopathies and be effective even when started 24 hours after envenomation.

• #1 Snake Envenomation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9854269/

  SNAKE ENVENOMATION REPRESENTS AN IMPORTANT HEALTH PROBLEM IN much of the world. […] Not all bites by venomous snakes involve envenomation; dry bites occur in 2 to 50% of cases. […] When envenomation does occur, the clinical effects depend on the toxins in the venom. […] Local tissue injury and inflammation are caused by enzymes such as hyaluronidase and collagenase, as well as proteinases and phospholipases. […] The effect of snake venom metalloproteinases on the extracellular matrix results in the release of extracellular matrix-derived peptides that exert diverse actions in the tissue. […] In snake envenomation, injury to the lymphatic system plays a role in the development of edema. […] Procoagulant toxins in snake venoms promote consumption coagulopathy, which causes the depletion of factors in the clotting cascade and may result in either spontaneous or uncontrolled bleeding.

• #1 The kidney histopathological spectrum of patients with kidney injury following snakebite envenomation in India: scoping review of five decades | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03508-y

  The pathogenesis of VICC distinguishes itself from Disseminated Intravascular Coagulation (DIC). While DIC arises from multifaceted mechanisms culminating in fibrin deposition, VICCs coagulation activation originates primarily from a snake procoagulant toxin, not the tissue factor/factor VIIa pathway implicated in DIC. […] The infiltration of various cells such as lymphocytes, monocytes, eosinophils, basophils, and mast cells in the interstitium in cases of ATN was hypothesized to be either a consequence of some immunologically mediated reaction to antigens released from necrotic renal tubules or due to homocytotropic antibody-mediated reaction. However, their activation and accumulation in the interstitium have also been argued to be a similar phenomenon as seen in delayed hypersensitivity reactions.

• #1 Pathophysiology of Snake Envenomation in Dogs and Cats | Our Blog | Animal Emergency Australia

  https://animalemergencyaustralia.com.au/blog/snake-envenomation-in-dogs-and-cats/

  Rhabdomyolysis from a myotoxin is common and can lead to elevated creatine kinase and subsequent renal tubular damage if not treated. Other intra-cellular components will also lead to hyperphosphatemia, hyperkalemia, hypermagnesemia and a metabolic acidosis. […] Haemolysis is also variable amongst snake venom, however, their potency tends to be more exaggerated in species seen in the eastern states of Australia and can require blood transfusions if global hypoxia is evident (ie: elevated lactate, low ScvO2, low base excess, tachycardia). Disruption to the cell membrane by phospholipase causes water to enter the cell, allowing it to swell and causing cell destruction. […] This is typically specific for Taicotoxin from the Taipan, and it has been shown to inhibit calcium channels in the myocardium, leading to prolonged repolarisation and arrhythmias.

• #1 Snake Bite Induced Acute Renal Failure: A Study of Clinical Profile and Predictors of Poor Outcome | Patil | World Journal of Nephrology and Urology

  https://wjnu.org/index.php/wjnu/article/view/13/21

  Snake bite is a common cause of morbidity and mortality worldwide, especially in tropical countries. Acute renal failure is mainly observed following bites by the viperidae group, sea snakes and the colubridae group, but the substantial number of cases result from viper bites. Tubular necrosis and cortical necrosis are the main causes of ARF. The exact pathogenesis of ARF following snake bite is not well established. However, a number of factors contribute, viz, bleeding, hypotension, circulatory collapse, intravascular hemolysis, disseminated intravascular coagulation, microangiopathic haemolytic anemia and direct nephrotoxicity of venom. Tubular necrosis (53.6%) and cortical necrosis (24.3%) are the main causes of acute renal failure. The mortality of snake bite induced acute renal failure is found to be 15.5% in this study. Coagulopathy is an important factor contributing to increased mortality. The prevalence of coagulopathy in this study (36.8%) is comparable to that noted by Athappan et al. By itself, coagulopathy is a marker of the vasculotoxicity and hemotoxicity of the poison, which means that these patients will have nephrotoxicity due to damage to renal microvasculature. This study concludes that acute renal failure occurs in 20.48% victims of snake bite. Common manifestations include cellulitis, oliguria, albuminuria, coagulopathy and thrombocytopenia. Presence of coagulopathy and uremic encephalopathy are predictors of poor outcome in snake bite patients who develop acute renal failure. […] The higher prevalence probably suggests delay in administration of ASV, as there is a delay in taking the patient to hospital after snake bite, which may be related to social factors, and the long distances that the tribal and rural people have to travel before reaching a health facility.

• #1 Managing snakebite | The BMJ

  https://www.bmj.com/content/376/bmj-2020-057926

  Some patients with acute kidney injury may progress to chronic renal failure. Limited data from case reports and observational studies from South Asia indicate that chronic hypopituitarism, a sequel of acute pituitary haemorrhage, can present as fatigue, arrested puberty, amenorrhoea, and hypothyroidism as late as 10 years after the bite.

• #1 Snakebite complications: Unveiling the link to myocarditis | European Journal of Cardiovascular Medicine

  https://healthcare-bulletin.co.uk/article/volume-14-issue-3-pages888-892-ra/

  Snake venom contains proteins that can disrupt human bodily functions. […] Cardiotoxins (CTXs), venom polypeptides with approximately 60 amino acid residues found in elapid snakes, have pharmacological functions such as hemolysis, cytotoxicity, and muscle depolarization. […] One unusual consequence of a snakebite is myocarditis. […] Snake bites can cause an autoimmune reaction in the heart, resulting in symptoms such as an acute rash, fever, peripheral eosinophilia, and ECG abnormalities like nonspecific ST segment changes or infarction patterns. This type of myocarditis, known as eosinophilic myocarditis (EM), is typically accompanied by hyper eosinophilia. […] Myocardial cell death is indicated by the presence of various proteins in the bloodstream, such as myoglobin, cardiac troponin T and I, CK, CK-MB, and LDH.

• #1 Snakebite – Special Pet Topics – Merck Veterinary Manual

  https://www.merckvetmanual.com/special-pet-topics/poisoning/snakebite

  Venomous snakes fall into two families: 1) the Elapidae, which include the cobra, mamba, and coral snakes; and 2) the Cortalidae, which include the true vipers (for example, puff adder, Russells viper, and the common European adder) and the pit vipers (for example, rattlesnakes, cottonmouth moccasin, copperhead, and fer-de-lance). Pit vipers and coral snakes are found in North America. […] Elapid snakes have short fangs and tend to hang on and chew venom into their victims. Elapid venom is toxic to the nervous system and paralyzes the breathing center. […] Crotalid snakes have long, hinged, hollow fangs; they strike, inject venom, and withdraw. Crotalid venom is typically toxic to the blood, killing cells and preventing normal clotting. The venom of some crotalid species, for example, the Mojave rattlesnake, also affects the nervous system.

• #1 Snakebite: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/168828-overview

  Certain pit viper species have unique toxins. Crotalocytin, found in the timber rattlesnake (Crotalus horridus), causes platelet aggregation. Mojave toxin, found in some populations of the Mojave rattlesnake (Crotalus scutulatus), inhibits the presynaptic release of acetylcholine, leading to weakness and paralysis. Pit viper venom may also include bradykinin-related peptides that can lead to angioedema and hypotension. […] Coral snake venoms are complex mixtures that include phospholipase A2, multiple proteases, high-molecular-weight protein, and a variety of neurotoxins. Approximately 380 isoforms of phospholipase A2 have been identified in snake venoms, and their effects include neuromuscular paralysis, bleeding, myonecrosis, edema, widespread inflammation, and platelet aggregation. In coral snakes, the neuromuscular effects are most pronounced.

• #1 Snakebites – Injuries; Poisoning – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/injuries-poisoning/bites-and-stings/snakebites

  The venom of most North American pit vipers causes very minor changes in neuromuscular conduction, except for Mojave and eastern diamondback rattlesnake venom, which may cause serious neurologic deficits (eg, muscle weakness, respiratory depression). […] Venom of these snakes contains primarily neurotoxic components, which cause a presynaptic neuromuscular blockade, potentially causing respiratory paralysis. The lack of significant proteolytic enzyme activity accounts for the paucity of symptoms and signs at the bite site. […] Rattlesnake envenomations may induce various coagulation abnormalities, including thrombocytopenia, prolongation of prothrombin time (PT, measured by the INR [international normalized ratio]) or activated partial thromboplastin time (PTT), hypofibrinogenemia, elevated fibrin degradation products, or a combination of these findings, causing a disseminated intravascular coagulation (DIC)-like syndrome.

• #1 Inflammation and Oxidative Stress in Snakebite Envenomation: A Brief Descriptive Review and Clinical Implications

  https://www.mdpi.com/2072-6651/14/11/802

  Snakebite envenoming is a pathological condition which may occur in response to the injection of venom. Snake venoms contain a complex mixture of biologically active molecules which are responsible for a broad spectrum of clinical manifestations, ranging from local tissue injuries to fatal complications. Snake venom administration commonly provokes local tissue injury often associated with systemic effects, including neurotoxic and cardiotoxic manifestations, bleeding, acute kidney injury, and rhabdomyolysis. An important spectrum of pathogenesis of snake envenomation is the generation of reactive oxygen species (ROS), which can directly provoke tissue damage and also potentiate the deleterious consequences of inflammation at the bite site. […] Clear evidence is mounting suggesting that inflammation and oxidative stress participate in the destructive effects of envenoming, including acute renal failure, tissue necrosis, and unusual susceptibility to bleed (hemorrhage), mostly due to hypocoagulability, neuro/cardio toxicity, and myonecrosis.

• #1 Inflammation and Oxidative Stress in Snakebite Envenomation: A Brief Descriptive Review and Clinical Implications

  https://www.mdpi.com/2072-6651/14/11/802

  The group of 3FTxs cardiotoxins plays an important role in envenoming by Naja species and cobra elapids, eliciting plasma membrane damage, myonecrosis, and cytotoxicity. […] Many components of snake venoms (PLA2s, SVMPs, and SVSPs) contribute to local and systemic inflammatory processes, which is initiated by an increase of vascular permeability, followed by immune cell infiltration leading to the release of bioactive mediators. […] The production of bioactive molecules by leukocytes, such as ROS and proteinases, as well as the formation of neutrophil extracellular traps (NETs), are involved in the mechanisms of local tissue injuries following administration of snake venoms. […] Another important feature of the pathogenesis of snake envenomation is the production of reactive oxygen species (ROS). Typically, the generation of ROS can potentiate tissue damage at inflammatory sites following snakebite.

• #1 Inflammation and Oxidative Stress in Snakebite Envenomation: A Brief Descriptive Review and Clinical Implications

  https://www.mdpi.com/2072-6651/14/11/802

  The involvement of oxidative stress in the pathogenesis of snake envenomation was initially reported in the early 1980s. […] The injection of elapid venoms of the Egyptian cobra (Naja haje) also induced increases in serum levels of malonaldehyde, while serum levels of GSH, superoxide dismutase (SOD), and catalase (CAT) were consistently reduced. […] Overall, these results suggest that oxidative stress may occur in experimental in vivo envenomation and may be responsible, at least in part, for hepatic and renal damage in both viperid and elapid species. […] The most frequent delayed complications observed in patients with snake envenomation on long-term follow-up are ulceration, amputation, renal failure, and musculoskeletal disabilities. […] In human envenomation, growing evidence suggests that oxidative stress can play a critical role in the pathophysiology of snakebite, predominantly from viperids.

• #1 The Role of the Lymphatic System in Systemic Toxicity of Snakebites

  https://www.jscimedcentral.com/jounal-article-info/Journal-of-Pharmacology-and-Clinical-Toxicology/The-Role-of-the-Lymphatic–System-in-Systemic-Toxicity-of–Snakebites-6131

  Toxic effects of snakebites consist of local toxicity at the site of the bite and systemic toxicity, with coagulopathy and neurotoxicity occurring, depending on the species and composition of the venom. Research has established that the lymph system is the mechanism of systemic spread of venom […] The reviewed articles describe experimental studies of lymphatic inhibition on systemic toxicity of snakebites. […] Experimental studies establish that inhibition of lymph flow by several mechanisms results in reduced systemic toxicity of snakebites. […] To produce systemic toxicity, venom must reach the vascular system and be distributed throughout the body. […] The lymphatic system is the major source of systemic spread of venom. […] Techniques identified in the literature that have been studies in snake envenomations include lymphatic channel ligation, pharmaceuticals that inhibit lymph flow, splints, and devices to apply pressure significant to block lymph flow while preserving arterial flow and venous return.

• #1 Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10960010/

  The mechanisms of tissue damage induced by venom toxins discussed above have direct implications in the pathology and pathophysiology of snakebite envenoming. […] Cytotoxic 3FTxs and PLA2s induce necrosis in vivo as well as in cells in culture, as described above. […] The cytotoxic mechanisms described in this section highlight the complexity of the actions of venom components in cells.

• #1 Snakebite – Wikipedia

  https://en.wikipedia.org/wiki/Snakebite

  A snakebite is an injury caused by the bite of a snake, especially a venomous snake. A common sign of a bite from a venomous snake is the presence of two puncture wounds from the animal’s fangs. Sometimes venom injection from the bite may occur. This may result in redness, swelling, and severe pain at the area, which may take up to an hour to appear. The venom may cause bleeding, kidney failure, a severe allergic reaction, tissue death around the bite, or breathing problems. Bites may result in the loss of a limb or other chronic problems or even death. […] The outcome depends on the type of snake, the area of the body bitten, the amount of snake venom injected, the general health of the person bitten, and whether or not anti-venom serum has been administered by a doctor in a timely manner. Problems are often more severe in children than adults, due to their smaller size. Allergic reactions to snake venom can further complicate outcomes and can include anaphylaxis, requiring additional treatment and in some cases resulting in death.

• #1 Snakebite Envenomization | VCA Animal Hospitals

  https://vcahospitals.com/know-your-pet/snakebite-envenomization

  The correct treatment of venomous snakebites depends on the type of snakebite. […] Rattlesnake envenomization is immediately life threatening and prompt medical assistance must be sought. […] Treatment to counter shock, low blood pressure, infection and respiratory distress is necessary in most cases of venomous snakebites. […] The prognosis depends on several factors, including: the size and species of the snake; the amount of venom injected; the number of bites; the location and depth of the bite (bites to the head and body tend to be more severe than bites to the legs or paws); the age, size, and health of the dog; the time elapsed before treatment; and the dog’s individual susceptibility to the venom. […] Copperhead, cottonmouth, and coral snake envenomization cases have a better prognosis for complete recovery than rattlesnake bites.

• #1 Snakebite envenoming | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201763

  Snakebite envenoming is a neglected tropical disease that kills 100,000 people and maims 400,000 people every year. […] Snake venoms are complex mixtures of proteins that exert a wide range of toxic actions. The high variability in snake venom composition is responsible for the various clinical manifestations in envenomings, ranging from local tissue damage to potentially life-threatening systemic effects. […] Novel therapeutic alternatives based on recombinant antibody technologies and new toxin inhibitors are being explored. […] This review summarizes the mechanisms by which zinc-dependent SVMPs induce microvascular damage and haemorrhage. […] This paper reviews the mechanisms by which venom PLA2s induce myotoxicity and neurotoxicity. […] A comprehensive view of the structural and functional alterations of extracellular matrix by snake venom metalloproteinases (SVMPs): novel perspectives on the pathophysiology of envenoming.

• #1 Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10960010/

  Snakebite envenoming is an important public health issue responsible for mortality and severe morbidity. […] The snake venom toxins responsible for tissue damage, their mechanisms of action and pathological effects are reviewed, together with the search of novel therapeutic alternatives to abrogate their effects. […] Tissue-damaging effects are the leading cause of snakebite morbidity, including life-long disabilities such as permanent muscle tissue loss, contractures, hypertrophic scars, chronic ulceration, chronic renal disease, ocular damage and other debilitating pathologies. […] Toxins with tissue-damaging capabilities can be broadly divided into two main groups based on the way they affect cells (and thus tissues). These include (a) cytotoxins, defined as toxins that are truly cytotoxic by directly affecting the viability of cells and (b) extracellular matrix (ECM) degrading enzymes, which, in addition to this action, may be indirectly cytotoxic, meaning that cell death occurs as a secondary effect and not by directly damaging the cells.

• #1 Managing snakebite | The BMJ

  https://www.bmj.com/content/376/bmj-2020-057926

  Antivenoms are whole or fragmented immunoglobulins fractionated from the plasma of domesticated animals hyper-immunised with venom from one or more snake species over variable periods. They are highly specific and will neutralise only the venoms used in their production and those of a few closely related species. […] Early administration of antivenom prevents or limits haemodynamic alterations, progression of coagulopathy to clinically overt bleeding, postsynaptic neurotoxicity, myotoxicity, acute kidney injury, and local tissue damage. […] The effectiveness of antivenoms in treating established neurotoxicity, soft tissue damage, and acute kidney injury is not established. […] There is insufficient data on long term sequelae after a snakebite. Amputations following snakebite-related soft tissue injuries range from 5908 to 14614 annually in sub-Saharan Africa. Even in patients not requiring amputations, tissue loss may result in chronic ulcers, malignant transformation, and scarring.

• #1 Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10960010/

  Here, we review the molecular mechanisms of venom-induced tissue damage, revealing that snake venoms exert their cytotoxic effects via a number of distinct mechanisms, both direct and indirect. […] Understanding the mechanisms of action of snake venom toxins that inflict tissue damage may shed light on other diseases involving similar cytotoxic effects. […] The classification based on affected tissue type likely originates from the cell type on which the effect was initially tested. […] However, this categorisation is primarily phenomenological and not mechanistic. […] A thorough understanding of the pathological and pathophysiological effects caused by tissue-damaging toxins is crucial to grasp the complexity of snakebite envenoming and to develop effective therapies for treating venom-induced morbidity.

• #2 Snakebite envenoming | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201763

  Snakebite envenoming is a neglected tropical disease that kills 100,000 people and maims 400,000 people every year. […] Snake venoms are complex mixtures of proteins that exert a wide range of toxic actions. The high variability in snake venom composition is responsible for the various clinical manifestations in envenomings, ranging from local tissue damage to potentially life-threatening systemic effects. […] Novel therapeutic alternatives based on recombinant antibody technologies and new toxin inhibitors are being explored. […] This review summarizes the mechanisms by which zinc-dependent SVMPs induce microvascular damage and haemorrhage. […] This paper reviews the mechanisms by which venom PLA2s induce myotoxicity and neurotoxicity. […] A comprehensive view of the structural and functional alterations of extracellular matrix by snake venom metalloproteinases (SVMPs): novel perspectives on the pathophysiology of envenoming.

• #2 Snake Bite and Its Treatment | Medical Science

  https://www.biologydiscussion.com/medical-science-2/snake-bite/snake-bite-and-its-treatment-medical-science/85073

  Snake Venoms: The venoms of most species which have been analysed have been found to be a mixture of several toxic proteins, and enzymes with diversified and complicated pharmacological effects. Venomous properties come from specific toxins, peptides with 60-70 amino acids. Most of these are cardiotoxins or neurotoxin. […] In addition to the toxins, the crude venoms contain many enzymes, e.g. phospholipases, endopeptidase, exopeptidases, proteinases. These are also toxic causing rapid decrease of blood pressure, change in the clotting properties of blood or damage to blood vessels and tissues.

• #2 Snake Envenomation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9854269/

  SNAKE ENVENOMATION REPRESENTS AN IMPORTANT HEALTH PROBLEM IN much of the world. […] Not all bites by venomous snakes involve envenomation; dry bites occur in 2 to 50% of cases. […] When envenomation does occur, the clinical effects depend on the toxins in the venom. […] Local tissue injury and inflammation are caused by enzymes such as hyaluronidase and collagenase, as well as proteinases and phospholipases. […] The effect of snake venom metalloproteinases on the extracellular matrix results in the release of extracellular matrix-derived peptides that exert diverse actions in the tissue. […] In snake envenomation, injury to the lymphatic system plays a role in the development of edema. […] Procoagulant toxins in snake venoms promote consumption coagulopathy, which causes the depletion of factors in the clotting cascade and may result in either spontaneous or uncontrolled bleeding.

• #2 Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10960010/

  Snakebite envenoming is an important public health issue responsible for mortality and severe morbidity. […] The snake venom toxins responsible for tissue damage, their mechanisms of action and pathological effects are reviewed, together with the search of novel therapeutic alternatives to abrogate their effects. […] Tissue-damaging effects are the leading cause of snakebite morbidity, including life-long disabilities such as permanent muscle tissue loss, contractures, hypertrophic scars, chronic ulceration, chronic renal disease, ocular damage and other debilitating pathologies. […] Toxins with tissue-damaging capabilities can be broadly divided into two main groups based on the way they affect cells (and thus tissues). These include (a) cytotoxins, defined as toxins that are truly cytotoxic by directly affecting the viability of cells and (b) extracellular matrix (ECM) degrading enzymes, which, in addition to this action, may be indirectly cytotoxic, meaning that cell death occurs as a secondary effect and not by directly damaging the cells.

• #2 Snake Envenomation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9854269/

  Snake envenomation can result in myocardial infarction, stroke, or other thrombotic effects. […] In severe cases of envenomation from Crotalinae (New World pit vipers), thrombocytopenia is common. […] Neuromuscular paralysis is one of the leading clinical disorders due to envenomation from elapids (snakes in the Elapidae family) such as naja, bungarus, and micrurus species. […] Myotoxicity may develop as a result of the direct effect of venom on muscle through myotoxic phospholipase A2, which disrupts the integrity of the plasma membrane and provokes calcium influx. […] Snake envenomation can result in acute kidney injury, which may progress to chronic kidney disease or renal failure. […] Other systemic effects of venom can include nausea, vomiting, diarrhea, and diaphoresis.

• #2 Inflammation and Oxidative Stress in Snakebite Envenomation: A Brief Descriptive Review and Clinical Implications

  https://www.mdpi.com/2072-6651/14/11/802

  Injection of snake venom provokes local tissue damage often associated with systemic effects, including neurotoxic and cardiotoxic manifestations, bleeding, acute kidney injury, and rhabdomyolysis. […] The variable biochemical and toxicological profile of venom composition determines a wide range of clinical manifestations. Snake venom metalloproteinase (SVMP), serine proteinase (SVSP) inhibitors, and phospholipase A2 (PLA2) are widely present in snake venoms of elapids and viperids. […] SVMP and SVSP affect aggregation function of platelets, coagulation of the blood, fibrinolysis, and the complement system. […] PLA2s exhibit a high degree of toxic activities, on pre- or post-synaptic sites, skeletal and cardiac muscles, coagulation factors, platelet aggregation, as well as hemorrhagic, hemolytic, cytolytic, and muscarinic inhibitor activities.

• #2 Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies | Communications Biology

  https://www.nature.com/articles/s42003-024-06019-6

  The degradation of the basement membrane by SVMPs affects a variety of cell types, including endothelial cells, skeletal muscle cells, keratinocytes and kidney cells. […] By causing microvessel disruption and haemorrhage, SVMPs exert an indirect cytotoxic activity. […] The mechanisms of tissue damage induced by venom toxins discussed above have direct implications in the pathology and pathophysiology of snakebite envenoming.

• #2 Snakebite: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/168828-overview

  Certain pit viper species have unique toxins. Crotalocytin, found in the timber rattlesnake (Crotalus horridus), causes platelet aggregation. Mojave toxin, found in some populations of the Mojave rattlesnake (Crotalus scutulatus), inhibits the presynaptic release of acetylcholine, leading to weakness and paralysis. Pit viper venom may also include bradykinin-related peptides that can lead to angioedema and hypotension. […] Coral snake venoms are complex mixtures that include phospholipase A2, multiple proteases, high-molecular-weight protein, and a variety of neurotoxins. Approximately 380 isoforms of phospholipase A2 have been identified in snake venoms, and their effects include neuromuscular paralysis, bleeding, myonecrosis, edema, widespread inflammation, and platelet aggregation. In coral snakes, the neuromuscular effects are most pronounced.

• #2

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/01000/neurological_and_neuro_ophthalmological.61.aspx

  Hematotoxic venoms, on the other hand, can cause neurological symptoms like ptosis, ophthalmoplegia, and weakness due to three mechanisms: presynaptic inhibition of neurotransmission by phospholipase A2 in Russells viper venom, intracranial haemorrhage, or acute brain infarction. […] Most patients in this review report ptosis followed by neurological weakness of limbs and ophthalmoplegia, while nystagmus, delayed neuropathy, and dysarthria were reported in fewer patients. A moderate number of patients reported decrease in the visual acuity with snake bites. In neurotoxic snake bites, ptosis followed by neuroparalysis are the most common ocular signs and symptoms, while hematotoxin snake bites can cause symptoms ranging from accommodation deficiency and ptosis to ophtalmoplegia, neck muscle weakness, and dysphagia.

• #2 Snakebites – Injuries; Poisoning – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/injuries-poisoning/bites-and-stings/snakebites

  The venom of most North American pit vipers causes very minor changes in neuromuscular conduction, except for Mojave and eastern diamondback rattlesnake venom, which may cause serious neurologic deficits (eg, muscle weakness, respiratory depression). […] Venom of these snakes contains primarily neurotoxic components, which cause a presynaptic neuromuscular blockade, potentially causing respiratory paralysis. The lack of significant proteolytic enzyme activity accounts for the paucity of symptoms and signs at the bite site. […] Rattlesnake envenomations may induce various coagulation abnormalities, including thrombocytopenia, prolongation of prothrombin time (PT, measured by the INR [international normalized ratio]) or activated partial thromboplastin time (PTT), hypofibrinogenemia, elevated fibrin degradation products, or a combination of these findings, causing a disseminated intravascular coagulation (DIC)-like syndrome.

• #2 Snake bite: a current approach to management – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/snake-bite-a-current-approach-to-management.html

  Snake envenoming is uncommon but potentially life-threatening. It is characterised by systemic effects including coagulopathy, neurotoxicity, myotoxicity and renal impairment. […] The majority of dangerous Australian snakes cause a procoagulant coagulopathy. The venom contains a prothrombin activator that leads to consumption of major coagulation factors including fibrinogen, resulting in a defibrination coagulopathy which should be referred to as venom-induced consumptive coagulopathy. This is characterised by very high d-dimers, undetectable fibrinogen, and unrecordable prothrombin time and activated partial thromboplastin time. […] Paralysis is a classic effect of snake bite and is due to presynaptic or postsynaptic neurotoxins in the venom. Presynaptic neurotoxins disrupt neurotransmitter release from the terminal axon. This takes days to resolve and does not respond to antivenom. Postsynaptic neurotoxins competitively block acetylcholine receptors but the effect can be reversed by antivenom.

• #2

  https://www.vin.com/apputil/content/defaultadv1.aspx?pId=11372&catId=35323&id=5709822

  Coagulopathy is one of the most important effects of snakebites and occurs in many viper, elapid and colubrid envenomations. Haemorrhage after envenomation can occur as a result of abnormal functioning of coagulation factors, but also due to venom factors affecting capillary endothelium and platelets. Viperid and crotalid (rattlesnake) venoms are rich in metalloproteinases, responsible for the rapid development of local haemorrhage following intradermal or subcutaneous injection. Snakebites have been thought to be a cause of DIC for decades based on the current criteria used for the diagnosis of DIC, which include thrombocytopenia, increased d-dimer, prolonged PT and aPTT and fibrinogen depletion. More recently, some authors have referred to the coagulopathy associated with snakebites as a venom-induced consumptive coagulopathy (VICC). VICC is characterized by prolonged clotting times, depletion of fibrinogen and co-factors V and VIII and high concentrations of fibrin degradation products (FDPs); however, it is not characterized by the other important features of DIC, such as evidence of systemic microthrombi and end-organ failure. Extended coagulation studies are appropriate in cases of snakebite envenomation, especially in cases envenomed by snake species known to induce haemostatic defects. These tests should include PT, aPTT, fibrinogen, FDPs and/or d-dimer and antithrombin. Thromboelastography (TEG) may prove very useful in such cases. A recent study using TEG, comparing the coagulopathies present in dogs envenomed by puff adder and snouted cobra (Naja annulifera), showed that hypocoagulability was a common feature in puff adder-envenomed dogs with significantly delayed clot initiation (prolonged R-time), and reduced clot kinetics (reduced K-time and angle) at presentation. Dogs envenomed by snouted cobra were normo- to hypercoagulable. At 24 hours post-envenomation, both dogs envenomed by puff adders and cobras were hypercoagulable. This may be an indication of the presence of a heparin-like component in the venom of puff adders.

• #2 Pathophysiology of Snake Envenomation in Dogs and Cats | Our Blog | Animal Emergency Australia

  https://animalemergencyaustralia.com.au/blog/snake-envenomation-in-dogs-and-cats/

  Rhabdomyolysis from a myotoxin is common and can lead to elevated creatine kinase and subsequent renal tubular damage if not treated. Other intra-cellular components will also lead to hyperphosphatemia, hyperkalemia, hypermagnesemia and a metabolic acidosis. […] Haemolysis is also variable amongst snake venom, however, their potency tends to be more exaggerated in species seen in the eastern states of Australia and can require blood transfusions if global hypoxia is evident (ie: elevated lactate, low ScvO2, low base excess, tachycardia). Disruption to the cell membrane by phospholipase causes water to enter the cell, allowing it to swell and causing cell destruction. […] This is typically specific for Taicotoxin from the Taipan, and it has been shown to inhibit calcium channels in the myocardium, leading to prolonged repolarisation and arrhythmias.

• #2 The kidney histopathological spectrum of patients with kidney injury following snakebite envenomation in India: scoping review of five decades | BMC Nephrology | Full Text

  https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03508-y

  Snakebite is a public health problem leading to about 58,000 deaths every year in India. Kidney injury subsequent to snakebite envenomation is common with a reported prevalence of up to 32%. The current study aims to elucidate the spectrum of kidney histopathology in acute kidney injury (AKI) cases associated with snake bites. […] The mechanism of kidney injury in snakebite envenomation is usually multifactorial, it is an interplay of various cytokines, vasoactive substances like endothelin, and other immune mediators. It can be attributed to numerous reasons such as direct nephrotoxicity of the venom, circulatory collapse, intravascular hemolysis with hemoglobinuria, extensive myonecrosis causing myoglobinuria, or Venom-Induced Coagulopathy (VICC). Various proteases, amino acid esterase enzymes, and hemorrhagic proteins present in viperine snake venom can activate procoagulant factors and induce coagulation cascade abnormalities including bleeding diathesis and VICC.

• #2 Snake Bites — Maimonides Emergency Medicine Residency

  https://www.maimonidesem.org/blog/snake-bites

  Coral snake venom primarily consists of neurotoxins that affect the nervous system. These neurotoxins which include micrurotoxin and micruroidin, target the neuromuscular junction at acetylcholine receptors, to which they inhibit. This can lead to respiratory depression. […] Crotaline venom primarily consists of enzymes and peptides that exert cytotoxic, hemotoxic, and proteolytic effects. Metalloproteinases and serine proteinases in the venom contribute to swelling and damage to capillaries. They also lead to coagulation abnormalities.

• #2 Snakebites – Injuries and Poisoning – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/injuries-and-poisoning/bites-and-stings/snakebites

  Severe venom injection (envenomation) can cause damage to the bitten extremity, bleeding, and vital organ damage. […] The venom of rattlesnakes and other pit vipers damages tissue around the bite. Venom may cause changes in blood cells, prevent blood from clotting, and damage blood vessels, causing them to leak. These changes can lead to internal bleeding and to heart, respiratory, and kidney failure. […] The venom of coral snakes affects nervous system activity but causes little damage to tissue around the bite. […] Envenomation is recognized by the development of characteristic symptoms. […] Antivenom contains antibodies that neutralize venoms toxic effects. It is important to elevate the extremity as soon as the antivenom is started to minimize local swelling. The effectiveness of antivenom depends on how soon it is given. Antivenom is more effective when it is given within a short time after a snakebite. […] Prognosis depends on the persons age and overall health and on the location and venom content of the bite. Almost everyone bitten by a venomous snake survives if treated early with appropriate amounts of antivenom.

• #2 Snakebite: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/168828-overview

  Several other neurotoxins are found in coral snake species. Most are alpha-toxins, which competitively antagonize postsynaptic acetylcholine receptors on the neuromuscular junction. Weakness and paralysis result, though these can be overcome by increasing local acetylcholine concentrations. Myotoxic and edematogenic effects have also been detected in several coral snake venoms, with particularly strong activity in the eastern coral snake (Mfulvius). Coral snake venom components can also activate the classic complement pathway and subsequently generate anaphylatoxins, which contribute to vasodilation and allow greater distribution of other venom components. […] Because of the substantial heterogeneity of nonnative venomous snakes, a comprehensive review of their venom components is not possible in this article. In general, however, the venom of these snakes may have cytotoxic, neurotoxic, hematologic, myotoxic, or cardiotoxic effects, often attributable to venom components similar to those described above.

• #2 Snakebite – Special Pet Topics – Merck Veterinary Manual

  https://www.merckvetmanual.com/special-pet-topics/poisoning/snakebite

  Venomous snakes fall into two families: 1) the Elapidae, which include the cobra, mamba, and coral snakes; and 2) the Cortalidae, which include the true vipers (for example, puff adder, Russells viper, and the common European adder) and the pit vipers (for example, rattlesnakes, cottonmouth moccasin, copperhead, and fer-de-lance). Pit vipers and coral snakes are found in North America. […] Elapid snakes have short fangs and tend to hang on and chew venom into their victims. Elapid venom is toxic to the nervous system and paralyzes the breathing center. […] Crotalid snakes have long, hinged, hollow fangs; they strike, inject venom, and withdraw. Crotalid venom is typically toxic to the blood, killing cells and preventing normal clotting. The venom of some crotalid species, for example, the Mojave rattlesnake, also affects the nervous system.

• #2 Inflammation and Oxidative Stress in Snakebite Envenomation: A Brief Descriptive Review and Clinical Implications

  https://www.mdpi.com/2072-6651/14/11/802

  The group of 3FTxs cardiotoxins plays an important role in envenoming by Naja species and cobra elapids, eliciting plasma membrane damage, myonecrosis, and cytotoxicity. […] Many components of snake venoms (PLA2s, SVMPs, and SVSPs) contribute to local and systemic inflammatory processes, which is initiated by an increase of vascular permeability, followed by immune cell infiltration leading to the release of bioactive mediators. […] The production of bioactive molecules by leukocytes, such as ROS and proteinases, as well as the formation of neutrophil extracellular traps (NETs), are involved in the mechanisms of local tissue injuries following administration of snake venoms. […] Another important feature of the pathogenesis of snake envenomation is the production of reactive oxygen species (ROS). Typically, the generation of ROS can potentiate tissue damage at inflammatory sites following snakebite.

• #2 Inflammation and Oxidative Stress in Snakebite Envenomation: A Brief Descriptive Review and Clinical Implications

  https://www.mdpi.com/2072-6651/14/11/802

  The involvement of oxidative stress in the pathogenesis of snake envenomation was initially reported in the early 1980s. […] The injection of elapid venoms of the Egyptian cobra (Naja haje) also induced increases in serum levels of malonaldehyde, while serum levels of GSH, superoxide dismutase (SOD), and catalase (CAT) were consistently reduced. […] Overall, these results suggest that oxidative stress may occur in experimental in vivo envenomation and may be responsible, at least in part, for hepatic and renal damage in both viperid and elapid species. […] The most frequent delayed complications observed in patients with snake envenomation on long-term follow-up are ulceration, amputation, renal failure, and musculoskeletal disabilities. […] In human envenomation, growing evidence suggests that oxidative stress can play a critical role in the pathophysiology of snakebite, predominantly from viperids.

• #2 The Role of the Lymphatic System in Systemic Toxicity of Snakebites

  https://www.jscimedcentral.com/jounal-article-info/Journal-of-Pharmacology-and-Clinical-Toxicology/The-Role-of-the-Lymphatic–System-in-Systemic-Toxicity-of–Snakebites-6131

  Toxic effects of snakebites consist of local toxicity at the site of the bite and systemic toxicity, with coagulopathy and neurotoxicity occurring, depending on the species and composition of the venom. Research has established that the lymph system is the mechanism of systemic spread of venom […] The reviewed articles describe experimental studies of lymphatic inhibition on systemic toxicity of snakebites. […] Experimental studies establish that inhibition of lymph flow by several mechanisms results in reduced systemic toxicity of snakebites. […] To produce systemic toxicity, venom must reach the vascular system and be distributed throughout the body. […] The lymphatic system is the major source of systemic spread of venom. […] Techniques identified in the literature that have been studies in snake envenomations include lymphatic channel ligation, pharmaceuticals that inhibit lymph flow, splints, and devices to apply pressure significant to block lymph flow while preserving arterial flow and venous return.

• #2 The Role of the Lymphatic System in Systemic Toxicity of Snakebites

  https://www.jscimedcentral.com/jounal-article-info/Journal-of-Pharmacology-and-Clinical-Toxicology/The-Role-of-the-Lymphatic–System-in-Systemic-Toxicity-of–Snakebites-6131

  Different techniques to inhibit lymph flow from an extremity after a poisonous snakebite establish that systemic spread of venom occurs by lymph flow. Techniques include lymphatic channel ligation, pharmacological lymph flow inhibitors, splints, and mechanical pressure application at the bite site with sufficient pressure to inhibit lymph flow while preserving arterial and venous flow.

• #2

  https://www.who.int/news-room/fact-sheets/detail/snakebite-envenoming

  Bites by venomous snakes can cause paralysis that may prevent breathing, bleeding disorders that can lead to a fatal haemorrhage, irreversible kidney failure and tissue damage that can cause permanent disability and limb amputation. […] Bites by venomous snakes can cause acute medical emergencies involving severe paralysis that may prevent breathing, cause bleeding disorders that can lead to fatal haemorrhage, cause irreversible kidney failure and severe local tissue destruction that can cause permanent disability and limb amputation. […] Most deaths and serious consequences of snake bites are entirely preventable by making safe and effective antivenoms more widely available and accessible. High quality snake antivenoms are the most effective treatment to prevent or reverse most of the venomous effects of snake bites.

• #2 Managing snakebite | The BMJ

  https://www.bmj.com/content/376/bmj-2020-057926

  Antivenoms are whole or fragmented immunoglobulins fractionated from the plasma of domesticated animals hyper-immunised with venom from one or more snake species over variable periods. They are highly specific and will neutralise only the venoms used in their production and those of a few closely related species. […] Early administration of antivenom prevents or limits haemodynamic alterations, progression of coagulopathy to clinically overt bleeding, postsynaptic neurotoxicity, myotoxicity, acute kidney injury, and local tissue damage. […] The effectiveness of antivenoms in treating established neurotoxicity, soft tissue damage, and acute kidney injury is not established. […] There is insufficient data on long term sequelae after a snakebite. Amputations following snakebite-related soft tissue injuries range from 5908 to 14614 annually in sub-Saharan Africa. Even in patients not requiring amputations, tissue loss may result in chronic ulcers, malignant transformation, and scarring.

• #2 Snakebite clinics and pathogenesis: from preclinical to resource mapping studies [2023]

  https://repositorio.butantan.gov.br/entities/publication/bc976fd4-afb0-428d-9a8c-4998eb111706

  This case provides pivotal insights, affirming that venom from V. berus subspecies in the Carpathian Basin region can indeed induce neurotoxic effects. […] This case report emphasizes the need for a comprehensive healthcare approach, including physiotherapy, plastic surgery, orthopedics, and social support, to aid in the reintegration of snakebite survivors into their communities. […] Antivenom treatments for SBE patients have existed for more than 130 years, remaining the only therapeutics available for this neglected problem.

• #2 Snake bites: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000031.htm

  Snake bites occur when a snake bites the skin. They are medical emergencies if the snake is venomous. […] Venomous animals account for a large number of deaths and injuries worldwide. Snakes alone are estimated to inflict 2.5 million venomous bites each year, resulting in about 150,000 deaths. The actual number may be much larger. Southeast Asia, India, Brazil, and areas of Africa have the most deaths due to snakebite. […] Snake bites can be deadly if not treated quickly. Because of their smaller body size, children are at higher risk for death or serious complications due to snake bites. […] The right antivenom can save a person’s life. Getting to an emergency room as quickly as possible is very important. If properly treated, many snake bites will not have serious effects. […] Most species of snake are harmless and their bites are not life threatening.

• #2 Inflammation and Oxidative Stress in Snakebite Envenomation: A Brief Descriptive Review and Clinical Implications

  https://www.mdpi.com/2072-6651/14/11/802

  Snakebite envenoming is a pathological condition which may occur in response to the injection of venom. Snake venoms contain a complex mixture of biologically active molecules which are responsible for a broad spectrum of clinical manifestations, ranging from local tissue injuries to fatal complications. Snake venom administration commonly provokes local tissue injury often associated with systemic effects, including neurotoxic and cardiotoxic manifestations, bleeding, acute kidney injury, and rhabdomyolysis. An important spectrum of pathogenesis of snake envenomation is the generation of reactive oxygen species (ROS), which can directly provoke tissue damage and also potentiate the deleterious consequences of inflammation at the bite site. […] Clear evidence is mounting suggesting that inflammation and oxidative stress participate in the destructive effects of envenoming, including acute renal failure, tissue necrosis, and unusual susceptibility to bleed (hemorrhage), mostly due to hypocoagulability, neuro/cardio toxicity, and myonecrosis.

• #2 Snakebite envenoming | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201763

  This study highlights the relationship between snakebite envenoming and poverty. […] This paper describes the socioeconomic consequences of snakebites in an impoverished rural setting. […] This review discusses some of the main research areas that need to be developed to generate novel diagnostic and therapeutic tools to confront snakebite envenoming. […] A summary of novel therapeutic alternatives to approach snakebite envenomings, including recombinant antibodies and natural and synthetic venom inhibitors.

• #3

  https://www.vin.com/apputil/content/defaultadv1.aspx?pId=11372&catId=35323&id=5709822

  Snake venom can be defined as highly modified saliva that has undergone evolutionary adaptation to immobilize the prey and aids its digestion by means of the actions of protein-degrading enzymes. The venom composition of each snake is species-specific with up to 25 variable toxic and nontoxic compounds. Snake venoms were initially classified into three groups: cytotoxic, neurotoxic and coagulopathic. This classification is a gross over-simplification, since most snake venoms possess a combination of these actions. Neurotoxic components adversely affect the central nervous system. Cardiotoxic components adversely affect the myocardium and cardiac conduction by increasing cellular membrane permeability to ions. Haemorrhagic toxins cause considerable bleeding into tissues by damaging vascular endothelium in capillary walls. Endothelial damage promotes coagulation and bleeding is often accompanied by clotting and haemolysis. Thrombins (procoagulants) induce coagulation and disrupt the normal haemostatic balance and induce intravascular coagulation. Cytolysins lyse body tissue cells and leukocytes. The venom of elapids (e.g., cobras and mambas) consists primarily of neurotoxins, cardiotoxins and haemolytic agents. Viperid venom consists of haemorrhagic elements, thrombins and cytolysins. The venom of colubrids (e.g., Boomslang and vine snake) is mainly haemorrhagic, and exsanguination is the main observed complication.

• #3 Snake Envenomation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9854269/

  SNAKE ENVENOMATION REPRESENTS AN IMPORTANT HEALTH PROBLEM IN much of the world. […] Not all bites by venomous snakes involve envenomation; dry bites occur in 2 to 50% of cases. […] When envenomation does occur, the clinical effects depend on the toxins in the venom. […] Local tissue injury and inflammation are caused by enzymes such as hyaluronidase and collagenase, as well as proteinases and phospholipases. […] The effect of snake venom metalloproteinases on the extracellular matrix results in the release of extracellular matrix-derived peptides that exert diverse actions in the tissue. […] In snake envenomation, injury to the lymphatic system plays a role in the development of edema. […] Procoagulant toxins in snake venoms promote consumption coagulopathy, which causes the depletion of factors in the clotting cascade and may result in either spontaneous or uncontrolled bleeding.

• #3 Snakebite: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/168828-overview

  Several other neurotoxins are found in coral snake species. Most are alpha-toxins, which competitively antagonize postsynaptic acetylcholine receptors on the neuromuscular junction. Weakness and paralysis result, though these can be overcome by increasing local acetylcholine concentrations. Myotoxic and edematogenic effects have also been detected in several coral snake venoms, with particularly strong activity in the eastern coral snake (Mfulvius). Coral snake venom components can also activate the classic complement pathway and subsequently generate anaphylatoxins, which contribute to vasodilation and allow greater distribution of other venom components. […] Because of the substantial heterogeneity of nonnative venomous snakes, a comprehensive review of their venom components is not possible in this article. In general, however, the venom of these snakes may have cytotoxic, neurotoxic, hematologic, myotoxic, or cardiotoxic effects, often attributable to venom components similar to those described above.

• #3 Neurotoxic Snake Bite: Management

  https://www.scitechnol.com/peer-review/neurotoxic-snake-bite-management-tk4R.php?article_id=23679

  Principally there are two types of neurotoxic snakes seen in Indian subcontinent, namely Indian cobra and common krait. Venom acts at myoneural junction and paralyses muscle. […] Krait venom contains B-bungarotoxin which is presynaptic Acetyl choline (Ach) Ach receptor blocker with phospholipase A2 activity. Action is irreversible even with administration of Anti-Snake Venom (ASV). Action is much stronger compared to that due to cobra. […] Cobra has a post-synaptic neurotoxin which is present in alpha neurotoxin of its venom. It inhibits nicotinic Ach receptor. […] Snakes cause acute reversible muscle paralysis by inhibiting neuromuscular transmission. Naja naja neurotoxins (alfa-bungaro toxins have post-synaptic in action and their binding is reversible. Improvement occurs within 30-60 minutes of initial dose of Anti-Snake Venom (ASV). Anticholinesterase drugs like neostigmine sometimes are even more effective. Krait venoms have pre-synaptic action and bind irreversibly. Anticholinesterases are usually not effective to neutralize B-bungarotoxins.

• #3 Snakebite – Wikipedia

  https://en.wikipedia.org/wiki/Snakebite

  The venom itself evolved through the process of natural selection; it retained and emphasized the qualities that made it useful in killing or subduing prey. […] Venom in many snakes, such as pit vipers, affects virtually every organ system in the human body and can be a combination of many toxins, including cytotoxins, hemotoxins, neurotoxins, and myotoxins, allowing for an enormous variety of symptoms. Snake venom may cause cytotoxicity as various enzymes including hyaluronidases, collagenases, proteinases and phospholipases lead to breakdown (dermonecrosis) and injury of local tissue and inflammation which leads to pain, edema and blister formation. […] In venom-induced consumption coagulopathy, toxins in snake venom promote hemorrhage via activation, consumption, and subsequent depletion of clotting factors in the blood. […] Snake venom is known to cause neuromuscular paralysis, usually as a flaccid paralysis that is descending; starting at the facial muscles, causing ptosis or drooping eyelids and dysarthria or poor articulation of speech, and descending to the respiratory muscles causing respiratory compromise.

• #3 Snake bite: a current approach to management – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/snake-bite-a-current-approach-to-management.html

  Some Australian snakes, such as the mulga snakes and tiger snakes, have venom containing myotoxins that cause rhabdomyolysis with muscle pain, tenderness and weakness, a rapidly rising creatine kinase and myoglobinuria. […] Renal impairment or acute renal failure can occur secondary to severe rhabdomyolysis, in association with microangiopathic haemolytic anaemia (reported with brown snakes) or can occur rarely in isolation. […] The snake venom detection kit is a useful diagnostic test to confirm which of the five major snake groups is responsible for the envenoming. This will determine which antivenom is needed. […] Antivenom is the mainstay of treatment in patients with systemic envenoming. It is not recommended in patients who only manifest non-specific features as these may be misleading. Antivenom should always be administered intravenously after 1:10 dilution with normal saline or Hartmann’s solution.

• #3

  https://journals.lww.com/sjkd/fulltext/2003/14020/snake_bites_and_acute_renal_failure.7.aspx

  The exact pathogenesis of ARF following snake bite in not well established. This is due to the lack of a reproducible animal model. However, a number of factors may contribute viz. bleeding, hypotension, circulatory collapse, intravascular hemolysis, disseminated intravascular coagulation, microangiopathic hemolytic anemia and also direct nephrotoxicity of the venom. […] Although nearly all snakes with medical relevance can induce acute renal failure (ARF), it is unusual except with bites by Russell’s viper, E. Carinatus and members of the genera Crotalus and Bothrops. […] The presence of fibrin thrombi in the renal microvasculature and in the glomerular capillaries, and the findings of microangiopathic hemolytic anemia and thrombocytopenia in patients with cortical necrosis strongly suggest that DIC plays a major pathogenetic role in snake-bite induced cortical necrosis.

• #3 Snakebite – Special Pet Topics – Merck Veterinary Manual

  https://www.merckvetmanual.com/special-pet-topics/poisoning/snakebite

  Venomous snakes fall into two families: 1) the Elapidae, which include the cobra, mamba, and coral snakes; and 2) the Cortalidae, which include the true vipers (for example, puff adder, Russells viper, and the common European adder) and the pit vipers (for example, rattlesnakes, cottonmouth moccasin, copperhead, and fer-de-lance). Pit vipers and coral snakes are found in North America. […] Elapid snakes have short fangs and tend to hang on and chew venom into their victims. Elapid venom is toxic to the nervous system and paralyzes the breathing center. […] Crotalid snakes have long, hinged, hollow fangs; they strike, inject venom, and withdraw. Crotalid venom is typically toxic to the blood, killing cells and preventing normal clotting. The venom of some crotalid species, for example, the Mojave rattlesnake, also affects the nervous system.

• #3 Snakebites – Injuries; Poisoning – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/injuries-poisoning/bites-and-stings/snakebites

  The venom of most North American pit vipers causes very minor changes in neuromuscular conduction, except for Mojave and eastern diamondback rattlesnake venom, which may cause serious neurologic deficits (eg, muscle weakness, respiratory depression). […] Venom of these snakes contains primarily neurotoxic components, which cause a presynaptic neuromuscular blockade, potentially causing respiratory paralysis. The lack of significant proteolytic enzyme activity accounts for the paucity of symptoms and signs at the bite site. […] Rattlesnake envenomations may induce various coagulation abnormalities, including thrombocytopenia, prolongation of prothrombin time (PT, measured by the INR [international normalized ratio]) or activated partial thromboplastin time (PTT), hypofibrinogenemia, elevated fibrin degradation products, or a combination of these findings, causing a disseminated intravascular coagulation (DIC)-like syndrome.

• #3 Snakebites – Injuries and Poisoning – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/injuries-and-poisoning/bites-and-stings/snakebites

  Severe venom injection (envenomation) can cause damage to the bitten extremity, bleeding, and vital organ damage. […] The venom of rattlesnakes and other pit vipers damages tissue around the bite. Venom may cause changes in blood cells, prevent blood from clotting, and damage blood vessels, causing them to leak. These changes can lead to internal bleeding and to heart, respiratory, and kidney failure. […] The venom of coral snakes affects nervous system activity but causes little damage to tissue around the bite. […] Envenomation is recognized by the development of characteristic symptoms. […] Antivenom contains antibodies that neutralize venoms toxic effects. It is important to elevate the extremity as soon as the antivenom is started to minimize local swelling. The effectiveness of antivenom depends on how soon it is given. Antivenom is more effective when it is given within a short time after a snakebite. […] Prognosis depends on the persons age and overall health and on the location and venom content of the bite. Almost everyone bitten by a venomous snake survives if treated early with appropriate amounts of antivenom.

• #3 Inflammation and Oxidative Stress in Snakebite Envenomation: A Brief Descriptive Review and Clinical Implications

  https://www.mdpi.com/2072-6651/14/11/802

  The group of 3FTxs cardiotoxins plays an important role in envenoming by Naja species and cobra elapids, eliciting plasma membrane damage, myonecrosis, and cytotoxicity. […] Many components of snake venoms (PLA2s, SVMPs, and SVSPs) contribute to local and systemic inflammatory processes, which is initiated by an increase of vascular permeability, followed by immune cell infiltration leading to the release of bioactive mediators. […] The production of bioactive molecules by leukocytes, such as ROS and proteinases, as well as the formation of neutrophil extracellular traps (NETs), are involved in the mechanisms of local tissue injuries following administration of snake venoms. […] Another important feature of the pathogenesis of snake envenomation is the production of reactive oxygen species (ROS). Typically, the generation of ROS can potentiate tissue damage at inflammatory sites following snakebite.

• #3 Rattlesnake Bite: Symptoms, Treatment, and Recovery Timeline

  https://www.healthline.com/health/rattlesnake-bite

  Rattlesnake bites are a medical emergency and can be fatal if left untreated. Seek help within half an hour. Left untreated, it can lead to organ failure and death in two to three days. […] The venom from the majority of rattlesnake bites will damage tissue and affect your circulatory system by destroying skin tissues and blood cells and by causing you to hemorrhage internally. Most rattlesnake venom is composed mainly of hemotoxic elements. […] Once bitten, the venom takes only seconds to travel from the rattlesnakes retractable fangs, through your skin, and into your bloodstream. You’ll begin to see symptoms immediately, but your symptoms will worsen over time. […] If the bite is left untreated, your bodily functions will break down over a period of 2 or 3 days and the bite may result in severe organ damage or death.

• #3 Snake bite: a current approach to management – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/snake-bite-a-current-approach-to-management.html

  The postsynaptic neurotoxicity seen with death adder bites is reversed by antivenom, but presynaptic neurotoxicity seen with taipan and tiger snakes is irreversible once it has developed and antivenom will only prevent further progression. Procoagulant toxins are neutralised by antivenom, but recovery of normal coagulation takes 612 hours on average. Anticoagulant coagulopathy is rapidly reversed by antivenom. Development or progression of rhabdomyolysis can be prevented by antivenom but it cannot be reversed.

• #3  

  https://www.saem.org/about-saem/academies-interest-groups-affiliates2/cdem/for-students/online-education/m4-curriculum/group-m4-environmental/snake-bites

  Viperidae venom is a complex solution of various proteins, peptides and enzymes that allow the snake to kill its prey quickly and begin the digestive process. […] Elapidae Venom has various toxins which produce systemic neurotoxicity. Coral snake envenomation may present with serious systemic toxicity with little findings at the actual site of envenomation due to the venoms lack of cytotoxicity. […] Because children have smaller body mass, smaller limbs, and less subcutaneous tissue, they can potentially receive more venom per kilogram body weight and therefore have more clinical severity than adults.

• #3 Managing snakebite | The BMJ

  https://www.bmj.com/content/376/bmj-2020-057926

  Antivenoms are whole or fragmented immunoglobulins fractionated from the plasma of domesticated animals hyper-immunised with venom from one or more snake species over variable periods. They are highly specific and will neutralise only the venoms used in their production and those of a few closely related species. […] Early administration of antivenom prevents or limits haemodynamic alterations, progression of coagulopathy to clinically overt bleeding, postsynaptic neurotoxicity, myotoxicity, acute kidney injury, and local tissue damage. […] The effectiveness of antivenoms in treating established neurotoxicity, soft tissue damage, and acute kidney injury is not established. […] There is insufficient data on long term sequelae after a snakebite. Amputations following snakebite-related soft tissue injuries range from 5908 to 14614 annually in sub-Saharan Africa. Even in patients not requiring amputations, tissue loss may result in chronic ulcers, malignant transformation, and scarring.

• #3 SciELO Brazil – Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping review Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping

  https://www.scielo.br/j/jvatitd/a/HzyqxwrYDxPhkgKHHxH3mRh/

  Venom-induced consumption coagulopathy (VICC) is the most likely pathway in AKI due to Bothrops snakes: the association between AKI and abnormal coagulation, including abnormal aPTT, hypofibrinogenemia and hemorrhagic symptoms. […] The formation of microthrombi in blood and leukocyte migration through endothelial cells into renal interstitial compartment could contribute to vascular dysfunction. […] Immunologic phenomena seem to contribute to the snake venom related AKI in a minor role. […] The pathogenesis of Bothrops venom related AKI includes immunologic mechanisms, coagulation disorders, pigmenturia, direct nephrotoxicity and the inflammatory response with systemic and renal hemodynamic effects.

• #4

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/01000/neurological_and_neuro_ophthalmological.61.aspx

  When neurotoxin enters the body by a snake bite, it causes neurological symptoms like muscle weakness, paralysis, altered sensation, and coordination issues. It can also impact the visual system, resulting in neuro-ophthalmological manifestations such as blurred vision, double vision, drooping eyelids, and vision loss. […] Neurotoxins present in snake venom bind to neuromuscular junctions both pre-synaptically and post-synaptically, resulting in muscle weakness. For instance, alpha-bungarotoxin found in krait venom binds to acetylcholine receptors, leading to a reduction in acetylcholine receptor sites in the postsynaptic membrane. On the other hand, alpha-cobra toxin produces features of myasthenia gravis in experimental animals due to its similar action. Neurotoxicity is caused by the pre-synaptic actions of phospholipase A2 enzyme and Beta-bungarotoxin.

• #4 Pathophysiology of Snake Envenomation in Dogs and Cats | Our Blog | Animal Emergency Australia

  https://animalemergencyaustralia.com.au/blog/snake-envenomation-in-dogs-and-cats/

  The severity of neurological impairment depends on whether the particular toxin attaches to the pre-synaptic terminal or post-synaptic terminal at the neuromuscular junction (NMJ). Neurotoxins attached to the pre-synaptic terminal tend to have a greater affinity for their receptors, are less responsive to antivenene administration, and cause more severe neurological disease. […] There are varying degrees of coagulopathies amongst snake species, and their severity depends on whether they are caused pro-coagulant or anti-coagulant toxins. The most severe coagulopathies are caused by pro-thrombotic toxins and mimic factor-Xa, combining with endogenous factor Va to cleave prothrombin into thrombin and proceed into Venom Induced. […] Although this is not well understood, nephrotoxicity from snake envenomation is thought to arise from indirect actions of tubular damage associated with myoglobinuria and bilirubinuria, hypovolaemia, procoagulation and hypoxaemia-ischemia injury at the glomerulus.

• #4 Snakebite – Special Pet Topics – Merck Veterinary Manual

  https://www.merckvetmanual.com/special-pet-topics/poisoning/snakebite

  Venomous snakes fall into two families: 1) the Elapidae, which include the cobra, mamba, and coral snakes; and 2) the Cortalidae, which include the true vipers (for example, puff adder, Russells viper, and the common European adder) and the pit vipers (for example, rattlesnakes, cottonmouth moccasin, copperhead, and fer-de-lance). Pit vipers and coral snakes are found in North America. […] Elapid snakes have short fangs and tend to hang on and chew venom into their victims. Elapid venom is toxic to the nervous system and paralyzes the breathing center. […] Crotalid snakes have long, hinged, hollow fangs; they strike, inject venom, and withdraw. Crotalid venom is typically toxic to the blood, killing cells and preventing normal clotting. The venom of some crotalid species, for example, the Mojave rattlesnake, also affects the nervous system.

• #4 Managing snakebite | The BMJ

  https://www.bmj.com/content/376/bmj-2020-057926

  Some patients with acute kidney injury may progress to chronic renal failure. Limited data from case reports and observational studies from South Asia indicate that chronic hypopituitarism, a sequel of acute pituitary haemorrhage, can present as fatigue, arrested puberty, amenorrhoea, and hypothyroidism as late as 10 years after the bite.

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